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:This study aimed to clarify clinicopathologic characteristics, postoperative complications, and related risk factors of elderly patients with gastric cancer.Methods:A total of 395 patients(≥65 years old)who underwent radical gastrectomy for gastric cancer in Beijing Hospital from January 2014 to December 2021 were enrolled in this study.The patients were divided into the common elderly group(age<80 years, n=340)and the high-age group(age ≥ 80 years, n=55). Postoperative complications were classified into medical and surgical types.The clinicopathological characteristics and complications were compared between the two groups.Logistic regression models(univariate and multivariate)were used to identify the risk factors for postoperative complications.Results:The common elderly group was 65-79 years old(mean age: 71.5±4.3 years), with 263 male(77.4%); The high-age group was 80-89 years old(mean age: 82.6±2.6 years), with 42 male(76.4%). The comorbidity rate and the number of comorbidities in the high-age group were significantly higher than those in the common elderly group.The American Society of Anesthesiologists(ASA)scores and nutritional risk screening(NRS)2002 scores in the high-age group were significantly higher than those in the common elderly group(both P<0.05), and the activities of daily living(ADL)scores in the high-age group were significantly lower than that in the common elderly group( P<0.001). There were no statistically significant differences in tumor location, degree of differentiation, pathological type, T stage, and N stage between the two groups(all P>0.05). The overall postoperative complication rate in the high-age group was significantly higher than that in the common elderly group(38.2% vs.24.7%, P=0.036); the medical complications were significantly increased in the high-age group(21.8% vs.10.9%, P=0.022), whereas the surgical complications did not increase significantly(25.5% vs.17.1%, P=0.135). Multivariate analysis revealed that the number of comorbidities ≥2( HR=2.502, 95% CI: 1.275-4.911, P=0.008), preoperative NRS 2002 scores ≥5( HR=2.714, 95% CI1.294-5.693, P=0.008), and preoperative ADL scores<100( HR=2.012, 95% CI1.010-4.009, P=0.047)were independent risk factors for medical complications.Additionally, ASA grade ≥ 3( HR=2.586, 95% CI: 1.444-4.632, P=0.001)and proximal or distal gastrectomy( HR=2.397, 95% CI: 1.237-4.574, P=0.009)were independent risk factors for surgical complications. Conclusions:The occurrence of postoperative medical complications in very elderly patients with gastric cancer undergoing radical surgery has increased, while the rate of surgical complications has not increased.Moreover, advanced age itself is not an independent risk factor for postoperative complications.More attention should be paid to medical complications, and the management of commodities and nutritional support should be strengthened during the perioperative period.

Objective A randomized controlled trial was conducted on colonoscopy inpatient and outpatients to compare the efficacy and safety of water exchange(WE)colonoscopy and CO2 convention insufflation colonoscopy in elderly patients.Methods 340 patients underwent fully sedated colonoscopy were randomly divided into two groups according to colonoscopy with either WE colonoscopy group(WE group)and CO2 insufflation colonoscopy group(CO2 group).The two groups were compared in terms of Boston bowel preparation scale(BBPS),withdrawal time,cecal intubation time,cecal intubation success rate,abdominal compression,willingness to repeat,polypdetectionrate(PDR),adenoma detection rate(ADR),and safety.Results The cecal intubation success rate was significantly higher in WE group(100.0%)compared with CO2 group(96.5%),the difference was statistically significant(P=0.013).The average cecal intubation time of WE group was(10.50±1.79)min,which was longer than that of CO2 group(7.55±1.50)min,and the difference was statistically significant(P<0.01).Comparison of withdrawal time and BBPS between the two groups,the differences were not statistically significant(P>0.05).The abdominal pressure rate was lower in WE group(5.9%)compared with CO2 group(13.5%),the difference was statistically significant(P=0.017).The rate of willingness to re-examination in the WE group was 98.2%,which was significantly higher than the 93.5%in the CO2 group.The PDR in WE group(80.6%)was higher than that in CO2 group(70.6%),the ADR in WE group(67.1%)was higher than that in CO2 group(50.6%),the differences were statistically significant(P<0.05).Multivariate Logistic regression analysis showed that WE group was an effective factor in improving ADR(O＾R=2.027,P<0.01).The overall adverse events were less than 3%,with no difference between the two groups(P=1.000).Conclusion The use of WE colonoscopy has a better improved efficacy in elderly patients,and safety should be ensured by individualized assessment of the patient's co-morbidities,bowel preparation tolerance,and willingness prior to the procedure.

