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.

A qualitative analysis by high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-QTOF-MS/MS) was performed for the identification of main constituents in Gentiana veitchiorum. High-performance liquid chromatography (HPLC) was developed for the quantification of seven major components, including loganic acid (1), swertiamarin (2), gentiopicroside (3), sweroside (4), isoorientin (5), isoscoparin (6), and gentiournoside A (7). A total of 42 compounds, including 31 flavonoids, and 11 Iridoids, were identified based on their retention behaviors, and MS fragment information. Furthermore, regression equations for these seven chemical components were established, with good linear relationships (r2 > 0.9999), and the sample recovery rate was 97.02%-103.08%. This method was successfully applied for simultaneous determination of seven components in 7 batches of G. veitchiorum samples by HPLC-UV method. The method established in this study is simple and reliable, capable of qualitatively and quantitatively analyzing the main chemical components of G. veitchiorum, and is applicable to its quality evaluation.

With the advancement of China's healthcare reform,enhancing the capacity of primary healthcare services has become a pivotal task.Colorectal cancer,one of the most prevalent malignancies in China,highlights the critical importance of early screening and diagnosis to improve patient survival rates.This study,guided by the principles of Party building and Xi Jinping Thought on Socialism with Chinese Characteristics,examines the implementation and outcomes of a rural outreach program focused on colorectal cancer screening and diagnostic technologies.By promoting the dissemination of colorectal cancer screening initiatives,the paper aims to provide empirical evidence to support the deepening of primary-care services,foster high-quality ad-vancement of grassroots health services,and align with the national Healthy China Initiative,thereby more effectively safeguarding population health.

With the advancement of China's healthcare reform,enhancing the capacity of primary healthcare services has become a pivotal task.Colorectal cancer,one of the most prevalent malignancies in China,highlights the critical importance of early screening and diagnosis to improve patient survival rates.This study,guided by the principles of Party building and Xi Jinping Thought on Socialism with Chinese Characteristics,examines the implementation and outcomes of a rural outreach program focused on colorectal cancer screening and diagnostic technologies.By promoting the dissemination of colorectal cancer screening initiatives,the paper aims to provide empirical evidence to support the deepening of primary-care services,foster high-quality ad-vancement of grassroots health services,and align with the national Healthy China Initiative,thereby more effectively safeguarding population health.

Objective: To investigate the expression and significance of NF-κB in oral squamous cell carcinoma and paracancerous tissues. Methods: Cancerous and paracancerous tissues about 5 mm outside the tumor boundary were cut from 47 patients with OSCC. NF-κB expression in these tissues were detected by the immunohistochemical SP method and compared with that in 32 normal oral mucosa tissues. Results : The average optical density (OD value) of immunohistochemical-positive cells in cancer tissues and paracancerous tissues was higher than that in normal tissues, and the difference was statistically significant (P < 0.001). There was no significant difference in the OD values between cancer tissues and paracancerous tissues (P=0.356). The rate of NF-κB positive expression in cancer tissue and paracancerous tissue was significantly higher than that in normal mucosa tissue, and the difference was statistically significant (P < 0.001). There was no significant difference in the rate of NF-κB positive expression between cancer tissues and paracancerous tissues (P=0.117), but the rate of moderate-to-strong positive expression in cancer tissues was significantly higher than that in paracancerous tissues (P < 0.001). Conclusion NF-κB may be involved in the development of OSCC.

