BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.

Objective:To explore the impacts of Yiqi Wenfei Tongqiao Formula on inflammatory response and T helper cell(Th)1/Th2 immune balance in rats with lung Qi deficiency cold type allergic rhinitis.Methods:Sixty SD rats were randomly divided into model group,low dose Yiqi Wenfei Tongqiao Formula group,medium dose Yiqi Wenfei Tongqiao Formula group,high dose Yiqi Wenfei Tongqiao Formula group,and desloratadine group,with 12 rats in each group,using a combination of smoking,cold stimula-tion combined with ovalbumin(OVA)sensitization and stimulation construct lung Qi deficiency cold type allergic rhinitis model.An-other 12 normal SD rats were selected as control group.Each group of rats was treated with corresponding drugs once a day for 14 days.Model group and control group rats were given physiological saline.Scoring method was used to analyze the behavioral score and lung index of rats with allergic rhinitis.HE staining was applied to detect pathological changes in rat nasal mucosa tissue.ELISA was ap-plied to detect levels of IFN-γ,IL-4 and TNF-α in rats serum;flow cytometry was applied to detect Th1/Th2.Western blot was applied to detect expressions of T-bet and GATA-3 protein in nasal mucosa tissues of rats in each group.Results:Compared with control group,pathological damage to nasal mucosa tissue of model group rats was severe,allergic rhinitis behavior score(days 41,48,56),lung index,levels of IL-4 and TNF-α,Th2 and protein expression of GATA-3 were increased,while levels of IFN-γ,Th1,Th1/Th2,and protein expression of T-bet were decreased(P<0.05);compared with model group,pathological damage to nasal mucosa tissue of rats in low,medium,high doses Yiqi Wenfei Tongqiao Formula groups and desloratadine group were alleviated,the allergic rhinitis behavior score(days 48,56),lung index,levels of IL-4 and TNF-α,Th2 and protein expression of GATA-3 were decreased,while levels of IFN-γ,Th1,Th1/Th2,and protein expression of T-bet were increased(P<0.05).Conclusion:Yiqi Wenfei Tongqiao Formula can inhibit inflammatory response of lung Qi deficiency cold type allergic rhinitis rats By regulating Th1/Th2 immune balance.

As the "main force" for providing health services, there has been a constant increase in the number of health service and management graduates in recent years, but with a lack of satisfactory quality. The concept of outcome-based education (OBE) takes the needs of all parties as the starting point and foothold for practice, which can ensure the consistency between the goal of talent training and the learning achievements of students to the greatest extent. This article proposes to integrate the educational concept of OBE into the training path of health service and management talents, clarify talent training objectives by understanding the needs of all parties, optimize the curriculum system according to training objectives, and construct a diversified evaluation system with the organic combination of process evaluation and summative assessment, in order to continuously optimize the training path of health service and management talents and cultivate applied health management talents with knowledge, ability, and quality.

Objective To investigate the features of resting-state electroencephalography(EEG)in stroke patients with limited upper limb movement,and assess its potential utility in evaluating upper limb motor function.Methods From March to August,2024,a total of 71 stroke patients with limited upper limb movement were enrolled as stroke group at the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine;while 63 healthy participants matched for age and sex were recruited as control group.They were tested with 19-chan-nel resting-state EEG(rsEEG),calculating of the pairwise derived brain symmetry index(pdBSI)and Delta/Al-pha ratio(DAR).The motor function was assessed with Fugl-Meyer Assessment-Upper Extremities(FMA-UE),the upper limb recovery was evaluated with Brunnstrom Stages and the activities of daily living was assessed with modified Barthel index(MBI)in stroke patients,Results Compared with the control group,the pdBSI of Global lead,Frontal region,Central region and Posterior region across Delta,Alpha and Beta1 frequency bands were significantly higher in the stroke group than in the control group(|Z|>2.289,P<0.05);as well as the pdBSI of Global lead,Central region and Posterior region across The-ta bands(|Z|>3.016,P<0.01),the pdBSI of Global lead,Frontal region,Central region and Posterior region across Beta2 bands(|Z|>3.222,P<0.01),DAR of Global lead,Frontal region,Central region and Posterior re-gion(|Z|>6.565,P<0.001).In the stroke group,the pdBSI of Global lead(r=-0.280,P=0.018)and Central region(r=-0.304,P=0.010)across the Delta band were significantly negatively correlated with FMA-UE,as well as the pdBSI of Global leads(r=-0.289,P=0.014),Central region(r=-0.244,P=0.040)and Posterior region(r=-0.356,P=0.002)across the Beta1 band,and the DAR of Global lead(r=-0.431,P<0.001),Fron-tal region(r=-0.429,P<0.001),Central region(r=-0.491,P<0.001)and Posterior region(r=-0.482,P<0.001).Conclusion Asymmetry in spectral power between hemispheres in the Delta(0.5 to 4 Hz)and Beta(13 to 20 Hz)bands is found in stroke patients,especially in the central region,which correlates with upper limb function limitations.pdBSI Delta,pdBSI Beta1 and DAR are potential neuroelectrophysiological markers for assessing upper limb motor function in stroke patients.

