2.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
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.
3.A Preliminary Study on the Efficacy of Percutaneous Coronary Intervention for Complex Left Main Stem Combined With Chronic Total Occlusion of the Right Coronary Artery
Zun HU ; Hu HU ; Yubo LONG ; Junshan LI ; Jingjing RONG ; Jin HE ; Changlu WANG ; Yu ZHANG ; Jianqiang PENG ; Hongwei PAN
Chinese Circulation Journal 2024;39(6):562-567
Objectives:to analyze the efficacy of percutaneous coronary intervention(PCI)for complex left main(LM)lesions combined with chronic total occlusion(CTO)of the right coronary artery. Methods:Ninety patients with complex left main lesions hospitalized in Hunan Provincial People's Hospital from January 2019 to December 2022 were consecutively included.According to the coronary angiographic vascular lesions,patients were divided into complex left main lesions combined with right coronary artery CTO(observation group,n=30)and complex left main lesions without right coronary artery CTO(control group,n=60).The baseline clinical data,intraoperative conditions,angiographic results,and postoperative follow-up results of the patients were analyzed and compared between the two groups. Results:Fifty-eight(64.4%)out of the 90 patients were male.There was no statistically significant difference between the two groups in terms of baseline clinical data(all P>0.05),left main lesion condition(P=1.000),left main calcification condition(P=0.249),and preoperative TIMI flow grading(P=1.000).In the comparison between observation group and the control group,intraoperative occurrence of no-reflow(3.3%vs.5.0%,P=1.000),hypotension(10.0%vs.8.3%,P=1.000),pericardial effusion(3.3%vs.0%,P=0.333),the percentage of intravascular ultrasound(IVUS)use(86.7%vs.90.0%,P=0.635),and the use of circulatory assist device(P=0.699),and the proportion of intraoperative coronary spinning(26.7%vs.21.7%,P=0.597)were all similar between the two groups.The median follow-up time was 14.50(11.83,15.85)months,and the differences in the incidence of major adverse cardiovascular events(MACE)such as recurrent angina,acute myocardial infarction,rebleeding,readmission for heart failure,and cardiac death(31.0%vs.32.1%,P=1.000)were not statistically significant between the observation group and the control group. Conclusions:PCI revascularization may be a viable approach for elderly patients with complex LM lesions with multiple underlying disease,and combined right coronary artery CTO,intolerance and reluctance to CABG.
4.Value of Hounsfield units measured by chest computed tomography for assessing bone density in the thoracolumbar segment of the thoracic spine
Congyang XUE ; Guangda SUN ; Nan WANG ; Xiyu LIU ; Gansheng HE ; Yubo WEI ; Zhipeng XI
Asian Spine Journal 2024;18(3):336-345
Methods:
This retrospective study analyzed patients who underwent chest CT and DXA at our hospital between August 2021 and August 2022. Thoracic thoracolumbar segment HU values, lumbar T-scores, and hip T-scores were computed for comparison, and thoracic thoracolumbar segment HU thresholds suggestive of potential bone density abnormalities were established using receiver operating characteristic curves.
Results:
In total, 470 patients (72.4% women; mean age, 65.5±12.3 years) were included in this study. DXA revealed that of the 470 patients, 90 (19%) had osteoporosis, 180 (38%) had reduced osteopenia, and 200 (43%) had normal bone mineral density (BMD). To differentiate osteoporosis from osteopenia, the HU threshold was established as 105.1 (sensitivity, 54.4%; specificity, 72.2%) for T11 and 85.7 (sensitivity, 69.4%; specificity, 61.1%) for T12. To differentiate between osteopenia and normal BMD, the HU threshold was 146.7 for T11 (sensitivity, 57.5%; specificity, 84.4%) and 135.7 for T12 (sensitivity, 59.5%; specificity, 80%).