Objective: To assess the interobserver variations in delineating the planning target volume (PTV) and organs at risk (OAR) using different contouring methods during intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC), aiming to provide references for the quality control of multi-center clinical trials. Methods: The PTV and OAR of CT image of 1 NPC patient manually delineated by 10 physicians from 8 different radiation centers were defined as the " manual contour group" , and the OAR auto-contoured using the ABAS software and modified by the physicians were defined as the " auto+ manual contour group" . The maximum/minimum ratio (MMR) of the PTV and OAR volumes, and the coefficient of variation (CV) for different delineated contours were comparatively evaluated. Results: Large variation was observed in the PTV and OAR volumes in the manual contour group. The MMR and CV of the PTV were 1.72-3.41 and 0.16-0.39, with the most significant variation in the PTV_nd (MMR=3.41 and CV=0.39 for the PTV_nd-L). The MMR and CV of the manually contoured OAR were 1.30-7.89 and 0.07-0.67. The MMR of the temporal lobe, spinal cord, temporomandibular joint, optic nerve and pituitary gland exceeded 2.0. Compared with the manual contour group, the average contouring time in the auto+ manual group was shortened by 68% and the interobserver variation of the OAR volume was reduced with an MMR of 1.04-2.44 and CV of 0.01-0.37. Conclusions Large variation may occur in the PTV and OAR contours during IMRT plans for NPC delineated by different clinicians from multiple medical centers. Auto-contouring+ manually modification can reduce the interobserver variation of OAR delineation, whereas the variation in the delineation of small organs remains above 1.5 times. The consistency of the PTV and OAR delineation and the possible impact upon clinical outcomes should be reviewed and evaluated in multi-center clinical trials.

Amyloidosis of salivary glands is a rare disease. The case of a 62-year-old male patient with 20 years of progressive swelling of the floor of the mouth and raising of the tongue that impacted the swallowing, phonation, and tongue movement of the patient is reported in this paper. Clinical examination revealed a large mass in the floor of the mouth. The lip and cheek mucosae had a considerable number of hard, soybean-sized, light-yellow nodules. The surgical removal of the mass under and in front of the tongue was performed. A pathology examination and Congo red staining confirmed the diagnosis of amyloidosis of the submandibular glands and sublingual glands. No recurrence was observed after 5 years of follow-up. The literature on the relevant problems was reviewed.

Objective To investigate the role of long noncoding RNA-AJ227913 in the pathogenesis of primary gout arthritis (GA). Methods The subjects were divided into three groups:30 acute gout patients (AGA), 30 non-acute gout patients (NAGA), 30 healthy controlsand 30 hyperuricemia patients (HUA). Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to examine the expression of AJ227913 in peripheral blood mononuclear cells(PBMCs) from four groups. 100 μg/ml monosodium urate (MSU) was used to stimulate the peripheral blood of NAGA and healthy controls patients. Then the expression ofAJ227913 was detected by RT-qPCR. Kruskal-Wallis test, Mann-Whitney test, Spearman correlations were used for statistical analysis. Results The expression level of AJ227913 in the AGA group (0.0557 ±0.0156) was higher than that in the NAGA group (0.0223±0.018) and healthy controls group (0.0038±0.0013). There was significant difference between the NAGA group and healthy controls group (P>0.05). Compared with the control group, the expression of AJ227913 in NAGA group which were stimulated by MSU was significantly increased. The Spearman correlation analysis found that the AJ227913 expression levels in GA groups were correlated with UREA (r=0.608, P<0.01), CREA (r=0.337, P<0.05), CYSC (r=0.422, P<0.01). Conclusion Altered expression of AJ227913 may be involved in the inflammatory process of GA and the balance of uricacid.

Objective To investigate the expression profile variation of long non-coding RNAs (lncRNAs) in ankylosing sporidylitis (AS) and explore the role of lncRNAs in the pathogenesis of AS.Methods The peripheral blood mononuclear cells of AS patients and health controls (HC) were used to detect for differently expressed lncRNAs by microarray.The roles of lncRNAs were predicted with GO and pathway analysis.The results were verified by real time-polymerase chain reaction (PCR).Results A total of 148 lncRNAs and 134 mRNAs were detected,which had more than 2-fold differentially expressed in AS patients.Bioinformatics analysis found that GO term enrichment included protein binding,regulation of transcription,metabolism,signal transduction,et al.and might involve in toll-like receptor pathway,protein kinase,complement pathway,notch signaling pathway and so on.The expressions of three lncRNAs were estimated by real time-PCR which found that consistent with that of microarrays.Among these,D90064 was the most aberrantly expressed lncRNAs.Conclusions Several lncRNAs expression was changed significantly in AS patients in comparison with HC,which implies that those different lncRNAs may have an important role in the development and progression of AS.

