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.

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objective To investigate the effect of Tan Ⅰ on SA-AKI in rats by mediating Wnt/β-catenin signaling pathway.Methods Sprague-Dawley rats were randomly divided into the following groups(n=8 per group,including 2 reserve animals per group):Sham,SA-AKI,SA-AKI+5 mg/kg Tan I,SA-AKI+10 mg/kg Tan I,SA-AKI+15 mg/kg Tan I(SA-AKI+Tan I),SA-AKI+salinomycin sodium(SS,Wnt signal inhibitor,SA-AKI+SS),SA-AKI+SS+Tan I,SA-AKI+laduviglusib(LG,Wnt signal activator,SA-AKI+LG),and SA-AKI+LG+Tan I.Rat SA-AKI model was induced by cecal ligation and puncture(CLP),with Tan I,SS,and LG administered via intraperitoneal injection.Hematoxylin-eosin and TUNEL staining were used to observe renal tissue pathological damage.Enzyme-linked immunosorbent assay was used to detect serum concentrations of neutrophil gelatinase-associated lipocalin(NGAL),IL-1β,IL-8,IL-6,and TNF-α.Creatinine(Cre)and blood urea nitrogen(BUN)kit were used to detect serum Cre and BUN concentrations.Western blot and immunofluorescence staining were used to detect the expression and fluorescence intensity of Wnt1,GSK3β,and β-catenin.Results Administration of Tan I at doses of 10 mg/kg and 15 mg/kg significantly attenuated renal injury in rats with SA-AKI(P<0.05),suppressed the levels of SA-AKI biomarkers NGAL,Cre,and BUN and pro-inflammatory cytokines(P<0.05),reduced apoptosis,and downregulated Wnt1 and GSK3β while upregulating β-catenin expression(P<0.05).Although Tan I at 5 mg/kg exhibited a modest protective effect against SA-AKI in rats,no statistically significant difference was observed compared to the sham group(P>0.05).SS weakened CLP-induced kidney injury and the production of inflammatory cytokines in rats(P<0.05),and LG further aggravated CLP-induced kidney injury in rats(P<0.05).Tan Ⅰ reversed the promoting effect of LG on kidney injury in SA-AKI rats(P<0.05).Conclusion Tan Ⅰ provides a protective effect on CLP-induced SA-AKI rat by inhibiting Wnt/β-catenin signaling pathway.

Objective:To investigate the effects of ultrasound-guided percutaneous microwave ablation on postoperative conditions,thyroid hormone levels and nodule volume in patients with micropapillary thyroid cancer.Methods:A total of 176 patients with micropapillary thyroid cancer admitted to Hefei Cancer Hospital of Chinese Academy of Sciences and the First Affiliated Hospital of Anhui Medical University from February 2022 to December 2023 were selected,and they were divided into control group(92 cases)and observation group(84 cases)according to the difference of the treatment protocols.In them,3 cases were lost to visit in the control group and 2 cases were lost to visit in the observation group,and finally 89 cases were in the control group and 82 cases were in the observation group in the study.The control group was treated with surgical resection,and the observation group was treated with ultrasound-guided percutaneous microwave ablation.Both groups were followed up for 12 months after surgery.The surgical indexes,hospitalization cost,hospitalization time,and the thyroid hormone levels and quality of life before and 12 months after surgery between two groups were compared,and the occurrence of complications,postoperative recurrence and metastasis during the follow-up period were compared also between the two groups.The changes in nodule volume in the observation group were analyzed before and 3rd,6th and 12th month after surgery.Mental component summary(MCS),physical component summary(PCS)score and the MOS 36-item short-form health survey(SF-36)score were used in this study.Results:The surgical incision,the amount of surgical blood loss,the duration of surgery,the duration of hospitalization and the cost of hospitalization of the observation group were respectively(2.09±0.32)mm,(2.13±0.16)ml,(26.73±6.54)min,(2.10±0.52)d and(10 976.23±1132.56)CNY,which were less,or lower,or shorter,or less than these of the control group,and the differences were significant(t=51.031,31.853,27.924,27.028 and 21.925,P<0.05).Compared with preoperative serum thyroid stimulating hormone(TSH)level,that of control group increased at the 12th months after surgery,which was higher than that of observation group,and the difference between the two groups was statistically significant(t=22.482,P<0.05).The difference of the serum TSH level in the observation group between before and at the 12th month after surgery was not statistically significant(P>0.05).Compared with preoperative nodule volume,that of observation group first increased and then decreased at the 6th month and 12th month after surgery,and nodule volume at the 12th month after surgery was less than that before surgery(t=13.731,P<0.05).The MCS,PCS score,and SF-36 score both two groups at the 12th month after surgery increased than preoperative them,and these indicators of observation group were higher than them of control group,and the differences were statistically significant(t=14.624,11.986,and 13.582,P<0.05).The total incidence of complication during the follow-up period was 2.44%in observation group,which was lower than 10.11%in control group,and the difference was statistically significant(x2=4.175,P<0.05).There was no recurrence or metastasis in the two groups after surgery.Conclusion:Compared with surgery,ultrasound-guided percutaneous microwave ablation can improve the surgical index of patients with micropapillary thyroid cancer,and shorten the time of hospitalization,and reduce the hospitalization cost,and reduce the occurrence of complications.The recovery of patients are well after surgery,and there is not obvious recurrence and metastasis.At the same time,this treatment plan can significantly shorten the volume of the patient's nodules,and does not have significant effect on thyroid hormone.

