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 investigate the application value of real-time ultrasound elastography in the treatment of fibroids radiofrequency ablation (RFA).Methods:Transvaginal ultrasonography,Real-time ultrasound elastography (RTE) and contrast-enhanced ultrasonography (CEUS) were performed on 34 patients with a total of 38 uterine fibroids who had the treatment of RFA before,1 hour and 3 months after the treatment of RFA.Detected the diameters of the lesions with the three methods of CEUS,RTE and 2D.Analysed the elastic image features and divided into groups,Measured the elastic strain ratio and compared the E/E0 in and between the group.The difference of lesion diameter between 2D,RTE and CEUS was compared.When the image of lesions showed blue and green was taken as the cirterion of incomplete ablation after RFA,conpared with CEUS,analysed the consistency of RTE and CEUS in evaluating the degree of ablation.Results:The lesions were divided into 3 groups according to the preoperative elastic image,with 8 (21.1％) in the blue group,20 (52.6％) in blue-based and 10 (26.3％) in green-based group.The difference was obvious in E/E0 between the 3 groups before RFA.There was no significant difference in E/E0 between 1 hour and 3 months after RFA (P ＞ 0.05).In each group the E/E0 of lesions were significantly increased at 1 hour and 3 months after the treatment of FRA,and the hardness of 3 months after RFA was harder than that of 1 hour after RFA(P＜0.05).The diameter measured by RTE was larger than that by 2D and CEUS before RFA(P＞0.05).The diameter measured by 2D was larger than that by RTE and CEUS at 1 hour after RFA (P＜0.05).No statistically significant difference was found in the lesion diameters among the three methods of2D,RTE and CEUS at 3 months after the treatment ofRFA (P＞0.05).CEUS and RTE had the basic consistent in the evaluation of lesions ablation degree at 1 hour (kappa=0.46) and 3 months (kappa=0.54) after the treatment of RFA.Conclusions:After RFA,the myoma gradually hardens,and RTE can reflect the change of the hardness,RTE can clearly show the boundary of uterine ftbroids especially after the treatment of RFA,can be used in the prediction of lesions ablation degree,so there was a certain application value of RTE used in RFA.

Objective:To investigate the safety and efficacy of ultrasound-guided transvaginal radiofrequency ablation in the treat ment of symptomatic uterine fibroid.Methods:39 patients with symptomatic uterine fibroid underwent transvaginal radiofrequency ablation therapy were selected Before treatment,the fibroid size and volume were measured using ultrasound.The fibroid-related symptom severity and quality of life were scored using uterine fibroid symptom and quality of life survey.The fibroid volume reduction rate,improvement in clinical symptom and quality of life,and ovarian function of patients were observed before treatment and at three,six,nine and 12 months after treatment.Results:The average operation time of radiofrequency ablation was 25 minutes.There was no clear intraand postoperative complication.Preoperative fibroid volume was 65.2± 49.3cm3,which was reduced to 32.2± 27.6 cm3,21.2± 18.2 cm3,15.3± 12.1 cm3 and 10.3± 9.8 cm3 at 3,6,9 and 12 months after treatment,respectively(P＜0.05).The symptom severity score (SSS) was 60.23± 13.2 before treatment,and gradually decreased to 42.2± 11.4,21.1± 10.2,15.4± 10.3 and 12.2± 9.7 at 3,6,9 and 12 months after treatment(P＜0.05).The quality of life (QOL) score gradually increased from 58.24± 16.24 before treatment to 70.3± 20.3,81.4± 8.6,86.3± 7.6 and 88.2± 9.1 at 3,6,9 and 12 months after treatment (P＜0.05).The levels of follicle stimulating hormone,luteinizing hormone and estradiol at 3,6,9 and 12 months after treatment showed no difference compared with these before treatment (P＞0.05).Conclusions:Ultrasound-guided transvaginal radiofrequency therapy was a minimally invasive,safe,and effective therapy for symptomatic uterine fibroid.