Objective To compare the effect of laparoscopy-assisted gastrectomy (LAG) and open D2 radical gastrectomy (OG) for gastric cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 117 patients who underwent D2 radical gastrectomy at the Guangdong General Hospital from January 2014 to December 2014 were collected.Of 117 patients,60 undergoing LAG and 57 undergoing OG were respectively allocated into the LAG group and OG group.Total gastrectomy,distal subtotal gastrectomy and proximal subtotal gastrectomy were performed according to the location of the tumor.The perigastric lymph nodes dissection was performed according to the Japanese " Gastric cancer treatment protocol" (the 14th edition).Eligible patients received the adjuvant chemotherapy of XELOX regimen according to the Guideline published by National Comprehensive Cancer Network (NCCN).Observation indicators:(1) comparison of intra-and postoperative recovery between groups;(2) stratified analysis of number of lymph node dissected;(3) relationship among surgical method,number of lymph node dissected and postoperative complication;(4) follow-up and survival.Follow-up using outpatient examination and telephone interview was performed to detect the postoperative adjuvant chemotherapy,tumor-free survival and tumor recurrence or metastasis up to December 2016.Measurement data with normal distribution were represented as (x)± s and comparison between groups was analyzed using the independent-sample t test.Count data were analyzed using the chi-square test or Fisher exact probability.The relationship between number of lymph node dissected and postoperative complication was done using the Logistic regression model.Results (1) Comparison of intra-and post-operative recovery between groups:all the patients completed the operation successfully.Volume of intraoperative blood loss,time to postoperative anal exsufflation and duration of postoperative hospital stay were (113±36) mL,(4.3±2.1) days,(9.7±2.9) days in the LAG group and (209 ± 77) mL,(5.3 ± 2.2) days,(11.2 ± 3.9) days in the OG group,respectively,with statistically significant differences between groups (t =6.850,-2.604,-2.405,P＜0.05).Number of lymph node dissected,numbers of patients with overall complication,incisional infection,intestinal obstruction,digestive tract fistula,intra-abdominal bleeding,cardiovascular accident,pulmonary infection,urinary tract infection and death within postoperative 30 days were respectively 31±7,6,1,0,4,0,0,1,0,0 in the LAG group and 34±6,12,0,1,2,2,1,4,1,1 in the OG group,with no statistically significant difference between groups (t=0.177,x2=2.743,0.126,0.563,0.837,P＞0.05).All the patients with complications received symptomatic treatment,1 patient with abdominal bleeding in the OG group died and other patients recovered smoothly.(2) Stratified analysis of number of lymph node dissected:number of lymph node dissected in patients with total gastrectomy,distal subtotal gastrectomy and proximal subtotal gastrectomy were 35±8,29±5,27±4 in the LAG group and 34± 5,34±6,29±6 in the OG group,respectively,with no statistically significant difference between groups (t =0.846,1.052,0.934,P＞0.05).Number of lymph node dissected in patients with stage Ⅰ,Ⅱ and Ⅲ of TNM staging were respectively 31±5,32±9,31±6 in the LAG group and 34±7,32±4,35±6 in the OG group,with no statistically significant difference between groups (t =0.494,1.657,0.136,P＞0.05).(3) Relationship among surgical method,number of lymph node dissected and postoperative complication:surgical method (LAG and OG) and number of lymph node dissected were used as the independent variable and postoperative complication between groups was used as the dependent variable,the Logistic regression model showed that surgical method and number of lymph node dissected were not related factors affecting the postoperative complication (OR =1.062,2.049,95％ confidence interval:0.998-1.140,0.695-6.042,P＞0.05).(4) Follow-up and survival:108 of 117 patients (54 in each group) were followed up for 2-35 months,with a median time of 28 months.During the follow-up,numbers of patients undergoing postoperative adjuvant chemotherapy,with tumor-free survival and with tumor recurrence were 45,43,10 in the LAG group and 42,42,10 in the OG group,respectively,with no statistically significant difference in the tumor-free survival and tumor recurrence between groups (x2 =0.055,0.002,P＞0.05).Conclusion Laparoscopy-assisted D2 radical gastrectomy is safe and feasible,which equivalent to clinical effect of open radical gastrectomy,meanwhile,it also can reduce volume of intraoperative blood loss and duration of postoperative hospital stay,and accelerate recovery of postoperative gastrointestinal function.