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.

Dendritic cell-based cancer vaccines (DC vaccines) have been proved efficient and safe in immunotherapy of various cancers, including melanoma, ovarian and prostate cancer. However, the clinical responses were not always satisfied. Here we proposed a novel strategy to prepare DC vaccines. In the present study, a fusion protein SNU containing a secretin-penetratin (SecPen) peptide, NY-ESO-1 and ubiquitin was designed and expressed. To establish the DC vaccine (DC-SNU), the mouse bone marrow-derived DCs (BMDCs) were isolated, pulsed with SNU and maturated with cytokine cocktail. Then peripheral blood mononuclear cells (PBMCs) from C57BL/6 mice inoculated intraperitoneally with DC-SNU were separated and cocultured with MC38/MC38

Objective To analyze the death characteristics and disease burden of the labor force in Jingzhou City from 2015 to 2018, and to provide a basis for formulating policies to protect the labor force population and propose effective prevention and control measures to reduce the death level and disease burden. Methods The death data of the labor force in Jingzhou City from 2015 to 2018 was collected and statistically analyzed. The death levels, causes of death, and disease burden of the labor force in different years, sexes, ages, and regions were analyzed. Results From 2015 to 2018, the death toll of the labor force accounted for 24.79% of total deaths in Jingzhou City, with a mortality rate of 219.61/100 000 and a standardized mortality rate of 192.17/100 000. There was no significant difference in the mortality rate in different years (P=0.34). The male and female mortality rates were 297.77/100 000 and 139.63/100 000, and the standardized mortality rates were 257.36/100 000 and 119.57/100 000, respectively. The male and female YLL rates were 9.55% and 4.47%, and the standardized YLL rates were 6.75% and 3.12%, respectively. The male mortality and YLL rates were higher than those of the female (P<0.01). The mortality and YLL rate of different age groups increased with age (P<0.01). The mortality rates of urban and rural population were 187.37/100 000 and 229.07/100 000, respectively, the standardized mortality rates were 141.87/100 000 and 208.58/100 000, respectively, the YLL rates were 5.90% and 7.37% respectively, and the standardized YLL rates were 4.13% and 5.20%, respectively. The mortality rate and YLL rate of rural population were higher than those of urban population (P<0.01). The first cause of death in the labor force population was malignant tumor, with the mortality and YLL rate being 87.19/100 000 and 2.90%, respectively. The second cause was injury, with the mortality and YLL rate of 42.60/100 000 and 1.56%, respectively. The leading cause of death was injury in the 15 and 25 years old groups, and malignant tumor in the 35, 45 and 55 years old groups. Lung cancer and liver cancer were the main types of lethal cancers. Transportation accidents and suicide were the main types of lethal injuries. Conclusion The disease burden of the rural labor force was heavy. It is important to strengthen health education for the rural labor force, especially male laborers over the age of 45, and to implement early cancer diagnosis and treatment and injury intervention programs to effectively improve the health of the labor population.

Objective To develop a MOSAIQ Integration PlatformCHN (MIP) based on the workflow of radiotherapy (RT) and to meet the actual requirements in China and the special needs for the radiotherapy department.Methods MIP used C/S (client-server) structure mode running on the local network in the hospital and its database was based on the Treatment Planning System (TPS) and MOSAIQ database.Five network servers,as the core hardware,supplied data storage and network service based on cloud services.The core software was developed based on Microsoft Visual Studio Platform using C# network programming language.The MIP server could simultaneously offer network service for about 200 workstations,including entry,query,statistics,and print of data.Results MIP had 15 core function modules,such as Notice,Appointment,Billing,Document Management (application/execution),and System Management,which almost covered the whole workflow of radiotherapy.Up to June 2016,the recorded data in the MIP were as follows:13546 patients,13533 plan application forms,15475 RT records,14656 RT summaries,567048 billing records,and 506612 workload records.Conclusions The MIP based on the RT workflow has been successfully developed and used in clinical practice.It is an important part of radiotherapy information system construction with the advantages of intuitive operation,real-time performance,data security,and stable operation.It is digital,paperless,user-friendly,and convenient for the retrieval and statistics of data as well as information sharing and department management,and can significantly improve the efficiency of the department.More functions can be added or modified to enhance its potentials in research and clinical practice.

