1.Progress of research on disease-modifying osteoarthritis drugs
SU Boya ; XU Yuansheng ; WANG Hua ; TANG Yuqing ; ZHANG Shiqun ; SONG Yan
Journal of China Pharmaceutical University 2021;52(2):253-260
Osteoarthritis (OA) is a common chronic joint disease,whose main pathological changes are the degeneration of articular cartilage and secondary bone hyperplasia.The limitation of current treatment methods including pain relief and joint replacement surgery is that they cannot fundamentally improve the damage of articular cartilage.The emergence of disease-modifying osteoarthritis drugs (DMOAD) may break the above limitations.They fundamentally inhibit the structural degeneration of articular cartilage by participating in the regulation of cartilage metabolic balance, regulation of subchondral bone remodeling,and control of local inflammation.Thereby,OA patients will get symptom improvement including pain relief and joint function restoration,delay the artificial joint replacement surgery, and improve the quality of life. There are still no DMOAD drugs widely available on the market worldwide.This paper reviews the background of R&D,the classification of mechanisms of action and research progress of representative drugs under different inechanisms so as to provide reference for future research.
2.Application and research progress of minimally invasive technique in pediatric cardiac surgery
Shiqun WU ; Shixiong WANG ; Zehui CAO ; Qiliang ZHANG ; Debin LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(7):428-435
With the continuous in-depth study of minimally invasive cardiac surgery(MICS), minimally invasive cardiac surgery in children has also been developed in this period, but there is still a certain gap compared with adults. Because of the large difference in body size and the low tolerance of surgery in children, minimally invasive cardiac surgery in children still has a short board on complex cardiac diseases. This article reviews several commonly used minimally invasive techniques: (1) small incision cardiac surgery; (2) thoracoscopic and robot-assisted cardiac surgery; (3) minimally invasive cardiopulmonary bypass(MiECC) and cardiac surgery to avoid cardiopulmonary bypass; (4) hybrid surgery and enhanced cardiac rehabilitation surgery(ERACS) in pediatric cardiac surgery and their application and research progress.
3.Open versus endovascular treatment of thoracoabdominal aortic aneurysms: parallel and controversia
Zehui CAO ; Qiliang ZHANG ; Shiqun WU ; Debin LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(10):634-640
Open surgery is currently the gold standard for the treatment of thoracoabdominal aortic aneurysm(TAAA), while endovascular aortic repair(EVAR) has also been widely carried out. Because it involves important branches supplying internal organs, the technical system for treating TAAA is particularly complex. However, with the advent of newer, low-cost, flexible stent systems, total endovascular repair techniques have become more feasible and attractive. For young and low-risk patients, the choice of open or endovascular treatment remains controversial. Despite the advantages of a minimally invasive procedure, EVAR carries a greater risk of spinal cord injury and may require secondary endovascular intervention to repair endoleak when its unique complication occurs, and the long-term durability after EVAR is not clear. This article reviews the open and endovascular treatment of TAAA, introduces the development of open surgery and endovascular repair, the advantages and disadvantages of various types of stents, and discusses how to select a more suitable surgical method for patients, providing clinicians with a treatment reference.
4.Mediating effect of children's effortful control between home environment and emotional behavioral problems among preschool children with malignant tumors
Xiaorong PAN ; Lin MO ; Qian LIU ; Xianqiao HUANG ; Shiqun ZHANG ; Xiaoli GUO
Chinese Journal of Behavioral Medicine and Brain Science 2020;29(7):629-634
Objective:To explore the mediating effect of children's effortful control on the relationship between home environment and children's behavioral emotional problems in preschool children with malignant tumors and to provide evidences for family intervention on behavioral emotional problems in children.Methods:Totally 353 preschool children with malignant tumors were investigated with family adaptation and cohesion evaluation scales II (FACES II), child behavior questionnaire-very short form(CBQ-VSF) and strengths and difficulties questionnaire (SDQ), AMOS 22.0 software was used to construct a structural equation model in data analysis and the Bootstrap method was used to test the mediation effect.Results:The scores of family adaptation and cohesion, children's effortful control, difficulty questionnaire were(51.63±12.41), (55.43±10.16), (3.23±0.80) and (13.75±3.66). The scores of dimensions including emotion, conduct, hyperactivity, peer problems, prosocial of difficulty questionnaire were(2.83±0.90), (2.73±0.96), (2.67±0.93), (2.76±0.85), (2.67±0.85), respectively. Family adaptation and cohesion were positively correlated with children's effortful control ( r=0.244, 0.289, P<0.01). Children's effortful control was negatively correlated with children's behavioral emotional problems ( r=-0.365--0.302, all P<0.05). Family adaptation and cohesion were negatively correlated with children's behavioral/emotional problems ( r=-0.323--0.124, r=-0.342--0.181, all P<0.05). The direct effect value was -0.469, indirect effect value was -0.102, accounting for 17.86% of the total effect. Conclusion:Children's effortful control exert a significant mediating effect on the relationship between home environment and children's behavioral/emotional problems in preschool children with malignant tumors, suggesting that medical staff should pay attention to the level of effortful control of preschool children with malignant tumors in order to take effective actions to reduce children's behavioral/emotional problems and improve social applicability.
5.Effect of glucagon-like peptide 1 receptor agonists on body fat redistribution and muscle mass in overweight and obese type 2 diabetic patients.
