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.

The rich club, as a community of highly interconnected nodes, serves as the topological center of the network. However, the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown. In this study, we first detected and validated the rich club in the structural networks of mouse, monkey, and human brains using neuronal tracing or diffusion magnetic resonance imaging data. Further, we assessed the role of rich clubs in functional integration, segregation, and balance using quantitative metrics. Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species, with the functional networks of higher species exhibiting greater integration. These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
Animals ; Humans ; Brain/diagnostic imaging* ; Mice ; Male ; Nerve Net/diagnostic imaging* ; Macaca ; Female ; Neural Pathways/diagnostic imaging* ; Magnetic Resonance Imaging ; Biological Evolution ; Adult ; Diffusion Magnetic Resonance Imaging ; Brain Mapping ; Species Specificity ; Mice, Inbred C57BL

Objective To investigate the relationship between the expression of CENPF in NSCLC adenocarcinoma (LUAD) and the clinical prognosis of patients and its effect on the metastasis of lung adenocarcinoma cells. Methods The expression of CENPF in LUAD and its relationship with patient prognosis were analyzed by online bioinformatics. The expression of CENPF was verified by LUAD tissue microarray immunohistochemical staining. Kaplan-Meier analysis was performed to analyze the relationship between the expression of CENPF and the prognosis of patients with lung adenocarcinoma. Cox survival hazard ratio was used to analyze the factors affecting the survival of patients. Chi-square analysis was adopted to examine the relationship between CENPF expression and clinicopathological stage and grade of patients. The expression of CENPF in NCI-H2126 cells were knocked out by lentivirus, and then the proliferation, invasion, and migration abilities of the cells were detected. Changes in mRNA expression profiles after CENPF knockout were detected by RNA-seq. Bioinformatics analysis of downstream signaling pathways and the target genes of CENPF was also performed. Western blot was used to verify the target gene. Results CENPF was significantly upregulated in LUAD tumor tissue (P < 0.05) and significantly correlated with pathological stage (P=0.013). The higher expression of CENPF, the worse the prognosis of patients (P=0.01, P=0.027). After the expression was CENPF of knocked out, the cell proliferation, migration, and invasion abilities significantly reduced (P < 0.01). The expression of chemokine pathway genes in cells was enriched significantly (P < 0.001). ACKR3/CXCR7 and CDH2/N-cadherin were significantly downregulated, whereas CDH1/E-cadherin was significantly upregulated. After CENPF was knocked out, ACKR3/CXCR7 and N-cadherin were significantly downregulated, whereas E-cadherin significantly increased. Conclusion The expression of CENPF is negatively correlated with the clinical prognosis of patients with LUAD, and it promotes the occurrence of EMT by regulating the expression levels of N-cadherin and E-cadherin related to EMT through ACKR3/CXCR7.

Objective To evaluate the effectiveness of perioperative fasting abbreviation in traumatic patients undergoing selective surgeries.Methods The traumatic patients undergoing selective surgeries from November 2016 to January 2017 at our department were selected for this prospective cohort study.They were divided into an intervention group (69 patients) and a control group (121 patients) according to the wards where they stayed.The intervention group was fasted for solids 6 hours prior to surgery and received oral solution with maltodextrin 2 hours prior to surgery.After surgery,they were allowed to drink liquids as soon as they were awakened.Normal food was allowed 2 hours later.The control group was fasted for either liquids or solids the night before surgery.After surgery,the patients who had received brachial plexus block only were allowed liquids with no limitation while the other patients were allowed liquids 6 hours after surgery and then were free for solids and liquids if no discomfort was observed.The time periods for preoperative liquids and solids fasting and for postoperative intake of liquids and solids were recorded and compared between the 2 groups.The perioperative well-beings (including anxiety,thirst,hunger,nausea,fatigue,dizziness,sweating and stomach discomfort) and serum glucose levels were compared between the 2 groups.Adverse reactions were observed.Results The preoperative fasting time for liquids for the intervention group (4.5 ± 2.9 hours) was significantly shorter than that for the control group (14.3 ±3.9 hours) (P ＜ 0.05).The preoperative fasting time for solids for the intervention group (17.6 ± 3.0 hours) were significantly longer than that for the control group (16.1 ±3.8 hours) (P ＜ 0.05).The postoperative fasting time periods for both liquids [1 (0,3) h] and solids [2 (1,4) h] for the intervention group were significantly shorter than those for the control group [6(6,6) h] hours and [6(6,6) h] (P ＜ 0.05).Compared with the control group,the perioperative anxiety,thirst,hunger,nausea,fatigue,dizziness and stomach discomfort were significantly improved in the intervention group (P ＜ 0.05).The average serum glucose level was similar in both groups upon admission (P ＜ 0.05);it was significantly higher in the intervention group immediately before surgery (P ＜ 0.05) but was gradually decreased after surgery until there was no significant difference between the 2 groups (P ＞ 0.05).No major adverse reaction was observed in either group.Conclusion The protocol of perioperative fasting abbreviation may be safe and feasible in traumatic patients for selective surgeries,showing benefits of decreased anxiety,thirst,hunger,nausea,fatigue,dizziness and stomach discomfort.

