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.

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Objective:To investigate the preventive efficacy of triamcinolone acetonide injection on esophageal stenosis after endoscopic submucosal dissection (ESD).Methods:From February 1, 2021 to October 31, 2023, 82 patients who underwent ESD for esophageal lesions at the Affiliated Cancer Hospital of Nanjing Medical University (Jiangsu Cancer Hospital) were enrolled. According to the treatment of the surface after ESD, the patients were divided into the triamcinolone acetonide group (49 cases) and the no-special-treatment group (33 cases). The patients of triamcinolone acetonide group received multiple injections of triamcinolone acetonide solution post-ESD (immediate), week 1, and week 4, while the patients of no-special-treatment group did not receive additional pharmacological intervention. The patients were followed up for 3 months after ESD. The occurrence of esophageal stenosis after ESD was observed under endoscopy. The incidence of esophageal stenosis and the improvement of dysphagia after ESD were compared between the triamcinolone acetonide group and no-special-treatment group. Univariate and multivariate logistic regression analyes were performed to identify influencing factors of esophageal stenosis after ESD. Chi-square test was used for statistical analysis.Results:The incidence of esophageal stenosis after ESD in the triamcinolone acetonide group was lower than that in the no-special-treatment group (16.3% (8/49) vs. 66.7% (22/33)), and the proportion of patients without dysphagia (Stooler′s grading score of 0) was higher than that in the no-special-treatment group (83.7% (41/49) vs. 33.3% (11/33)), and the differences were statistically significant ( χ2=19.42 and 24.31, both P<0.001). In 42 patients with circumferential esophageal lesions involving >75%, the incidence of esophageal stenosis in the triamcinolone acetonide group was lower than that in the no-special-treatment group (28.6% (6/21) vs. 85.7% (18/21)), and the proportion of patients without dysphagia (Stooler′s grading score of 0) was higher than that in the no-special-treatment group (71.4% (15/21) vs. 14.3% (3/21)), and the differences were statistically significant ( χ2=11.76 and 15.33, both P<0.001). There was no statistically significant differences in the incidence of adverse events between the triamcinolone acetonide group and no-special-treatment group (4.1% (2/49) vs. 0; χ2=0.20, P=0.656), and no serious adverse reactions occurred in 2 groups. The results of multivariate logistic regression analysis showed that the long distance from the proximal lesion margin to the incisors was a protective factor of whether esophageal stenosis occured or not after ESD ( OR=0.795, 95% confidence interval (95% CI): 0.652 to 0.947, P=0.014), while the incidence of esophageal stenosis increased in patients with circumferential lesions involving >75% ( OR=7.064, 95% CI: 1.893 to 32.408, P=0.006), and the incidence of esophageal stenosis effectively reduced after the use of triamcinolone acetonide post ESD ( OR=0.062, 95% CI: 0.013 to 0.229, P<0.001). Conclusion:After ESD, triamcinolone acetonide can reduce the incidence of esophageal stenosis and improve patients′ dysphagia.

Objective:To analyze the relationship between Cardiovascular Health(CVH)and Pelvic Inflamma-tory Disease(PID)using data from the National Health and Nutrition Examination Surveys(NHANES).Meth-ods:Participants from the NHANES database were extracted based on the inclusion of PID,LE8 scores,and mul-tiple potential confounding factors,excluding those with missing variables.Multivariate Logistic regression analysis was conducted using R to assess the relationship between the CVH and the risk of PID.Additionally,subgroup a-nalysis and interaction tests were performed for age,race,poverty,marital status,education,BMI,menstrual regu-larity,and pregnancy history.Results:A total of 3934 female participants were included,with an average age of 39.95±11.42 years.Multivariable Logistic regression analysis showed that after adjusting for age,race,BMI,edu-cation level,marital status,household income,menstrual cycle,and pregnancy history,the risk of PID gradually decreased with an increase in CVH assessment metric LE8 scores(OR 0.98,95％CI 0.97-0.99,P＜0.001).Stratified analysis indicated significant interactions between age,race,and marital status in the association be-tween CVH and PID(interaction P＜0.05 for all),while household income level,education level,BMI,menstrual regularity,and pregnancy history showed no significant interactions with the CVH and PID association(P＞0.05).Conclusions:There is a significant negative relationship between CVH and PID in adult women in the United states,suggesting that better cardiovascular health may help reduce the risk of PID.

