IL4/IL4R signaling promotes the osteolysis in metastatic bone of CRC through regulating the proliferation of osteoclast precursors.

BACKGROUND: Bone metastasis of colorectal cancer (CRC) often indicates a poor prognosis. Osteolysis can be observed in metastatic sites, implying an aberrant activation of osteoclasts. However, how osteoclastogenesis is regulated in metastatic microenvironment caused by colorectal cancer is still unclear. METHODS: In this study, mice bone metastatic model of CRC was established through injection of MC-38 or CT-26 cells. BrdU assays showed primary CD115 ( +) osteoclast precursors (OCPs) proliferated at the first 2 weeks. Transcriptomic profiling was performed to identify differentially expressing genes and pathways in OCPs indirectly co-cultured with CRC cells RESULTS: The expression of IL4Rα was found to be significantly upregulated in OCPs stimulated by tumor conditioned medium (CM). Further investigation indicated that IL-4 signaling regulated proliferation of OPCs through interacting with type I IL4 receptor, and neutrophils were the main source of IL-4 in bone marrow. The proliferation of OCPs can be inhibited in IL4 deficiency mice. In addition, ERK pathway was activated by IL4/IL4R signaling. Ravoxertinib, an ERK antagonists, could significantly prevent bone destruction through inhibiting the proliferation of OCPs. CONCLUSION: Our study indicates the essential role of IL4/IL4R signaling for the proliferation of OCPs in early metastasis of CRC predominantly through activating ERK pathway, which remarkedly impacts the number of osteoclasts in later stage and leads to osteolytic lesions. Moreover, Ravoxertinib could be a new therapeutical target for bone metastasis of CRC.

Risk factors for cow's milk protein allergy in infants: a multicenter survey / 中国当代儿科杂志

OBJECTIVE@#To investigate the risk factors for cow's milk protein allergy (CMPA) among infants through a multicenter clinical study.@*METHODS@#A total of 1 829 infants, aged 1-12 months, who attended the outpatient service of the pediatric department in six hospitals in Shenzhen, China from June 2016 to May 2017 were enrolled as subjects. A questionnaire survey was performed to screen out suspected cases of CMPA. Food avoidance and oral food challenge tests were used to make a confirmed diagnosis of CMPA CMPA. A multivariate logistic regression analysis was used to investigate the risk factors for CMPA.@*RESULTS@#Among the 1 829 infants, 82 (4.48%) were diagnosed with CMPA. The multivariate logistic regression analysis showed that maternal food allergy (OR=4.91, 95%CI: 2.24-10.76, P6 months (OR=0.38, 95%CI: 0.17-0.86, P<0.05) were protective factors.@*CONCLUSIONS@#The introduction of complementary food at an age of <4 months, maternal food allergy, and antibiotic exposure during pregnancy are risk factors for CMPA in infants.

Development of new targeted drugs for pulmonary arterial hypertension / 国际药学研究杂志

Pulmonary arterial hypertension(PAH)is a rare disease characterized by progressive elevation of pulmonary vascular resistance that leads to right heart failure and even death. The prognosis of PAH is poor. Before 1990, the era of conventional therapy, patients with PAH were mainly treated with general supportive therapy and calcium channel blockers (CCB). Since 1990, with the coming of the era of new drugs, the advent of compounds targeted at three pathways (prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors) has improved the clinical symptoms, exercise capacity, and even survival of patients with PAH. In recent years, there have been great research advances in the pathogenesis of PAH, and now more novel drugs are being investigated in clinical trials, which will lead to a burst in the treatment of PAH.

