Objective To design a novel bromodomain-containing protein 4(BRD4)and histone deacetylase(HDAC)dual-target inhibitor(11b),and to elucidate its therapeutic efficacy and mechanisms in suppressing prostate cancer through epigenetic regulation.Methods BRD4 and HDAC expression levels were assessed via immunohistochemistry(IHC)using prostate cancer tissue microarrays.The inhibitory activity of 11b was screened across three prostate cancer cell lines,with the half-maximal inhibitory concentration(IC50)determined by CCK-8 assay.Western blot was employed to analyze changes in the expression of target proteins,including BRD4,c-Myc proto-oncogene protein(c-Myc),and Ac-H3K27,with parallel comparisons to single-target agents,including suberoylanilide hydroxamic acid(SAHA),a HDAC inhibitor,and JQ-1,a BRD4 inhibitor.Cell invasion and proliferation were evaluated using Transwell and colony formation assays,and the autophagy mechanism was validated using 3-methyladenine(3-MA),an autophagy inhibitor.A PC-3 xenograft model was established in nude mice.Then,11b(7.5 mg/kg or 15 mg/kg),normal saline,SAHA,and JQ-1 were administered via intraperitoneal injection,and their tumor growth inhibition effects were observed.The percentage of target protein-positive cells and the expression levels of target genes were quantified via IHC and RT-PCR,respectively.Results BRD4 and HDAC expression levels were both higher in tumor tissues than those in normal tissues(P<0.01).11b exhibited the strongest inhibitory activity against PC-3 cells(IC50=8.28 μmol/L),outperforming SAHA(22.61 μmol/L)and JQ-1(22.09 μmol/L).Treatment with 11b reduced BRD4 and c-Myc expression by(41.58±3.28)%and(63.21±6.91)%,respectively(P<0.01),and increased the Ac-H3K27 level to 6.52-fold that of the negative control(NC)group(P<0.01),demonstrating greater modulation than either SAHA or JQ-1 did.The in vitro experiment showed that 8 μmol/L 11b treatment reduced PC-3 colony formation and migration by 97.5%and 96.3%,respectively(P<0.001),and co-treatment with 3-MA reversed its cytotoxic effects.The in vivo experiment showed that 11b at both 7.5 mg/kg and 15 mg/kg significantly reduced tumor volume and weight compared with the control,SAHA,and JQ-1 groups(all P<0.01),with the proportion of percentage of target protein-positive cells and the expression of target genes showing trends consistent with in vitro findings.Conclusion The dual-target inhibitor 11b exerts potent antitumor effects in prostate cancer by synergistically modulating the BRD4/HDAC pathways.11b demonstrates therapeutic efficacy superior to that of the single-target agents SAHA and JQ-1 in suppressing prostate cancer progression,highlighting its potential for clinical translation.

Familial hypercholesterolemia (FH) is a group of autosomal co-dominant genetic diseases mainly characterized by abnormal low-density lipoprotein related metabolism. It is one of the most common inherited diseases in children and one of the most serious lipid metabolism diseases which results in various life-threatening cardiovascular diseases and the complications. In recent years, the treatment protocols for FH have diversified thanks to the deeper understanding of the disease in China and abroad and the development of new lipid-lowering drugs. However, the current awareness and diagnosis rate of FH are very low. The treatment of the disease is much inadequate. This paper summarizes the clinical characteristics, diagnosis, screening strategy, and treatment of FH hoping to enhance the understanding and awareness of the disease in the society.

Objective To evaluate the rupture risk of carotid atherosclerotic plaque under cervical rotatory manipulation. Methods The fluid-structure interaction (FSI) model of carotid atherosclerotic plaque was established, and tensile deformation of the plaque and lumen under cervical rotatory manipulation was simulated.Mechanical parameters such as the maximum flow shear stress(FSS), the maximum wall shear stress (WSS), the maximum plaque wall stress (PWS), wall tensile stress (WTS) and wall pressure (WP) of the plaque and lumen were recorded. Results Under 16% carotid tensile deformation, the maximum WSS of the plaque was 40.54 Pa. The maximum PWS was 66.16 kPa, which was far smaller than the threshold of plaque rupture.The maximum WTS of fiber cap and the maximum strain were 156.75 kPa and 0.56, which were larger than the fracture strain range. The maximum WTS of the lumen was 1 040.30 kPa, which approached the threshold of medial membrane rupture and might cause vascular injury. Conclusions When the cervical spine rotates to the end range of motion, large carotid artery stretch may cause damage to epidermal tissues of the plaque, leading to abscission. Lesions, ulcers, bleeding and vascular damage may form inside the plaque, which will affect stability of the plaque. Cervical rotatory manipulation should be performed cautiously in patients with cervical diseases who also have carotid atherosclerotic plaques.The finite element assessment of plaques before manipulation may be an effective safety screening method.