Conclusions
This study supports the significance of HU values from chest CT for BMD assessment. Chest CT provides a new method for clinical opportunistic screening of osteoporosis. When the T11 HU is >146.7 or the T12 HU is >135.7, additional osteoporosis testing is not needed unless a vertebral fracture is detected. If the T11 HU is <105.1 or the T12 HU is <85.7, further DXA testing is strongly advised. In addition, vertebral HU values that fall faster than those of the T11 and L1 vertebrae may explain the high incidence of T12 vertebral fractures.
5.Design of variable stiffness insole based on diabetics plantar pressure during gait period
Fang WANG ; Tao YANG ; Yaoguang HE ; Zijun CAO ; Guoqing LIU ; Jun HU ; Jianguo ZHANG ; Yubo FAN
Chinese Journal of Rehabilitation Theory and Practice 2023;29(4):408-415
ObjectiveTo analyze the characteristics of plantar pressure of diabetic patients during gait cycle, and to design a offloading insole with variable stiffness. MethodsThe plantar pressure experiment was carried out and a database including 157 subjects was established. The differences of plantar pressure distribution were analyzed among diabetic patients with and without peripheral neuropathy, and healthy people. The insole pressure area was divided, and porous units were filled in different insole areas according to the pressure gradient. The fed-calf-insole finite element model of diabetic patients was constructed. The simulation analysis of different insole schemes was carried out under the conditions of push-off, footheel-strike and dynamic neutrality posture, and to explore the most reasonable insole stiffness design. ResultsCompared with the healthy group, the percentage of peak pressure and high pressure in the left and right heel areas of diabetic neuropathy patients showed a decreasing trend, in which the left peak pressure was significantly reduced by 11% (P = 0.026) and the percentage of high pressure was significantly reduced by 9.8% (P = 0.02). When the porous elements of 2.5 MPa and 1.9 MPa were used in the high pressure area of the insole metatarsal and high pressure area of the heel, the peak plantar pressure of footheel-strike, dynamic neutral and push-off was reduced by 42.4%, 27.4% and 26.4%, and the peak stress of the soft tissue was reduced by 49.8%, 43.6% and 25.1%, respectively. ConclusionThere is a higher risk of ulcer in the metatarsal region than in the heel region for diabetic patients. The variable stiffness insoles based on the optimization of plantar pressure and internal stress under multi-posture can effectively reduce the peak pressure of plantar and peak stress of soft tissue during walking, which provides a reference for the design of variable stiffness insoles.
6.Research progress in quality studies and antiviral effect of Qingyan Dropping Pills
Yuli WANG ; Mingrui ZHANG ; Hong ZHOU ; Xuehai ZHOU ; Yubo LI ; Huling LI ; Dandan SHANG ; Jinlei WANG ; He HUANG ; Yitao WANG ; Changxiao LIU
International Journal of Biomedical Engineering 2023;46(3):258-263
Qingyan Dropping Pills have the effects of relieving wind and heat, detoxifying, and promoting the pharynx. It is commonly used in traditional Chinese medicines to treat acute and chronic pharyngitis, as well as sore throats and dry throats caused by surgery. Recently, many studies have shown that Qingyan Dropping Pills have certain effects on bacteriostasis, anti-inflammatory, antioxidant, and antiviral activities. As the coronavirus disease 2019 (COVID-19) pandemic enters the post-epidemic era, the regular use of drugs for COVID-19 pandemic symptoms has become a new trend. Therefore, there is a good market prospect to explore and develop Chinese patent medicines with antiviral effects. A preliminary study on the herbal formula and material basis of Qingyan Dropping Pills revealed that they have potential for antiviral applications. In this paper, the research on the quality study and antiviral effect of Qingyan Dropping Pills was reviewed, and the research direction of its secondary development was discussed to provide ideas and references for the new use of old traditional Chinese medicines.
