BACKGROUND:Cryopreservation can better ensure the integrity of the vascular structure.How to reduce its immunogenicity to improve rejection after transplantation has attracted more and more attention. OBJECTIVE:To review the research progress of freezing treatment to reduce vascular immunogenicity after allogeneic vascular transplantation in order to provide a reference for clinical research. METHODS:A systematic search of Chinese and English databases CNKI,WanFang and PubMed,as well as online websites Baidu and Google Scholar since the establishment of the database has published literature on reducing vascular immunogenicity after allogeneic vascular transplantation.Keywords were"cardiovascular disease,endothelial cells,cryopreservation,blood vessel transplantation or vascular graft,immunogenicity,immune rejection,allograft or allogeneic transplantation or allograft transplantation and cryoprotectant".A total of 68 articles were included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)The review found that the rejection of allogeneic vascular transplantation can be reduced by improving the existing freezing technology,which mainly involves the selection of freezing and thawing methods and cryoprotectants.(2)The existing research suggests that the freeze-drying method is superior to the low-temperature cryopreservation,but due to the limited conditions,it is still dominated by low-temperature cryopreservation.Among them,vitrification cryopreservation,slow rewarming and the use of stainless steel and even silver-containing materials are better than programmed cryopreservation and rapid rewarming.(3)The combined selection of permeable and non-permeable cryoprotectants can further reduce the occurrence of rejection while reducing their toxicity.

Thioredoxin-interacting protein (TXNIP), which mainly regulates glucose homeostasis in pancreatic β cells, is a novel target in the treatment of diabetes.In this study, 4-hydroxybenzopyrimidine was used as the raw material, four nitrogen-containing rings (imidazole, methylpiperazine, pyrazole, morpholine) were introduced, benzopyrimidine skeleton with nitrogen-containing rings derivatives targeting TXNIP was designed and synthesized, and the protective effect of compounds on palmitic acid-stimulated islet β cells was investigated.A total of 20 benzopyrimidine derivatives were designed and synthesized, and the structures were confirmed by 1H NMR and ESI-MS.Pharmacological studies showed that most of the compounds exhibited protective effects on islet β cells, with better axtivity for compounds C-1, C-2, C-4 and D-2 (cell survival rate > 70%) compared with PA model group (38.3%), Among the four compounds, D-2 had the highest activity of 87.2%, so it could become a potential new anti-diabetic chemical entity.

OBJECTI VE To establish the high performan ce liquid c hromatography（HPLC）fingerprint of carotenoid in Lycium barbarum，and to investigate the spectrum-effect relationship between its common peak and antioxidant activity. METHODS HPLC method was adopted. The fingerprints of carotenoid in 34 batches of L. barbarum from different producing areas were established by Similarity Evaluation System of TCM Fingerprint （2012 edition），and similarity evaluation and common peak identification were carried out. Taking scavenging rate of DPPH free radical as index ，in vitro antioxidant activity of carotenoid in L. barbarum was investigated. The spectrum-effect relationship between the common peaks of carotenoids in L. barbarum and antioxidant activity was analyzed by grey correlation method. RESULTS There were 4 common peaks in the fingerprints of carotenoids in 34 batches of L. barbarum ，and the similarity was not less than 0.903. Peak 1 was identified as zeaxanthin ，and peak 4 as zeaxanthin dipalmitate. The scavenging rates of them to DPPH free radical were 1.792％-3.160％. The common peaks of carotenoids in L. barbarum were positively correlated with scavenging rate of DPPH free radical ，and the correlation degree was greater than 0.6；the correlation degree of peak 2 and peak 4（zeaxanthin dipalmitate ）with scavenging rate of DPPH free radical was greater than 0.8. According to the correlation degree ，the contribution of each common peak to scavenging rate of DPPH free radical was determined as peak 2＞ peak 4（zeaxanthin dipalmitate ）＞peak 1（zeaxanthin）＞peak 3. CONCLUSIONS In this study ，HPLC fingerprint of carotenoid in L. barbarum is successfully established ，and two common peaks are identified. The chemical components represented by peak 2 and zeaxanthin palmitate may be the material basis of antioxidant activity of carotenoid in L. barbarum .

