Objective To investigate the tumor-inhibitory effect of cytokine-induced killer cells(CIK)co-cul-tured with dendritic cells (DC)pulsed by breast cancer stem cell antigen on the same tumor-bearing mice. Methods Breast cancer stem cells were isolated from the cell line of MCF-7/ADR and extract lyses antigen of the stem cell was saved. DC and CIK derived from peripheral blood mononuclear cells of healthy individuals were co-cultured and pulsed or un-pulsed by the above antigen lyses. This DC+CIK were injected to breast tumorbearing mice (BCSC-AP-DC+CIK group), and were used to compared with the common breast cancer cell antigen (rather than breast cancer stem cell antigen) pulsed DC+CIK group(AP-DC+CIK group), DC+CIK group, CIK CIK group and normal saline group(NS group). The tumor-inhibitory effect were evaluated and compared among all 5 groups through the tumor size, TdT-mediated dUTP nick end labeling test (TUNEL), examining expression level of bcl-2 and bax by immunohistochemistry. Results The tumor size in each group before and after therapy and the tumor size after therapy between each group was of significant difference(P＜0.05). The maximum size is NS group(3.625±0.093)cm3 and BCSC-AP-DC+CIK group is minimum,which is (1.234±0.131)cm3. BC-SC-AP-DC+CIK group is of highest expression of bax and apoptotic index value, lowest bcl-2 expression in all 5 groups. Conclusion The CIK co-cultured with DC pulsed breast cancer stem cell antigen was more effective to induce apoptosis of breast cancer cells than those of CIK cells co-cultured with DC pulsed breast cancer cell antigen,CIK cells co-cultured with DC and CIK cells.

Objective To explore the effects of human umbilical cord mesenchymal stem cells (HUC?MSCs) on podocytic apoptosis and injury induced by high glucose (HG) and the underlying mechanisms. Methods Podocytes were divided into six groups according to treatment: ⑴ normal glucose group (NG);⑵high glucose group (HG);⑶mannitol control group (NG+Ma);⑷HUC?MSC co?culture group (HUC?MSCs); ⑸ recombinant human hepatocyte growth factor treatment group (rhHGF);⑹ neutralizing antibody group(HGF?NtAb). Cytometry and Hoechst staining were used to detect the apoptosis rates. Western blot was used to measure the ratio of active PARP to total PARP and the level of Bcl?2. Immunofluorescence was used to study podocytic apoptosis and injury. Neutralizing antibody (NtAb) was used to block its function and the recombinant cytokine was added to induce its function. Results High glucose induced podocytic apoptosis in a time?dependent manner, HUC?MSCs co?culture decreased the podocytic apoptosis rate and the expression of PARP (all P﹤0.05), increased the expression of Bcl?2, prevented the reduced expression and maintained the normal arrangement of podocytic podoplanin. The rhHGF prevented podocytic apoptosis and injury similarly to HUC?MSCs, the beneficial effect of HUC?MSC decreased when blockade of HGF. Conclusions HUC?MSCs co?culture ameliorates podocytic apoptosis and injure induced by HG, probably through secreting soluble HGF.

Objective To observe the members' dynamic change of renin-angiotensin system (RAS) and angiotensin converting enzyme 2(ACE2)-Ang(1-7)-Mas axis during the continuous venovenous hemodiafiltration (CVVHDF) treating the dogs with multiple organ dysfunction syndrome (MODS),and to investigate the efficacy mechanism on cardiac function.Methods Dogs were subjected to hemorrhagic shock plus resuscitation and endotoxemia to establish MODS model,then they were randomly divided into 2 groups:CVVHDF group (n=8) and MODS group (n=6).After endotoxin injection completion,the CVVHDF group received CVVHDF for 12 h,MODS group didn't.Radioimmunoassay,euzymelinked mmunosorbent assay (ELISA) were used to detect the content of renin,Ang Ⅰ,Ang Ⅱ,Ang (1-7).Real-time PCR was used to detect the expression of renin mRNA and ACE2 mRNA.Western blotting was used to detect the protein content of renin,Ang Ⅱ,ACE2 and Ang (1-7).Results (1) Organ function:Compared with the MODS group,the vital signs,heart,lung and renal function were significantly ameliorated in the CVVHDF group,the difference had statistical significance (P＜ 0.05).(2) RAS changes:To detect index from the level of organs,genetic and molecular in arterial tissue,the results displayed that the content of renin,Ang Ⅰ,Ang Ⅱ,the expression of renin mRNA,the protein content of renin,Ang Ⅱ in CVVHDF group were lower than that in MODS group,the difference had statistical significance (P ＜ 0.01).(3)ACE2-Ang(1-7)-Mas axis's changes:Using the same methods above to detect corresponding indicators,the results displayed that the content of ACE2,Ang(1-7),the expression of ACE2 mRNA and the protein content of ACE2,Ang(1-7) in CVVHDF group were significantly improved than that in MODS group,the difference had statistical significance (P ＜ 0.01).Conclusions In the process of CVVHDF treating MODS,the ACE2 -Ang(1-7)-Mas axis plays the role which antagonizes the RAS system,and to protect the cardiac function.This research may be important for MODS' clinical rescue.