Objective A randomized controlled trial was conducted on colonoscopy inpatient and outpatients to compare the efficacy and safety of water exchange(WE)colonoscopy and CO2 convention insufflation colonoscopy in elderly patients.Methods 340 patients underwent fully sedated colonoscopy were randomly divided into two groups according to colonoscopy with either WE colonoscopy group(WE group)and CO2 insufflation colonoscopy group(CO2 group).The two groups were compared in terms of Boston bowel preparation scale(BBPS),withdrawal time,cecal intubation time,cecal intubation success rate,abdominal compression,willingness to repeat,polypdetectionrate(PDR),adenoma detection rate(ADR),and safety.Results The cecal intubation success rate was significantly higher in WE group(100.0%)compared with CO2 group(96.5%),the difference was statistically significant(P=0.013).The average cecal intubation time of WE group was(10.50±1.79)min,which was longer than that of CO2 group(7.55±1.50)min,and the difference was statistically significant(P<0.01).Comparison of withdrawal time and BBPS between the two groups,the differences were not statistically significant(P>0.05).The abdominal pressure rate was lower in WE group(5.9%)compared with CO2 group(13.5%),the difference was statistically significant(P=0.017).The rate of willingness to re-examination in the WE group was 98.2%,which was significantly higher than the 93.5%in the CO2 group.The PDR in WE group(80.6%)was higher than that in CO2 group(70.6%),the ADR in WE group(67.1%)was higher than that in CO2 group(50.6%),the differences were statistically significant(P<0.05).Multivariate Logistic regression analysis showed that WE group was an effective factor in improving ADR(O＾R=2.027,P<0.01).The overall adverse events were less than 3%,with no difference between the two groups(P=1.000).Conclusion The use of WE colonoscopy has a better improved efficacy in elderly patients,and safety should be ensured by individualized assessment of the patient's co-morbidities,bowel preparation tolerance,and willingness prior to the procedure.

Objective:This study aimed to clarify clinicopathologic characteristics, postoperative complications, and related risk factors of elderly patients with gastric cancer.Methods:A total of 395 patients(≥65 years old)who underwent radical gastrectomy for gastric cancer in Beijing Hospital from January 2014 to December 2021 were enrolled in this study.The patients were divided into the common elderly group(age<80 years, n=340)and the high-age group(age ≥ 80 years, n=55). Postoperative complications were classified into medical and surgical types.The clinicopathological characteristics and complications were compared between the two groups.Logistic regression models(univariate and multivariate)were used to identify the risk factors for postoperative complications.Results:The common elderly group was 65-79 years old(mean age: 71.5±4.3 years), with 263 male(77.4%); The high-age group was 80-89 years old(mean age: 82.6±2.6 years), with 42 male(76.4%). The comorbidity rate and the number of comorbidities in the high-age group were significantly higher than those in the common elderly group.The American Society of Anesthesiologists(ASA)scores and nutritional risk screening(NRS)2002 scores in the high-age group were significantly higher than those in the common elderly group(both P<0.05), and the activities of daily living(ADL)scores in the high-age group were significantly lower than that in the common elderly group( P<0.001). There were no statistically significant differences in tumor location, degree of differentiation, pathological type, T stage, and N stage between the two groups(all P>0.05). The overall postoperative complication rate in the high-age group was significantly higher than that in the common elderly group(38.2% vs.24.7%, P=0.036); the medical complications were significantly increased in the high-age group(21.8% vs.10.9%, P=0.022), whereas the surgical complications did not increase significantly(25.5% vs.17.1%, P=0.135). Multivariate analysis revealed that the number of comorbidities ≥2( HR=2.502, 95% CI: 1.275-4.911, P=0.008), preoperative NRS 2002 scores ≥5( HR=2.714, 95% CI1.294-5.693, P=0.008), and preoperative ADL scores<100( HR=2.012, 95% CI1.010-4.009, P=0.047)were independent risk factors for medical complications.Additionally, ASA grade ≥ 3( HR=2.586, 95% CI: 1.444-4.632, P=0.001)and proximal or distal gastrectomy( HR=2.397, 95% CI: 1.237-4.574, P=0.009)were independent risk factors for surgical complications. Conclusions:The occurrence of postoperative medical complications in very elderly patients with gastric cancer undergoing radical surgery has increased, while the rate of surgical complications has not increased.Moreover, advanced age itself is not an independent risk factor for postoperative complications.More attention should be paid to medical complications, and the management of commodities and nutritional support should be strengthened during the perioperative period.

