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 explore the role and its clinical significance of P300 in biphasic differentiation and epithelial mesenchymal transition ( EMT) process in synovial sarcoma (SS) by detecting the expression of histone acetyltransferase P300 and EMT related molecules. Methods : 40 cases of SS paraffin embedded tissue samples were collected , and the SYT⁃SSX fusion gene subtype was detected by RT⁃PCR. Immunohistochemistry was used to detect the expression of P300 and EMT⁃related molecules. : Results Conclusion P300 may be involved in the biphasic differentiation and the EMT process of SS , suggesting that P300 plays a certain role in SS invasion and migration.

Retinopathy of prematurity (ROP) is a proliferative vascular retinal disease. Cryotherapy, laser photocoagulation, intravitreal injection of anti-vascular endothelial growth factor, scleral buckling surgery and vitrectomy are the main treatments. Treated with cryotherapy or laser photocoagulation or intravitreal injection of anti-vascular endothelial growth factor, patients with a history of ROP have thicker foveas, and the morphology of the fovea and the development of the retinal vessels in the macular area are affected, resulting in abnormal vision development. However, the specific mechanisms by which different treatments of ROP affecting the development of the macula are not yet clear. It still need further study with large samples to verify and explore, whether changes in the levels of intraocular vascular endothelial growth factor changing the process of normal macular development and how the abnormal development of the macula affects visual function.

Objective:To investigate the effect of serum lipid level on prognosis of patients with small cell lung cancer (SCLC) at the initial treatment.Methods:The clinical data of patients with SCLC from 2012 to 2017 in our hospital were retrospectively analyzed. According to the standard of appropriate level and abnormal stratification of blood lipid in Chinese population, the lipids included total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol (LDLC) at the time of initial treatment were grouped. Then the relationship between different lipid levels and clinicopathological characteristics was analyzed. Finally, Cox proportional hazard model was used to analyze the independent prognostic factors of patients.Results:A total of 129 patients with SCLC were included in this study. At the time of initial treatment, there were 90 (69.8%) cases whose TC < 5.2 mmol/L, while 39 (30.2%) cases ≥5.2 mmol/L; 95 (73.6%) cases whose TG <1.7 mmol/L, while 34 (26.4%) cases ≥1.7 mmol/L; 27 (20.9%) cases whose HDLC <1.0 mmol/L while 102 cases (79.1%) ≥1.0 mmol/L; 90 (69.8%) cases whose LDLC <3.4 mmol/L while 39 cases (30.2%) ≥3.4 mmol/L. The patients′ triglyceride initial treatment was associated with their body mass index ( P<0.05). The median disease-free survival (PFS) of SCLC patients was related with their serum TC level and clinical stage ( P<0.05) and the overall survival (OS) was related with clinical stage of SCLC patients ( P<0.05). The median PFS of SCLC patients in the TC <1.7 mmol/L group at the initial treatment was 10.5 months, significantly longer than 8.8 months of the TC ≥1.7 mmol/L group ( P=0.024). The median OS of SCLC patients in the TG <1.7 mmol/L group at the initial treatment was 20.2 months, marginally longer than 15.6 months of the TG ≥1.7 mmol/L group ( P=0.097). Multivariate analysis result showed that, the TG level was an independent risk factor of SCLC progression at the time of initial treatment ( P=0.024). There was no significant correlation of TC, HDLC, LDLC and SCLC prognosis ( P>0.05). Conclusion:TG level is an independent risk factor for the progression of SCLC at the time of initial treatment, and the increase of TG level indicates rapid disease progression and poor prognosis.