Objective To obtain the parameters of optimal spectral scanning mode in chest spectral CT imaging,radiation doses,image quality,CNR and subjective scores are compared in spectral and conventional scan modes with anthropomorphic chest phantom.Methods An anthropomorphic chest phantom underwent both conventional scan and spectral scan using three different protocols:GSI assist mode (protocol A);GSI mode with mean tube current (protocol B);GSI mode with maximum tube current (protocol C).All above scans were performed with the noise index (NI) as 9 and 11 respectively.The radiation dose was recorded,and the SD values of adipose tissue and muscle tissue of 5 different sections were measured in regions of interest (ROls) to evaluate the image quality.All scans were subjectively scored in 5 score system by two senior radiologists on lung markings and branches with the lung window technique.Results The effective dose (E) values of conventional CT scan and protocols A,B and C were 8.0,8.5,6.2,10.4 and 5.3,5.1,4.3,6.2 mSv.When NI =9,the difference of SD values had statistically significance between conventional scan and protocols A,C (F =4.496,P ＜ 0.05).When NI =11,there was statistically significant difference of SD value between conventional scan and protocols A,B,C (F =8.425,P ＜ 0.05).In conventional chest scan,the difference of SD values was statistically significant between NI =9 and 11 (t =-2.570,P ＜ 0.05),while other protocols had no statistically significant difference (P ＞ 0.05).The difference of CNR and subjective score had no statistically significance in either the same NI different scanning modes or the same scanning mode with different NIs.Conclusions Appropriate spectral scanning mode had no significant difference with conventional CT scanning in radiation dose,yet higher image quality can be obtained.Furthermore,appropriate NI can reduce the radiation dose obviously while the similar image quality was achieved.Considering the two factors,GSI assist mode can achieve balance between radiation dose and image quality.

In order to investigate the molecular evolution and spatio-temporal migration of Getah viruses (GETV) isolated around the world,the nucleotide and deduced amino acid sequence of GETVs were analyzed and phylogenetic trees were constructed by using informatics software including ClustalX1.83,MegaAlign,GeneDOC and Mega6.0.The Bayesian Stochastic Search Variable Selection (BSSVS) program in the BEAST v 1.8.1 software package was used to analyze the spatial dynamics of the Getah virus.Results showed that the full-length of Getah virus E2 gene consists of 1 266 nueleotides,encoding 422 amino acids.And the homology of nucleotide and amino acid were 94.5％ 100％ and 96.4％ 100％ respectively.The molecular evolution analysis revealed that there were no species and geographical distribution difference existing among GETV host animals (e.g.horses and pigs) and vectors (e.g.mosquitoes).Bioinformatics analysis showed that GETV originated in Malaysia,then it was spread to Japan,China,South Korea,Mongolia,Russia,etc.GETV E2 gene was relatively stable since GETV was first isolated in 1955.The differences of species and geographical distribution did not exist among GETV host animals and vectors,and the virus has spread from tropical regions to Eurasian continent.Thus,strengthening the detection and monitoring of GETV and its infections in humans and livestock is critical.

Ischemia-reperfusion injury (IRI) refers to the reperfusion injury caused by the recovery of blood supply of ischemic tissues or organs, which commonly occurs in organ transplantation and other surgical procedures. IRI may cause a series of severe clinical issues, such as delayed graft function, acute kidney injury, myocardial infarction, ischemic stroke and circulatory arrest, etc. These events yield high incidence and fatality. At present, no effective solution has been available. Transient receptor potential canonical 6 (TRPC6), a member of Ca²⁺ channel family, is highly expressed in multiple types of cells. It may adjust many physiological functions by regulating intracellular Ca²⁺ concentration, which has become an important target for developing therapeutic drugs for multiple diseases. In this article, research progresses on the introduction and function of TRPC6, the association between TRPC6 and IRI and the therapeutic prospect of TRPC6 targeted drugs in IRI were reviewed, aiming to provide novel insights into the prevention and treatment of IRI during organ transplantation