Objective To observe the protective effect of growth differentiation factor 11(GDF11) on myocardial injury and the changes of myocardial apoptosis in type 2 diabetic C57BL/6J mice.Methods Sixty male C57BL/6J mice weighing 20-25 g were randomly divided into three groups: control group (control), type 2 diabetes mellitus group (DM) and GDF11 intervention group (DM + GDF11).To establish mouse model of type 2 diabetes, the mice were fed with high fat and high sugar diet for 4 weeks, and i.p.injected consecutively three times of streptozotocin (STZ) in a dose of 60 mg/kg.After the continuous high-fat and high-sugar diet for 4 weeks, the cardiac function was detected by small animal ultrasound, TUNEL staining was used to detect the apoptosis in myocardium, and the expressions of cleaved-caspase-3, Bcl-2, Bax were measured.Results Diabetic injury significantly reduced the left ventricular ejection fraction and left ventricular short axis shortening rate, and increased myocardial apoptosis.Recombinant GDF11 protein significantly improved cardiac function and reduced myocardial apoptosis.Conclusions Exogenous GDF11 can significantly reduce myocardial apoptosis and improve heart function after diabetic injury.

Objective To perform a preclinical test of a delineation software based on atlas-based auto-segmentation (ABAS),to evaluate its accuracy in the delineation of organs at risk (OARs) in radiotherapy planning for nasopharyngeal carcinoma (NPC),and to provide a basis for its clinical application.Methods Using OARs manually contoured by physicians on planning-CT images of 22 patients with NPC as the standard,the automatic delineation using two different algorithms (general and head/neck) of the ABAS software were applied to the following tests:(1) to evaluate the restoration of the atlas by the software,automatic delineation was performed on copied images from each patient using the contours of OARs manually delineated on the original images as atlases;(2) to evaluate the accuracy of automatic delineation on images from various patients using a single atlas,the contours manually delineated on images from one patients were used as atlases for automatic delineation of OARs on images from other patients.Dice similarity coefficient (DSC),volume difference (Vdiff),correlation between the DSC and the volume of OARs,and efficiency difference between manual delineation and automatic delineation plus manual modification were used as indices for evaluation.Wilcoxon signed rank test and Spearman correlation analysis were used.Results The head/neck algorithm had superior restoration of the atlas over the general algorithm.The DSC was positively correlated with the volume of OARs and was higher than 0.8 for OARs larger than 1 cc in volume in the restoration test.For automatic delineation with the head/neck algorithm using a single atlas,the mean DSC and Vdiff were 0.81-0.90 and 2.73％-16.02％,respectively,for the brain stem,temporal lobes,parotids,and mandible,while the mean DSC was 0.45-0.49 for the temporomandibular joint and optic chiasm.Compared with manual delineation,automatic delineation plus manual modification saved 68％ of the time.Conclusions A preclinical test is able to determine the accuracy and conditions of the ABAS software in specific clinical application.The tested software can help to improve the efficiency of OAR delineation in radiotherapy planning for NPC.However,it is not suitable for delineation of OAR with a relatively small volume.

