The plasma cell malignancy, multiple myeloma (MM), has significantly improved by the application of new drugs and autologous hematopoietic stem cell transplantation. However, MM remains incurable. A number of studies have revealed an anti‐MM effect of natural killer (NK) cells; however, their clinical efficacy is limited. Furthermore, glycogen synthase kinase (GSK)‐3β inhibitors show an antitumor function. In this study, we aimed to evaluate the potential roles of a GSK‐3β inhibitor (TWS119) in the regulation of NK cell cytotoxicity against MM. Our results showed that, in the presence of TWS119, the NK cell line, NK‐92, and in vitro‐expanded primary NK cells exhibited a significantly higher degranulation activity, expression of activating receptors, cellular cytotoxicity, and cytokine secretion when they were exposed to MM cells. Mechanistic studies indicated that TWS119 treatment markedly upregulated RAB27A expression, a key molecule for NK cell degranulation, and induced the colocalization of β‐catenin with NF‐κB in the nucleus of NK cells. More importantly, GSK‐3β inhibition combined with the adoptive transfer of TWS119‐treated NK‐92 cells significantly reduced tumor volume and prolonged the survival time of myeloma‐bearing mice. In summary, our novel findings suggest that targeting GSK‐3β through the activation of β‐catenin/NF‐κB pathway may be an important approach to improve therapeutic efficacy of NK cell transfusion for MM.

Objective To identify of vital genes in the blood exosome related to the process of gastric carcinogenesis and help to reduce mortality rates through early diagnosis and the development of new anticancer therapies. Methods: The RNAs data of blood exosomes from patients with GC and healthy controls were downlinked from exoRBase database, and the differential expression of messenger RNA (mRNA), long non coding RNA (lncRNA), and circular RNA (circRNA) were analyzed using R language. Then the relevant RNAs and their corresponding miRNA data predicted by ENCORI, miRcode and other databases, were imported into the ceRNA network. Finally, the DAVID was accessed to investigate the DEmRNAs’ GO annotations and KEGG analysis. Results: A total of 62 mRNAs, 3 lncRNAs and 15 circRNAs were differentially expressed. The ceRNA network was constructed with Cytoscape software, including 192 mRNA nodes, 32 lncRNA nodes, 28 circRNA nodes, and 152 miRNA nodes, with the top 10 hub genes EMSY, ZEB2, LCOR, MFSD14A, ERBIN, hsa-miR-363-3p, hsa-miR-137, hsa-miR-27a-3p, hsa-miR-23b-3p and hsa_circ_0000038. According to GO annotation, the biological processes mainly in cytoplasmic translation, the cell component were mostly in the ribosome and its subunit and the major molecular functions included structural constituent of ribosome, etc. The KEGG revealed that the DEmRNA were primarily enriched in mRNA monitoring pathway. Conclusion: A ceRNA network in the blood exosome of GC were built, the hub genes were screened out, the biological process, cell component, molecular function and enrichment pathway of DEmRNA were explored, which proved that the ribosome biogenesis was a major player in the exosome of gastric cancer and this provide precise targets for making a diagnosis and giving treatment of GC.

The present study aimed to investigate whether co-administration of mesenchymal stromal cells (MSC) and linezolid (LZD) into a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA)-infected pneumonia would bring a synergistic therapeutic effect. Human umbilical cord-derived MSCs (hUMSCs) were isolated and characterized. A rabbit model of pneumonia was constructed by delivering 1 × 1010 CFU MRSA via a bronchoscope into the basal segment of lower lobe of right lung. Through analyzing vital sign, pulmonary auscultation, SpO2, chest imaging, bronchoscopic manifestations, pathology, neutrophil percentage, and inflammatory factors, we verified that a rabbit model of MRSA-induced pneumonia was successfully constructed. Individual treatment with LZD (50 mg/kg for two times/day) resulted in improvement of body weight, chest imaging, bronchoscopic manifestations, histological parameters, and IL-10 concentration in plasma (P<0.01), decreasing pulmonary auscultation, and reduction of IL-8, IL-6, CRP, and TNF-α concentrations in plasma (P<0.01) compared with the pneumonia model group at 48 and 168 h. Compared with LZD group, co-administration of hUMSCs (1 × 106/kg for two times at 6 and 72 h after MRSA instillation) and LZD further increased the body weight (P<0.05). The changes we observed from chest imaging, bronchoscopic manifestations and pathology revealed that co-administration of hUMSCs and LZD reduced lung inflammation more significantly than that of LZD group. The plasma levels of IL-8, IL-6, CRP, and TNF-α in combined group decreased dramatically compared with the LZD group (P<0.05). In conclusion, hUMSCs administration significantly improved therapeutic effects of LZD on pneumonia resulted from MRSA infection in a rabbit model.

We state the concept,tasks of diagnostics,and then put forward the main development direction of it in this paper.We hope experts and scholars to point out mistakes.We should constantly study the concept and tasks of diagnostics,then adjust and improve the development direction of it.We should try to finish the heavy and arduous tasks of diagnostics and combine the traditional diagnosis technology and methods with the modern closely,then apply them to clinic and serve the patients.We should study the diagnostic thinking,behavior and art constantly and attempt to create teaching methods and evaluation system of diagnostics,which accord with the situation of China.We should strengthen the education and training of clinical basic ability of clinicians.Diagnostics should be developed by the way of subject.