Objective:To investigate the effect of serum lipid level on prognosis of patients with small cell lung cancer (SCLC) at the initial treatment.Methods:The clinical data of patients with SCLC from 2012 to 2017 in our hospital were retrospectively analyzed. According to the standard of appropriate level and abnormal stratification of blood lipid in Chinese population, the lipids included total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol (LDLC) at the time of initial treatment were grouped. Then the relationship between different lipid levels and clinicopathological characteristics was analyzed. Finally, Cox proportional hazard model was used to analyze the independent prognostic factors of patients.Results:A total of 129 patients with SCLC were included in this study. At the time of initial treatment, there were 90 (69.8%) cases whose TC < 5.2 mmol/L, while 39 (30.2%) cases ≥5.2 mmol/L; 95 (73.6%) cases whose TG <1.7 mmol/L, while 34 (26.4%) cases ≥1.7 mmol/L; 27 (20.9%) cases whose HDLC <1.0 mmol/L while 102 cases (79.1%) ≥1.0 mmol/L; 90 (69.8%) cases whose LDLC <3.4 mmol/L while 39 cases (30.2%) ≥3.4 mmol/L. The patients′ triglyceride initial treatment was associated with their body mass index ( P<0.05). The median disease-free survival (PFS) of SCLC patients was related with their serum TC level and clinical stage ( P<0.05) and the overall survival (OS) was related with clinical stage of SCLC patients ( P<0.05). The median PFS of SCLC patients in the TC <1.7 mmol/L group at the initial treatment was 10.5 months, significantly longer than 8.8 months of the TC ≥1.7 mmol/L group ( P=0.024). The median OS of SCLC patients in the TG <1.7 mmol/L group at the initial treatment was 20.2 months, marginally longer than 15.6 months of the TG ≥1.7 mmol/L group ( P=0.097). Multivariate analysis result showed that, the TG level was an independent risk factor of SCLC progression at the time of initial treatment ( P=0.024). There was no significant correlation of TC, HDLC, LDLC and SCLC prognosis ( P>0.05). Conclusion:TG level is an independent risk factor for the progression of SCLC at the time of initial treatment, and the increase of TG level indicates rapid disease progression and poor prognosis.

Hospice care is the product of the development of social civilization. Our country has gradually promoted the development of hospice care from the government, society, education and other levels, but has invested less in systematic education. This article reviews the development status of hospice care education at home and abroad in order to provide a reference for the development of related education in our country.

Objective:To investigate the changes of liver spin-lattice relaxation time (T 1rho) values in the rotating frame in the progression and regression of carbon tetrachloride (CCl 4)-induced model rats with liver fibrosis and the diagnostic values for staging liver fibrosis. Methods:Eighty rats were prospectively enrolled and randomly divided into the CCl 4 group ( n=49), the regression group ( n=20) and the control group ( n=11). All rats were labeled and then examined using MRI at baseline. The liver fibrosis model was established by subcutaneous injection of 40% CCl 4 in hackles. The CCl 4 group underwent black-blood T 1rho imaging at the end of the 4th, 6th, 8th, 10th, 12th week post CCl 4 injection. The regression group underwent black-blood T 1rho imaging at the end of the 4th, 6th week post CCl 4 injection and the end of 1st, 2nd, 4th, 6th week post CCl 4 withdrawal (the injection was stopped at the end of the 6th week). The control group was injected with the same amount of corn oil at the same time point and underwent black-blood T 1rho imaging at the end of 4th, 6th, 8th, 10th, 12th week. The liver T 1rho values were measured in each group over time. Independent-samples t test was used to analyze the differences of liver T 1rho values in adjacent time points. The experimental mice were divided into no liver fibrosis group (S0), mild liver fibrosis group (S1, 2) and moderate or severe liver fibrosis group (S3, 4). The differences of liver T 1rho values were analyzed in different fibrosis stages by Kruskal-Wallis H test. The receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic ability of T 1rho values in staging liver fibrosis. The correlation between liver T 1rho values and fibrosis stages was analyzed using Spearman correlation coefficient. Results:Fifty-nine rats completed the whole experiment, including 28 rats in the CCl 4 group, 20 rats in the recovery group and 11 rats in the control group. In the CCl 4 group, the liver T 1rho values gradually increased, reached the maximum at the end of week 8, and then gradually decreased. There was statistically significance in liver T 1rho values at the adjacent time points ( P<0.05) except at the 4th to 6th week ( P=0.112) and 10th to 12th week ( P=0.487) in the CCl 4 group. In regression group, the liver T 1rho values gradually increased post CCl 4 injection and decreased post CCl 4 injection withdrawal. There was statistically significance in liver T 1rho values at the adjacent time points ( P<0.05) in regression group. There was no statistically significance in liver T 1rho values at the adjacent time points ( P>0.05) in control group. The T 1rho values in the no liver fibrosis group (S0, n=15), the mild liver fibrosis group (S1, 2, n=23) and the moderate or severe liver fibrosis group (S3, 4, n=21) were [36.3(34.4,41.4)], (47.2±8.4), (48.8±9.0) ms, respectively. The liver T 1rho values increased with the aggravation of the liver fibrosis, and there was a low positive correlation between them ( r=0.402, P=0.001). There were statistically significant differences in T 1rho values among the three groups ( P<0.01).The area under the curve values to distinguish no liver fibrosis (S0) from liver fibrosis (S1 to 4) and no or mild liver fibrosis (S0 to 2) from moderately or severe liver fibrosis (S3,4) were 0.825 (95% confidence intervals is 0.720 to 0.931) and 0.668 (95% confidence intervals is 0.540 to 0.796), separately. Conclusion:The liver T 1rho values are useful for evaluating the progression and regression of liver fibrosis. It has a moderate diagnostic value to assess the presence of liver fibrosis, but a low diagnostic value to differentiate no or mild liver fibrosis from moderately to severe liver fibrosis.

