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

BACKGROUND:The study of the lumbar spine and pelvis in patients with Lenke type 5 lordosis is limited to the coronal and sagittal planes,and the three-dimensional relationship between the scoliosis and the pelvis has not yet been clarified. OBJECTIVE:To analyze the effect of lumbar scoliosis on the pelvis in patients with Lenke type 5 lordosis and to study the correlation between the lumbar spine and the three-dimensional spatial position of the pelvis. METHODS:Imaging data of 60 patients with Lenke type 5 lordosis scoliosis admitted to the 3D Printing Reception Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2019 to September 2023 were retrospectively analyzed,including Cobb angle,coronal pelvic tilt,lumbar lordosis,left and right pelvic hip width ratio(sacroiliac-anterior superior iliac spine),spinal rotation angle,pelvic tilt,sacral slope,pelvic incidence,coronal deformity angular ratio,sagittal deformity angular ratio,C7 plumb line-center sacral vertical line,apical vertebral translation,and coronal sacral inclination.The information was summarized as a database.SPSS 22.0 software was used to analyze the data related to the lumbar spine and pelvis of the patients with Lenke type 5 primary lumbar curvature adolescent idiopathic scoliosis using Spearman's correlation analysis and linear regression. RESULTS AND CONCLUSION:(1)Cobb angle was highly positively correlated with coronal deformity angular ratio,apical vertebral translation,and spinal rotation angle(r=0.91,r=0.841,r=0.736).(2)Coronal deformity angular ratio was highly positively correlated with apical vertebral translation(r=0.737),moderately positively correlated with C7 plumb line-center sacral vertical line(r=0.514),and moderately negatively correlated with sagittal deformity angular ratio(r=-0.595).(3)There was a high positive correlation between lumbar lordosis and sagittal deformity angular ratio(r=0.942)and a moderate negative correlation with coronal deformity angular ratio(r=-0.554).(4)There was a moderate positive correlation between Cobb angle with coronal pelvic tilt and coronal sacral inclination(r=0.522,r=0.534)and a moderate positive correlation between C7 plumb line-center sacral vertical line and coronal pelvic tilt(r=0.507).Apical vertebral translation with coronal pelvic tilt and coronal sacral inclination showed a moderate positive correlation(r=0.507,r=0.506).Lumbar lordosis with sacral slope and pelvic incidence showed a moderate positive correlation(r=0.512,r=0.538).Sagittal deformity angular ratio was moderately positively correlated with sacral slope and pelvic incidence(r=0.614,r=0.621).(5)Studies have found that the relative position of the lumbar spine and the pelvis is closely related in the horizontal,sagittal and coronal planes.When the lumbar spine affects scoliosis and is rotated,the relative position of the pelvis will also change to compensate,which indicates that while correcting scoliosis,the correction of the pelvis cannot be ignored.

Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

Spinal cord injury (SCI) is a disabling and destructive central nervous system injury that has not yet been successfully treated at this stage. Three-dimensional (3D) bioprinting has become a promising method to produce more biologically complex microstructures, which fabricate living neural constructs with anatomically accurate complex geometries and spatial distributions of neural stem cells, and this is critical in the treatment of SCI. With the development of 3D printing technology and the deepening of research, neural tissue engineering research using different printing methods, bio-inks, and cells to repair SCI has achieved certain results. Although satisfactory results have not yet been achieved, they have provided novel ideas for the clinical treatment of SCI. Considering the potential impact of 3D bioprinting technology on neural studies, this review focuses on 3D bioprinting methods widely used in SCI neural tissue engineering, and the latest technological applications of bioprinting of nerve tissues for the repair of SCI are discussed. In addition to introducing the recent progress, this work also describes the existing limitations and highlights emerging possibilities and future prospects in this field.

Objective:To evaluate the clinic efficacy of channel bone grafting [preservation of the sclerotic bone at the broken nonunion ends and fixation with limited contact dynamic compression plate (LC-DCP)] in the treatment of postoperative atrophic nonunion of middle clavicular fracture.Methods:The 41 patients were retrospectively analyzed who had been treated at Department of Orthopaedics and Traumatology, Xi'an Hong-Hui Hospital for atrophic nonunion after internal fixation of middle clavicular fracture from June 2015 to December 2019. They were 23 males and 18 females, with a mean age of 47.6 years (from 28 to 63 years). The left side was affected in 25 cases and the right side in 16 cases. The time interval between initial fracture surgery and nonunion surgery averaged 18.5 months (from 9 to 40 months). Thirty-six cases had undergone one operation and 5 cases 2 operations before admission. The length of bone defect was measured during operation. All nonunions were treated with construction of a graft channel, iliac bone graft and LC-DCP internal fixation above the clavicle. The upper limb function of the affected side was evaluated by the Disabilities of Arm, Shoulder and Hand (DASH) 12 months after operation.Results:The 41 patients were followed up for an average of 13.6 months (from 12 to 15 months). A bone defect ≤2.0 cm was found in 25 cases and that >2.0 cm in 16 ones. Nonunion healed in all patients after an average time of 14 weeks (from 12 to 16 weeks). One patient reported continuous pain in the donor area after operation and the other developed deep venous thrombosis at the right lower limb. The DASH upper limb scores at 12 months after operation averaged 14.7.Conclusion:Channel bone grafting is a feasible clinical treatment of postoperative atrophic nonunion of middle clavicular fracture, because it preserves the sclerotic bone at the broken nonunion ends, reduces the amount of iliac bone graft and leads to fine clinic efficacy.

