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.

Palliative and hospice care is an emerging medical care model for the development of modern medicine,and its emergence is not only a sign of social demand and the development of human civilization,but also an important manifestation of the change in the modern medical model.Hospice care is the final stage of palliative care,which is of great significance for the end-of-life treatment of incurable diseases.Palliative and hospice care has become an independent discipline in many countries,and its development has been rapid.However,the develop-ment of hospice and palliative care in China is not satisfactory,and the lack of money and human resources are the main reasons limiting its development.Many scholars have carried out a lot of useful practices in this regard.How to explore a road of hospice and palliative care development suitable for China′s national conditions is an urgent problem to be solved.By reviewing domestic and foreign literature,this paper summarizes the development mode and payment method of palliative and hospice care abroad,identifies the challenges encountered in the practice of hospice care in China,and draws on the development experience of palliative and hospice care in foreign countries.We aimed to identify pain points and difficulties faced in developing palliative and hospice care in China,so as to better serve patients at the end of life,gradually promote the concept of palliative and hospice care,and contribute to the sustainable development of palliative and hospice care in China.

Objective:To investigate the association between body mass index (BMI) trajectories in children and adolescents and subclinical renal damage (SRD) in adulthood.Methods:4 623 participants aged 6-18 years old were recruited from the ongoing cohort of Hanzhong adolescent hypertension study in 1987, and the subjects were followed up in 1989, 1992, 1995, 2005, 2013 and 2017, respectively. Group-based trajectory modeling was used to identify distinct BMI trajectories in longitudinal analysis. Generalized linear model was applied to examine the association between different BMI trajectories and SRD incidence in adulthood.Results:A total of 2 678 subjects from childhood to adulthood were enrolled in this study. All subjects were divided into three groups according to three distinct BMI trajectories: low-increasing BMI group ( n=1 017), moderate-increasing BMI group ( n=1 353), and high-increasing BMI group ( n=308). Over follow up for 30 years, a total of 248 participants (9.3%) developed SRD. Urinary albumin-to-creatinine ratio (uACR) in low to high-increasing BMI group was 0.9(0.6, 1.4), 1.0(0.7, 1.7), 1.6(0.8, 3.2), respectively ( P trend<0.001), and estimated glomerular filtration rate was 98.5(87.6, 111.6) , 96.2(86.4, 109.7), 95.3 (87.5, 125.0) ml·min -1·(1.73 m 2) -1, respectively ( P trend=0.025). The generalized linear model analysis showed that uACR was increased linearly from low to high-increasing BMI group [ β=3.16(95% CI 1.02-5.31), Ptrend=0.004]. There was no correlation or linear trend between BMI trajectory and estimated glomerular filtration rate [ β=-2.30(95% CI-5.18-0.57), Ptrend=0.117]. Compared with the low-increasing BMI group, the high-increasing BMI group had greater odds of experiencing SRD in adulthood after adjusting for multiple confounders such as age, gender, medical history and lifestyle ( OR=2.83, 95% CI 1.84-4.36, Ptrend<0.001). Conclusions:Higher BMI trajectorie is correlated with higher level of uACR and risk of SRD in middle age. Identifying long-term BMI trajectorie from early age may assist in predicting individuals′ renal function in later life.

Purpose: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, and Th17 cells are key factors in the pathogenesis of human inflammatory conditions, such as RA. Catalpol (CAT), a component in Rehmanniae Radix (RR), has been found to regulate human immunity. However, the effects of CAT on Th17 cell differentiation and improvement of RA are not clear. Materials and Methods: Collagen-induced arthritis (CIA) mice were constructed to detect the effects of CAT on arthritis and Th17 cells. The effect of CAT on Th17 differentiation was evaluated with let-7g-5p transfection experiments. Flow cytometry was used to detect the proportion of Th17 cells after CAT treatment. Levels of interleukin-17 and RORγt were assessed by qRT-PCR and enzyme-linked immunosorbent assay. The expression of signal transducer and activator of transcription 3 (STAT3) was determined by qRT-PCR and Western blot. Results: We found that the proportion of Th17 cells was negatively associated with let-7g-5p expression in CIA mice. In in vitro experiments, CAT suppressed traditional differentiation of Th17 cells. Simultaneously, CAT significantly decreased Tregs-to-Th17 cells transdifferentiation. Our results demonstrated that CAT inhibited Tregs-to-Th17 cells transdifferentiation by up-regulating let-7g-5p and that the suppressive effect of CAT on traditional differentiation of Th17 cells is not related with let-7-5p. Conclusion Our data indicate that CAT may be a potential modulator of Tregs-to-Th17 cells transdifferentiation by up-regulating let-7g-5p to reduce the expression of STAT3. These results provide new directions for research into RA treatment.