Objective To investigate the value of real-time elastography (RTE) in evaluating the characteristics and elasticity index (E-index) changes at different echo level of uterine fibroids before and after radiofrequency ablation (RFA).Methods A total of 43 patients (with 55 lesions) accepted RFA under ultrasound guidance in the Fourth Affiliated Hospital of Harbin Medical University from September 2013 to January 2015.All lesions were confirmed to have no perfusion through ultrasonography 1 h after RFA.The diameter of lesions ranging from 1.0 cm to 3.0 cm (with an average of 1.9± 1.2 cm).Preoperative lesions were classified into 3 groups for comparison based on ultrasonic echo type,group A:hypo echo (n=30);group B:hyper echo (n=12);and group C:mixed echo (n=12).Measured elasticity index E-index and internal uniformity (△ E) were analyzed.Comparisons of E value and△ E value were performed with repeated measures.RTE images features using x2 test of Fisher inspection comparison at the same time differences between groups.Results (1) Before RFA,RTE images showed blue alternating with green with green being dominated accounting for 70％ (21/30).50％ of RTE images in group B were completely covered in blue (6/12),while group C exhibited 53.9％ blue alternating with green with blue being dominated (7/13).There were statistically significant characteristics of RTE images among 3 groups (P ＜ 0.01).1 h after RFA,74.5％ lesions exhibited with blue being dominated (41/55).However,83.6％ (41/55) exhibited with blue 3 months after RFA.The difference in characteristics of RTE among 3 groups displayed no statistical significance (P ＞ 0.05).(2) The comparison of E-index revealed that before RFA,the E value was the lowest in the group A and the highest in the group B,while the group C was between them.There was significant difference between group A and B (F=19.25,P ＜ 0.01).E-index elevated in all the three groups and significant differences were found 1 h,3 month after RFA in comparison with that before RFA in the group A (F=386.75,294.68,both P ＜ 0.01).In addition,significant differences were also found 1 h,3 month after RFA in comparison with the treatment in the group B (F=29.98,45.88,both P ＜ 0.01).As for the group C,there were significant differences in E-index 1 h,3 month after RFA compared with before RFA (F=120.29,139.64,both P ＜ 0.01).3 months after RFA,E-index further elevated in the three groups and no significant inter-group difference was found at the same time points (P ＞ 0.05).(3)Before RFA,the△ E value was lower in group A and group B,while higher in the group C,group C presenting significant difference from group A and B (F=484.68,344.15,both P ＜ 0.01).At 1 h after RFA,△ E value was higher in group A and group C,while lower in group B,with group B showing significant difference from the low and mixed echo groups (F=53.58,94.79,both P ＜ 0.01).Significant difference was observed 1 h after surgery compared to before RFA in group A (F=154.35,P ＜ 0.01).Significant difference was also found 1 h after RFA compared to 3 month after RFA in group A (F=266.85,P ＜ 0.01).As for group C,there were also significant differences in△ E-index before treatment and 1 h after RFA compared with 3 month after RFA (F=103.24,76.53,both P ＜ 0.01).At 3 months after RFA,△ E-index decreased in all three groups.No significant inter-group difference was found at the same time points (all P ＞ 0.05).Conclusions RTE characteristics and the elasticity index are distinctly different among uterine fibroid at various echo intensities.RTE contributes to judging changes in hardness before and after RFA.The application of RTE for quantitative comparison of lesion hardness and uniformity can be served as the foundation for evaluating therapeutic effects of RFA.

Objective To study the anatomical characteristics of the medial sural vessels and the clinical effects of treatment for leg skin and soft tissue defect with free flaps.Methods 6 adult lower limbs were treated by latex perfusion and then observed the origin of the blood supply to gastrocnemius muscle,measure the number of the arteries and veins,the length and diameter of the medial sural vessels.From July 2009 to May 2013,15 clinical cases of serious skin and soft tissue defect were repaired by using free flap with medial sural vessels.The areas of wound surface were ranging from 13 cm × 7 cm-24 cm × 12 cm.10 of them were treated by anterolateral thigh flap,the other of them were treated by latissimus dorsi flap.The donor site were directly sutured or repaired by free skin graft.Results The blood supply of gastrocnemius mucle was multifocal.The medial sural arteries and lateral sural arteries were both origin from popliteal artery.The medial sural vessels include 1 artery and 2 veins.With the length 4-7 cm (average,5.4 cm),the arterial diameter of the origin 2.6-2.9 mm (average,2.7 mm) and the entry point 1.9-2.3 mm (average,2.1 mm),the vein diameter of the origin 1.8-2.2 mm (average,2.0 mm)and the entry point 2.7-3.4 mm(average,2.9 mm).Totally 15 cases flaps were survived with primary healing.The mean follow-up period was 16.5 months(range,11-21 months),The flaps had satisfactory appearance,soft texture,good elasticity and achieved protective sensation at the last followed-up.Conclusions The medial sural vessels are with constant anatomical position,deeply position,hardly damage,long pedicle.Thus,the medial sural vessels combine with free flap is an good choice for the reconstruction of leg skin and soft tissue defect.

Objective To study the anatomical characteristics of the medial sural vessels and the clinical effects of treatment for leg skin and soft tissue defect with free flaps.Methods 6 adult lower limbs were treated by latex perfusion and then observed the origin of the blood supply to gastrocnemius muscle,measure the number of the arteries and veins,the length and diameter of the medial sural vessels.From July 2009 to May 2013,15 clinical cases of serious skin and soft tissue defect were repaired by using free flap with medial sural vessels.The areas of wound surface were ranging from 13 cm × 7 cm-24 cm × 12 cm.10 of them were treated by anterolateral thigh flap,the other of them were treated by latissimus dorsi flap.The donor site were directly sutured or repaired by free skin graft.Results The blood supply of gastrocnemius mucle was multifocal.The medial sural arteries and lateral sural arteries were both origin from popliteal artery.The medial sural vessels include 1 artery and 2 veins.With the length 4-7 cm (average,5.4 cm),the arterial diameter of the origin 2.6-2.9 mm (average,2.7 mm) and the entry point 1.9-2.3 mm (average,2.1 mm),the vein diameter of the origin 1.8-2.2 mm (average,2.0 mm)and the entry point 2.7-3.4 mm(average,2.9 mm).Totally 15 cases flaps were survived with primary healing.The mean follow-up period was 16.5 months(range,11-21 months),The flaps had satisfactory appearance,soft texture,good elasticity and achieved protective sensation at the last followed-up.Conclusions The medial sural vessels are with constant anatomical position,deeply position,hardly damage,long pedicle.Thus,the medial sural vessels combine with free flap is an good choice for the reconstruction of leg skin and soft tissue defect.