Objective:To investigate the effects of ultrasound-guided percutaneous microwave ablation on postoperative conditions,thyroid hormone levels and nodule volume in patients with micropapillary thyroid cancer.Methods:A total of 176 patients with micropapillary thyroid cancer admitted to Hefei Cancer Hospital of Chinese Academy of Sciences and the First Affiliated Hospital of Anhui Medical University from February 2022 to December 2023 were selected,and they were divided into control group(92 cases)and observation group(84 cases)according to the difference of the treatment protocols.In them,3 cases were lost to visit in the control group and 2 cases were lost to visit in the observation group,and finally 89 cases were in the control group and 82 cases were in the observation group in the study.The control group was treated with surgical resection,and the observation group was treated with ultrasound-guided percutaneous microwave ablation.Both groups were followed up for 12 months after surgery.The surgical indexes,hospitalization cost,hospitalization time,and the thyroid hormone levels and quality of life before and 12 months after surgery between two groups were compared,and the occurrence of complications,postoperative recurrence and metastasis during the follow-up period were compared also between the two groups.The changes in nodule volume in the observation group were analyzed before and 3rd,6th and 12th month after surgery.Mental component summary(MCS),physical component summary(PCS)score and the MOS 36-item short-form health survey(SF-36)score were used in this study.Results:The surgical incision,the amount of surgical blood loss,the duration of surgery,the duration of hospitalization and the cost of hospitalization of the observation group were respectively(2.09±0.32)mm,(2.13±0.16)ml,(26.73±6.54)min,(2.10±0.52)d and(10 976.23±1132.56)CNY,which were less,or lower,or shorter,or less than these of the control group,and the differences were significant(t=51.031,31.853,27.924,27.028 and 21.925,P<0.05).Compared with preoperative serum thyroid stimulating hormone(TSH)level,that of control group increased at the 12th months after surgery,which was higher than that of observation group,and the difference between the two groups was statistically significant(t=22.482,P<0.05).The difference of the serum TSH level in the observation group between before and at the 12th month after surgery was not statistically significant(P>0.05).Compared with preoperative nodule volume,that of observation group first increased and then decreased at the 6th month and 12th month after surgery,and nodule volume at the 12th month after surgery was less than that before surgery(t=13.731,P<0.05).The MCS,PCS score,and SF-36 score both two groups at the 12th month after surgery increased than preoperative them,and these indicators of observation group were higher than them of control group,and the differences were statistically significant(t=14.624,11.986,and 13.582,P<0.05).The total incidence of complication during the follow-up period was 2.44%in observation group,which was lower than 10.11%in control group,and the difference was statistically significant(x2=4.175,P<0.05).There was no recurrence or metastasis in the two groups after surgery.Conclusion:Compared with surgery,ultrasound-guided percutaneous microwave ablation can improve the surgical index of patients with micropapillary thyroid cancer,and shorten the time of hospitalization,and reduce the hospitalization cost,and reduce the occurrence of complications.The recovery of patients are well after surgery,and there is not obvious recurrence and metastasis.At the same time,this treatment plan can significantly shorten the volume of the patient's nodules,and does not have significant effect on thyroid hormone.