Objective To compare lateral orbital keyhole approach(LOK) with conventional keyhole approach including supraorbital keyhole approach (SOK) and pterional approach(PTK) for exposuring the sellar region and oper-ation ability, to provide theoretical and practical basis for the clinic. Methods From January, 2017 to Feburary, 2018, 15 cadaver head specimens of Chinese (30 sides) fixed by formalin were randomly divided into 3 groups, simu-lating SOK, LOK and PTK, application of frameless neuronavigation system, intersection of the posterior margin of the optic chiasma and the lamina terminalis served as the base point. Six different reference points were selected to radi-ate into the parasellar region of the skull base. The direction of the 2 adjacent reference points were connected to the base point to form a triangle. Six triangles constituted the sellar region to represent the total area. The supratentorial area, ipsilateral area, inferior area and contralateral area were calculated by stacking triangle. The comparison was made between groups. The Salma operation exposure scale was used to simulate the aneurysms of the common parts in the brain and the quantitative scores were performed. Results The total parasellar regions by SOK, LOK and PTK respectively were:(1641.6±295.6)mm2, (1782.3±294.6)mm2 and (1552.5±307.4)mm2. There was no statistical differ-ence(P>0.05); To compare the supratentorial region, SOK and LOK were both bigger than PTK ( P<0.05); To compare the ipsilateral and infratentorial area, LOK and PTK were both bigger than SOK respectively ( P<0.05);To compare the contralateral area, SOK, LOK and PTK were increased in turn (P<0.05). Salma operation exposure scale was used to get the scores:the score of SOK was 29.7 (39.08％), LOK was 37.0 (48.68％), and PTK was 36.1 (47.50％). Conclusion Anatomical analysis displayed that the 3 keyhole approaches showed different exposure of each part the parasellar re-gions, the LOK had a good exposure to the parasellar region and so as the higher maneuverability. But the clinical appli-cation should be comprehensive analysis, pay attention to specific lesions and make an appropriate choice. It has impor-tant clinical significance to improve the prognosis of patients.

OBJECTIVE:To investigate the effects of leukotriene receptor antagonist montelukast on inflammatory factor,air-way anatomy and lung function of children with cough variant asthma. METHODS:A total of 86 children with cough variant asth-ma selected from our hospital during Apr. 2010 to Aug. 2015 were divided into control group and observation group according to random number table,with 43 cases in each group. Control group was given Budesonide aerosol 0.4 mg,bid;observation group was given Montelukast sodium chewable tablets with different dose according to age(4 mg for 2-6 year-old,tid;5 mg for 7-12 year-old,tid).A treatment course of 2 groups lasted for 4 weeks,and both groups received 2 courses of treatment. The levels of inflammatory factor,airway anatomy and lung function indexes were detected in 2 groups before and after treatment,and the oc-currence of ADR was also observed. RESULTS:Before treatment,there was no statistical significance in above indexes between 2 groups(P>0.05). Compared to before treatment,the levels of IL-4,IL-6,IL-8,TNF-α and hs-CRP in 2 groups were de-creased significantly after treatment;airway wall thickness,basement membrane thickness,airway wall thickness/outside diameter ratio,total area of airway wall,total area of airway wall/total area of airway were decreased significantly,while FVC,FEV1, FEV1/FVC,PEF were increased significantly;the indexes in observation group were significantly better than control group,with statistical significance(P<0.05). There was no statistical significance in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:For pediatric cough variant asthma,montelukast can significantly improve inflammatory reaction,airway status and lung function with good safety.

[Objective] To refer a geographical distribution rule of alpha-L-fucosidase (AFU) reference values for the health adults in China via exploring its spatial distribution trend and its correlation with geographical factors.[Methods] A total of 6564 samples of AFU reference values from 66 administrative units in the years 2004-2015 were collected,male and female of which were 3701 cases (56.4％) and 2863 cases (46.3％).A research concerning AFU reference values in whole country were calculated using methods of information content and ridge regression.[Results] AFU reference values for Chinese healthy adults were influenced by geographical factors and presented autocorrelation,and it showed eastern and northern areas were highery than western and southern areas.[Conclusions] AFU reference values have a spatial variation and the regional disparities should be considered in practice.