Objective To understand the prevalence and risk factors of hyperuricemia in electronics factory workers in Wuhan, and to provide evidence for the health protection of electronics factory workers. Methods A total of 1 415 employees in an electronics factory in Wuhan were selected as the research subjects, and the physical examination and determination of various biochemical indicators, as well as questionnaire survey were carried out. Results The detection rate of hyperuricemia among workers in the electronics factory in Wuhan was 32.43%, with 36.33% for men and 14.11% for women, and the difference was statistically significant ( χ²＝46.077，P＜0.001). The detection rate of hyperuricemia was the highest (33.77%) among those with university or college education, followed by graduate students and above (31.50%). Compared with subjects with good lifestyle habits, people with drinking habits had higher hyperuricemia detection rate (49.38%), and the difference was statistically significant (P =0.001). The detection rates of hyperuricemia in those with central obesity and elevated alanine aminotransferase were 48.23% and 61.29%, respectively, which were significantly higher than those in the subjects without the above diseases (26.91% and 27.21%, respectively), and the differences were statistically significant (P <0.001). Obese people had the highest detection rate of hyperuricemia (66.95%), followed by overweight people (43.75%), and the difference was statistically significant (P <0.001). Multivariate logistic analysis showed that alcohol drinking (OR=1.836, 95% CI=1.139-2.961, P =0.013) and body mass index ≥ 24 kg/m² (OR=2.175, 95% CI=1.686 -2.806, P <0.001) were risk factors for hyperuricemia in electronic factory workers. Elevated alanine aminotransferase (ALT) was significantly correlated with hyperuricemia (OR=2.964, 95%CI=2.146-4.095 , P <0.001). Female gender was a protective factor for hyperuricemia in workers in the electronics factory (OR=0.441, 95%CI=0.297-0.653 , P <0.001). Conclusion The detection rate of hyperuricemia among workers in an electronics factory in Wuhan is high, and the detection rate of hyperuricemia in men is higher than that in women. Alcohol consumption, overweight and obesity will increase the risk of hyperuricemia. Elevated ALT is associated with hyperuricemia. Maintaining an ideal body mass index and establishing a good lifestyle play an important role in preventing hyperuricemia.

Objective To investigate the mechanism of astragaloside Ⅰ,the active constituent of milkvetch root,in inhibiting podocyte injury and improving diabetic kidney disease.Methods According to the body weight,60 male db/db mice were randomly divided into the model group,astragaloside Ⅰ low-dose group(10 mg/kg),astragaloside Ⅰ medium-dose group(20 mg/kg),astragaloside Ⅰ high-dose group(40 mg/kg),and valsartan group(10mg/kg),with 12 mice per group.Twelve db/db littermate control db/m mice were used as the control group.The drug was administered by gavage for 8 weeks.Transmission electron microscope was used to observe the ultrastructure of the kidney;immunohistochemistry and Western blotting were used to detect the expression of nephrotic protein(nephrin),a marker of renal podocytes;enzyme-linked immunosorbent assay was used to detect the contents of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the serum of mice;Western blotting was used to detect the protein expressions of NOD-like receptor thermoprotein domain-related protein 3(NLRP3),cysteinyl aspartate specific proteinase 1(Caspase-1),and Gasdermin D(GSDMD)in kidney tissue.Results Compared with the control group,the glomeruli of the model group showed obvious podocyte loss and foot process fusion;the protein expression of nephrin was decreased(P＜0.05);the contents of IL-1 β and IL-18 in serum were increased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were increased(P＜0.05).Compared with the model group,the renal pathological damage in the astragaloside Ⅰ administration groups were alleviated;the protein expression of nephrin was increased(P＜0.05);the contents of IL-1β and IL-18 in serum were decreased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were decreased(P＜0.05).Conclusion Astragaloside Ⅰ may play a role in intervening diabetic kidney disease by inhibiting pyroptosis and improving podocyte injury.

Objective:To examine the occurrence of complications in elderly patients who have undergone radical surgery for colorectal cancer.Additionally, this study aims to identify the various risk factors associated with these complications.Methods:This study included elderly patients with colorectal cancer who underwent radical surgery at Beijing Hospital between January 2013 and December 2020.These patients were divided into two groups based on their age.In this study, we examined a total of 906 patients who underwent surgery, with 695 patients under the age of 80 and 211 patients aged 80 and above.We classified postoperative complications into two categories: medical and surgical complications.Our analysis compared comorbidities, clinicopathological factors, perioperative variables, and postoperative morbidity and mortality between the two age groups.We utilized both univariate and multivariate analyses to identify any potential risk factors for postoperative morbidity.Results:When comparing patients under 80 years old to those aged 80 or older, it was found that the latter group had a lower body mass index, worse ASA scores, and more comorbidities.Additionally, the proportion of elderly patients with right colon cancer, pT3-4, and pN+ disease was higher compared to those under 80 years old.Furthermore, the elderly patients aged 80 or older had a lower rate of laparoscopic surgery compared to those under 80 years old.The study found that elderly patients aged 80 years and older had significantly shorter operation times compared to those younger than 80 years[(191.0±70.6)min vs.(214.0±83.3)min, t=3.642, P<0.001]. However, the overall complication rate was higher in the elderly group(32.7%)than in the younger group(22.6%)( χ2=8.839, P=0.004). Upon further analysis, it was found that medical complications increased significantly(20.9% vs.7.5%, χ2=30.547, P<0.001), whereas the rate of surgical complications did not show any statistical difference(15.6% vs.16.4%, χ2=0.069, P=0.832). The mortality rate during the perioperative period was found to be significantly higher in elderly patients aged 80 years and above compared to those below 80 years(1.9% vs.0.3%, χ2=6.316, P=0.029). Further analysis revealed that age was an independent risk factor for medical complications( HR=2.822, 95% CI: 1.804-4.414, P<0.001). Laparoscopic surgery has been shown to significantly decrease surgical complications( HR=0.475, 95% CI: 0.317-0.711, P=0.001). However, if the operation time exceeds 200 minutes, there is a significant increase in surgical complications( HR=1.942, 95% CI: 1.278-2.888, P=0.002). Conclusions:The incidence of postoperative medical complications in very elderly patients with colorectal cancer who undergo radical surgery has risen, although the rate of surgical complications has remained steady.Radical surgery for elderly patients with colorectal cancer is both safe and feasible, but it is important to prioritize the prevention and management of medical complications.

