Objective To explore the relationship between postoperative restenosis and vascular endothelial function in patients with lower extremity arterial disease(LEAD).Methods A retrospective analysis was performed on 133 patients with diabetic lower extremity arteriopathy who had successfully undergone interventional therapy in our hospital,and the patients were followed up for one year,and the patients were grouped according to whether restenosis occurred,with 25 cases in the restenosis group and 108 cases in the non-stenosis group.The patient's vascular endothelial function index,inflammatory factor level,blood lipid four items and hemoglobin A1c(HbAlc)were detected,and peripheral blood cells of patients in the stenosis group and non-stenosis group were isolated for transcriptome sequencing.Multivariate unconditional logistic regression analysis was used to screen for independent risk factors for vascular endothelial function in postoperative restenosis.Results Serum endothelin-1(ET-1),von Willebrand factor(vWF),thromboxane B2(TXB2),vascular cell adhesion protein 1(VCAM-1),and nitric oxide(NO)were significantly higher in the stenosis group than in the non-stenosis group,while endothelial nitric oxide synthase(eNOS)and vascular endothelial growth factor(VEGF)were significantly lower than those in the non-stenosis group(P<0.01).There was no significant difference in blood lipids between the two groups(P>0.05).The HbAlc of the stenosis group was significantly higher than that of the non-stenosis group(P<0.01).The inflammatory factors in the stenosis group were significantly higher than those in the non-stenosis group(P<0.05).Transcriptome sequencing analysis results are consistent with test results.Multivariate Logistic regression analysis showed that TNF-α,IL-6,ET-1,and vWF were independent risk factors for LEAD vascular restenosis(P<0.05).Conclusion Vascular endothelial function indexes(ET-1,vWF)and inflammatory factors(TNF-α,IL-6)are independent risk factors for restenosis after interventional surgery.

Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess anti-insomnia properties.However,the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear.Herein,we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry(LC-MS/MS)-based pharmaco-metabolomics and mass spectrometry imaging(MSI)-based spatial resolved metabolomics.According to the results,17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain,which might be the major components contributing to the sedative-hypnotic effects.Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction,serotonergic synapse,dopaminergic synapse,and dopaminergic synapse,among other pathways.LC-MS/MS-based targeted metabolomics and Western blot(WB)revealed that tryptophan-serotonin-melatonin(Trp-5-HT-Mel)and tyrosine-norepinephrine-adrenaline(Tyr-Ne-Ad)are the key regulated pathways.Dopa decarboxylase(DDC)upregulation and phenylethanolamine N-methyltransferase(PNMT)downregulation further confirmed these pathways.Furthermore,MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland(PG),and Ad in the brainstem,including the middle brain(MB),pons(PN),and hypothalamus(HY).In summary,this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine,YZ.

With the development of population aging, the incidence of lower limb artery ischemic diseases is gradually increasing. Although various treatments such as medication and endovascular surgery are currently available, patients with compromised microcirculation in the distal limbs and poor outflow pathways often do not achieve satisfactory results. Additionally, these treatments can be costly, and long-term patency rates are not ideal. The amendment in situ autologous great saphenous vein arterialization surgery utilizes the patient′s great saphenous vein to provide arterial blood in a retrograde manner and re-establishes blood supply to the tissues through the venous microcirculation system in the distal foot. This approach can achieve good limb salvage results and long-term patency. Therefore, this article aims to elaborate on the methods and value of amendment in situ autologous great saphenous vein arterialization surgery.