Objective:To investigate the transcriptomic mechanisms and clinical efficacy of D-CAG regimen for the treatment of acute myeloid leukemia (AML) after failure to initial induction of remission.Methods:The transcriptome data of AML cells before and after the use of dexitabine before August 28, 2021 was searched in Gene Expression Omnibus (GEO) database with "decitabine" as the search term. The R language package was used for differential expression analysis and Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis of the data. Protein-protein interaction network (PPI) analysis was conducted on the STRING online analysis website. The accurate treatment prediction platform designed based on logistic omics theory (EpiMed) was used to make drug-disease-target correlation analysis. The clinical data of 18 AML patients treated with D-CAG regimen after failure to induction of remission with standard anthracycline and cytarabine regimen ("3+7" regimen) in the 305th Hospital of Chinese PLA from October 8, 2015 to July 9, 2018 were searched and analyzed, and the curative effect was evaluated. The effects of the dose and duration of each drug on the efficacy were analyzed.Results:The transcriptome data of AML cells before and after the use of decitabine in GSE40442 dataset of the GPL5188 platform were finally selected, updated on July 10, 2014. A total of 366 differentially expressed genes were screened, including 201 up-regulated genes and 165 down-regulated genes. The differential genes were mainly related to cell cycle regulation, bone marrow leukocyte migration and differentiation, transcriptional regulation, bone marrow hematopoiesis and other signaling pathways. Ten core genes such as ANXA5, IL-10, THBS1, TLR4, JUN and CXCL12 were screened by PPI analysis. Drug-disease-target analysis showed that dexitabine had a potential therapeutic effect on various blood diseases such as diffuse large B-cell lymphoma, thrombocytopenia, T-cell acute lymphocytic leukemia, aplastic anemia, and AML. Of the 18 patients, after initial induction of remission, 7 (38.8%) patients achieved partial remission (PR), and 11 (61.2%) patients had no response (NR); after one cycle of re-induction remission therapy, 9 patients had complete remission (CR), 5 patients had PR, 4 patients had NR, and the overall response rate (ORR) was 77.8% (14/18). Compared with patients with NR, the CR rate was higher in patients with PR after initial induction therapy, which were 85.7% (6/7) and 27.3% (3/11), and the difference was statistically significant ( χ2=5.84, P = 0.025). The median duration of cytarabine in CR patients was longer than that in NR patients [10 d (7-14 d) vs. 5 d (2-8 d), Z = 3.89, P = 0.002] and the median ratio of the number of bone marrow blast cells to the duration cytarabine was lower in CR patients than that in NR patients [2.29 (0.89-9.10) vs. 8.10 (3.00-38.50), Z = -2.19, P = 0.006]; the median dose of cytarabine in CR patients was lower than NR patients, which were 50 mg·m -2·d -1 (30-150 mg·m -2·d -1) and 100 mg·m -2·d -1 (50-500 mg·m -2·d -1), and the difference was not statistically significant ( Z = -1.80, P = 0.074). Conclusions:AML patients with PR after initial induction and failure to initial induction of remission may be more likely to achieve CR after the treatment of D-CAG regimen, and this change may be related to the epigenetic regulation of decitabine.

Objective:To anylyze the combination rule of prescriptions containing Cmnamomi Mmulus in the book of Treatise on Typhoid and Miscellaneous Diseases based on tree analysis algorith method. Methods:By collecting prescriptions contain Cmnamomi Mmulus in the book of Treatise on Typhoid and Miscellaneous Diseases, and applying the tree analysis algorithm method on the Ancient and Modern Medical Case Cloud Platform to co-occurrence calculate each layer of the prescriptions, we got the hierarchical tree structure diagram of Cmnamomi Mmulus prescriptions. Results:79 prescriptions containing 96 medicines were included, which appeared 529 times, with 7 different functions. The medicines that are frequently appeared include Cmnamomi Mmulus, Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle, Zingiberis Rhizoma Recens, Jujubae Fructus, etc. The main effects include relieving the exterior, warming the meridians, warming yang and promoting diuresis. The tree structure diagram of the prescription is divided into seven layers, including the largest items of Cmnamomi Mmulus, Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle,Zingiberis Rhizoma Recens, Jujubae Fructus, Paeoniae Radix Alba, Ephedrae Herba, Puerariae Lobatae Radix, and the collateral drugs of Poria, Atractylodis macrocephalae rhizoma, Alismatis Rhizoma, Zingiberis Rhizoma, etc. Conclusion:The formula tree analysis algorithm can connect the correlation between drugs in series, and show the relationship between a series of high-frequency co-occurrence drugs in the formula, which can be used for the learning of classics.