Objective:To investigate the expression of soluble T cell immunoglobulin and mucin domain-3 (Tim-3) in peripheral blood of patients with pancreatic cancer and its diagnostic value in combination with serum Carbohydrate antigen 19-9 (CA19-9) .Methods:106 newly diagnosed pancreatic cancer patients and 65 age and sex matched healthy individuals were enrolled. Tim-3 concentration was quantitatively determined by enzyme-linked immunosorbent assay (ELISA). According to the expression levels of soluble Tim-3 and serum CA19-9, a binary logistic regression model of receiver operating characteristic (ROC) curve was established to compare the diagnostic effects of serum CA19-9 and soluble Tim-3 alone or combined with the two tests.Results:The levels of soluble Tim-3 in the pancreatic cancer group were significantly higher than those in the healthy control group ( P<0.001). The expression level of soluble Tim-3 was significantly higher in patients with stage III-IV pancreatic cancer than in patients with stage I-II ( P=0.003). The AUC of soluble Tim-3 diagnosis for stage I-II pancreatic cancer was 0.856 (95%CI: 0.765 to 0.992 P<0.001), Serum CA19-9 The AUC used for the stage I-II pancreatic cancer diagnosis was 0.862 (95%CI: 0.772 to 0.926 P<0.001), The AUC for the combined diagnosis was 0.949 (95%CI: 0.880 - 0.985 P<0.001) ; In a healthy population and in patients with stage III-IV pancreatic cancer, the AUC of soluble T I I-IV pancreatic cancer in stage III was 0.927 (95%CI: 0.873 to 0.963 P<0.001), the AUC of serum CA19-9 used for the diagnosis of stage III-IV pancreatic cancer was 0.933 (95%CI: 0.881 to 0.968 P<0.001), the AUC for the combined diagnosis was 0.989 (95%CI: 0.956 to 0.999 P<0.001) . Conclusions:The combination of soluble Tim-3 and serum CA19-9 can improve the diagnostic rate of pancreatic cancer patients.

Objective:To analyze the risk factors for postoperative adverse cardiovascular events(PACE)in elderly patients after treatment with colectomy.Methods:Clinical data of 720 elderly patients aged 65 years and over treated with colectomy from January 2012 to December 2019 in Beijing Hospital, National Center of Gerontology were analyzed retrospectively.According to the occurrence of PACE(non-fatal myocardial infarction, acute coronary syndrome, arrhythmia, heart failure/cardiac insufficiency, etc.), the cases were divided into the PACE group and the non-PACE group.Clinical data of the two groups were compared and the risk factors for PACE were investigated using multivariate Logistic regression.Results:The overall incidence of PACE was 5.8%(42/720). Statistically significant differences were found between the PACE and non-PACE groups in patient age, the American Society of Anesthesiologists(ASA)classification, the Goldman index score and comorbidities(coronary heart disease, arrhythmia, old myocardial infarction, chronic renal insufficiency), preoperative serum levels of BNP and D-dimmer, and postoperative length of stay( P<0.05). A further multivariate Logistic regression analysis showed that significant differences existed between the groups in NYHA Ⅲ and Ⅳ, ASA Ⅲ and old myocardial infarction, with the overall risk of PACE increasing by 4.017, 2.320 and 2.746, respectively. Conclusions:The incidence of PACE following colectomy is related to multiple perioperative factors.For elderly colorectal cancer patients with one or more of the above risk factors, we should be on high alert for PACE during hospitalization.