OBJECTIVE：To prov ide reference for the improvement of quality standards of Shiwei yipi granules. METHODS ： According to the general rules of 2015 edition of Chinese Pharmacopeia （part Ⅳ），microscopic identification was used to identify Massa Medicata Fermentata and Galli Gigerii Endothelium Corneum ；TLC method was used to qualitatively identify Crataegi Fructus and Semen Raphani ；the content of sinapine thiocyanate in Semen Raphani was determined by HPLC. RESULTS ：The microscopic characteristics were obvious for Massa Medicata Fermentata （palisade cells of testa and stone cells of testa ）and Galli Gigerii Endothelium Corneum （irregular fragments ）. The same fluorescent spots of Crataegi Fructus and Semen Raphani were displayed at the same position of ursolic acid ，sinapine thiocyanate control and Semen Raphani reference substance. The linear range of sinapine thiocyanate was 23.27-9 574.42 ng （r＝1.000 0）. The LOD and LOQ were of 0.50 μ g/mL and 1.68 μ g/mL， respectively. RSDs of precision ，repeatability，intermediate precision and stability tests （24 h）were all less than 1.5％. The average recoveries were 99.40％-100.89％（RSDs were 0.18％-0.49％，n＝3）. The contents of sinapine thiocyanate in 3 batches of Shiwei yipi granules were 0.086 4-0.220 6 mg/g，the average was 0.168 4 mg/g. CONCLUSIONS ：The identification method of Massa Medicata Fermentata ，Galli Gigerii Endothelium Corneum ，Crataegi Fructus and Semen Raphani in Shiwei yipi granules as well as the method for content determination of sinapine thiocyanate in Semen Raphani are established successfully. The content of Semen Raphani in the Shiwei yipi granules is no less than 0.16 mg/g calculated by sinapine thiocyanate （C16H24NO·5 SCN）.

Objective: To analyze the prognostic factors and the value of radiotherapy (RT) for the early stage (T_1-2N₁M₀) triple-negative breast cancer (TNBC) patients after modified radical mastectomy, and provide a basis for the selection of the clinical treatment strategy. Methods: The retrospective analysis was performed in 87 TNBC patients at T_1-2N₁M₀ stage. All patients were admitted to the Second Affiliated Hospital of Dalian Medical University from Jan 2006 to Oct 2011. Fifty-three cases received postoperative RT (RT group), and the other 34 cases without RT (non-RT group). Factors enrolled in Kaplan-Meier analysis were postoperative RT, age, menstruation, histological grade, vascular tumor thrombus, T staging, the number of positive lymph node and metastasis rate, surgery procedure, Ki-67 index. The endpoints were local regional recurrence rate (LRR), distant metastasis rate (DM), recurrence free survival (RFS), and overall survival (OS) rate for 5 years. Results: The significant difference was found in the 5-year LRR (9.4% vs. 15.2%) and RFS (81.3% vs. 66.7%) between RT group and non-RT group (χ²=8.073, 12.789, P<0.05). No significant difference in the DM and OS was observed between the two groups (P>0.05). The univariate analysis showed that RT, lymph node metastasis, age, and Ki-67 index were the risk factors for 5-year LRR (P<0.05), while vascular thrombus and lymph node metastasis rate were risk factors for 5-year DM (P<0.05), RT, vascular tumor thrombus, lymph node metastasis rate, and Ki-67 index 5-year RFS (P<0.05). The multivariate analysis showed that RT and lymph node metastasis were the independent risk factors for 5-year LRR (HR=0.279, 5.277, P<0.05), vascular thrombus was an independent risk factor 5-year DM (HR=2.313, P<0.05), while RT, vascular tumor thrombus and lymph node metastasis rate were the independent risk factors for 5 years RFS (HR=0.378, 2.350, 5.084, P<0.05). Conclusions Postoperative RT might improve the local control rate of TNBC patients at T_1-2N₁M₀ stage, while the effect on DM and OS in 5 years was little. Postoperative RT, lymph node metastasis rate, vascular tumor thrombus, Ki-67 index and age are related to patient′s prognosis of early stage TNBC.