7.Research Progress on Changes and Interaction Mechanisms of Aging Articular Cartilage and Subchondral Bone
Pengling REN ; Haijun NIU ; He GONG ; Yubo FAN
Journal of Medical Biomechanics 2020;35(2):E253-E258
Aging is a major risk factor for diseases such as osteoarthritis (OA) and osteoporosis. However, they are not necessarily the results of aging, and the relationship between changes in bone and cartilage associated with aging and disease progression is still unclear. Studies have shown that the development and progression of OA is not a simple cartilage wear process, while its occurrence involves complex biological, chemical and mechanical changes in the tissues of the entire joint, especially the interaction of mechanics and biochemistry between cartilage and subchondral bone. Aging contributes to the occurrence and development of OA, but it is not the cause of OA. Changes associated with aging provide a foundation for OA to start, making joints more susceptible to other factors such as abnormal biomechanics and biochemistry, thereby promoting the development of OA. Therefore, understanding the basic mechanisms by which aging affects joint tissue may provide new targets for slowing or preventing the development of OA. In this paper, the related research progresses are reviewed from three aspects, i.e. age-related changes in cartilage and subchondral bone, mechanical conduction and angiogenesis.
8.Opinions on the corona virus disease 2019
Chongqing Medicine 2020;49(0):E021-E021
The corona virus disease 2019 (COVID-19) has drawn much attention lately. It has the characteristics of hidden infection sources, diverse transmission channels, great differences in clinical characteristics and limited diagnostic methods. Additionally, the population is generally susceptible, and no specific medicines are available now, therefore, the prevention and control of the disease faces greater challenges. Mastering the characteristics of it for comprehensive prevention and control is the main strategy against the disease. This article systematically expounded the latest understanding of the disease.
9.Effect of arterial flow on muscle atrophy.
Sili HE ; Wentao JIANG ; Ruiqi DONG ; Fei YAN ; Zhi XU ; Yubo FAN
Journal of Biomedical Engineering 2019;36(1):68-72
This study analyzed the inherent relation between arterial blood mass flow and muscle atrophy of residual limb to provide some necessary information and theoretical support for the clinical rehabilitation of lower limb amputees. Three-dimensional arterial model reconstruction was performed on both intact side and residual limb of a unilateral transfemoral amputee who is the subject. Then hemodynamic calculation was carried out to comparatively analyze the mass flow state at each arterial outlet of both lower extremities. The muscle atrophy ratio of residual limb was calculated by measuring the cross-sectional area of bilateral muscles. Based on the blood supply relationship, the correlation between arterial blood flow reduction ratio and muscle atrophy ratio was discussed. The results showed that the mass flow of superficial femoral arteries and lateral circumflex femoral arteries severely reduced. Meanwhile rectus femoris, vastus lateralis and vastus medialis which were fed by these arteries showed great atrophy too. On the contrary, the mass flow of deep femoral arteries and medial femoral circumflex arteries slightly reduced. Meanwhile gracilis, adductor longus, long head of biceps which were fed by these arteries showed mild atrophy too. These results indicated that there might be a positive and promotion correlation between the muscle atrophy ratio and the blood mass flow reduction ratio of residual limb during rehabilitation.
10.Advances in Predicting Fracture Risk Based on Hip Bone Properties
Yangyang CUI ; He GONG ; Xiali GUAN ; Aiqi HOU ; Yubo FAN
Journal of Medical Biomechanics 2019;34(5):E555-E559
With the increasing life span of the population and the increasing proportion of the elderly population, the elderly with osteoporosis are prone to hip fractures, which brings heavy economic burdens to the family and society. The progress in predicting hip fractures from the aspects of the proximal femur geometry, bone mineral density (BMD), fracture risk assessment tool (FRAX) and finite element analysis (FEA) based on computed tomography (CT) imaging was reviewed, in order to understand the influencing factors of fracture risk, improve the accuracy of hip fracture risk prediction for the elderly, detect the high fracture risk group at an early stage, and hence to reduce the occurrence of fractures with appropriate preventing measures, and provide theoretical references for the prevention and treatment of hip fractures.


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