Objective: To analyze the correlation between the changes of fibrinogen and the treatment effect of all-frequency sudden deafness, and to explore the individualized treatment strategy for the use of Batroxobin. Methods: Patients with all-frequency sudden deafness who were admitted to Department of Otorhinolaryngology, People′s Hospital of Peking University, from January 2010 to September 2016 were selected. All patients were given standard treatment and regular use of Batroxobin. Value of fibrinogen on D1 (before treatment) / D3 / D7 (±1) and D14 (±2) were recorded, at the same time, the correlation between the changes of fibrinogen and prognosis of all-frequency sudden deafness by the audiograms of onset and after-treatment of all patients were analyzed. Independent t-test was used to analyze normal distributed measurement data and chi square linear trend test was used to analyze the curative effect of different fibrinogen groups. Results: A total of 148 patients were included, the outcomes were worst when the patient′s fibrinogen was below 2 g/L or above 4 g/L before treatment, ineffective rate were both 50%. The fibrinogen was lowest when the treatment came to the third day. Normally, the patient′s prognosis was best when this value waved between 0.7 and 0.9 g/L, with a total effective rate between 73.9% and 83.3%. The fibrinogen value of the 7th day was a good indicator of the outcome, and Fib7 value was significant lower in patients of effective group than ineffective ones ((1.25±0.37)g/L vs (1.38±0.35) g/L, t=-0.27, P=0.04). Patients found a best recovery when Fib7 was below 1 g/L, and the higher the Fib7 value, the higher the inefficiency (χ²=7.55, P=0.01). Batroxobin showed safety during the treatment and found no complications. Conclusion The change of fibrinogen in the process of all-frequency sudden deafness is closely related to the curative effect.

Incidence of ankle fractures is relatively high.Malunited ankle fractures result from inappropriate nonoperative treatment and incorrect surgery as well.It is not difficult to diagnose a malunited ankle fracture when taking history,symptoms and imaging examinations into consideration.Orthopaedic surgeons used to do ankle fusion for this kind of patients as the effect of reconstructive surgery is not clear.This article summarizes the diagnostic and therapeutic methods for ankle fracture malunion based on the articles from 1976 to 2015.More detailed therapeutic methods for deformities involving lateral malleolus,tibiofibular syndesmosis,medial malleolus and posterior malleolus are also reviewed.

Objective To evaluate primary open reduction and wire-pin fixation for total dislocation of talus.Methods A retrospective study was conducted of the 12 patients who had been admitted into our hospital from October 2009 to December 2013 for total talar dislocation without fracture of the talar neck or body and had been available for complete follow-up.They were 10 males and 2 females.Their range of age was from 17 to 56 years (average,34.2 years).The total dislocation was open in 4 cases and close in 8.All of them underwent primary open reduction and wire-pin fixation.The functions of ankle joint and hindfoot were evaluated according to the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale.Results The follow-up time ranged from 22 to 72 months (average,35.6 months).Postoperatively,one case suffered skin necrosis and another superficial infection,both of whom responded to skin flap transferring after debridement.Traumatic arthritis of the talotibial or subtalar joint was found more or less in 7 cases,one of whom complained of severe pain but refused the subtalar arthrodesis advised.Their AOFAS scores at the final follow-up ranged from 42 to 96 points (average,72.2 points).Five cases developed avascular necrosis of the talus,but no talar collapse happened.Conclusions Primary open reduction and wire-pin fixation is effective for treatment of close total talar dislocation and open total dislocation of Gustilo type Ⅲ A or below.Although avascular necrosis and traumatic arthritis are common postoperative complications,satisfactory functions can be achieved if there is no collapse,severe pain or infection.