Objective:To study the regulatory effect of miR-9 on the proliferation of breast cancer cells by targeting hexokinase 2 (HK2) .Methods:Breast cancer tissues and paracancer tissues were collected and the expression levels of miR-9 and HK2 were detected. MCF-7 cells were cultured and divided into blank control group, NC group, miR-9 group, NC-siRNA group and HK2-siRNA group. The cell viability, expression levels of HK2 and cleaved caspase-3 were detected, the targeted binding of miR-9 to HK2 was verifed.Results:the expression level of miR-9 in breast cancer was lower than that in paracancer tissue (0.52±0.08 vs 1.05±0.25, t=16.685, P<0.000) , and the expression level of HK2 was higher than that in paracancer tissue (0.73±0.14 vs 0.34±0.08, t=17.587, P<0.000) , and the expression level of miR-9 was negatively correlated with HK2; the OD490 level, the expression level of HK2 and the fluorescence activity of double luciferase reporter gene containing HK2 mRNA 3 'UTR in miR-9 group were lower than those in NC group (0.58±0.09 vs 1.04±0.21, 0.51±0.08 vs 1.18±0.24, 41.11±9.28 vs 148.28±29.59, t/P=4.027/0.007, 5.297/0.002, 6.912/0.001) , and the expression level of cleaved caspase-3 was higher than that in NC group (1.08±0.26 vs 0.42±0.09, t/P=4.797/0.003) . The OD490 level and the expression level of HK in HK-siRNA group were higher than that in NC-siRNA group, and the expression level of cleaved caspase-3 was higher than that of NC-siRNA group. Conclusion:miR-9 can inhibit the proliferation of breast cancer cells, and its mechanism may be related to the targeted inhibition of HK2 expression and the increase of downstream cleaved caspase-3 expression.

Objective:To analyze the inflammatory mechanism and potential intervention drugs related to angiotensin converting enzyme 2 (ACE2) inhibitory mutations in order to provide reference for the treatment of corona virus disease 2019 (COVID-19).Methods:The data of lung adenocarcinoma with ACE2 mutations were screened from the cancer genome atlas (TCGA) database. The data were analyzed by R program language edgeR package and cluster Profiler package, gene ontology (GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Using String online analysis website for protein-protein interaction (PPI) network analysis, screening out the core genes, and finally using the Epigenomic Precision Medicine Prediction Platform (EpiMed) for multi-group association analysis of key genes, and drug candidates prediction.Results:A total of 1 005 differential genes were obtained, of which 91 were up-regulated and 914 down-regulated. A total of 71 GO were enriched, including 45 items related to biological processes, 16 items related to cell components, and 10 items related to molecular function. A total of 13 KEGG pathways were enriched, mainly in inflammatory pathways, various viral infectious diseases, transcriptional regulation, drug metabolism and protein digestion and absorption pathways. The differentially expressed genes were introduced into String online analysis website for PPI network analysis, a total of 252 proteins were obtained, and 10 core genes were H2A clustered histone 16(HIST1H2AL), H3 clustered histone 2 (HIST1H3B), H3 clustered histone 7 (HIST1H3F), H3 clustered histone 11 (HIST1H3I), H3 clustered histone 3 (HIST1H3C), H2B clustered histone 3 (HIST1H2BB), H2B clustered histone 6 (HIST1H2BI), H4 clustered histone 2 (HIST1H4B), H1-4 linker histone (HIST1H1E), H2A clustered histone 4 (HIST1H2AB). Interferon-α, resveratrol, celecoxib, heartleaf houttuynia herb, weeping forsythia capsule, dexamethasone, Chinese pulsatilla root, tumor necrosis factor-α inhibitors, liquorice root and famciclovir might be drugs for the treatment of ACE2 mutation-related inflammation.Conclusions:Inflammation associated with ACE2 inhibitory mutations is similar to the pathogenesis of COVID-19, which could lead to disease by promoting the activation of inflammatory pathways such as mitogen-activated protein kinase (MAPK), the Janus kinase signal transducer and activator of transcription (JAK/STAT), mammalian target of rapamycin (mTOR). Celecoxib, interferon and resveratrol may have the potential therapeutic effects on COVID-19.