Objective:To investigate the effectiveness of gastric-soleal turndown flap and knotless anchor bridging fixation via a modified incision in the treatment of chronic Achilles tendon rupture of Myerson type Ⅲ.Methods:A retrospective case series study was conducted to analyze the clinical data of the 18 patients who had been treated at Department of Minimally Invasive Orthopedics, Zhengzhou Orthopaedic Hospital from February 2020 to July 2023 for chronic Achilles tendon rupture of Myerson type Ⅲ by means of gastric-soleal turndown flap and knotless anchor bridging fixation via a modified incision. There were 15 males and 3 females, with an age of (37.2±6.8) years. All patients suffered from unilateral injury, involving 13 left sides and 5 right sides. Their body mass index was (22.6±2.5) kg/m 2. The operation time, blood loss, incision length, wound healing and complications were documented. The ankle dorsiflexion and plantar flexion at the last follow-up were compared between the affected side and the healthy side. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Achilles tendon total rupture score (ATRS) before operation were compared with those at the last follow-up. Results:All the 18 patients were followed up for (18.0±5.5) months. Their operation time was (69.1±5.2) minutes, blood loss (71.6±9.2) mL, incision at the broken end of the Achilles tendon (12.4±2.6) cm and incision at the proximal end (2.5±0.4) cm. At the last follow-up, the ankle dorsiflexion was 12.7°±1.9° and the ankle plantar flexion 35.2°±2.0° at the affected side, showing no significant difference from those at the healthy side (13.0°±2.1° and 34.7°±1.8°) ( P>0.05). The AOFAS ankle-hindfoot score was (89.4±3.4) points and the ATRS (85.3±3.2) points for the affected side at the last follow-up, showing significant improvements compared with the preoperative values [(54.2±4.2) points and (51.1±4.6) points] ( P<0.05). All the incisions healed at one stage after operation, with no such complications as incision infection or re-rupture of the Achilles tendon. One patient experienced mild pain at the anchor insertion site, but the pain disappeared 6 months after operation without any treatment. One patient had the symptoms of sural nerve injury which responded to 3 months of oral neurotrophic medication. Conclusion:In the treatment of chronic Achilles tendon rupture of Myerson type Ⅲ, gastric-soleal turndown flap and knotless anchor bridging fixation via a modified incision can result in limited invasion, a low incidence of complications, and definite effectiveness.

Objective To investigate the effect of Yiqi Wenfei Tongqiao decoction on the inflammatory response in rats with allergic rhi-nitis(AR)of lung qi deficiency and cold type based on the Janus kinase 1(JAK1)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods A AR model of lung qi deficiency and cold type was established in rats using ovalbumin(OVA)combined with smoking and cold stimulation.After modeling,the rats were randomly divided into model,loratadine,low-dose Chinese medicine,high-dose Chinese medicine,and high-dose Chinese medicine+RO8191(JAK1/STAT3 signaling pathway activator)groups,with 12 rats per group.Twelve healthy rats were used as controls.After 14 days of drug intervention,the changes in the symptoms of lung qi deficiency and cold syndrome and AR were observed in the rats.Enzyme-linked immunosorbent assay was used to detect the serum levels of tumor necrosis factor α(TNF-α),interleukin(IL)-4,interferon-γ(IFN--γ),and ovalbumin-specific immunoglobulin E(OVA-sIgE).The number of inflammatory cells in the nasal lavage fluid was determined and the eosinophil(EOS)percentage was calculated.Pathological changes in the nasal mucosal tissue were observed after hematoxylin and eosin(HE)staining.Western blotting was used to detect the expression of JAK1/STAT3 signaling pathway-related proteins in nasal mucosal tissue.Results Compared with those in the model group,the AR symptom score,serum IL-4,TNF-α,and OVA-sIgE levels,EOS percentage in nasal lavage fluid,and levels of p-JAK1/JAK1 and p-STAT3/STAT3 in the nasal mucosal tissue of rats in the loratadine,low-dose Chinese medicine,and high-dose Chinese medicine groups were lower,whereas the serum IFN-γ level was higher(P＜0.05).RO8191 weakened the inhibitory effect of Yiqi Wenfei Tongqiao decoction on the inflammatory response in rats with AR of lung qi deficiency and cold type.Conclusion Overall,Yiqi Wenfei Tongqiao decoction can alleviate the inflammatory response in rats with AR of lung qi deficiency and cold type by inhibiting JAK1/STAT3 signaling pathway acti-vation and regulating the balance of Th1/Th2 cytokines.

