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 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 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 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 short-term and long-term efficacy of laparoscopic surgery for colorectal cancer in elderly patients aged 80 and over.Methods:This study included patients aged 80 and over with sigmoid or rectal cancer who had undergone radical surgery in Beijing Hospital between January 2013 and December 2020.Of the enrolled patients, 47 underwent laparoscopic surgery, and 44 received open surgery.After 1∶1 propensity score matching(PSM), there were 32 cases in each group.Patient clinicopathological characteristics, surgery data, post-operative outcomes and long-term survival were compared.Results:Before PSM, there were significant differences in sex composition and tumor locations between the open surgery and laparoscopic surgery groups.After PSM, there was no significant difference in clinicopathological characteristics between the two groups.Before and after PSM, the operative time for laparoscopic surgery was statistically longer than that for open surgery.The intraoperative blood loss, the postoperative complication rate and the number of harvested lymph nodes were not significantly different between the two groups before and after PSM.Before and after PSM, the postoperative hospital stay in the laparoscopic operation group was shorter than that in the open surgery group, but the difference was not statistically significant.Before PSM, the 1-year, 3-year and 5-year survival rates of the open surgery group were 92.4%, 69.5% and 58.1%, respectively, and the 1-year, 3-year and 5-year survival rates of laparoscopic group were 91.3%, 79.8% and 69.5%, respectively.There was no significant difference in overall survival between the two groups before PSM( χ2=0.591, P=0.422). After PSM, the 1-year, 3-year and 5-year survival rates in the open surgery group were 89.3%, 67.1% and 52.2%, respectively, and the 1-year, 3-year and 5-year survival rates in the laparoscopic surgery group were 90.6%, 74.3% and 65.0%, respectively.There was no significant difference in the overall survival between the two groups after PSM( χ2=1.316, P=0.251). Conclusions:For elderly colorectal cancer patients aged 80 and over, laparoscopic surgery and open surgery have similar rates of complications and long-term survival.This study provides evidence for the safety of laparoscopic surgery.Further prospective randomized controlled clinical trials are needed to confirm these findings.

Objective:To analyze the cognitive dysfunction and its influencing factors in patients with multisystem atrophy(MSA).Methods:A total of 143 hospitalized patients with MSA in our hospital from January 2015 to January 2020 were selected as the research objects.The cognitive function was evaluated by Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA)scales, meanwhile, the influencing factors of cognitive function were analyzed.Results:The average score of MMSE scale of 143 MSA patients ranged from 9 to 30 points, and the MMSE test identified 86 patients(60.1%)with cognitive impairment, including 58 cases(40.6%)with mild cognitive impairment, 27 cases(18.9%)with moderate cognitive impairment and 1 case(0.7%)with severe cognitive impairment.The average score of MoCA scale of 143 MSA patients ranged from 5 to 30 points, among which 111 cases(77.6%)had cognitive impairment, including 69 cases with mild cognitive impairment(48.3%), 35 cases with moderate cognitive impairment(24.5%)and 7 cases with severe cognitive impairment(4.9%). Both the total scores of MMSE and MoCA scores of MSA patients were not correlated with age of onset, old age, gender, disease duration, type of MSA(MSA-C), orthostatic hypotension(OH), urinary retention, positivity of anal sphincter electromyography(ASEMG), triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C), fasting blood glucose and glycosylated hemoglobin, serum uric acid and residual urine volume(all P>0.05). Logistic regression analysis showed that fasting blood glucose was a risk factor for cognitive impairment identified by MMSE( OR=2.224, 95% CI: 1.108-4.462, P=0.024); MSA-C( OR=3.905, 95% CI: 1.302-11.713, P=0.015)and TG( OR=3.494, 95% CI: 1.061-11.501, P=0.040)were risk factors for cognitive impairment identified by MoCA.There were no significant differences in above clinical characteristics between moderate to severe cognitive impairment patients and mild cognitive impairment patients identified by MMSE scale( P>0.05). Similarly, there were no significant differences in the above clinical characteristics between moderate to severe cognitive impairment patients and mild cognitive impairment patients by MoCA scale( P>0.05). Logistic regression analysis showed that TG was a risk factor for moderate to severe cognitive impairment identified by MMSE( OR=17.624, 95% CI: 2.596-119.669, P=0.003), while TC was a protective factor( OR=0.006, 95% CI: 0.000-0.714, P=0.036). Logistic regression analysis did not find the influencing factors of moderate to severe cognitive impairment as suggested by MoCA score. Conclusions:There is a high incidence of cognitive impairment in MSA patients.The type of MSA(MSA-C), blood glucose and blood lipid may be influence factors of cognitive impairment in MSA patients.Age of onset, old age, gender, disease duration, autonomic dysfunction, and uric acid have no significant correlation with cognitive impairment of MSA.

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.

