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

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.

AIM:To investigate the effects of astragalin(AST)on activation status of astrocytes and the ex-pression level of autophagy-related proteins in the cortex of the anterior cingulate cortex of mice with a complete Freund's adjuvant(CFA)-induced inflammatory pain model.METHODS:Twenty-four 6-month-old male C57BL/6 mice were ran-domly divided into four groups:control group,saline group,CFA model group and CFA+60 mg/kg AST administration group,and six mice in each group.Mice in the AST administration group received 60 mg/kg AST by intraperitoneal injec-tion on a body weight basis for 21 d.The paw withdrawal threshold in each group of mice was evaluated by the von Frey test.The expression levels of autophagy-related factors LC3,p62,ATG12 and beclin-1,and astrocyte activation were de-tected by multiplex immunofluorescence staining in the anterior cingulate cortex of mice in each group.Western blot was used to measure the levels of autophagy-related proteins LC3,p62,ATG12 and beclin-1 in the anterior cingulate cortex of mice in each group.RESULTS:Behavioural tests showed that AST significantly increased mechanical pain thresholds in CFA mice(P＜0.05).The results from multiple immunofluorescent staining showed that AST significantly increased the fluorescence intensity of LC3(P＜0.01),ATG12(P＜0.01)and beclin-1(P＜0.05),attenuated the fluorescence intensi-ty of p62(P＜0.05),and inhibited the activation of astrocytes in the anterior cingulate cortex of CFA mice.Western blot results further confirmed that AST significantly increased the expressions of LC3(P＜0.01),ATG12(P＜0.01),beclin-1(P＜0.01),and decreased the expression of p62(P＜0.05)in the anterior cingulate cortex of CFA mice.CONCLU-SION:AST relieves CFA-induced inflammatory pain of mice,and its analgesic mechanism may be related to the inhibi-tion of activation of cortical astrocytes in the anterior cingulate cortex and the promotion of autophagy in CFA mice.

Acromicric dysplasia(AD) is a rare skeletal dysplasia characterized by severe short stature, short hands and feet, normal intelligence, mild facial dysmorphism, and radiological characteristics. The clinical data and genetic test results of one patient with AD in our hospital were analyzed, and the clinical characteristics of this case were summarized. The main manifestations of the child were short stature, short hands and feet, mild facial dysmorphism, short and stubby metacarpals and phalanges on hand X-ray. One mutation, FBN1: c.5141T>G(p.Met1714Arg), was identified in this child, the mutation is inherited from her short mother and grandfather. AD is a rare congenital skeletal dysplasia disorder associated with mutations in the FBN1 gene. It conforms to the pathogenesis of autosomal dominant genetic disease.

Dermatofibrosarcoma protuberans ( DFSP ) is very rare in clinic, and its diagnosis is not specific. According to the literature domestic and abroad, only 18 cases of patients during gestation period suffered from DFSP have been reported. This paper reported a case from the Department of Plastic Surgery, the First Affiliated Hospital of Bengbu Medical College in April 2022 diagnosed with DFSP during pregnancy.The DFSP showed rapid growth and pain during pregnancy, and stopped rapid growth after delivery. Extensive local resection was performed and the incision margin exceeded 3 cm diameter of the tumor. One-stage skin graft was used to repair the defect. HE staining showed a single spindle cell, arranged in a vortex, with large and dark nuclei. Some nuclei were heteromorphic, and few mitotic figures were observed. Postoperative pathology showed negative margins and basement. Immunohistochemistry showed CD34 (+ + ), Ki-67 (+, 10% ), bcl-2 (-), s-100 (-), SMA (-), CD163 (-), CD68 (-), which were consistent with the diagnosis of DFSP. The pathogenesis of DFSP is not yet clear. As a special population, patients during gestation period need special treatment and diagnosis. Through literature review, this paper summarizes the reports domestic and abroad, and discusses the diagnosis, treatment and prognosis of patients with DFSP during pregnancy.

Dermatofibrosarcoma protuberans ( DFSP ) is very rare in clinic, and its diagnosis is not specific. According to the literature domestic and abroad, only 18 cases of patients during gestation period suffered from DFSP have been reported. This paper reported a case from the Department of Plastic Surgery, the First Affiliated Hospital of Bengbu Medical College in April 2022 diagnosed with DFSP during pregnancy.The DFSP showed rapid growth and pain during pregnancy, and stopped rapid growth after delivery. Extensive local resection was performed and the incision margin exceeded 3 cm diameter of the tumor. One-stage skin graft was used to repair the defect. HE staining showed a single spindle cell, arranged in a vortex, with large and dark nuclei. Some nuclei were heteromorphic, and few mitotic figures were observed. Postoperative pathology showed negative margins and basement. Immunohistochemistry showed CD34 (+ + ), Ki-67 (+, 10% ), bcl-2 (-), s-100 (-), SMA (-), CD163 (-), CD68 (-), which were consistent with the diagnosis of DFSP. The pathogenesis of DFSP is not yet clear. As a special population, patients during gestation period need special treatment and diagnosis. Through literature review, this paper summarizes the reports domestic and abroad, and discusses the diagnosis, treatment and prognosis of patients with DFSP during pregnancy.