Objective To investigate the effects and mechanism of Zhachong Shisanwei Pills on rats with cerebral ischemia.Methods Totally 75 rats were randomly divided into sham-operation group,model group,positive drug group(Ginaton,21.6 mg/kg),and Zhachong Shisanwei Pills low-,medium-,and high-dosage groups(81,162,324 mg/kg).Each treatment group was given the corresponding drug by gavage for 5 days.On the 6th day,a cerebral ischemia rat model was prepared by suture method.After 24 hours of modeling,the drugs were given in the same manner for 2 days.Neurological function scoring,horizontal beam walking scoring,and grip strength testing were performed on rats.TTC staining was used to detect the cerebral infarction rate,HE staining and Nissl staining were used to observe the morphology of brain tissue.TUNEL staining was used to detect the apoptosis rate of brain tissue cells.Differential genes in the treatment of cerebral ischemia using Zhachong Shisanwei Pills were screened by transcriptomics,and RT-qPCR,immunohistochemistry and Western blot were used to detect differential gene mRNA and protein expression.Results Compared with the sham-operation group,the model group rats showed a decrease in neurological function scores,horizontal beam walking scores,grip strength,an increase in cerebral infarction rate,neuronal nucleus condensation,vacuolar changes,widened intercellular spaces,the number of Nissl bodies reduced,and the apoptosis rate increased(P<0.01,P<0.001);compared with the model group,the Zhachong Shisanwei Pills medium-dosage group showed an increase in neurological function score,horizontal beam walking score,and grip strength in rats,a decrease in cerebral infarction rate,a lower degree of neuronal damage,an increase in the number of Nissl bodies,and a decrease in cell apoptosis rate(P<0.05,P<0.01).Transcriptome and bioinformatics analysis screened the Hippo signaling pathway related to the anti-cerebral ischemia effect of Zhachong Shisanwei Pills.The key genes of this pathway,mammalian sterile line 20 like kinase(MST1)1,Yes related protein(YAP)1,large tumor suppressor kinase(LATS)1,and TEA domain family member(TEAD)1 were detected.The results showed that the expression of MST1 mRNA and protein in brain tissue of model rats significantly increased,while the expressions of YAP1,LATS1,TEAD1 mRNA and protein significantly decreased;Zhachong Shisanwei Pills could down-regulate the expression of MST1 in brain tissue of model rats,and up-regulate the expressions of YAP1,LATS1 and TEAD1.Conclusion Zhachong Shisanwei Pills may exert anti-cerebral ischemia effects through the Hippo signaling pathway.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Understanding the regulatory networks for germ cell fate specification is necessary to developing strategies for improving the efficiency of germ cell production in vitro. In this study, we developed a coupled screening strategy that took advantage of an arrayed bi-molecular fluorescence complementation (BiFC) platform for protein-protein interaction screens and epiblast-like cell (EpiLC)-induction assays using reporter mouse embryonic stem cells (mESCs). Investigation of candidate interaction partners of core human pluripotent factors OCT4, NANOG, KLF4 and SOX2 in EpiLC differentiation assays identified novel primordial germ cell (PGC)-inducing factors including BEN-domain (BEND/Bend) family members. Through RNA-seq, ChIP-seq, and ATAC-seq analyses, we showed that Bend5 worked together with Bend4 and helped mark chromatin boundaries to promote EpiLC induction in vitro. Our findings suggest that BEND/Bend proteins represent a new family of transcriptional modulators and chromatin boundary factors that participate in gene expression regulation during early germline development.
Animals ; Cell Differentiation/genetics* ; Chromatin/metabolism* ; Embryonic Stem Cells ; Germ Cells/metabolism* ; Germ Layers/metabolism* ; Mice

Adenine ; Animals ; Gene Editing ; Mice ; Zygote ; metabolism

Objective To study the platelet inhibition rate of foreign clopidogrel,domestic clopidogrel,combined domestic clopidogrel and tongxinluo and their effct on major adverse cardiovacular events (MACE) after PCI.Methods Two hundred and twenty patients after PCI were divided into foreign clopidogrel treatment group (n=77),domestic clopidogrel treatment group (n=80),combined domesticclopidogrel and tongxinluo treatment group (n =63).The high platelet reactivity (HPR) in 3 groups was detected by thrombelastography after PCI.The incidence of MACE in 3 groups was compared.Results The incidence of left anterior descending branch lesion was lower,the number of sacculi was smaller,and the incidence of HPR was higher in foreign clopidogrel treatment group than in domestic clopidogrel treatment group and combined domestic clopidogrel and tongxinluo treatment group after PCI (63.6％ vs 87.5％ vs 77.8％,P=0.002;2.3±1.1 vs 2.8±1.4 vs 2.7±1.5,P=0.026;24.7％ vs 21.3％ vs 11.1％,P=0.030).The incidence of HPR was significantly higher in foreign clopidogrel treatment group than in combined domestic clopidogrel and tongxinluo treatment group (24.7 ％ vs 11.1％,P =0.040).No significant difference was found in the incidence of MACE in 3 groups (P ＞ 0.05).Conclusion The incidences of MACE of domestic clopidogrel and foreign clopidogrel are similar.Combined clopidogrel and tongxinluo can improve the platelet inhibition rate after PCI.