Objective:To investigate the omics mechanism of SARS-related immune injury and predict targeted therapeutic drugs through clinical bioinformatics analysis of the transcriptome data of SARS virus in order to provide reference for clinical treatment of COVID-19.Methods:The transcriptome data of SARA virus were collected from the Gene Expression Oibus (GEO) and used to screen differential genes. Enrichment analysis and protein interaction analysis were performed to investigate the mechanism of immune damage associated with SARS. A platform of epigenetics in precision medicine (EpiMed) was established to predict potential therapeutic drugs.Results:The mechanism of SARS-related immune injury was complex, involving affecting the function of immune cells through signaling pathways such as Toll-like receptors, increasing cytokines in plasma through Th17 signaling pathway and inducing autoimmune responses after autoantibodies were generated by molecules such as IL-6, NF-κB, and TNF. Drugs such as Chuanqiong and Etanercept might have therapeutic effects on SARS-related immune damage.Conclusions:SARS virus could cause abnormal expression of many immune-related molecules and signaling pathways. Drugs such as Chuanqiong and Etanercept might have therapeutic effects on SARS-related immune damage. This study might provide reference for clinical treatment of COVID-19.

Objective To investingate the effect of SGK1 expression level on the prognosis of patients with NSCLC,and provide new biological predictors for the prognosis assessment of patients with NSCLS.Methods One hundred and twenty patients with NSCLC received radical resection in Hanzhong 3201 hospital from Jan 2011 to Dec 2013 were selected.There were 75 males and 45 females,age (63.15 ± 16.44) years,age range 45-80 years.According to the results of immunohistochemical staining,the SGK1 cut-off value determined by the integral was determined,and NSCLC patients were divided into SGK1 high expression group (n =70) and SGK1 low expression group(n =50).The relationship between the expression of SGK1 and clinicopathological features (age,sex,smoking history,alcoholism history,BMI,tissue type,tumor diameter,T stage,N stage,TNM stage,differentiation degree) in NSCLC were analyzed,and the overall survival rate in NSCLC were also analyzed.Followup was carried out by telephone or patient admission.The follow-up period was up to June 1,2018.Chest X-ray and ultrasonography were reviewed every 3 to 6 months after operation,and enhanced CT or MRI were performed if the results were abnormal.The measurement data conforming to normal distribution were expressed by t test and showed by (Mean ± SD);the counting data were tested by x2 test;the 5-year overall survival rate was used as the endpoint event for univariate analysis,and the significant variables for univariate analysis were analyzed by COX risk ratio model for multivariate analysis.The cumulative survival curve was drawn by Kaplan-Meier method,and the difference was tested by Log-rank method.Results The expression level of SGK1 in tissues was not related to age,sex,smoking history,alcoholism,BMI,tissue type and tumor diameter (P ＞ 0.05),but it was related to T stage,N stage,TNM stage and differentiation degree (P ＜ 0.05).The univariate and multivariate COX risk ratio model showed that TNM stage and SGK1 expression were independent factors affecting the 5-year overall survival rate of NSCLC patients (P ＜ 0.05).The results of Kaplan-Meier survival curve showed that the 5-year overall survival rate in NSCLC with low expression of SGK1 was significantly higher than that in NSCLC with high expression of SGK1 (P ＜ 0.05).Conclusions The expression of SGK1 in tissues is closely related to the prognosis of patients with NSCLC.The high expression of SGK1 in tissues is not conducive to the prognosis of patients with NSCLC.

Reform of public hospitals is key to the healthcare system reform.This article introduced how Hangzhou implemented such a reform of " Hangzhou characteristics" by referring to the hospital reform framework of the World Bank, and the theoretical achievements and practical experiences of domestic public hospitals′reform.Led by the service concept of " Medicine has its limitations but we have the courage to overcome, service is boundaryless and we must pursue excellence" , Hangzhou has established a public hospital value system of " reorientation to public welfare".The smart healthcare system serves as a focus, to support the delicacy management of the hospitals. The construction of hierarchical medical care system functions as the pillar, to support the coordinated development of hospitals, primary health institutions and public health institutions.This way a public hospital comprehensive reform mode is established featuring " one value system, 2 levels of organization structure, 6 mechanisms, and 19 supporting measures ". Its experiences may serve as reference to streamline hospital internal operation and external cooperation mechanism.