OBJECTIVES: To explore the mechanism that mediate the therapeutic effect of quercetin on heart failure. METHODS: We searched the TCMSP and Swiss ADME databases for the therapeutic targets of quercetin and retrieved heart failure targets from the Genecards and OMIM databases. The intersecting targets were analyzed with GO and KEGG pathway analysis using DAVID database, and the key genes were identified via PPI analysis. Molecular docking between the core targets and quercetin was performed using PyMOL and AutoDock Tools. In a heart failure model established in H9C2 cardiomyocytes by treatment with isoproterenol, the effect of quercetin on the expressions of the MAPK signaling pathway was tested. RESULTS: A total of 60 intersecting targets were identified. Enrichment analysis revealed that quercetin may inhibit heart failure through the MAPK signaling pathway. The core genes, including AMPK3 and BCL-2, were identified as potential key regulators in quercetin-mediated improvement of heart failure. Cellular experiments demonstrated that quercetin significantly reduced isoproterenol-induced apoptosis of cardiomyocytes in a dose-dependent manner and obviously decreased the Bax/Bcl-2 ratio and the expression levels of caspase-3, ERK and p38 in the cells. CONCLUSIONS Quercetin improves heart failure possibly by inhibiting cardiomyocyte apoptosis through the MAPK signaling pathway.
Quercetin/pharmacology* ; Myocytes, Cardiac/drug effects* ; Heart Failure/metabolism* ; Apoptosis/drug effects* ; MAP Kinase Signaling System/drug effects* ; Rats ; Animals ; Isoproterenol

Objective:To investigate the feasibility, safety and reasonable operation of nasointestinal canal indwelling guided by miniature system in severe neurosurgery patients, and compare its advantages and disadvantages with traditional blind insertion.Methods:A prospective randomized controlled trial design was used to select 128 critically ill patients in need of enteral nutrition support at the Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University from March 2022 to October 2023 by convenient sampling method. They were divided into blind insertion group and visualization group by random number table method, with 64 cases in each group. Nasointestinal canal indwelling was performed in the blind insertion group by traditional blind insertion method, and in the visualization group, nasointestinal canal indwelling was performed by indentations guided by the miniature visualization system. The success rate of initial catheterization, the time of catheterization, complications, changes of vital signs during catheterization and changes of nutritional indexes after catheterization were evaluated in 2 groups.Results:In the blind insertion group, there were 35 males and 29 females, aged (59.44 ± 13.84) years old. In the visualization group, there were 41 males and 23 females, aged (58.28 ± 12.08) years old. The success rate of the first catheter placement in the visual group was 96.8% (62/64), higher than that in the blind group 82.8% (53/64), and the difference was statistically significant ( χ2=6.94, P<0.05). The catheter placement time of the visualization group was (20.08 ± 2.69) min, which was shorter than that of the blind insertion group (38.19 ± 3.79) min, and the difference between the two groups was statistically significant ( t=29.99, P<0.05). There was no significant difference in the incidence of complications, changes of vital signs during catheterization and the changes of nutritional indexes after catheterization between two groups (all P>0.05). Conclusions:Compared with traditional blind nasointestinal canal indwelling, nasointestinal canal indwelling guided by the miniature visualization system can improve the success rate of the first catheterization and shorten the catheterization time. Although there is no difference in the complication rate, changes in vital signs during catheterization and changes in nutritional indexes after catheterization, it is believed that with the continuous development and upgrading of this technology, it will further reflect the advantages of this technology, which is worthy of further clinical trials and application.