Objective To investigate the effect of lung protective and ventilatory management strategies for brain death donors on eligibility and availability of lungs for transplantation.Method The clinical data of two brain dead patients who accepted lung protective ventilatory management strategies from Feb.2015 to Mar.2015 were retrospectively analyzed.Two cases of brain-dead patients,due to severe cerebral trauma,accepted the aggressive lung protective ventilatory management strategies and airway management for 9 days and 4 days respectively.PaO2/FiO2,chest imaging manifestations,surface of the lung harvested and pulmonary rehabilitation of recipients after operation were observed.Result Two lung recipients were liberated from ventilation and pulmonary function improved significantly after double lung transplantation.Conclusion The application of lung protective ventilatory strategies in potential organ donors with brain death can increase the number of eligible and harvested lungs.

Objective To explore the effects of mangiterin on behaviors and brain-derived neurotrophic factor(BDNF) of hippocampus in chronic stress depression mice.Methods 60 male mice were randomly divided into normol control group,model group,fluoxetin control group and mangiterin groups (low,medium and high dose),10 mice in each group.All mice except normal control group were singly housed and subjected to chronic stress-induced depression model for 21 consecutive days.The behaviors of mice were detected by open-field test and tail-suspension test.The expression of BDNF in the hippocampus were assessed using western blot.Results Compared with the normal group,mice exposed chronic stress showed decreased body weight((5.33 ±1.20) g),crossing lines (102 ± 18) and distances ((3425 ± 112) mm) notably decreased in open-field behavior test.The duration of immobility during tail-suspension was increased significantly.BDNF expression in the hippocampus(0.45 ± 0.03) was downregulated significantly(P＜ 0.01),while it was upregulated in the groups of mangiterin(P ＜ 0.01).Mangiterin group in high dose had the similar effects to fluoxetin group(P ＞ 0.05).Conclusion Mangiterin can ameliorate behavior impairment of chronic stress induced-depression mice and it may be related to the upregulation of BDNF expression in the hippocampus.

BACKGROUND: Bone morphogenetic protein (BMP) is a protein possesses potential activity, which can increase and enhance its activity when the bone issues are damaged, so it can be used to repair the bone defects when combined with carrier. However,there are few reports concerning it as gene therapy.OBJECTIVE: To construct recombinant retroviral vector expressing human BMP2 gene and to discuss its biological function in ostecblasts.METHODS: BMP2-specific primers were designed and synthesized according gene sequence of human BMP2 gene in Genbank, then BMP2 gena was amplified by Hifi PCR, which was recombined with cloning vector pDNR-CMV homologousiy into pDNR-CMV-BMP2 plasmid identified by BMP2 PCR and enzyme digestion of Sail and EcoRI as well as gene sequencing; recombinant plasmid pDNR-CMV-BMP2 and retroviral plasmid pLP-LNCX were recombined homologously in IoxP sites into pLP-LNCX-BMP2 plasmid transferred into packing cell line PT67 and the supernatant was collected to assay viral titre. Human osteoblast was infected with retrovirus, then the growth of cells were observed by MTT, and the expression of BMP2 protein was detected by Western blotting at 48 hours transfectionRESULTS AND CONCLUSION: Digestion, BMP2 PCR and gene sequencing of pDNR-CMV-BMP2 were coincided with expected. After transfected with plasmid pLP-LNCX-BMP2, PT67 cells could be screened with G418 only to get stably integrated in BMP2, of whose supemanant viral titra amounted to 5×10~8 pfu/mL. MTT assay showed that there had no evident difference in cellular inhibition between the normal and retrovirus groups at 72 hours after transfection (P ＞ 0.05); Western blotting showed that the BMP2 was strong expressed at 48 hours after transfection. It demonstrated that BMP2 gene was successful cloned and its retrovirus vector was constructed.

In the present study, the expression, purification, toxicity detection and the adjuvant effect of the heat-labile enterotoxin in non-toxic mutant mLT63 of Escherichia coli were investigated, in which the inductive expression was performed under optimal condition for inductive expression and the toxicity of the products obtained from inductive expression were tested for toxicity after being purified and concentrated with affinity chromatography. BALB/c mice were immunized orally with the mutant mLT63 associated with Helicobacter pylori (Hp) subunit vaccine UreB, Omp11. After immunization, the specific antibody levels in serum, extract from gastric tissues and fecal extract were determind by means of ELISA assay and the results were subjected to statistical analysis. It was demonstrated that the mutant mLT63 of heat-labile entrotoxin of E.coli constructed in our laboratory devoided of any toxic effect as revealed by the rabbit ileal loop assay, but its adjuvant effect could be demonstrated in the associated immunization of mice with Hp subunit vaccine UreB and Omp11.