BACKGROUND: Acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma (AR-NHL) is a high-risk factor for morbidity and mortality in patients with AIDS. This study aimed to determine the prognostic factors associated with overall survival (OS) and to develop a prognostic nomogram incorporating computed tomography imaging features in patients with acquired immune deficiency syndrome-related non-Hodgkin lymphoma (AR-NHL). METHODS: A total of 121 AR-NHL patients between July 2012 and November 2019 were retrospectively reviewed. Clinical and radiological independent predictors of OS were confirmed using multivariable Cox analysis. A prognostic nomogram was constructed based on the above clinical and radiological factors and then provided optimum accuracy in predicting OS. The predictive accuracy of the nomogram was determined by Harrell C-statistic. Kaplan-Meier survival analysis was used to determine median OS. The prognostic value of adjuvant therapy was evaluated in different subgroups. RESULTS: In the multivariate Cox regression analysis, involvement of mediastinal or hilar lymph nodes, liver, necrosis in the lesions, the treatment with chemotherapy, and the CD4 ≤100 cells/μL were independent risk factors for poor OS (all P < 0.050). The predictive nomogram based on Cox regression has good discrimination (Harrell C-index = 0.716) and good calibration (Hosmer-Lemeshow test, P = 0.620) in high- and low-risk groups. Only patients in the high-risk group who received adjuvant chemotherapy had a significantly better survival outcome. CONCLUSION A survival-predicting nomogram was developed in this study, which was effective in assessing the survival outcomes of patients with AR-NHL. Notably, decision-making of chemotherapy regimens and more frequent follow-up should be considered in the high-risk group determined by this model.
Acquired Immunodeficiency Syndrome ; Humans ; Lymphoma, Non-Hodgkin ; Neoplasm Staging ; Nomograms ; Prognosis ; Retrospective Studies

Objective:To analyze the characteristics of eyes with congenital optic disc pits (ODPs) through multimodal imaging.Methods:A cross-sectional study was conducted.Thirty-eight patients (38 eyes) diagnosed with congenital ODPs in the Second Hospital of Hebei Medical University from January 2009 to January 2020 were enrolled.A comprehensive summary analysis of the imaging results including fundus photography, spectral domain-optical coherence tomography (SD-OCT), infrared imaging, fundus autofluorescence (FAF), fluorescein fundus angiography (FFA) and indocyanine green angiography (ICGA) was performed.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of The Second Hospital of Hebei Medical University (No.2021-P011). Written informed consent was obtained from each subject prior to any medical examination.Results:Among the 38 eyes, there were 32 eyes with ODPs located in or below the temporal side of optic disc, 4 eyes with ODPs located above the temporal side of optic disc, and 2 eyes with ODPs located at the center of optic disc, which were round or quasi-circular pale depression, and dark red eminences with clear or unclear boundaries between milk spots were found in 29 eyes with optical-disc macular degeneration (ODP-M) by fundus photography.SD-OCT examination showed that the structure of lamina cribrosa in the lesion area in all ODPs patients was incomplete, which presented a dark area with no tissue reflection, and the fissure led to the deep optic nerve.Fluid was found in the outer nuclear layer in all ODP-M patients, and there were 27 eyes with fluid in the inner nuclear layer, 13 eyes in the ganglion cell layer, and 4 eyes under the inner limiting membrane.Among the 29 eyes with ODP-M, there were 21 eyes with retinoschisis in outer layer, 27 eyes with neuroepithelial detachment.In the 27 eyes with neuroepithelial detachment, spot-like high reflection and reduced or disappeared ellipsoid band reflectance were seen above the neuroepithelium in 18 eyes.In infrared images, there were circular or quasi-circular low-reflection areas in the temporal side of the optic disc, and the lesion of ODP-M eyes presented low-reflection areas.FAF examination showed that in 27 eyes with ODP-M, there was a hypofluorescent region at the posterior pole consistent with the lesion range, among which, there was a granular or sheet-like hyperfluorescence at the center of the hypofluorescent region in 18 eyes.FFA showed that the optic disc depression in the arterial phase of patients was in a localized hypofluorescence state.During the venous phase, fluorescein dye extravasation along the temporal side of the optic disc could be found.A strong fluorescent arc with unclear boundaries at the temporal edge of the optic disc was formed in the late stage of angiography.Among the 29 eyes with ODP-M, the area of the macular lesion showed hyperfluorescence during the late stage of angiography in 27 eyes with neuroepithelial detachment, and no extension of dye toward the macula was found.ICGA showed that the optic disc depression of ODPs patients presented a localized hypofluorescence, and the lesion showed hyperfluorescence in 27 of the 29 ODP-M eyes with neuroepithelial detachment.Conclusions:Multimodal imaging can be helpful to realize the early diagnosis, etiology analysis of ODPs and make treatment plan.