Objective    To investigate the value of esophageal activity examination under X-ray fluoroscopy and chest CT in evaluating the resectability of upper thoracic esophageal cancer. Methods    A total of 221 upper thoracic esophageal carcinoma patients underwent radical operation between 2009 and 2015 in our hospital were enrolled, including 141 males and 80 females with a median age of 59 (47-79) years. Preoperative routine esophageal activity examination under X-ray fluoroscopy and chest enhanced CT were performed to determine whether the tumor had external invasion. The results of the two methods were compared with that observed during the operation. Results    The number of patients with esophageal activity score 1-6 was 70, 85, 32, 29, 2 and 3, respectively. The area under the receiver operating characteristic (ROC) curve (AUC) of esophageal activity examination was 0.897 (95%CI 0.85-0.93, P<0.001), and the cut off value was >3. According to the ROC curve activity score, 4-6 points were considered as invasion, and 1-3 points were non-invasion. The sensitivity, specificity, accuracy and misdiagnosis rate of esophageal activity examination was 75.0%, 89.3%, 88.2%, 10.7%, respectively, and those of CT scan were 75.0%, 66.8%, 67.4%, 33.2%, respectively. Compared with CT scan, the specificity of esophageal activity examination was higher and the misdiagnosis rate was lower. Compared with the detection during the operation, 86.7% of patients with actual invasion of trachea and 85.7% of patients with actual invasion of other parts were in accordance with the esophageal activity examination results. Conclusion    Esophageal activity examination under X-ray fluoroscopy can accurately predict the resectability of upper thoracic esophageal cancer, which is a useful supplement to chest CT examination, especially in the aspect of judging the relationship between lesions and the trachea.

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we conducted chronic salt loading and potassium supplementation interventions, aiming to examine the association between genetic variants in renalase and blood pressure (BP) responses to dietary interventions of salt and potassium intake. 【Methods】 In 2004, 514 subjects from 126 families were recruited in Shaanxi Province to establish the salt-sensitive hypertension study cohort. Among them, 334 non-parent subjects were selected and sequentially maintained on a low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Ten single nucleotide polymorphisms (SNPs) in the renalase gene were genotyped on the MassARRAY platform. 【Results】 SNP rs2576178 of the renalasegene was significantly associated with systolic BP (SBP) and mean arterial pressure (MAP) responses to low-salt intervention (SBP: β=-2.730, P<0.05; MAP: β=-1.718, P<0.05). In addition, SNP rs12356177 was significantly associated with diastolic BP response to low-salt diet (β=-1.608, P<0.05). However, we did not find any association for the renalase SNPs with BP response to high-salt diet with potassium supplementation reached nominal statistical significance. 【Conclusion】 Genetic variants in renalase gene are significantly associated with BP response to low-salt diet, suggesting that renalase may be mechanistically involved in BP salt-sensitivity.