Objective:To investigate the clinical features and prognosis of MYC/BCL2 double-expression diffuse large B-cell lymphoma (DEL) .Methods:The clinical data, including clinical characteristics, survival, and prognostic factors, of 166 patients with DEL treated at Peking University Third Hospital from January 2016 to December 2020 were retrospectively analyzed.Results:A total of 410 patients with diffuse large B-cell lymphoma were collected, including 166 cases (40.5%) of DEL. There were 82 males and 84 females with a median age of 63.5 (21-95) years at diagnosis. A total of 110 patients (66.3%) were aged over 60 years at initial diagnosis, 106 patients (106/163, 65.0%) had elevated lactate dehydrogenase (LDH) at diagnosis, 74 patients (74/160, 46.2%) had β 2 microglobulin level over 3 mg/L at diagnosis, and 107 patients (107/163, 65.6%) had≥2 extranodal involvement. Sixty-five patients (65/166, 39.2%) had B symptoms, 131 patients (131/165, 79.4%) had stage Ⅲ and Ⅳ disease at initial diagnosis, 41 patients (41/161, 25.5%) had an International Prognostic Index (IPI) score of 0-2 at initial diagnosis, and 38 patients (38/161, 23.6%) had an IPI score of 3 at initial diagnosis. Eighty-two patients (82/161, 50.9%) had an IPI score of 4-5 at initial diagnosis. Nine (9/56, 16.1%) patients with DEL had MYD88 and CD79B mutations. Univariate analysis showed that age over 60 years ( P=0.004) , increased β 2 microglobulin level ( P=0.002) , and high IPI score ( P=0.003) were associated with poor overall survival (OS) . Increased β 2 microglobulin level ( P=0.031) , LDH level ( P=0.017) , stage Ⅲ-Ⅳ ( P=0.001) , high IPI score ( P=0.013) , immunohistochemical p53 mutation ( P=0.049) , and PIM1 mutation ( P=0.039) were associated with poor progression-free survival (PFS) . Multivariate analysis showed that IPI score of 4-5 was an independent risk factor for the prognosis of DEL ( HR=2.622, 95% CI 1.398-4.917, P=0.003) . Survival analysis showed that there was a significant difference in the PFS between patients with DEL and those without DEL (65.6% vs 75.1%, P=0.002) . However, there was no significant difference in the OS (81.8% vs 83.6%, P=0.226) . In patients with DEL, the overall response rate of R-EPOCH regimen was higher than that of RCHOP or RCHOP-like regimen (81.5% vs 63.4%, P=0.004) . Conclusion:DEL is a group of aggressive lymphomas with relatively poor PFS. The R-EPOCH regimen may improve the overall prognosis of patients.

Objective:To explore the effects of infant sleep patterns on maternal sleep quality.Methods:Three hundred and nineteen pairs of mothers and infants from two grade three class-a hospitals in Nantong City were enrolled. Infant sleep patterns were assessed by the Brief Infant Sleep Questionnaire (BISQ). Maternal sleep quality was evaluated using the Pittsburgh sleep quality index (PSQI). The effect of infant sleep patterns on maternal sleep quality was analyzed by one-way ANOVA followed with multivariate analysis.Results:The maternal sleep quality scored 7.08±2.60. Single factor analysis pointed out that the sleep quality of women whose infants slept in bed near parents, woke up more than 3 times a night, was nocturnal wakefulness more than 60 minutes or nocturnal sleep duration less than 8 hours was significantly worse. After controlling for confounding variables, the way of baby falling asleep, numbers of night wakings, nocturnal sleep duration, maternal age, infant′s gender and primary caregiver were independent factors of maternal sleep quality.Conclusion:Infant sleep pattern is an important factor affecting maternal sleep quality. Nurses should provide information about the sleep patterns of infants to mothers and their family members to promote their babies′ sleep habits so as to improve the maternal sleep quality.

Objective:To study the basic characteristics and gene evolution of M segment of fever and thrombocytopenia syndrome virus (SFTSV)in China.Methods:The full sequence of M fragment of SFTSV strain isolated in China before June 25, 2020 was obtained from GenBank. The BioEdit software was used for multi-sequence alignment and MEGA5.0 software was used to construct the phylogenetic tree to compare the homology of SFTSV, which came from different types and sources.Results:M fragments of 203 SFTSV isolated in China was collected from GenBank database.. Among them, 185 strains were isolated from humans (91.1%), 11 strains were isolated from ticks(5.4%), and 5 strains were isolated from goat, mice and hedgehog (3.5%). Phylogenetic tree analysis showed that C2 genotype was dominant in China, accounting for 42.4% of total. The nucleotide sequence and amino acid sequence homology were 96.4%~100.0%, 94.5%~100.0%, respectively. The homology of human and animal isolates was very high. The nucleotide sequence and amino acid sequence homology were 92.5%~100.0% and 92.0%~100.0%, respectively.Conclusions:Phylogenetic tree analysis of SFTSV isolates in China based on the M fragment showed that C2 genotype was dominant, and there are multiple types of co-circulation. By comparing M and S-segment-based phylogenetic tree, it suggests that SFTSV may potential undergo adaptive conversion from C-type to J-type.

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.