HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective To investigate the improvement effect of Necrostatin-1 (Nec-1) on mouse models with immune checkpoint inhibitor (ICI) -associated myocarditis (ICIAM) and potential mechanism. Methods Ten male BALB/c mice aged 6-8 weeks were selected to construct the ICIAM models. The echocardiography and serum myocardial injury markers were used to assess cardiac function of mice. The levels of inflammatory markers including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Hematoxylin-eosin (HE) staining was used to evaluate myocardial inflammation, and Masson staining was used to evaluate myocardial fibrosis. The expressions of myocardial necroptosis proteins including receptor-interacting protein kinase 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) and their phosphorylated forms were detected by Western blotting. The spleen lymphocytes were extracted and co-cultured with HL-1 cell line. Cell viability was measured by cell counting kit-8 (CCK-8). The release of reactive oxygen species (ROS) and changes of mitochondrial membrane potential were observed. RIP1, RIP3, MLKL and their phosphorylated forms were determined. The levels of markers of oxidative stress, including malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were measured. Results Nec-1 significantly improved the cardiac function injury of mice induced by ICI, and inhibited the release of TNF-α and IL-1β in plasma of ICIAM mice (P＜0.001); inhibited expressions of phosphorylated RIP1, RIP3 and MLKL (P＜0.05); decreased MDA activity, and increased SOD and GSH-Px activity (P＜0.001). In HL-1 cells, Nec-1 intervention inhibited the RIP1-RIP3-MLKL pathway (P＜0.05), improved decrease of the cell viability induced by lymphocytes (P＜0.001), decreased ROS release, increased mitochondrial membrane potential, inhibited MDA activity, and increased SOD and GSH-Px activities (P＜0.001). Conclusions Necroptosis plays an important role in the occurrence and development of ICIAM，but Nec-1 could alleviate the progression of ICIAM by inhibiting necroptosis induced by oxidative stress in cardiomyocytes; RIP1 maybe a new target in treatment of ICIAM.

Objective To explore the effect of seminar based on case-based learning(CBL)in practical teaching of physical therapy. Methods From July,2021 to June,2022,42 rehabilitation therapy students for internships in Rehabilitation Medicine Center,the First Affiliated Hospital of Nanjing Medical University were non-directionally recruited,and random-ly divided into control group(n = 21)and experimental group(n = 21).The experimental group received instruc-tion using seminar and CBL,while the control group received CBL alone,for three months.The scores of theoret-ical and practical assessments were observed,and the satisfaction was investigated using a self-designed question-naire. Results The scores of both theoretical and practical assessments were better in the experimental group than in the control group(t>2.421,P<0.05);while the satisfaction was better in terms of motivating learning enthusiasm,enhanc-ing learning abilities,cultivating clinical reasoning skills,improving teacher-student communication,promoting teamwork,enhancing overall competence,and satisfying to the teaching in the experimental group than in the control group(χ2>6.667,P<0.05). Conclusion The combination of seminar with CBL would enhance the effect of practical teaching in physical therapy.

MicroRNA(miRNA)is a kind of small non-coding single stranded RNA that can participate in multiple biological processes.It also plays an important role in regulating the immune function of the body.Immune thrombocytopenia(ITP)is an autoim-mune disease,whose cause and deterioration are closely related to miRNA regulates immune function of CD4+T cells subsets.In ITP patients,different expression of miRNA can affect the immune function of CD4+T cells subsets,which causes not only unbalanced ex-pression of Th1/Th2,Th17/Treg and excessive differentiation of TFH,but also abnormal cytokine secretion furthermore.This paper summarizes the unbalanced mechanism of miRNA regulating immune function of CD4+T cells subsets in ITP,so as to provide inspira-tion for exploring the immunology and immunotherapy of ITP.