ObjectiveMyelodysplastic syndromes （MDS） is a group of clonal hematopoietic stem cell disorders，and this study aims to investigate the expression of hypoxia-inducible factor-1α（HIF-1α） in the bone marrow cells of patients with MDS and its correlation with the clinical features of MDS，the therapeutic efficacy of arsenic-containing Chineseherbal compound，and the survival prognosis. MethodAccording to the inclusion and exclusion criteria，27 MDS patients treated with arsenic-containing Chinese herbal compound in the Department of Hematology，Xiyuan Hospital，China Academy of Chinese Medical Sciences from January 2022 to September 2022 were included，and their bone marrow samples were collected by myelotomy. HIF-1α expression level in bone marrow cells was detected by real-time polymerase chain reaction （PCR） to analyze its correlation with clinical features，and logistic and Cox regression was used to analyze the risk factors affecting the efficacy and prognostic survival of MDS patients. ResultThe HIF-1α mRNA expression level was lower in bone marrow cells of MDS patients than in healthy subjects. HIF-1α was positively correlated with the degree of myelodysplasia（r=0.384，P<0.05） and bone marrow granulocytic system%（G%）（r=0.560，P<0.01）. Logistic regression showed that HIF-1α was a risk factor for the prognosis in the follow-up of the efficacy of treatment（P<0.05）and Cox regression showed that HIF-1α was an independent factor affecting the survival prognosis of MDS patients ［odds ratio（OR）=398.968，95% confidence interval（CI）（1.281，116 858.743），P<0.05］. ConclusionThe level of HIF-1α expression in bone marrow cells of MDS patients was closely related to the degree of clinical myelodysplasia and G%，and HIF-1α was a risk factor for the efficacy for and survival prognosis of MDS patients.

Objective To explore the performance of routine blood test parameters,bone marrow parameters and the risk factors of leukemia conversion in higher-risk patients with myelodysplastic syndrome(MDS)treated with Bushen Jiedu Huayu Method in the real world.Methods The clinical data of 162 patients with higher-risk MDS who were admitted to the Department of Hematology,Xiyuan Hospital,China Academy of Chinese Medical Sciences from September 2017 to September 2022 were collected,and their clinical data,blood routine parameters,and bone marrow parameters were analyzed.Results A total of 162 higher-risk MDS patients were included,and the overall effective rate of the combination of traditional Chinese and Western medicine treatment,mainly using Bushen Jiedu Huayu Method being 48.8%.Patients with higher-risk MDS who were younger than 70 years old were more likely to obtain curative effect when treated with Bushen Jiedu Huayu Method combined with chemotherapy(P<0.05).After treatment with Bushen Jiedu Huayu Method,PLT levels in higher-risk MDS patients were significantly higher than those before treatment(P<0.05),and PLT levels in the ineffective group increased more significantly(P<0.05).After treatment,the HGB level in the effective group significantly increased(P<0.05).After treatment,the proportion of bone marrow granulocytes,megakaryocytes and lymphocytes in higher-risk MDS patients were significantly higher than those before treatment(P<0.05).Conclusion Bushen Jiedu Huayu Method,mainly using arsenic containing TCM compound,can treat higher-risk MDS.It can increase the HGB content and PLT level of patients,increase the proportion of bone marrow granulocytes,megakaryocytes and lymphocytes,and also play a certain role in reducing the proportion of bone marrow primitive cells,namely demethylation.

ObjectiveTo explore the effects of Bushen Jianpi prescription on the autophagy and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway in the patients with aplastic anemia （AA）. MethodA total of 30 AA patients admitted to Xiyuan Hospital and 6 healthy donors who were prepared to undergo peripheral blood hematopoietic stem cell transplantation in 304 Hospital from September 2020 to August 2021 were enrolled and assigned into an AA group and a control group. The AA group was treated with Bushen Jianpi prescription combined with cyclosporin A （CsA） and androgen for 3 months. The mononuclear cells from bone marrow in the AA group before and after treatment and the peripheral blood of the control group were collected. Transmission electron microscopy was then employed to detect autophagosomes. Western blotting was employed to determine the protein levels of microtuble-associated protein 1 light chain 3 （LC3）Ⅰ， LC3Ⅱ， mTOR， phosphorylated （p）-mTOR， Akt， p-Akt， PI3K， and p-PI3K， and real-time polymerase chain reaction （PCR） to determine the mRNA levels of LC3， mTOR， Akt， and PI3K. ResultIn the AA group， the treatment was completed in 29 patients， and the total response rate was 51.72% （15/29）. ① The AA group showed lower levels of white blood cell （WBC）， hemoglobin （HGB）， platelet （PLT）， and absolute neutrophil count （ANC） in the peripheral blood （P<0.01） and lower number of intracellular autophagosomes than the control group before treatment. Moreover， the AA group showed lower mRNA level of LC3 （P<0.01） and protein levels of LC3Ⅰ and LC3Ⅱ （P<0.01） and higher mRNA levels of mTOR， Akt， and PI3Kα （P<0.01） and protein levels of Akt， p-Akt， PI3K， p-PI3K， mTOR， and p-mTOR （P<0.01） than the control group. ② In AA group， the levels of HGB and PLT elevated （P<0.05） and the number of intracellular autophagosomes increased after treatment compared with those before treatment. Moreover， the mRNA level of LC3 and the protein levels of LC3Ⅰ and LC3Ⅱ were up-regulated （P<0.01）， the mRNA levels of mTOR， Akt， and PI3Kα （P<0.01） and the protein levels of Akt， p-PI3K （P<0.01）， p-Akt， PI3K， mTOR， p-mTOR （P<0.05） were down-regulated after treatment. ConclusionAA patients show lower autophagy levels， while Bushen Jianpi prescription can effectively improve the autophagy level and down-regulated the expression of PI3K/Akt/mTOR signaling pathway in AA patients.