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

The phenomenon of coronary artery ectasia is typically discovered incidentally during coronary angiography.As a relatively uncommon manifestation of coronary arteries,it has attracted the interest of numerous researchers.However,despite extensive research on coronary artery ectasia,substantial controversies persist regarding both its etiology and treatment modalities.This article provides a comprehensive summary of recent research on coronary artery ectasia,elucidates various aspects of research progress,with the aim of offering substantive support and guidance for subsequent investigations.

Objective To analyze the influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation. Methods Clinical data of 66 patients with airway stenosis requiring clinical interventions after lung transplantation were retrospectively analyzed. Univariate and multivariate Cox’s regression models were adopted to analyze the influencing factors of survival of all patients with airway stenosis and those with early airway stenosis. Kaplan-Meier method was used to calculate the overall survival and delineate the survival curve. Results For 66 patients with airway stenosis, the median airway stenosis-free time was 72 (52,102) d, 27% (18/66) for central airway stenosis and 73% (48/66) for distal airway stenosis. Postoperative mechanical ventilation time [hazard ratio (HR) 1.037, 95% confidence interval (CI) 1.005-1.070, P=0.024] and type of surgery (HR 0.400, 95%CI 0.177-0.903, P=0.027) were correlated with the survival of patients with airway stenosis after lung transplantation. The longer the postoperative mechanical ventilation time, the higher the risk of mortality of the recipients. The overall survival of airway stenosis recipients undergoing bilateral lung transplantation was better than that of their counterparts after single lung transplantation. Subgroup analysis showed that grade 3 primary graft dysfunction (PGD) (HR 4.577, 95%CI 1.439-14.555, P=0.010) and immunosuppressive drugs (HR 0.079, 95%CI 0.022-0.287, P<0.001) were associated with the survival of patients with early airway stenosis after lung transplantation. The overall survival of patients with early airway stenosis after lung transplantation without grade 3 PGD was better compared with that of those with grade 3 PGD. The overall survival of patients with early airway stenosis after lung transplantation treated with tacrolimus was superior to that of their counterparts treated with cyclosporine. Conclusions Long postoperative mechanical ventilation time, single lung transplantation, grade 3 PGD and use of cyclosporine may affect the survival of patients with airway stenosis after lung transplantation.

Objectives:Primary cardiac involvement (SSc-PHI) in systemic sclerosis is an important prognostic factor. We aimed to characterize and identify subclinical SSc-PHI using cardiovascular MRI to determine whether disease severity and serum biomarkers are associated with subclinical SSc-PHI.Methods:A total of 26 patients with SSc who had no history of cardiovascular disease or pulmonary hypertension underwent 3 T-enhanced cardiovascular MRI. Measurements included native T 1, extracellular volume, advanced gadolinium enhancement, T 2 mapping, and left ventricular volume function. Troponin T and N telencephalic natriuretic peptide precursors were also determined. Results:LGE was observed in 13 of 26 patients (50.0%), suggesting focal fibrosis, and T 2 mapping was significantly higher in the dcSSc group than in the lcSSc group ( P=0.009). Left ventricular volume and function were within the normal range in all patients, but final systolic left ventricular volume was significantly higher in dcSSc than in lcSSc ( P=0.021). The modified Rodnan skin score (mRSS) was significantly higher in patients with LGE focal fibrosis ( P=0.019). Logistic regression analysis confirmed the association between mRSS and LGE ( OR=1.224, P=0.037). In multivariate analysis, T 2 mapping was negatively correlated with disease course, and was correlated with dcSSc and fingertip ulcer ( R2=0.711, P=0.018, P=0.013, P=0.030). Troponin T was correlated with T 2 mapping ( r=0.555, P=0.049). Conclusions:Subclinical SSc-PHI is characterized by diffuse and focal myocardial fibrosis, but preserves myocardial systolic function. Subclinical SSC-Phi is associated with TNT, SSc disease severity, and complex peripheral vascular disease. These data provide information for identifying individuals at risk of SSc-PHI.