Yudan ZHANG ; Shiqun LIU ; Cunxia FAN ; Yanmei ZENG ; Jimin LI ; Cuihua XIE ; Yaoming XUE ; Meiping GUAN
Journal of Southern Medical University 2019;39(4):450-455
OBJECTIVE:
To investigate the effect of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on body fat redistribution and muscle mass in overweight/obese patients with type 2 diabetes (T2DM).
METHODS:
We retrospectively analyzed the data of 76 patients with body mass indexes (BMI)≥24 kg/m, who had an established diagnosis of T2DM in our department between December, 2014 and September, 2015. We divided these patients according to their BMI in overweight group (BMI of 24-27.9 kg/m, =14), obese group (BMI of 28-31.9 kg/m, =35) and severely obese group (BMI≥32 kg/m, =27). All the patients received treatment with GLP-1RAs (Exenatide or Liraglutide) for 3.0 to 29.0 weeks (mean 8.9 weeks), and their blood glucose, HbA1c and serum lipids were analyzed. For each patient, the fat and muscle masses were analyzed using a human body composition analyzer (JAWON-IOI353, Korea) before and after GLP-1RAs treatment.
RESULTS:
Treatment with GLP-1RAs significantly decreased BMI and visceral adiposity index (VAI) in all the patients in the 3 groups ( < 0.05). The treatment significantly decreased the body weight in the overweight group and obese group by 2.70 kg (0.60-4.95 kg) and 2.65 kg (1.45-6.40 kg), respectively ( < 0.05), and significantly decreased the waist-to-hip ratio (WHR) in the overweight group ( < 0.05). The obese and severely obese patients showed significantly decreased percentage body fat (including both subcutaneous and visceral fat) and increased muscle mass after the treatment ( < 0.05). Compared with those in the overweight group, the percentage body fat and VAI were significantly decreased in the obese group after the treatment ( < 0.05), and the percentage of subcutaneous fat reduced and the muscle ratio increased more obviously in the obese and severely obese patients ( < 0.05).
CONCLUSIONS
GLP-1RAs treatment can significantly lower BMI and improve body fat distribution in obese patients with T2DM, especially in patients with a greater BMI.
Adipose Tissue
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Body Mass Index
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Diabetes Mellitus, Type 2
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Glucagon-Like Peptide-1 Receptor
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Humans
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Hypoglycemic Agents
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Obesity
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Overweight
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Retrospective Studies
6.TBC1D15 deficiency protects against doxorubicin cardiotoxicity via inhibiting DNA-PKcs cytosolic retention and DNA damage.
Wenjun YU ; Haixia XU ; Zhe SUN ; Yuxin DU ; Shiqun SUN ; Miyesaier ABUDUREYIMU ; Mengjiao ZHANG ; Jun TAO ; Junbo GE ; Jun REN ; Yingmei ZHANG
Acta Pharmaceutica Sinica B 2023;13(12):4823-4839
Clinical application of doxorubicin (DOX) is heavily hindered by DOX cardiotoxicity. Several theories were postulated for DOX cardiotoxicity including DNA damage and DNA damage response (DDR), although the mechanism(s) involved remains to be elucidated. This study evaluated the potential role of TBC domain family member 15 (TBC1D15) in DOX cardiotoxicity. Tamoxifen-induced cardiac-specific Tbc1d15 knockout (Tbc1d15CKO) or Tbc1d15 knockin (Tbc1d15CKI) male mice were challenged with a single dose of DOX prior to cardiac assessment 1 week or 4 weeks following DOX challenge. Adenoviruses encoding TBC1D15 or containing shRNA targeting Tbc1d15 were used for Tbc1d15 overexpression or knockdown in isolated primary mouse cardiomyocytes. Our results revealed that DOX evoked upregulation of TBC1D15 with compromised myocardial function and overt mortality, the effects of which were ameliorated and accentuated by Tbc1d15 deletion and Tbc1d15 overexpression, respectively. DOX overtly evoked apoptotic cell death, the effect of which was alleviated and exacerbated by Tbc1d15 knockout and overexpression, respectively. Meanwhile, DOX provoked mitochondrial membrane potential collapse, oxidative stress and DNA damage, the effects of which were mitigated and exacerbated by Tbc1d15 knockdown and overexpression, respectively. Further scrutiny revealed that TBC1D15 fostered cytosolic accumulation of the cardinal DDR element DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Liquid chromatography-tandem mass spectrometry and co-immunoprecipitation denoted an interaction between TBC1D15 and DNA-PKcs at the segment 594-624 of TBC1D15. Moreover, overexpression of TBC1D15 mutant (∆594-624, deletion of segment 594-624) failed to elicit accentuation of DOX-induced cytosolic retention of DNA-PKcs, DNA damage and cardiomyocyte apoptosis by TBC1D15 wild type. However, Tbc1d15 deletion ameliorated DOX-induced cardiomyocyte contractile anomalies, apoptosis, mitochondrial anomalies, DNA damage and cytosolic DNA-PKcs accumulation, which were canceled off by DNA-PKcs inhibition or ATM activation. Taken together, our findings denoted a pivotal role for TBC1D15 in DOX-induced DNA damage, mitochondrial injury, and apoptosis possibly through binding with DNA-PKcs and thus gate-keeping its cytosolic retention, a route to accentuation of cardiac contractile dysfunction in DOX-induced cardiotoxicity.