Glioblastoma multiforme (GBM) is the most malignant form of glioma, and its treatment through traditional surgery combined with chemotherapy and radiotherapy has limited efficacy. Chimericantigen receptor T-cells (CAR-T) are recombinant receptors for antigen, which, in a single molecule, redirect and mediateantigen recognition, T-cell activation, and, in the case of second-generation chimeric antigen receptors (CARs) costimulation (CD28 or 4-BB), augment T-cell functionality and persistence. CARs are the focus of attention in emerging treatment options for GBM. This article mainly introduces the development process of CAR-T therapy and the recent success of adoptive transfer of CAR-T cells. Effective targets of the treatment of GBM with CAR-T according to this research are discussed as well. Some of the most extensively studied targets on GBM, especially interleukin-13 receptor α chain variant 2, epidermal growth factor receptor-Ⅷ(EGFRⅧ), human epidermal growth factor receptor 2 (ErbB2), and ephrinA2 receptor (ErbA2), and the different characteristics of each kind of alloantigen-specific CAR-T cells, are the basis for CAR-T therapy and indicate their different characteristics or utilities and the prospect of further clinical research. The discovery of selective expression of interleukin-13 receptor alpha 2 in glioma cells more than 20 years ago prompted the clinical trial of CAR-T therapy in stage I GBM tumors, and the therapy was proven safe and effective. EGFRⅧ is a neoantigen presenting only in cancer cells and glioblastoma stem cells. Its presence is correlated with poor prognosis, and a phase Ⅰ/Ⅱ trial is ongoing at different institutes. ErbB2-specific CARs were also expressed in human Tcells.Adoptive transfer of EphA2 (or ErbB2)-specific T cells resulted in the regression of glioma xenografts. Thus, target-specific CAR-T immunotherapy may be a promising approach for the treatment of different target-positive GBM. Finally, we summarize the application value and challenge of CAR-T cell therapy in the treatment of GBM.

Objective: In comparison with thrombus aspiration, to study the safety and effcacy of precise intracoronary retrograde thrombolysis during primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI).
Methods: A total of 123 consecutive patients with acute STEMI received primary PCI in our hospital from 2014-01 to 2015-12 were enrolled.The patients were randomly divided into 2 groups: RT group, the patients received precise intracoronary retrograde thrombolysis (RT),n=60 and TA group, the patients received thrombus aspiration (TA),n=63, among them, 3 patients with failed TA were excluded. Primary end points included occurrence rates of no-lfow after PCI and ST-segment resolution (STR)≥50% at (60-90) min after PCI; primary safety end points included occurrence rates of in-hospital stroke and TIMI-hemorrhage events.
Results:①Compared with TA group, RT group showed decreased no-lfow rate after PCI (1.7% vs 15.0%),P=0.008 and increased rate of STR≥50% after PCI (65.0% vs 45.0%),P=0.028, improved LVEF by echocardiography (50.7±8.6) % vs (46.7±8.3)%,P=0.011. The in-hospital MACE occurrence rate was similar between 2 groups,P>0.05.②No in-hospital stroke or TIMI-hemorrhage events occurred in neither group.
Conclusion: Intracoronary retrograde precise thrombolysis had the similar safety to thrombus aspiration during primary PCI in patients with acute STEMI, it may reduce no-relfow rate and improve left ventricular function after PCI.