ObjectiveTo explore the predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating aplastic anemia （AA） in non-elderly adults， so as to provide a reference for predicting the prognosis of this therapy. MethodA retrospective study was conducted with the clinical data of non-elderly adult AA patients who visited 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 and were treated with Yiqi Yangxue Prescription combined with western medicine. According to the efficacy evaluation results at the 6^th month of treatment， the patients were assigned into effective and ineffective groups. The two groups were compared in terms of the gender， age， disease classification ［non-severe aplastic anemia （NSAA）/severe aplastic anemia （SAA）］， course of disease， family history， complications， history of drug allergy， baseline blood routine examination ［hemoglobin （HGB）， white blood cell （WBC）， neutrophil （ANC）， platelet （PLT）， and reticulocyte （Ret）］， T lymphocyte subsets， degree of proliferation of nucleated cells in bone marrow， and expression of T-bet and GATA-3. ResultA total of 101 non-elderly adult AA patients were enrolled in this study， including 81 in the effective group and 20 in the ineffective group. The effective group had a higher proportion of the patients without a history of drug allergy than the ineffective group （P<0.05）. The body height， body weight， gender， age， disease classification， course of disease， family history， and complications showed no significant differences between two groups. The effective group had higher levels of ANC and PLT before treatment （P<0.05） and higher proportion of patients with ANC≥1.6×10⁹/L and PLT≥25×10⁹/L （P<0.05， P<0.01） than the ineffective group. The baseline levels of WBC， HGB， and Ret showed no significant statistical differences between two groups. The levels of CD3⁺HLA-DR⁺T cells in the effective group before treatment was higher than that in the ineffective group （P<0.05）. The levels of CD3⁺CD19^-T cells， CD4⁺T cells， CD8⁺T cells， Th1 cells， Th2 cells， and CD3⁺CD25⁺T cells showed no significant statistical differences between two groups before treatment. The proportion of patients with active bone marrow nucleated cells proliferation in the effective group before treatment were significantly higher than that in the ineffective group, while the proportion of patients with reduced or extremely reduced proliferation were significantly lower than that in the ineffective group （P<0.05）. The expression levels of T-bet and GATA-3 genes had no significant differences between two groups before treatment. The multivariate binary logistic regression analysis showed that the ANC level before treatment and history of drug allergy were independent influencing factors for efficacy （P<0.05， P<0.01）， while other indicators were not influencing factors for efficacy. The receiver operating characteristic （ROC） curve was applied to analyze the predictive value of the ANC level before treatment in the treatment of AA in non-elderly adults with Yiqi Yangxue prescription combined with western medicine. The area under the curve was 0.679 （P<0.05）， with the critical value of 1.595×10⁹/L， the sensitivity of 0.42， and the specificity of 0.95. ConclusionThe history of drug allergy， pre-treatment ANC， PLT， CD3⁺HLA-DR⁺ T cell levels， and proliferation of nucleated cells in bone marrow before treatment are predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating AA in non-elderly adults. This therapy tends to be more effective for the patients with no history of drug allergy， higher ANC and PLT levels before treatment， especially those with ANC≥1.6×10⁹/L， PLT≥25×10⁹/L， and higher CD3⁺ HLA-DR⁺T cell levels and the more active proliferation of nucleated cells in bone marrow before treatment.