Objective: To probe into the mechanism and interventional effects of silybin-phospholipid complex on amiodarone-induced steatosis in mice. Methods: Eight-week-old male C57BL/6 mice were divided into three groups (5 mice in each group): a control group (WT) with normal diet, a model group with amiodarone 150mg/kg/d by oral gavage (AM), and an intervention group on amiodarone 150mg/kg/d combined with silybin-phospholipid complex(AM+SILIPHOS. All mice were fed their assigned diet for one week. Then, one week later, serum alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol and high-density lipoprotein were detected of each group. A liver pathological change was observed by oil red O and H&E staining. Ultrastructural pathological changes of hepatocytes were observed to evaluate the intervention effect by transmission electron microscopy. RT-q PCR was used to detect the expression of peroxisome proliferator-activated receptor alpha and its regulated lipid metabolism genes CPTI, CPTII, Acot1, Acot2, ACOX, Cyp4a10 and Cyp4a14 in liver tissues. Intra-group comparison was done by paired t-test. One-way ANOVA was used for comparison between groups and semi-quantitative data were tested using Mann-Whitney U test. Results: Oil Red O and H&E staining results of liver tissue in the intervention group showed that intrahepatic steatosis was significantly reduced when compared to model group. Transmission electron microscopy showed that the model group had pyknotic nuclei, mitochondrial swelling, structural damage, and lysosomal degradation whereas the intervention group had hepatic nucleus without pyknosis, reduced mitochondrial swelling and slight structural damage than that of model group. RT-q PCR results showed that the expression of peroxisome proliferator-activated receptor alpha, CPTI, CPTII, Acot1, Acot2, ACOX, Cyp4a10 and Cyp4a14 were increased in the model group but the expression of CPTI, Cyp4a14, Acot1 and peroxisome proliferator-activated receptor alpha were decreased in the intervention group (P < 0.05). Conclusion Silybin-phospholipid complex can alleviate amiodarone-induced steatosis, and its mechanism may play a role in protecting mitochondrial function and regulating fatty acid metabolism. Thus, silybin-phospholipid complex has potential intervention effect on amiodarone-induced fatty liver.