Objective:To analyze the relationship between Cardiovascular Health(CVH)and Pelvic Inflamma-tory Disease(PID)using data from the National Health and Nutrition Examination Surveys(NHANES).Meth-ods:Participants from the NHANES database were extracted based on the inclusion of PID,LE8 scores,and mul-tiple potential confounding factors,excluding those with missing variables.Multivariate Logistic regression analysis was conducted using R to assess the relationship between the CVH and the risk of PID.Additionally,subgroup a-nalysis and interaction tests were performed for age,race,poverty,marital status,education,BMI,menstrual regu-larity,and pregnancy history.Results:A total of 3934 female participants were included,with an average age of 39.95±11.42 years.Multivariable Logistic regression analysis showed that after adjusting for age,race,BMI,edu-cation level,marital status,household income,menstrual cycle,and pregnancy history,the risk of PID gradually decreased with an increase in CVH assessment metric LE8 scores(OR 0.98,95％CI 0.97-0.99,P＜0.001).Stratified analysis indicated significant interactions between age,race,and marital status in the association be-tween CVH and PID(interaction P＜0.05 for all),while household income level,education level,BMI,menstrual regularity,and pregnancy history showed no significant interactions with the CVH and PID association(P＞0.05).Conclusions:There is a significant negative relationship between CVH and PID in adult women in the United states,suggesting that better cardiovascular health may help reduce the risk of PID.

Objective:To investigate the preventive efficacy of triamcinolone acetonide injection on esophageal stenosis after endoscopic submucosal dissection (ESD).Methods:From February 1, 2021 to October 31, 2023, 82 patients who underwent ESD for esophageal lesions at the Affiliated Cancer Hospital of Nanjing Medical University (Jiangsu Cancer Hospital) were enrolled. According to the treatment of the surface after ESD, the patients were divided into the triamcinolone acetonide group (49 cases) and the no-special-treatment group (33 cases). The patients of triamcinolone acetonide group received multiple injections of triamcinolone acetonide solution post-ESD (immediate), week 1, and week 4, while the patients of no-special-treatment group did not receive additional pharmacological intervention. The patients were followed up for 3 months after ESD. The occurrence of esophageal stenosis after ESD was observed under endoscopy. The incidence of esophageal stenosis and the improvement of dysphagia after ESD were compared between the triamcinolone acetonide group and no-special-treatment group. Univariate and multivariate logistic regression analyes were performed to identify influencing factors of esophageal stenosis after ESD. Chi-square test was used for statistical analysis.Results:The incidence of esophageal stenosis after ESD in the triamcinolone acetonide group was lower than that in the no-special-treatment group (16.3% (8/49) vs. 66.7% (22/33)), and the proportion of patients without dysphagia (Stooler′s grading score of 0) was higher than that in the no-special-treatment group (83.7% (41/49) vs. 33.3% (11/33)), and the differences were statistically significant ( χ2=19.42 and 24.31, both P<0.001). In 42 patients with circumferential esophageal lesions involving >75%, the incidence of esophageal stenosis in the triamcinolone acetonide group was lower than that in the no-special-treatment group (28.6% (6/21) vs. 85.7% (18/21)), and the proportion of patients without dysphagia (Stooler′s grading score of 0) was higher than that in the no-special-treatment group (71.4% (15/21) vs. 14.3% (3/21)), and the differences were statistically significant ( χ2=11.76 and 15.33, both P<0.001). There was no statistically significant differences in the incidence of adverse events between the triamcinolone acetonide group and no-special-treatment group (4.1% (2/49) vs. 0; χ2=0.20, P=0.656), and no serious adverse reactions occurred in 2 groups. The results of multivariate logistic regression analysis showed that the long distance from the proximal lesion margin to the incisors was a protective factor of whether esophageal stenosis occured or not after ESD ( OR=0.795, 95% confidence interval (95% CI): 0.652 to 0.947, P=0.014), while the incidence of esophageal stenosis increased in patients with circumferential lesions involving >75% ( OR=7.064, 95% CI: 1.893 to 32.408, P=0.006), and the incidence of esophageal stenosis effectively reduced after the use of triamcinolone acetonide post ESD ( OR=0.062, 95% CI: 0.013 to 0.229, P<0.001). Conclusion:After ESD, triamcinolone acetonide can reduce the incidence of esophageal stenosis and improve patients′ dysphagia.

OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis （HF） in rats based on the transforming growth factor-β（1 TGF-β1）/Smad2/extracellular signal-regulated protein kinase 1（ERK1） and Kelch-like epichlorohydrin-associated protein 1（Keap1）/nuclear factor-erythroid 2-related factor 2（Nrf2）/heme oxygenase-1（HO-1） pathways. METHODS Totally 60 rats were randomly divided into normal control group， model group， breviscapine low-dose， medium-dose and high-dose groups （5.4， 10.8， 21.6 mg/kg）， and colchicine group （positive control， 0.45 mg/kg）， with 10 rats in each group， half male and half female. Except for the normal control group， HF model of the other groups was induced by carbon tetrachloride. Subsequently， each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase （ALT） and aspartate aminotransferase （AST）in serum， those of ALT， AST， superoxide dismutase （SOD），malondialdehyde （MDA） and glutathione peroxidase （GSH- Px） in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1， Smad2， ERK1， Nrf2， Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group， the model group showed large areas of white nodular lesions in the liver， obvious inflammatory cell infiltration and collagen fiber deposition. The body weight， the levels of SOD and GSH-Px in liver tissue， the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group （P＜0.05）； the liver coefficient， the percentage of Masson staining positive area， ALT and AST levels of serum and liver tissue， MDA level of liver tissue， the protein and mRNA expressions of TGF-β1， Smad2， ERK1 and Keap1 were significantly increased （P＜0.05）. Compared with the model group， the liver lesions of rats in each drug group were improved， and the above quantitative indexes were generally reversed （P＜0.05）. CONCLUSIONS Breviscapine has a good intervention effect on HF rats， which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.

Objective:To investigate the association between the Doppler variables of the ophthalmic artery with the severity of preeclampsia(PE).Methods:Systematic literature was searched between January 1995 and March 2023 in PubMed,Web of Science,Embase,and the Cochrane Library.Studies comparing ophthalmic artery Doppler variables,including peak systolic velocity(PSV),end-diastolic velocity(EDV),resistive index(Rl),pulsa-tility index(PI),and peak ratio(PR,the ratio of the flow velocity of the second peak to that of the initial peak)in patients with PE,severe preeclampsia(sPE),and healthy pregnant women were included.The random-effects model was adopted as the method of pooled analysis,and the I2value was used to assess heterogeneity.The pooled standardized mean difference(SMD)with 95％confidence interval(CI)was used to estimate the associa-tion between ophthalmic artery Doppler variables and PE patient's characteristics.Results:Eight retrospective studies were eventually included in this Meta-analysis.Our pooled results suggested that compared with PE ca-ses,sPE patients had lower PI levels(SMD-0.56,95％CI-0.92～-0.20,P=0.000),higher EDV levels(SMD 0.47,95％CI 0.12～0.83,P=0.028)and higher PR levels(SMD0.96,95％CI 0.13～1.78,P=0.023).Howev-er,there was no significant difference between PE and sPE patients about the PSV and RI(P=0.361,P=0.626).Conclusions:This review demonstrates that ophthalmic artery Doppler variables(PI,EDV and PR)could be useful for predicting PE and PE development(especially in identifying sPE),which in turn may help the practitioner in the management of these complicated cases and in taking early necessary precautions.