Objective To observe the application effect of visual nasoenteric catheterization in severe neurosurgical patients.Methods A total of 107 patients who received nasoenteric tube im-plantation in the neurosurgical intensive care unit(ICU)were selected.According to the nasoenteric tube implantation method,they were divided into visual group(underwent nasoenteric tube implantation by visual technique,n=53)and blind group(inserted by traditional blind insertion,n=54).The success rate of first catheterization,catheterization time and complication rate were observed and com-pared.Results The success rate of first catheter placement in the visual group was higher than that in the blind group(96.23％versus 81.48％,P＜0.05).The catheter placement time in the visual group was(20.11±2.47)min,which was shorter than(38.00±3.59)min that in the blind group(P＜0.05).There was no significant difference in complication rate(nose bleeding,gastrointestinal bleed-ing,catheter straying into the airway)between the two groups(P＞0.05).Conclusion Visual naso-enteric catheterization has a higher success rate in the first catheterization and shorter catheterization time in severe neurosurgical patients,and it is a safer method.

Objective To observe the application effect of visual nasoenteric catheterization in severe neurosurgical patients.Methods A total of 107 patients who received nasoenteric tube im-plantation in the neurosurgical intensive care unit(ICU)were selected.According to the nasoenteric tube implantation method,they were divided into visual group(underwent nasoenteric tube implantation by visual technique,n=53)and blind group(inserted by traditional blind insertion,n=54).The success rate of first catheterization,catheterization time and complication rate were observed and com-pared.Results The success rate of first catheter placement in the visual group was higher than that in the blind group(96.23％versus 81.48％,P＜0.05).The catheter placement time in the visual group was(20.11±2.47)min,which was shorter than(38.00±3.59)min that in the blind group(P＜0.05).There was no significant difference in complication rate(nose bleeding,gastrointestinal bleed-ing,catheter straying into the airway)between the two groups(P＞0.05).Conclusion Visual naso-enteric catheterization has a higher success rate in the first catheterization and shorter catheterization time in severe neurosurgical patients,and it is a safer method.

Myelodysplastic syndromes (MDS) is a clinical heterogeneous disease characterized by impaired hematopoietic function and morphologic abnormalities of the bone marrow. Genomic studies show that MDS is usually driven by a series of multistep somatic cell genetic processes that affect the core genome. By definition, reproducible MDS drives mutations leading to cloning advantage. In addition, exposure factors, such as cytotoxic chemotherapy or genetic propensity of the reproductive system, could affect the pathogenesis and clinical outcomes of the disease. Combined with the reports in the 59th American Society of Hematology (ASH) Annual Meeting, the article introduces the genetic characteristics of MDS, in order to improve the diagnosis of MDS and the understanding of the pathogenesis of treatment-related MDS as well as the genetic tendency of MDS in the reproductive system.

The support treatment of low-risk myelodysplastic syndromes (MDS) patients whose revised international prognostic score system (IPSS-R) is defined as 3.5 points remains the main treatment. The erythropoiesis stimulating agent (ESA) is the best choice for patients with del (5q) MDS as long as the endogenous erythropoietin (EPO) level is less than 500 U/L (preferably<200 U/L). The application of EPO for patients with treatment failure or relapsed after transfusion, chooses are immunosuppressant, transforming growth factor beta inhibitors and lenalidomide. Del (5q) syndrome could benefit from lenalidomide, and some patients after discontinuation of treatment still have been stable in peripheral blood. Thrombocytopenia caused serious hemorrhage rarely; thrombopoietin receptor analogs could reduce bleeding and improve the platelet count. These drugs can be used in patients with bone marrow blast counts of < 0.05. If treatment failed or advanced to high-risk MDS or transformed to acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation might be required. Combined with reports in the 59th American Society of Hematology (ASH) Annual Meeting, this article describes the treatment strategies for low-risk MDS.