Objective To explore the efficacy difference of diffusion kurtosis imaging (DKI) and ultrasound elastography (UE) in the diagnosis of liver fibrosis. Methods Thirty-five patients whose serological examination showed hepatitis B or hepatitis C virus infection, disease course≥ 1 year, and finally liver biopsy confirmed pathological fibrosis grade in Tianjin Second People's Hospital from December 2015 to April 2017 were prospectively enrolled as patient group. During the same period, twenty healthy volunteers who matched the age, sex and BMI with patient group and showed normal liver function within the last month were enrolled as control group. All of the subjects underwent DKI experiment, and subjects in patient group underwent UE experiment in addition. Liver mean apparent diffusion (MD) and mean kurtosis (MK) were obtained in all subjects and liver stiffness measurement (LSM) was obtained in patient group. The patient group was staged for hepatic fibrosis based on liver biopsy results (S0 to S4). Differences in liver MD and MK values between control and patient groups were tested using independent sample t test (normal distribution) or Mann-Whitney U test (skewed distribution). Differences in liver MD, MK, and LSM between patients with different fibrosis stages were tested using One-way ANOVA (normal distribution) or Kruskal-Wallis test (skewed distribution). The correlation between liver MD, MK and LSM values with fibrosis stages were analyzed using Pearson correlation test. The diagnostic performance in staging fibrosis was analyzed using ROC analysis. Results Liver MD in patient group was lower than that in control group, and the difference was statistically significant (P<0.01). There was no significant difference in liver MK between the two groups (P>0.05). The AUC value for the diagnosis of liver fibrosis by MD was 0.950 (95％CI:0.855 to 0.990). Of the 35 patients, 15 were S1 (mild fibrosis), 13 were S2 (moderate fibrosis), 4 were S3, 3 were S4 (S3+S4 were severe fibrosis). The difference of MD and LSM between different stages of liver fibrosis was statistically significant (P<0.05), and there was no significant difference in MK (P>0.05). Liver fibrosis stages was highly correlated with MD (r=-0.757, P<0.01), and had no correlation with MK (r=-0.010, P=0.956), and moderately correlated with LSM (r=0.440, P<0.01). The AUC values of liver MD and LSM for characterization of ≥S2 stage liver fibrosis were 0.867 and 0.800, respectively, without statistically significant difference (P=0.486). The AUC values for characterization of≥S3 stage liver fibrosis were 0.918 and 0.653, respectively, with a statistically significant difference (P=0.032). Conclusion MD derived from DKI can be used for noninvasive assessment of liver fibrosis, and it is superior to LSM in distinguishing different fibrosis stages and detecting severe fibrosis.

Objective To analyze CT manifestations of chest wall Askin tumor and to illustrate its CT diagnostic and differentially diagnostic key points.Methods Eleven cases of chest wall Askin tumors were pathologically confirmed in our hospital between May 2006 and November 2014.Of them,10 cases were children and adolescents,and 9 cases had chest pain as the first symptom.All patients received plain CT scan,while 7 cases received contrast enhanced scan.CT signs of this group were retrospectively analyzed,including the location,quantity,shape,size,density,adjacent tissue invasion and distant metastasis of the tumors.Results CT examination showed a single oval mass on the chest wall in all 11 cases.The tumor was located completely within the thoracic cavity in 10 cases,while a tumor's main part was within thoracic cavity.Nine tumors had long diameters of more than 9 cm.All the tumors were heterogeneous without calcification,wherein 10 cases showed necrosis and cystic degeneration.On contrast enhanced scan,7 cases showed heterogeneously mild to moderate enhancement.All tumors invaded adjacent tissues,including 7 cases of bone damage of a single rib,and 7 cases of pleural involvement,wherein 6 cases had pleural effusion.No remote metastases were found in this group.Conclusions CT manifestations of Askin tumors of chest wall have some characteristics,and familiarity with these manifestations is conducive to diagnosis and differential diagnosis of this disease.