Mitochondrion is known as the energy factory of the cell, which is also a unique mammalian organelle and considered to be evolved from aerobic prokaryotes more than a billion years ago. Mitochondrial DNA, similar to that of its bacterial ancestor’s, consists of a circular loop and contains significant number of unmethylated DNA as CpG islands. The innate immune system plays an important role in the mammalian immune response. Recent research has demonstrated that mitochondrial DNA (mtDNA) activates several innate immune pathways involving TLR9, NLRP3 and STING signaling, which contributes to the signaling platforms and results in effector responses. In addition to facilitating antibacterial immunity and regulating antiviral signaling, mounting evidence suggests that mtDNA contributes to inflammatory diseases following cellular damage and stress. Therefore, in addition to its well-appreciated roles in cellular metabolism and energy production,mtDNA appears to function as a key member in the innate immune system. Here, we highlight the emerging roles of mtDNA in innate immunity.
Animals ; DNA, Mitochondrial ; genetics ; Humans ; Immunity, Innate ; immunology ; Mitochondria ; genetics ; immunology ; Signal Transduction

Since the establishment of eight-year clinical medicine specialty, in line with the princi-ple of "eight-year consistency and fusion of the bachelor and doctor degree", the training mode of "strength-ening the foundation, focusing on quality, overall optimization, facing the clinical" has been implemented. In order to reach the standard of professional doctorate, a series of courses of professional doctorate need to be fused in limited time and designed carefully by medical schools. However, grasping proper teaching time and opportunity is particularly important for students' learning and development. By collecting the courses information of 11 medical colleges and universities offering eight-year clinical medicine specialty, we have analyzed the teaching time, methods and course categories of scientific research training courses and graduate degree courses, aiming to find the appropriate teaching program.

Objective To investigate the clinical curative effect of Modified Gualou Xiebai Banxia Decoction in the treatment of stable angina pectoris(SAP)with internal resistance of phlegm and turbidity and its effect on gut microbiota.Methods The clinical data of 72 cases of SAP patients with phlegm turbidity and internal resistance type in our hospital were selected for prospective study,sorted according to the order of admission,and divided into control group and observer by random number table method,with 36 cases in each group.The control group was given standardized western medicine treatment,and the observation group was given the addition of Modified Gualou Xiebai Banxia Decoction on the basis of the control group.The clinical efficacy and gut microbiota composition of the two groups of patients were compared.Results After treatment,the clinical efficacy of the observation group was better than that of the control group(P<0.05);there was no significant difference in the ECG efficacy between the two groups(P>0.05).Based on 16S rDNA technology,at the phylum and genus levels,there was no difference in the abundance of Bacteroidota,Bacteroides and Faecalibacterium(P>0.05).After treatment,the abundance of Bacteroidota in the observation group increased more significantly than that in the control group(P<0.05).Conclusion Modified Gualou Xiebai Banxia Decoction can effectively improve the clinical efficacy of SAP patients with phlegm-turbid internal resistance by regulating gut microbiota,which provides new inspiration for the further development of Gualou Xiebai Banxia Decoction.

OBJECTIVE：To systematically evaluate the efficacy and safety of Kuanxiong aerosol in the treatment of coronary heart disease angina ，and to provide evidence-based reference for climical drug use . METHODS ：Retrieved from Cochrane Library，PubMed，Embase，CKNI，Wanfang data ，VIP，and CBM ，randomized controlled trials （RCTs）about Kuanxiong aerosol （trial group ）versus nitroglycerin （control group ）in the treatment of coronary heart disease angina were collected during the inception to Mar. 20th，2020. After literature screening and data extraction ，quality assessment was performed using the bias risk assessment tool recommended by the Cochrane System Evaluator Manual 5.1.0. Meta-analysis was performed by using Rev Man 5.3 statistical software. Sensitivity analysis was conducted for the stability of the result ，and trial sequential analysis （TSA）was performed by using TSA 0.9 software. RESULTS ：A total of 11 RCTs were included ，with a total of 1 847 cases. Meta-analysis showed that improvement rate of angina pectoris （within 3 min）[RR＝1.11，95％CI（1.02，1.22），P＝0.02] and total response rate of angina pectoris （within 5 min）[RR＝1.04，95％ CI（1.01，1.07），P＝0.01] in trial group were significantly higher than control group；the incidence of ADR [RR＝0.44，95％CI（0.35，0.57），P＜0.000 01] in trial group was significantly lower than control group. There was no statistical significance in total response rate of ECG [RR＝1.02，95％CI（0.97，1.09），P＝0.42] or the level of NO after treatment [SMD ＝－0.08，95％CI（－0.61，0.45），P＝0.76] between 2 groups. The results of sensitiv ity analysis and TSA showed that the efficacy evidence of Kuanxiong aerosol in the treatment of coronary heart disease pectoris was not accurate ，but the evidence of safety was accurate. CONCLUSIONS ：Kuanxiong aerosol can improve the efficacy in patients with coronary heart disease angina ，and the safety is better ，but the conclusions of efficacy needs to be further confirmed by enlarging sample size.

A significant proportion of non-small cell lung cancer (NSCLC) patients experience accumulating chemotherapy-related adverse events, motivating the design of chemosensitizating strategies. The main cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks (DSB). It is thus conceivable that DNA-dependent protein kinase (DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of chemotherapy. The present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on NSCLC. We identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis. M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549, H460 and H1703 NSCLC cell lines. In the four combinations based on two NSCLC xenograft models and two chemotherapy, we also observed tumor regression at tolerated doses

The abnormal activation of HER family kinase activity is closely related to the development of human malignancies. In this study, we used HER kinases as targets for the treatment of nasopharyngeal carcinoma (NPC) and explored the anti-tumor effects of the novel pan-HER inhibitor HM781-36B, alone or in combination with cisplatin. We found that HER family proteins were positively expressed in tumor tissues of some NPC patients, and the high levels of those proteins were significantly related to poor prognosis. HM781-36B inhibited NPC in vitro and in vivo. HM781-36B exerted synergistic effects with cisplatin on inhibiting proliferation and promoting apoptosis of NPC cells. In NPC xenograft models in nude mice, HM781-36B and cisplatin synergistically inhibited tumor growth. Downregulating the activity of HER family proteins and their downstream signaling pathways and regulating tumor microenvironment may explain the synergistic anti-tumor effects of HM781-36B and cisplatin. In conclusion, our study provides evidence for HER family proteins as prognostic biomarkers and potential therapeutic targets for NPC. The pan-HER inhibitor HM781-36B alone or in combination with cisplatin represents promising therapeutic effects for the treatment of NPC patients, which provides a new idea for the comprehensive treatment of NPC.
Humans ; Animals ; Mice ; Cisplatin/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Nasopharyngeal Carcinoma/drug therapy* ; Mice, Nude ; Nasopharyngeal Neoplasms/pathology* ; Tumor Microenvironment

The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.