Objective:In the operation of esophageal cancer, nano carbon suspension was used for lymph tracing, and the effect of lymph tracing in different regions and its influence on prognosis were analyzed.Methods:From July 2013 to August 2014, 100 patients under esophageal cancer surgery in our department were analyzed. Randomly divided into experimental group and control group, 50 cases each. During the operation, nano carbon suspension was used to trace the lymph nodes in the experimental group, while conventional operation was only used in the control group. The general baseline data, the number of lymph nodes and positive lymph nodes in each region in the two groups were compared, the lymph node metastasis and survival were followed up, and the prognosis of the two groups were compared.Results:There was no significant difference in baseline data between the two groups( P>0.05). The average number of lymph nodes in the experimental group was 18.6 per case, and that in the control group was 15.1 per case. There was significant difference between the two groups( P=0.003). There was no significant difference in the number and degree of metastasis between the two groups( P=0.233, P=0.463). The effect of nano carbon suspension on tracing lymph nodes around the lower mediastinal esophagus was better. In the experimental group, 4.38 lymph nodes were removed in this area on average, 0.34 of which were metastatic lymph nodes. In the control group, 2.52 lymph nodes were removed in each case on average, 0.10 of which were metastatic lymph nodes. The comparison between the two groups was significantly higher than that of the control group( P=0.001, P=0.011 respectively). In the upper mediastinum, abdominal cavity and other mediastinal lymph nodes, there was no significant difference in the number of lymph nodes, the number of lymph nodes and the degree of metastasis between the two groups( P>0.05). The time of lymph node metastasis in the experimental group was significantly later than that in the control group( P=0.048, log rank test). There was no significant difference in survival time between the two groups( P=0.692, log rank test) . Conclusion:The results show that the nano carbon suspension has a good effect on the lymph node tracing during the operation of esophageal cancer, and the effect on the lymph node tracing around the lower mediastinal esophagus is better.In the area close to the lung drainage area, the tracer effect is poor, and it has certain effect in reducing or delaying lymph node metastasis.

Objective To evaluate clinical efficacy and survival outcomes of neoadjuvant treatment on early stage bulky cervical carcinoma.Methods A total of 155 cases with bulky stage Ⅰ b2 or Ⅱ a2 cervical carcinoma in Affiliated Tumor Hospital of Shantou University Medical College from Nov.2010 to Feb.2015 was reviewed and divided into two groups according to pre-operative treatment 108 cases in the neoadjuvant treatment group and 47 cases in the control group who underwent radical surgery directly.The clinical,pathologic,and follow-up data were analyzed retrospectively.Results The total response rate of neoadjuvant treatment was 75.0％.Histological grade in neoadjuvant treatment group was better than the other group and the rate of deep myometrial infiltration was tend to low in neoadjuvant treatment group.There was no difference in pathological type,parametrial involvement,lymph node metastasis,and lymph vascular space invasion between two groups.The rate of postoperative treatment was similar (92.6％ vs 87.2％,P ＞ 0.05).The overall survival rate of neoadjuvant treatment group was 96.4％ and the other group was 88.9％ (P =0.069).Conclusions Neoadjuvant treatment was effective for early stage bulky cervical carcinoma.It might reduce tumor histological grade and maybe improve the overall survival of patients.

With the extensive use of information technology and the development of big data technology, the traditional treatment methods for cancer are not meeting our needs.The application of medical large data has now changed our tumor treatment model profoundly, but also brings a deeply cognition to the nature of malignant tumor.Development of medical big data analysis and management technologies are driving malignancy treatment model fromindividual treatment era into the precision medicine era, which allows us to change the prediction, diagnosis, treatment and monitor of malignancy.There are also a variety of challenges to resolve.

Objective To explore the value of serum CA125 level to the prognosis of epithelial ovarian cancer.Methods The clinicopathologic data and serum CA125 level of 76 patients with epithelial ovarian cancer from Jan.2003 to Dec.2009 were analyzed retrospectively, and the outcomes of patients were followed up.Results No relationship was found between CA125 concentration before therapy with prognosis and cytoreductive condition for epithelial ovarian cancer.The normal or abnormal CA125 concentration after 3 courses of treatment meant different prognosis, with the 5-year survival rates of 63.8 ％ and 25.0 ％, and the median survival time of 57 months and 28 months, respectively (x2 =19.951, P =0.000).The 5-year survival rates of patients with CA125 concentration≤ 10.0 U/ml and＞10.0 U/ml after therapy were 72.7 ％ and 42.8 ％, respectively (x2 =7.266, P =0.007).According to multivariate Cox proportional-hazard model, two independent factors , operative pathological staging and CA125 concentration after 3 courses, were related significantly to the prognosis of epithelial ovarian cancer (P ＜ 0.05).Conclusion Serum CA125 level, especially after 3 courses and therapy, plays an important role in the prognosis of epithelial ovarian cancer.