ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

A a novel composite ZIF-8/MWCNT was synthesized by combining zeolitic imidazolate framework-8(ZIF-8)with multi-walled carbon nanotubes(MWCNT).The composite was modified on glassy carbon electrode(GCE)to obtain ZIF-8/MWCNT/GCE,which was served as an effective electrochemical sensor for detection of Pb2+ and Cd2+.Benefiting from the high electrical conductivity of MWCNT and the synergistic effect between ZIF-8 and MWCNT,ZIF-8/MWCNT showed excellent electrocatalytic activity in individual and simultaneous detection of Cd2+ and Pb2+.Under the optimized conditions,the linear ranges were 0.03?8.00 μmol/L and 0.03?6.00 μmol/L with corresponding limits of detection(S/N=3)of 0.019 and 0.035 μmol/L for individual detection of Cd2+and Pb2+,respectively.Whereas for simultaneous detection of Cd2+and Pb2+in their mixture solutions,the linear ranges were 0.03?5.00 μmol/L and 0.03?5.00 μmol/L with corresponding limits of detection(S/N=3)of 0.022 and 0.048 μmol/L,respectively.In addition,the sensor exhibited good stability,reproducibility and anti-interference ability.Moreover,the sensor showed good feasibility and accuracy for determination of Cd2+ and Pb2+ in actual river water samples with spiking recoveries of 98.1%?104.0%and 98.3%?102.2%,respectively.

Objective To observe the efficacy of Asini Corii Colla for the treatment of women with pregnancy anemia induced by β-thalassemia and its effect on the expression of early growth response 2(EGR2).Methods Transcriptome sequencing(RNA-seq)was performed firstly.Twenty pregnant women with β-thalassemia were randomly assigned to the treatment group and the control group at the proportion of 3:1.There were 15 cases allocated to the treatment group,one case fell off during the trial,and eventually 14 cases were included.The control group had 5 cases.The treatment group was given Asini Corii Colla powder orally,and the control group had no intervention.The course of treatment covered 4 weeks.The peripheral blood of the two groups of pregnant women was sampled before and after treatment for RNA-seq analysis,and then the candidate targets were defined.Subsequently,a prospective clinical randomized controlled trial(RCT)was conducted.A total of 41 pregnant women with β-thalassemia were randomly assigned to the treatment group(24 cases)and the control group(17 cases)at the proportion of 3:2.The treatment group was treated with Asini Corii Colla powder orally,and the control group was treated with the simulant of Asini Corii Colla Powder orally.The course of treatment covered 4 weeks.The hematological parameters of the two groups of pregnant women were detected before and after treatment,and the mRNA and protein expression levels of candidate targets were detected by real-time polymerase chain reaction(real-time PCR)and western blotting respectively.Results(1)The results of RNA-seq analysis showed that EGR2 expression of patients with genotype βCD41-42(-TTCT)/βN in the treatment group was significantly up-regulated after treatment(log2 FC=1.915;Padj=9.84E-03),and EGR2 was named as the candidate target.(2)The results of RCT showed that after treatment,there was no significant difference in the average hemoglobin(Hb)concentration between the two groups of pregnant women with β-thalassemia(P＞0.05),but the average Hb of the patients with genotypeβCD41-42(-TTCT)/βN in the treatment group increased by(6.54±4.74)g/L,which was significantly higher than that of other genotypes of pregnant women with β-thalassemia(P＜0.05).The expression levels of EGR2 Mrna and protein in peripheral blood of the patients with genotypeβCD41-42(-TTCT)/Βn in the treatment group were significantly increased after treatment(P＜0.05).The pre-and post-treatment difference of Hb concentration in the two groups of pregnant women withβ-thalassemia was positively correlated with pre-and post-treatment difference of EGR2 Mrna level and EGR2 protein level,and the correlation coefficients were 0.701 and 0.683,respectively(P＜0.001).Conclusion The pregnant women with thalassemia of genotype Βcd41-42(-TTCT)/Βn can achieve satisfactory efficacy after oral administration of Asini Corii Colla.Its curative effect for improving anemia may be related to the transcriptional regulation of globin genes through up-regulating EGR2 expression,activating RNA polymerase Ⅱ promoter,and promoting nucleic acid binding.