Objective To investigate the protective effect of human umbilical cord mesenchymal stem cell-derived exosome (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI), and to clarify the critical role and regulating mechanism of transient receptor potential canonical (TRPC) 6/poly adenosine-diphosphate-ribose polymerase (PARP) 1 signaling pathway during this process. Methods The hucMSC-Exo was extracted by ultracentrifugation, and identified by transmission electron microscope (TEM), nanoparticle tracing analysis and Western blot. SD rats were randomly divided into the sham operation group (group S), sham operation+TRPC6 inhibitor SKF96365 group (group SS), renal IRI group (group IRI), exosome treatment group (group EXO) and exosome +TRPC6 inhibitor SKF96365 group (group ES), with 6 rats in each group. Serum creatinine and blood urea nitrogen levels were detected. Pathological changes of renal tissues were observed by hematoxylin-eosin (HE) staining and Paller score was calculated. The expression levels of key molecules of necroptosis in rat renal tissues, including receptor-interacting protein kinase (RIPK)1, RIPK3 and mixed-lineage kinase domain-like protein (MLKL), TRPC6 and PARP1, were detected by Western blot. Results Typical saucer-like structure was observed under TEM. Nanoparticle tracing analysis showed that the average diameter of the extracted substance was 125.9 nm. Western blot revealed that the surface markers of CD9, CD63 and CD81 were positively expressed, confirmed that the extracted substance was exosome. Compared with group S, the serum creatinine and blood urea nitrogen levels were up-regulated, the pathological damage of renal tissues was worsened, Paller score was elevated, the relative expression levels of TRPC6 and PARP1 proteins were down-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were up-regulated in group IRI (all P < 0.05). Compared with group IRI, the serum creatinine and blood urea nitrogen levels were down-regulated, the pathological damage of renal tissues was mitigated, Paller score was decreased, the relative expression levels of TRPC6 and PARP1 proteins were up-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were down-regulated in group EXO (all P < 0.05). Compared with group EXO, the serum creatinine and blood urea nitrogen levels were up-regulated, the pathological damage of renal tissues was aggravated, Paller score was increased, the relative expression levels of TRPC6 and PARP1 proteins were down-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were up-regulated in group ES (all P < 0.05). Conclusions hucMSC-Exo may alleviate the necroptosis induced by renal IRI in rat models, which is related to the activation of TRPC6/PARP1 signaling pathway.

Objective:To assess possible risk factors and their respective levels in the whole process of investigator initiated trial(IIT)projects proposed in the proposal stage, for reference in formulation of risk management plans.Methods:Through literature analysis and research group discussions, the risk factors of IIT projects and risk level assessment criteria were preliminarily identified, and a consultation questionnaire was developed as a result. Delphi method was used to further optimize the risk factors and determine their risk levels. Data obtained from the consulfation were analysied by descriptive.Results:The recovery rates of two rounds of expert consultation were both 100%, and the degree of expert authority was 0.942. The survey finalized 38 risk factors, including extremely high risk, high risk, medium risk, low risk and very low risk factors of 17(44.7%), 15(39.5%), 3(7.9%), 2(5.3%) and 1(2.6%) respectively.Conclusions:This study determined a risk evaluation system of IIT projects in the proposal stage. This system can identify risks of IIT projects at an early stage, facilitating early intervention of problems existing in such projects, and minimize risks to the rights and safety of patients.

Objective: To investigate the west nile virus (WNV) infection in Xinjiang, China. Methods: Serum samples were collected from patients with fever and chicken in southern Xinjiang, 2012. The presence of WNV-specific immunoglobulin M (IgM) antibodies and neutralizing antibodies was examined through enzyme-linked immunosorbent assay (ELISA) and plaque reduction neutraization test (PRNT₉₀). Results: A total of 1 712 serum samples of outpatients and inpatients were collected in 8 counties in southern Xinjiang. As a result , 22 samples were positive for WNV IgM antibody and 48 samples were positive for WNV neutralization antibody, among which 21 WNV IgM antibody positive samples and 42 WNV neutralization antibody positive samples were from Jiashi county. Of 383 chicken serum samples collected in 4 counties in southern Xinjiang, only 28 samples were positive for WNV neutralizing antibody, interestingly, all positive chicken serum samples were collected from Jiashi county. Conclusions This study revealed that WNV infection occurred in human and poultry in southern Xinjiang, 2012, mainly in Jiashi county.

Effective supervision of the clinical research management department can guarantee and improve the quality of the investigator initiated trials(IIT). The authors analyzed relevant clinical research regulations and literature and summarized the current situation of risk-based IIT project process quality management. On such basis, they determined the risk-based IIT project process quality management method in combination with the previous research of the research group.From 2021 to 2022, this method was used to implement process quality management for 353 IIT projects in Shanghai′s tertiary hospitals. More than 3 000 risk points were identified through centralized supervision, and then on-site supervision was carried out to correct the problems found. As proven by the results, the method could find existing problems in time and define the risk level of the project, and also formulate an individualized risk supervision plan accordingly, so as to effectively ensure the data reliability and scientific results. It is suggested that the clinical research management department implement risk based management for the whole process of IIT projects, increase funding and staffing, and implement hierarchical management for the projects by research types, so as to promote the sustainable development of IITs.