To design teaching course of problem-based learning (PBL) combined with case-based learning (CBL) for standardized training of clinicians based on clinical decision thinking mode (CDTM) of diagnosis and treatment process for primary liver cancer. The CDTM of treatment choice for primary liver cancer is multi-scheme selection model. The general decision rule includes decision condition, action plan and decision tree. For the theoretical study of clinical decision rules, it is suitable to design PBL teaching, but it is suitable to design CBL teaching course for clinical decision-making practice. The teaching course of PBL combined with CBL is conducive to improving the ability of clinicians' clinical decision thinking step by step.

Objective To develop a human Tim-3 specific monoclonal antibody and evaluate its biological activity and possible use in clinical diseases associated with dysregulated Tim-3 expression .Methods The BALB/c mice were immu-nized by conventional method, and positive clones were used to develop anti-human Tim-3 antibody, the binding and neutralization activities of which in vitro and in vivo were investigated.Results ①A monoclonal antibody (clone L3D) which could specifically bind to human Tim-3 protein in ELISA assay was obtained and the subtype of the monoclonal antibody was IgG2a .②Flow cytometry indicated that the monoclonal antibody could bind to Tim-3 expressed in human U937 cells.This antibody also showed a cross activity to mice′Tim-3.③The monoclonal antibody inhibited the apoptosis of THP1 cells induced by Gal-9, the ligand of Tim-3.④Injection of Tim-3 antibody exacerbated sepsis in mice as marked by the decreased survival rate and increased expression of pro-inflammatory cytokines .Conclusion An anti-human Tim-3 monoclonal antibody is successfully obtained.The excellent binding and neutralization activities of this antibody enable it to be widely used in clinical diseases associated with deregulated Tim-3 expression .

Although immunoglobulin A (IgA) nephropathy (IgAN) is considered as an immune-mediated inflammatory disease,the pathogenesis and mechanisms associated with its progression have not been completely understood.To date,the potential pathogenesis of IgAN is thought to be a possible increase of galactose-deficient IgA1,followed by binding to antiglycan antibodies to form immune complexes,which are deposited in the glomerular mesangium and lead to the activation of complement pathways and initiation of immune-mediated inflammation.Activation of alternative and lectin complement pathways,complement components,and complement regulatory proteins play important roles in the pathogenesis and progression of IgAN.Complement components and complement regulatory factors in the renal tissue,urine,and serum samples are considered to be useful predictive biomarkers to evaluate the activation of the complement system and determine the prognosis of IgAN.The application of novel techniques such as the genome-wide association study would promote further research to determine the role and mechanisms of action of the complement system,whereby it could be used as a new therapeutic target for the management of IgAN.

Objective: To compare the clinical effects of two different skin preparation methods for infant craniocerebral surgery. Methods: Totally 120 infants who were going to receive craniocerebral surgery were divided into two groups by random number table, 60 cases in the observation group and 60 cases in the control group. The scalp of both groups was cleaned with moisturizing oil every day from 3 days before operation. On 1 day before operation, the observation group used electric shaver to shave off all hair on the head, and then rinsed with warm water. The control group was treated with skin preparation knife to shave all the hair under soap water lubrication and rinse with warm water. The skin injury rate, incision infection rate and pain score of the two groups were evaluated. Results: The incidence of skin injury and incision infection were 0 and 1.7% (1/60) in the observation group, 18.3% (11/60) and 13.3% (8/60) in the control group, respectively. There were significant differences between the two groups (χ²= 12.110, 5.886, all P < 0.01 or 0.05). The median score of pain in the observation group was 0 (Q₁:0, Q₃:0), while 1.5 (Q₁:1, Q₃:2) in the control group, and there were significant differences between the two groups (Z= 3.286, P < 0.01). Conclusion Electric shaver is superior to skin preparation knife in shaving hair of infants. It not only reduces the incidence of head skin injury, incision infection and pain in the process of skin preparation, but also reduces the incidence of incision infection after craniocerebral surgery in infants. It is worth popularizing.

AIM: Yi Qi Yang Yin Decoction (YQYY) has been used to treat patients with rheumatoid arthritis (RA) and achieved good results in clinical applications, but the mechanism still needs to be explored. The purpose was to investigate the mechanism of YQYY in rats with collagen-induced arthritis. METHODS: The possible treatment target and signaling pathway were predicted by bioinformatics and network pharmacology analysis. Elisa,quantitative real-time polymerase chain reaction, and Western Blot were used to verify the mechanism of YQYY in treating RA. RESULTS: FABP4, MMP9 and PTGS2 were the most common predicational therapeutic targets. The results of pathology and CT showed that YQYY could improve ankle swelling, synovitis and bone erosion in CIA rats. Compared with the model group, YQYY or YQYY+MTX can significantly reduce the secretion of CRP, TNF-α, IL-1β and FABP4 in serum of CIA rats (P<0.05 or P<0.01), meanwhile, reduce the mRNA of FABP4, IKKα and p65 in synovial tissue (P<0.01), PPARγ was increased (P<0.01). YQYY could significantly reduce the expression of FABP4, IKKα and pp65 proteins in synovium, and suppress the activate of NF - κB signaling pathway. CONCLUSION: FABP4, MMP9 and PTGS2 may be the targets of YQYY decoction for RA treatment. YQYY can relieve joint symptoms in CIA rats, and regulate inflammation by inhibiting FABP4 / PPARγ/NF - κB signaling pathway, playing a role in the treatment of RA. The effect of YQYY combined with MTX was more prominent. This provided experimental evidence for the efficacy of YQYY decoction in clinical practice.

The continuing challenges that limit effectiveness of tumor therapeutic vaccines were high heterogeneity of tumor immunogenicity, low bioactivity of antigens, as well as insufficient lymph nodes (LNs) drainage of antigens and adjuvants. Transportation of in situ neoantigens and adjuvants to LNs may be an effective approach to solve the abovementioned problems. Therefore, an FA-TSL/AuNCs/SV nanoplatform was constructed by integrating simvastatin (SV) adjuvant loaded Au nanocages (AuNCs) as cores (AuNCs/SV) and folic acid modified thermal-sensitive liposomes (FA-TSL) as shells to enhance de novo antitumor immunity. After accumulation in tumor guided by FA, AuNCs mediated photothermal therapy (PTT) induced the release of tumor-derived protein antigens (TDPAs) and the shedding of FA-TSL. Exposed AuNCs/SV soon captured TDPAs to form in situ recombinant vaccine (AuNCs/SV/TDPAs). Subsequently, AuNCs/SV/TDPAs could efficiently transport to draining LNs owing to the hyperthermia induced vasodilation effect and small particle size, achieving co-delivery of antigens and adjuvant for initiation of specific T cell response. In melanoma bearing mice, FA-TSL/AuNCs/SV and laser irradiation effectively ablated primary tumor, against metastatic tumors and induced immunological memory. This approach served a hyperthermia enhanced platform drainage to enable robust personalized cancer vaccination.

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.
Animals ; Mice ; Candida albicans ; Candidiasis, Oral/drug therapy* ; Antifungal Agents/pharmacology* ; Hyphae ; Artemisinins/pharmacology*