Objective To investigate the related factors of early adverse outcomes in young patients with ischemic stroke.Methods From January 2006 to June 2016,685 young patients (18-45 years old) with acute ischemic stroke admitted to the Department of Neurology,Nanjing General Hospital of Nanjing Military Command were enrolled retrospectively.They were diagnosed as the first onset with head CT or MRI.According to the modified Rankin scale (mRS) at 90 d,the patients were divided into a favorable outcome (mRS 0-2) group (n=554) and a poor outcome (mRS 3-6) group (n=131).The collection of clinical data were completed on the day of admission,including the risk factors for cerebrovascular disease (oral contraceptives,etc),the National Institutes of Health stroke scale (NIHSS) score on admission,the mean systolic blood pressure (>140 mmHg was analyzed) and laboratory examination.The stroke subtypes were classified with the trial of org 10172 in acute stroke treatment (TOAST) classification criteria.Univariate analysis was used to analyze the difference of clinical data between groups,and multivariate logistic regression analysis was used to analyze the risk factors for early poor outcomes.Results Compared with the favorable outcome group,the patients with the ratio of mean systolic pressure >140 mmHg in the first 3 d after hospitalization (37.4% [49/131] vs.21.7% [120/554],χ2=14.131),NIHSS score on admission (10.0 [7.0,14.0] vs.1.5 [0,3.0],Z=-15.300),white blood cell count (7.5 [6.0,9.0] ×109/L vs.6.8 [5.7,8.2] ×109/L,Z=-3.157),fasting glucose (4.9 [4.6,6.0] mmol/L vs.4.8 [4.4,5.3] mmol/L,Z=-2.726),higher fibrinogen level (2.8 [2.3,3.4] g/L vs.2.6 [2.3,3.2] g/L,Z=-2.018,blood uric acid level (291[220,346] mmol/L vs.315 [261,374] mmol/L,Z=-3.443),and plasma albumin level (43.1[40.0,45.9] g/L vs.44.8 [42.4,47.4] g/L,Z=-4.708) were decreased in the poor outcome group.There were significant differences between the two groups (all P<0.05).TOAST classification comparison:the proportion of the patients with cardioembolism in the poor outcome group was higher than that in the favorable outcome group.There was significant difference between the two groups (6.9% [9/131] vs.2.5% [14/554];χ2=4.893,P<0.05).There were no significant differences in the remaining clinical data between the two groups (all P>0.05).Multivariate logistic regression analysis showed that the higher NIHSS score on admission (OR,1.474,95%CI 1.378-1.576,P<0.01),the mean systolic pressure >140 mmHg at the first 3 d after admission (OR,2.134,95%CI 1.210-3.764,P=0.009) and the cardioembolism(OR,4.902,95%CI 1.073-22.222,P=0.040) were the risk factors for early poor outcome,and the elevated plasma albumin level (OR,0.902,95%CI 0.850-0.956,P=0.001) was a protective factor of early favorable outcome.Conclusion The higher NIHSS score at admission,the cardioembolism and the increased mean systolic blood pressure in the first 3 d after admission may result in early poor outcome in young patients with ischemic stroke,while the elevated plasma albumin level is beneficial to the early outcome.

Objective To investigate the reference intervals of mean corpuscular volume (MCV) ,mean corpuscular hemoglo‐bin(MCH) and mean corpuscular hemoglobin concentration (MCHC) examined by the MindrayBC‐6800 hematological analyzer to establish the reference intervals suitable for our laboratory .Methods According to the method recommended by the NCCLS C28‐A3 ,600 healthy adult individuals were selected as the reference individuals .MCV ,MCH and MCHC levels were determined by the MindrayBC‐6800 hematological analyzer for constructing the reference intervals ;other 150 healthy persons undergoing the physical examination were selected and their MCH ,MCV and MCHC detection results were collected for verifying the established reference intervals .Results The detection results of MCV ,MCH and MCHC in healthy adults showed a normal distribution ,MCV had sta‐tistical difference among different age periods (P<0 .05);the reference intervals :82 .278 -94 .242 fL for young adults ,83 .032-94 .608 fL for the middle‐aged persons and 83 .137-96 .343 fL for the elderly .MCH had statistical differences between different se‐xes and among different age periods ;the reference intervals :27 .785-32 .415 pg for male young adults ,28 .324-32 .456 pg for male middle‐aged persons and 28 .274-32 .966 pg for male elderly ;27 .367-31 .973 pg for female young adults ,27 .445-32 .215 pg for female middle‐aged persons and 27 .532 -32 .468 pg for female elderly .MCHC had statistical difference between different sexes (P<0 .05) ;the reference intervals :328 .611-352 .810 g/L for male and 323 .771-348 .750 g/L for female .In 150 individuals un‐dergoing the physical examination ,the proportion of individuals locating at the outside of reference interval was less than 10 .0% , therefore the newly established intervals were suitable for this laboratory .Conclusion The sex difference or/and age differences of MCV ,MCH and MCHC exist among adult populations .So the reference intervals are respectively established according to the prac‐tical situation ,which are suitable for this laboratory by verification .