Endosomal TLRs (TLR3/7/8/9) are highly analogous innate immunity sensors for various viral or bacterial RNA/DNA molecular patterns. Among them, TLR7, in particular, has been suggested to be a target for various inflammatory disorders and autoimmune diseases including systemic lupus erythematosus (SLE); but few small-molecule inhibitors with elaborated mechanism have been reported in literature. Here, we reported a well-characterized human TLR7-specific small-molecule inhibitor, TH-407b, with promising potency and negligible cytotoxicity through a novel binding mechanism. Notably, TH-407b not only effectively inhibited TLR7-mediated pro-inflammatory signaling in a variety of cultured cell lines but also demonstrated potent inflammation suppressing activities in primary peripheral blood mononuclear cells (PBMCs) derived from SLE patients. Furthermore, TH-407b showed prominent efficacy in vivo, improved survival rate and ameliorated symptoms of SLE model mice. To obtain molecular insights into the TH-407b derivatives' inhibition mechanism, we performed the structural analysis of TLR7/TH-407b complex using cryogenic electron microscopy (cryo-EM) method. As an atomistic resolution cryo-EM structure of the TLR family, it not only of value to facilitate structure-based drug design, but also shed light to methodology development of small proteins using EM. Significantly, TH-407b has unveiled an inhibition strategy for TLR7 via stabilizing its resting/inactivated state. Such a resting state could be generally applicable to all TLRs, rendering a useful method for targeting this group of important immunological receptors.

Objective:To investigate the effects of Satir model group intervention on stress coping style, self-consistency and congruence and subjective well-being of re-employment nurses, in order to provide evidence for nursing managers to take targeted intervention measures.Methods:This was a quasi-experimental study. Convenience sampling was used to select 63 re-employment nurses from Shandong Provincial Third Hospital in 2021 as the research objects. The re-employment nurses were divided into control group (32 cases) and observation group (31 cases) by random number table method. The control group received humanistic care including heart-to-heart talk, group discussion and psychological lecture, and the observation group received Satir model group intervention for 6 weeks. Simplified Coping Style Questionnaire, Self Consistency and Congruence Scale and General Well-Being Scale were used to evaluate the intervention effect before intervention, immediately after intervention, 3 months after intervention, and 6 months after intervention.Results:There was no significant difference in coping style, self-consistency and congruence and subjective well-being between the two groups before intervention ( P>0.05). The positive coping scores of the observation group immediately after intervention, 3 months after intervention and 6 months after intervention were (28.94 ± 2.99), (28.71 ± 4.70) and (29.16 ± 3.23) points, significantly higher than the control group (23.38 ± 5.50), (24.72 ± 5.91), (24.65 ± 5.65) points, the differences were statistically significant ( t=4.96, 2.96, 3.87, all P<0.01); the total self-consistency and congruence scores were (94.52 ± 14.00), (99.87 ± 16.82), (91.84 ± 10.36) points, significantly lower than the control group (105.72 ± 10.75), (114.23 ± 20.10), (107.41 ± 13.39) points, the differences were statistically significant ( t=-3.57, -3.07, -5.15, all P<0.01); the total subjective well-being scores were (84.97 ± 7.37), (84.58 ± 10.33), (91.84 ± 7.01) points, which were higher than the control group (75.69 ± 7.94), (77.28 ± 8.27), (77.00 ± 8.48) points, and the differences were statistically significant ( t=4.80, 3.69, 7.56, all P<0.01). Conclusions:Satir model group intervention can improve the coping style, enhance the level of self-consistency and congruence and subjective well-being among re-employment nurses.