Objective To systematically compare the clinical efficacy of hepatectomy via anterior approach and the conventional approach for the treatment of giant liver cancer.Methods The database including Cochrane library,PubMed,Web of Knowledge,EMBASE,China National Knowledge Infrastructure (CNKI),Chinese Medical Current Contents(CMCC),Wanfang database were searched with the key words of原发性肝癌,转移性肝癌,手术,肝切除术,前入路,绕肝提拉法,传统入路,hepatocellular carcinoma,metastatic liver cancer,HCC,surgery,liver resection,hepatectomy,hepatic resection,anterior approach,conventional approach and liver hanging maneuver between the database establishment and December 2013.Chinese and English literatures on major hepatectomy via anterior approach and conventional approach for the treatment of giant liver cancer were retrieved,and data were analyzed by 2 independent researchers.Meta analysis was carried out using the software of Review Manager 5.1.2.The count data were analyzed using the odds ratio (OR).The quantitative data were analyzed by the weighted mean difference (WMD),and were presented by 95％ confidence interval (95％ CI).Results Thirteen literatures with 1 287 giant liver cancer patients were retrieved,including 603 patients receiving hepatectomy via anterior approach and 684 via conventional approach.Three literatures were enrolled in the randomly controlled studies,one had high risk of bias and the other 2 had low risk of bias.Ten literatures were enrolled in the non-randomly controlled studies with the mean score of 7 (range,5-9).The results of Meta analysis showed that hepatectomy via anterior approach could reduce the volume of intraoperative blood loss (MD =-349.39,95％ CI:-636.90--61.81,P ＜ 0.05),the blood transmission rate (OR =0.41,95％ CI:0.24-0.72,P ＜ 0.05),the operation time (MD =-40.81,95 ％ CI:-57.81--23.80,P ＜ 0.05),the mean time of hospital stay (MD =-4.52,95 ％ CI:-8.36--0.69,P ＜ 0.05) and the postoperative mortality and incidence of postoperative complications (OR =0.32,0.68,95 ％ CI:0.16-0.62,0.53-0.88,P ＜ 0.05) when compared with the conventional approach,further more,hepatectomy via the anterior approach could reduce the postoperative recurrence of giant liver cancer and had higher overall 1-and 3-year survival rates (OR =0.45,2.72,4.47,95％ CI:0.29-0.69,1.59-4.66,2.61-7.63,P ＜ 0.05).Conclusion The safety of hepatectomy via anterior approach is similar to that of the conventional approach,while the short-and long-term efficacy are superior to those of the conventional approach.

Objective To construct the recombinant expression vector encoding antisense Tcf fragment for the blockage of abnormal Wnt pathway, and to investigate its effect on the biological behaviors of human hepatocarcinoma cells. Methods Antisense expression vector was transfected into hepatocarcinoma cells SMMC-7721 with GeneJammer. RT-PCR and Western blot were used to detect Tcf expression. Cell proliferation and motility were compared by growth curves and Transwell plate assay. Cell apoptosis was determined by Annexin V and cell cycle was examined by fluorescent staining. Results The stable transfection of antisense Tcf in SMMC-7721 cells significantly reduced Tcf expression at both mRNA and protein levels. Compared with parental and mock-transfected 7721 (7721-vector) cells, antisense Tcf RNA transfected cells 7721-pTas showed much decreased activities of proliferation, migration and invasion in vitro. Furthermore, the apoptosis rate of 7721-pTas cells [(26.34±2.07)%] was significantly higher than that of 7721-vector cells [(6.53±1.02)%] and parental SMMC-7721 cells [(4.33±0.68)%] (P<0.001). The percentages of G0-G1 phase antisense transfected cells were 20.24% and 20.95%, higher than parental SMMC-7721 and 7721-vector cells, and percentages of S phase antisense transfected cells were 11.8% and 11.38%, lower than parental SMMC-7721 and 7721-vector cells, respectively. Conclusions Antisense RNA suppress the growth ability of liver cancer cells by inducing cell apoptosis and impeding the progress of cell cycle, which suggests that selective blockage of abnormal Wnt signal pathway by antisense Tcf RNA may be a potential new gene therapy for liver cancer.

Objective To study the biological changes and the collagen synthesis of the primary cultured skin fibroblast treated with Cigarette Smoke Extract (CSE). Methods The morphological changes of fibroblasts after 24 hours' treatment with CSE were observed with invert microscope. The inhibitory effect at different concentrations of CSE on fibroblast activities was determined by the tetrazolium dye colorimetric test (MTT Test). The growth curves of fibroblasts treated with CSE were drawn with MTT method. Cell aging was observed with β-galactosidase, which was the biological marker of senescence. Flow cytometry (FCM) was used to estimate cell cycle phases after the fibroblasts were treated at different concentrations of CSE and different time. The mRNA expression of type Ⅰ procollagen was detected by RT-PCR. Results After the treatment, the fibroblasts displayed morphological changes and the growth of fibroblasts was apparently slowed down by CSE. The positive β-galactosidase staining was observed in the treated fibroblasts, which were affected by CSE for 5 passages. FCM analysis demonstrated that CSE decreased the cells in S phase and increased the cells in G1 and G2 phase. The result of RT-PCR showed that type Ⅰ procollagen was decreased after the treatment with CSE. Conclusion CSE can not only inhibit the growth and proliferation of the skin fibroblasts, but also decrease collagen synthesis of dermal fibroblast which is very important to the skin health.