Application of peer education in mental health education for adolescent primary and middle school students / 中国学校卫生

Objective@#To assess the application effect of peer education in mental health education for adolescent primary and middle school students and to provide evidence for promoting the mental health of adolescent primary and middle school students in application.@*Methods@#The non-randomized controlled trial was performed, 4-5 th grade students of two primary and 7-8 th grade students of two middle schools in a district of Chongqing were chosen as peer-education experimental group, and students in the same grade of another two school were chosen as the blank control group. The Mental Health Inventory of Middle School Students scale and self-made questionnaire were used to exam in mental health status of the subjects before and after intervention.@*Results@#The detection rates after intervention of the mental health, compulsion, paranoia, hostility, interpersonal relationship, depression, anxiety, academic stress, emotional imbalance and psychological imbalance (36.8%, 46.1%, 36.6%, 33.3%, 37.2%, 38.8%, 40.9%, 45.7%, 49.2%, 30.3%) in experimental group were lower than those before intervention (39.9%, 55.3%, 38.8%, 37.9%, 43.9%, 40.5%, 42.7%, 48.0%, 52.5%, 32.1%). The detection rate after intervention of maladjustment(39.8%)was higher than that before intervention(37.7%)(P<0.05). Logistic regression analysis showed that the detection rate after intervention of the mental health, compulsion, paranoia, hostility, interpersonal relationship, depression, anxiety and academic stress status of adolescent primary and middle school students in experimental group was 0.63 times more than the rate of the control group(95%CI=0.49-0.81),0.73(95%CI=0.58-0.91),0.68(95%CI=0.54-0.86),0.71(95%CI=0.56-0.91)(P<0.05).@*Conclusion@#Peer education is an effective measure and method to improve compulsion,paranoia,hostility,interpersonal relationship,depression,anxiety and intervention effect of adolescent primary and middle school students.

Compare of Luteolin content in different types and different parts of Lonicare Japonica / 中华中医药杂志

blossam.This can be used as reference for cultivating and application of Lonicara Japonica.

Expression and purification of three fusion proteins containing a single B-cell epitope (beta5, beta9 or beta8) of human chorionic gonadotropin beta subunit / 生物工程学报

The possibility of using a subunit or fragment of human chorionic gonadotropin (hCG) as an immunogen for birth control has been actively explored for many years. This protein homone is produced by the fertilized egg and is required for implantation of the blastocyst into the maternal uterus and the maitenance of pregnancy. In previous studies, several bio-synthesized hCG chimeric peptides (CP) that contain three linear B-cell epitopes (beta5, beta9 and beta8) of beta-hCG subunit together with various foreign 'promiscuous' T-cell epitopes were constructed and expressed as potential new hCG vaccine immunogens. In order to detect antibodies to each of the individual B-cell epitopes present in the animal antiserum raised against the hCG CPs, we decided to construct three recombinant proteins, each contains a single target B-cell epitope (betaE) of beta-hCG. Two sets of DNA fragments were chemically synthesized encoding the beta5, beta9 and beta8 epitopes (betaE) 45 approximately 52, 113 approximately 116 or 133 approximately 144 of beta-hCG subunit and were inserted into the downstream of streptavidin (Stv) gene in pTSA18 separately, with or without an extra TAA codon at the 3'-terminals of the genes. SDS-PAGE analysis revealed that only Stv-betaE (-beta5, -beta9 or -beta8) fusion genes set with the TAA codon can be expressed in E. coli BL21 (DE3) pLysS strain at high level after 1mM IPTG induction for 4 hours. Additionally, these fusion proteins can all be recognized by specific polyclonal antiserum (RS-4157) generated upon immunization with the loop peptide 38 approximately 57 of beta-hCG, monoclonal antibody (mAb) FB12 to beta9 epitope and mAb OT3A that specially recognizes reporter sequence 133 approximately 139 of beta8 epitope 137 approximately 144. Each of the proteins can be purified to 95% relative homogeneity using an improved method of preparative gel polyacrylamide gel electrophoresis. The yields were 5 mg per 1 L culture. The three target Stv-betaE fusion proteins will be useful in determining the immunogenicity of designed hCG CPs and hCG vaccines, including hCG DNA vaccines.