Abstract Health literate schools (HeLit-Schools) play a significant role in fostering students health literacy. The paper elucidates the background and conceptual connotations of HeLit-Schools, and analyzes how HeLit-Schools effectively integrate and enhance the health literacy of schools in three aspects: philosophy and core drivers, strategy and method implementation, as well as evaluation mechanisms and standard setting. Furthermore, the paper explores the implications of foreign HeLit-Schools research and practice for China under the context of "Healthy China" construction, as well as the key strategies for Chinese schools in the implementation of HeLit-Schools, aiming to provide a new perspective and theoretical support for Chinese schools to practice the "Healthy China initiative" and strengthen school construction from the perspective of health literacy.

Objective:To summarize the clinical features and therapeutic outcomes of patients with hyperinsulinemic hypoglycemia (HH) auxiliarily diagnosed by 18F-DOPA positron emission tomography (PET) CT scanning. Methods:The clinical data of 123 patients who were diagnosed with hyperinsulinemic hypoglycemia by comprehensive clinical diagnostic procedures in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children′s Hospital of Fudan University between January 2016 and December 2020 were retrospectively analyzed. Clinical data such as gender, age of onset, province, concurrent serum insulin level measured during hypoglycemia, lesion type of pancreas by 18F-DOPA-PET CT scanning, genetic test results, and treatment were collected successively. The clinical features and therapeutic outcomes were compared between patients with focal and diffuse pancreatic lesions. T test, Rank sum test, and χ2 test were used for comparison between groups. Results:A total of 123 patients with hyperinsulinemic hypoglycemia (72 males and 51 females), whose average age of onset was 3 days (ranging from 1 day to 4 860 days), were recruited from 24 provinces. The concurrent serum insulin level was 7.1 (0.4-303.0) mU/L during hypoglycemia. 18F-DOPA-PET CT scanning identified focal lesions in 25.2% (31/123) and diffuse lesions in 74.8% (92/123) of the patients; 64.2% (79/123) of the HH cases were found to have pathogenic gene variants, in which 88.6% (70/79) were found to have K ATP channel related genes (61 in ABCC8 and 9 in KCNJ11 mutations). Thirty-seven patients (17 focal and 20 diffuse) received surgical treatment with a success rate of 67.6% (25/37). The effective rate of diazoxide for children with diffuse type was significantly higher than that of children with focal group (28.3% (26/92) vs. 9.7% (3/31), χ2=10.31, P=0.001). Conclusions:18F-DOPA-PET CT scan can improve the success rate of surgery. Comprehensive diagnosis of the etiology of hyperinsulinemic hypoglycemia by genetic analysis and 18F-DOPA-PET CT scanning can result in better treatment and prognosis.

Objective:To investigate the effect of inspiratory muscle training on the lung function and diaphragm movement of stroke survivors.Methods:Twenty-four stroke survivors were randomly divided into a control group and an experimental group. Both groups were given routine rehabilitation therapy, while the experimental group was additionally provided with 20 minutes of inspiratory muscle training, 5 times per week for 4 weeks. Before and after the treatment, the forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) expressed as percentages of the predicted values were used to assess ventilation. The maximum inspiratory pressure (MIP) and peak inspiratory flow (PIF) were used to assess inspiratory muscle function. Diaphragm mobility, as well as the diaphragm′s thickness at the end of expiration (DTee) and inspiration (DTei) and the diaphragm thickening fraction (DTF) were measured using ultrasonography. Any pulmonary infection was also recorded.Results:There was no significant difference between the two groups in any of the measurements before treatment. After the intervention the average FVC, FEV1, MIP, PIF, diaphragm mobility, DTei and DTF of the experimental group were all significantly better than before treatment and significantly better than the control group′s averages. However, no significant difference was found in the average PEF or DTee, nor in the rate of pulmonary infection between the two groups.Conclusion:Inspiratory muscle training can effectively improve ventilation, inspiratory muscle function, diaphragm mobility and diaphragm thickness at the end of inspiration among stroke survivors.