Objective:Previous studies have shown an association between programmed death-ligand 1 expression(PD-L1)in non-small cell lung cancer(NSCLC)and clinical factors and that PD-L1 is positively correlated with TNM staging.This study aimed to explore the prognostic significance of PD-L1 and its correlation with the maximum standardized uptake value(SUVmax).Methods:Clinicopath-ological data and the follow-up information of the 122 de novo primary NSCLC patients were analyzed.PD-L1 expression was detected by immunohistochemistry in this 122 surgically resected non-small cell lung carcinoma tissues.Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model.Correlation between SUVmax and PD-L1 expression was analyzed using Spearman's rank correlation analysis.Results:Multivariate analysis revealed that PD-L1 expression(HR=4.518,95% CI:1.176-17.352,P=0.028)and tumor size(HR=1.404,95%CI:1.020-1.933,P=0.037)were independent risk factors for overall survival(OS) in early NSCLC patients.Sex,age,pathological type,CEA level,and SUVmax group had no obvious effect on OS(P 0.05)in early NSCLC patients.In univariate analyses,sex,pathological type,tumor size,and SUVmax group affected OS in stageⅢ-ⅣNSCLC patients.How-ever,age,CEA level,and PD-L1 expression had no effect on OS.PD-L1 expression was not an independent risk factor for OS in stageⅢ-ⅣNSCLC patients.The SUVmax group had no association with PD-L1 in all patients.Conclusions:PD-L1 expression is an independent risk factor for OS in early NSCLC patients but not in stageⅢ-Ⅳpatients.

[Summary] Rare diseases are one of the major challenges we face today in the era of precision medicine, because of the low incidence and prevalence, difficulty in diagnosis, lack of sufficient therapeutic methods, as well as their significant impacts on affected individuals, families and the society. Integration of clinical phenotypic and biological omics data and the further analysis are providing a way to illustrate the mechanisms of rare diseases, discovering novel diagnostic and prognostic biomarkers, developing orphan drugs and other therapeutics, and improving clinical outcomes and quality of life for the patients. A nation-wide registry system and the cohorts studies based on the registry are vital to the research of rare diseases. National Rare Diseases Registry System ( NRDRS) of China will provide this essential platform to promote the rare diseases research in China. With the collaboration of 20 leading medical institutes and innovation in medical informatics technologies, this system will, for the first time in China, collect the epidemiological, clinical, socio-economical, genomics and metabolomics data of more than 50 rare diseases and not less than 50 000 cases. As a national strategy for enhancing the development of medical sciences and the improvement of population health in China, NRDRS and its cohort studies will provide the pivotal support to policy making, clinical care, novel drug discovery, patient advocacy, and finally scientific progress in the field of rare diseases.

Objective To design a kind of special support mattress for the endoscopic retrograde cholangiopancreatography (ERCP), and to improve the comfort of the patients during the procedure, and evaluate the efficacy and safety during clinical application. Methods By 3D modeling, we designed a special memory foam mattress for ERCP. From January 2014 to September 2014, 424 patients who underwent ERCP treatment without general anesthesia and could take semi-prone position, were divided into special mattress group (210 cases) and ordinary mattress group (214 cases) according to the random number table method. The satisfaction of the patients and the operators of the two groups were evaluated and compared. Results The operation times of the two groups were (32.9±18.5) min and (33.2±20.1) min, respectively, and there was no significant difference between the two groups (P>0.05). The overall satisfaction ratings of the patients in the two groups were (7.9±1.6) points and (6.3±1.3) points, respectively (P<0.01), and the discomfort ratings of the patients in the two groups were (1.3± 0.9) points and (3.8 ±1.2) points (t=116.45, 246.91, P<0.01). The operator satisfaction scores of two groups were (8.5±1.3) points and (8.5±1.8) points, respectively, and there was no significant difference (P>0.05). No mattress related complications were found. Conclusions The special memory foam mattress for ERCP can alleviate the discomfort and improve the tolerance during the procedure. Therefore, it is worth promoting the application.