OBJECTIVE To conduct a rapid qualitative study on the chemical constituents of the methanol extract in Thamnolia subuliformis (Ehrh.) W.Culb. by UHPLC-Q-Exactive Focus-MS/MS. METHODS The chromatographic separation was performed on a Waters Acquity UPLC BEH C18(2.1 mm×50 mm, 1.7 μm) column with acetonitrile(A)-0.1% formic acid aqueous solution(B) as mobile phase for gradient elution, the flow rate was 0.3 mL·min–1 and the column temperature was 30 ℃. Mass spectrometry was performed using an electrospray ionization and data was collected in negative ion modes, and the detection range was m/z 80−1 200. The chemical constituents in Thamnolia subuliformis (Ehrh.) W.Culb. were identified rapidly and comprehensively based on the accurate relative molecular and combined with literature data and reference substances. RESULTS A total of 39 chemical constituents were speculatively identified, including 9 mono-substituted phenyl rings, 11 depsides, 5 depsidones, 2 dibenzofuran, 10 lipids, and 2 others. CONCLUSION The chemical constituents in the Thamnolia subuliformis (Ehrh.) W.Culb. can be identified accurately and rapidly by this method. Among them, 3 compounds(β-resorcylic acid, usnic acid, atranorin) are unambiguously identified by comparing with reference standards, 19 compounds are found from Thamnolia subuliformis (Ehrh.) W.Culb. for the first time. This paper can provide the important basis for study on pharmacodynamic material and substitute development of Thamnolia subuliformis (Ehrh.) W.Culb..

OBJECTIVE: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone. METHODS: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B-IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis. RESULTS: Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change -13.67, 95% CI -22.70 to -4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52). CONCLUSION The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694).
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Male ; Middle Aged ; Female ; Lung Neoplasms/pathology* ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Chemotherapy, Adjuvant ; Patient Reported Outcome Measures ; Quality of Life ; Aged ; Postoperative Period ; Prospective Studies

OBJECTIVE: To investigate the correlation between plasmacytoid dendritic cell (pDC) dose in grafts and the occurrence of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 80 children who received allo-HSCT in Children's Hospital of Soochow University from August 20, 2020 to June 11, 2021 were retrospectively analyzed. Proportions of DC subsets and T-cell subsets in grafts were detected by flow cytometry in order to calculate infused cell dose of each cell. Weekly monitoring of CMV-DNA copies in peripheral blood for each child were performed after transplantation. The last follow-up date was December 31, 2021. RESULTS: All the children gained hematopoietic reconstitution. CMV infection was observed in 51 children (63.8%±5.4%) within the first 100 days after transplantation, including 2 cases developing CMV disease. Univariate analysis indicated that infused doses of DC and pDC were significantly associated with CMV infection within 100 days after allo-HSCT (P <0.05). Multivariate analysis indicated that a high dose infusion of pDC was an independent protective factor for CMV infection within 100 days after allo-HSCT (P <0.05). By the end of follow-up, 7 children died of transplantation-related complications, including 2 deaths from CMV disease, 2 deaths from extensive chronic graft-versus-host disease, and 3 deaths from capillary leak syndrome. The overall survival rate was 91.2%. CONCLUSION The pDC in grafts may be associated with early infection of CMV after allo-HSCT, while a high infused pDC dose may serve as a protective factor for CMV infection after transplantation.
Child ; Humans ; Retrospective Studies ; Graft vs Host Disease/complications* ; Cytomegalovirus Infections ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Dendritic Cells

Humans ; Embolic Stroke ; Cardiomyopathies ; Stroke ; Atrial Fibrillation ; Risk Factors

Humans ; Embolic Stroke ; Cardiomyopathies ; Stroke ; Atrial Fibrillation ; Risk Factors

Objective: To evaluate the efficacy of decitabine combined with low dose chemotherapy (LDC) in the treatment of high-risk, refractory and relapsed pediatric acute myeloid leukemia (AML). Methods: Clinical data of 19 AML children treated with decitabine combined with LDC in the Department of Hematology, Children's Hospital of Soochow University from April 2017 to November 2019 were analyzed retrospectively. The therapeutic response, adverse effects and survival status were analyzed,and the outcomes of patients were followed up. Results: Among 19 AML cases, there were 10 males and 9 females. Five cases were high-risk AML, 7 cases were refractory AML, and 7 cases were relapsed AML. After one course of decitabine+LDC treatment, 15 cases achieved complete remission, 3 cases got partial remission, and only 1 case didn't get remission. All patients received allogeneic hematopoietic stem cell transplantation as consolidation therapy. The follow-up time of all cases was 46 (37, 58) months, 14 children had survived. The cumulative three-year overall survival rate was (79±9) %, events free survival rates was (68±11) %, and recurrence free survival rate was (81±10) %. The most common adverse effects related to the induction treatment were cytopenia (19 cases) and infection (16 cases).There were no treatment-related death during the therapy. Conclusion: Decitabine combined with LDC is a safe and effective option for high-risk, refractory and relapsed AML children, which provides an opportunity for HSCT.
Female ; Male ; Humans ; Child ; Decitabine ; Retrospective Studies ; Leukemia, Myeloid, Acute/drug therapy* ; Drug-Related Side Effects and Adverse Reactions ; Hematopoietic Stem Cell Transplantation