Objective:To explore the impacts of Yiqi Wenfei Tongqiao Formula on inflammatory response and T helper cell(Th)1/Th2 immune balance in rats with lung Qi deficiency cold type allergic rhinitis.Methods:Sixty SD rats were randomly divided into model group,low dose Yiqi Wenfei Tongqiao Formula group,medium dose Yiqi Wenfei Tongqiao Formula group,high dose Yiqi Wenfei Tongqiao Formula group,and desloratadine group,with 12 rats in each group,using a combination of smoking,cold stimula-tion combined with ovalbumin(OVA)sensitization and stimulation construct lung Qi deficiency cold type allergic rhinitis model.An-other 12 normal SD rats were selected as control group.Each group of rats was treated with corresponding drugs once a day for 14 days.Model group and control group rats were given physiological saline.Scoring method was used to analyze the behavioral score and lung index of rats with allergic rhinitis.HE staining was applied to detect pathological changes in rat nasal mucosa tissue.ELISA was ap-plied to detect levels of IFN-γ,IL-4 and TNF-α in rats serum;flow cytometry was applied to detect Th1/Th2.Western blot was applied to detect expressions of T-bet and GATA-3 protein in nasal mucosa tissues of rats in each group.Results:Compared with control group,pathological damage to nasal mucosa tissue of model group rats was severe,allergic rhinitis behavior score(days 41,48,56),lung index,levels of IL-4 and TNF-α,Th2 and protein expression of GATA-3 were increased,while levels of IFN-γ,Th1,Th1/Th2,and protein expression of T-bet were decreased(P<0.05);compared with model group,pathological damage to nasal mucosa tissue of rats in low,medium,high doses Yiqi Wenfei Tongqiao Formula groups and desloratadine group were alleviated,the allergic rhinitis behavior score(days 48,56),lung index,levels of IL-4 and TNF-α,Th2 and protein expression of GATA-3 were decreased,while levels of IFN-γ,Th1,Th1/Th2,and protein expression of T-bet were increased(P<0.05).Conclusion:Yiqi Wenfei Tongqiao Formula can inhibit inflammatory response of lung Qi deficiency cold type allergic rhinitis rats By regulating Th1/Th2 immune balance.

Objective To investigate the effect of Yiqi Wenfei Tongqiao decoction on the inflammatory response in rats with allergic rhi-nitis(AR)of lung qi deficiency and cold type based on the Janus kinase 1(JAK1)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods A AR model of lung qi deficiency and cold type was established in rats using ovalbumin(OVA)combined with smoking and cold stimulation.After modeling,the rats were randomly divided into model,loratadine,low-dose Chinese medicine,high-dose Chinese medicine,and high-dose Chinese medicine+RO8191(JAK1/STAT3 signaling pathway activator)groups,with 12 rats per group.Twelve healthy rats were used as controls.After 14 days of drug intervention,the changes in the symptoms of lung qi deficiency and cold syndrome and AR were observed in the rats.Enzyme-linked immunosorbent assay was used to detect the serum levels of tumor necrosis factor α(TNF-α),interleukin(IL)-4,interferon-γ(IFN--γ),and ovalbumin-specific immunoglobulin E(OVA-sIgE).The number of inflammatory cells in the nasal lavage fluid was determined and the eosinophil(EOS)percentage was calculated.Pathological changes in the nasal mucosal tissue were observed after hematoxylin and eosin(HE)staining.Western blotting was used to detect the expression of JAK1/STAT3 signaling pathway-related proteins in nasal mucosal tissue.Results Compared with those in the model group,the AR symptom score,serum IL-4,TNF-α,and OVA-sIgE levels,EOS percentage in nasal lavage fluid,and levels of p-JAK1/JAK1 and p-STAT3/STAT3 in the nasal mucosal tissue of rats in the loratadine,low-dose Chinese medicine,and high-dose Chinese medicine groups were lower,whereas the serum IFN-γ level was higher(P＜0.05).RO8191 weakened the inhibitory effect of Yiqi Wenfei Tongqiao decoction on the inflammatory response in rats with AR of lung qi deficiency and cold type.Conclusion Overall,Yiqi Wenfei Tongqiao decoction can alleviate the inflammatory response in rats with AR of lung qi deficiency and cold type by inhibiting JAK1/STAT3 signaling pathway acti-vation and regulating the balance of Th1/Th2 cytokines.

As the "main force" for providing health services, there has been a constant increase in the number of health service and management graduates in recent years, but with a lack of satisfactory quality. The concept of outcome-based education (OBE) takes the needs of all parties as the starting point and foothold for practice, which can ensure the consistency between the goal of talent training and the learning achievements of students to the greatest extent. This article proposes to integrate the educational concept of OBE into the training path of health service and management talents, clarify talent training objectives by understanding the needs of all parties, optimize the curriculum system according to training objectives, and construct a diversified evaluation system with the organic combination of process evaluation and summative assessment, in order to continuously optimize the training path of health service and management talents and cultivate applied health management talents with knowledge, ability, and quality.