Allergy contact dermatitis is a type IV delayed type hypersensitivity that is induced by exogenous compounds and involves many cell types. Traditional animal testing uses guinea pigs or mice as a model. With progress of the adverse outcome pathway(AOP)on skin sensitization, a concept for development of alternative methods based on a molecular initiating event and key events is provided. Dendritic cell(DC)activation plays a key role in the AOP. Many alternative methods have been developed,with several methods validated and accepted as guidance for assays. This paper examines DC screening, characteristics of test parameters, and limitations and applicability of DC-derived methods. Progress on interactions between DCs and other cells, co-culture systems, and the human body-on-a-chip will also be introduced. Altogether,this paper will provide information for optimization of in vitro alternative methods for sensitization detection.

Aim To investigate the effects of Naotai formula extract(NTE)on the expression of heme oxygenase-1(HO-1) and hephaestin(Heph) in hippocampus of rats after cerebral ischemia/reperfusion by Keap1-Nrf2/ARE signaling pathway.Methods Eighty rats were randomly divided into five groups as follows: sham operation group(Sham), cerebral ischemia/reperfusion group(I/R), low dose group of NTE(4.5 g·kg-1), middle dose group of NTE (9 g·kg-1) and high dose group of NTE(18 g·kg-1).Rats were pretreated by intragastric administration for three consecutive days, and then subjected to middle cerebral artery occlusion (MCAO) 2 hours before reperfusion.The rats were administered with intragastric administration for two days.After cerebral ischemia reperfusion 72 hours, the behavioral activity of rats was recorded by Zea Longa neurological score, and the infarct volume was measured by TTC staining.The expressions of Nrf2, HO-1 and Heph in hippocampus of cerebral ischemia reperfusion rats were observed by real-time quantitative PCR and Western blot, respectively.Results Compared with model group, the neurobehavioral scores significantly decreased in NTE high-dose and middle-dose groups (P<0.01);the infarct volume of NTE groups markedly decreased (P<0.01);the expression of HO-1 mRNA apparently increased (P<0.05) in NTE groups;the expression of Heph mRNA significantly increased in NTE middle-dose and high-dose groups (P<0.05);the expression of Nrf2 and Heph protein evidently increased in the NTE middle and high dose groups (P<0.05, P<0.01);and the expression of HO-1 protein also increased in NTE groups(P<0.01).Conclusions Naotai formula can relieve cerebral ischemia-reperfusion injury.The mechanism might be associated with activating Keap1-Nrf2/ARE signaling pathways, promoting HO-1 generation, advancing the expression of Heph, and then reducing brain iron deposition, to achieve the protection of neurons after cerebral ischemia-reperfusion.

Objective: To study the feasibility of ¹⁸F-fluoro-L-dihydroxyphenylalanine positron emission tomography/Computed tomography (¹⁸F-DOPA PET/CT) scanning in the localization and differential diagnosing of focal versus diffuse form of pancreas lesions in patients with hyperinsulinemic hypoglycemia (HH). Method: Twenty-four patients were diagnosed with HH between January, 2016 and February, 2017 in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children′s Hospital of Fudan University using an integrated clinical and biochemical diagnostic protocol, domestic ¹⁸F-DOPA PET/CT imaging technique were applied after MRI and ultrasound failed to detect pancreas lesions. Pancreas ¹⁸F-DOPA standardized uptake values (SUV) were measured, and pancreas′ lesions were dually analyzed via visual method and pancreas percentage SUV method. Among these patients, 9 patients received surgical pancreatic lesion resections, the correlations among surgical outcomes, histopathological findings and ¹⁸F-DOPA PET/CT scan results were analyzed. Result: Seven patients were detected with focal form of pancreas lesions, the mean peak of SUV was 4.7±1.7(2.6-7.1), and 17 patients were found to have diffuse form lesions after ¹⁸F-DOPA-PET/CT scanning. Among the 24 cases, 9 patients (7 showed focal and 2 showed diffuse ¹⁸F-DOPA PET/CT pancreatic uptake)were euglycemic without any medical support after surgery; the resected pancreatic tissue histopathological results were consistent with that of PET/CT imaging. Only one patient, who responded to medical treatment before surgery, had temporary hyperglycemia after operation. Conclusion Domestic ¹⁸F-DOPA PET/CT could successfully locate and differentiate the pancreatic lesions and thus improve the success of surgery.