1.Treatment of patellofemoral instability in adolescent by anatomical double-bundle medial patellofemoral ligament reconstruction with double suture anchor technique
Weihong ZHU ; You CHEN ; Qi TANG ; Lele LIAO ; Ding LI
Journal of Central South University(Medical Sciences) 2017;42(7):808-813
Objective:To explore the clinical outcomes of anatomical double-bundle medial patellofemoral ligament (MPFL) reconstruction with double suture anchor technique in treating patellofemoral instability in adolescent.Methods:Twenty-five young people with patellofemoral instability (25 knees) in our department from January 2013 to December 2014 were enrolled for this study.All patients were performed anatomical double-bundle MPFL reconstruction with arthroscopic-assisted suture anchors technique in the patella,and fixed in the femoral socket with absorbable interference screw.All patients are evaluated by different methods,including patient's satisfaction,patellar apprehension test,recurrent subluxation/dislocation,CT assessment of bone tunnel and patellar tilt angle.Lysholm scores,Tegner scores and Kujala scores were recorded at the final follow-up.Results:The mean follow-up was 24 (range 20-40) months.All cases were observed in negative patellar apprehension test.Infection,recurrent subluxation/dislocation and patellar fracture were not found at the last follow-up.CT results demonstrated that the tunnel position were good.The patellar tilt angle was decreased from 21.6°±2.3° to 10.5°±1.6° (P<0.05);the Lysholm scores was increased from 51.7±5.3 to 93.8±6.5 (P<0.05).Tegner scores was increased from 4.1± 1.1 to 5.5±0.6 (P<0.05).Kujala scores was increased from 53.5±6.4 to 94.6±4.3 (P<0.05).Conclusion:Arthroscopic-assisted anatomical double-bundle MPFL reconstruction with the suture anchors technique is a safe,minimal invasive and effective surgical option for treating patellofemoral instability in adolescent.
2.Effect of DA on insulin secretion fromrat pancreatic cells and possible mechanism
Xiangqin ZHONG ; Yaqin DING ; Lele REN ; Tao BAI ; Mengmeng LIU ; Yunfeng LIU ; Yi ZHANG
Chinese Pharmacological Bulletin 2017;33(5):653-656
Aim To investigate the effects of dopamine(DA)on insulin secretion from rat islets and the possible mechanism.Methods Pancreatic islets were obtained from the pancreatic of male SD rats by collagenase P digestion and histopaque-1077 density gradient separation.Insulin secretion experiment was used to observe the change of insulin release after DA treatments.As to study the potential mechanisms of the effects of DA,patch-clamp experiment and calcuim image technique were applied to test the depolarization-evoked Ca2+ currents,action potential duration and intracellular Ca2+ concentration.Results In 2.8 mmol·L-1 glucose,DA had no effect on insulin secretion;in 16.7 mmol·L-1 glucose,dopamine inhibited insulin secretion in a dose-dependent manner.DA inhibited the inward calcium current,shorten the action potential duration,and reduced the intracellular Ca2+ concentration.Conclusion DA inhibits insulin secretion maybe by decreasing the inward calcium current leading to shorten the action potential duration and reduce the intracellular Ca2+ concentration.
3.Application of pie-crusting the medial collateral ligament release in arthroscopic surgery for posterior horn of medial meniscus in knee joint
Weihong ZHU ; Qi TANG ; Lele LIAO ; Ding LI ; Yang YANG ; You CHEN
Journal of Central South University(Medical Sciences) 2017;42(9):1053-1057
Objective:To explore the effectiveness and safety of pie-crusting the medial collateral ligament release (MCL) in treating posterior horn of medial meniscus (PHMM) tear in tight medial tibiofemoral compartment of knee joint.Methods:Thirty-two consecutive patients with PHMM tear in tight medial tibiofemoral compartment of knee joint were admitted to our department from January,2013 to December,2014.All patients were performed pie-crusting the MCL release at its tibial insertion with 18-gauge intravenous needle.All patients were evaluated by valgus stress test and bilateral valgus stress radiograph at postoperative 1st day,4th week and 12th week.Visual Analogue Scales (VAS),Lysholm scores,Tegner scores and International Knee Documentation Committee (IKDC) scores were recorded at the 1st,3th,6th month follow-up,then follow-up every 6 months.Results:The mean follow-up was 28 (24-36) months.All cases were negative in valgus stress test.MCL rupture,femoral fracture,articular cartilage lesion and neurovascular injury were not found at the last follow-up.The median medial joint space width of affected side and unaffected side for valgus stress radiographs were 6.8 mm and 4.3 mm (P<0.05) at the 1st day,5.5 mm and 4.2 mm (P<0.05) in the 4th week and 4.8 mm and 4.3 mm (P>0.05) at the 12th week,respectively.VAS scores was changed from 4.5±1.5 preoperatively to 1.7±1.0 at the final follow-up (t=16.561,P<0.05).Lysholm scores was changed from 52.3±5.8 preoperatively to 93.2±6.3 at the final followup (t=-41.353,P<0.05).Tegner scores was changed from 4.1±1.1 preoperatively to 5.5±0.6 at the final follow-up (t=-18.792,P<0.05).IKDC scores was changed from 54.5±6.2 preoperative to 93.8±4.5 at the final follow-up (t=-38.253,P<0.05).Conclusion:Pie-crusting the medial collateral ligament release is a safe,minimal invasive and effective surgical option for posterior horn of medial meniscus tear in tight medial tibiofemoral compartment of knee joint.
4.Transient expression of bioactive recombinant human plasminogen activator in tobacco leaf.
Jiexue MA ; Lele WU ; Xiangzhen DING ; Zhiying LI ; Sheng WANG
Journal of Southern Medical University 2019;39(5):515-522
OBJECTIVE:
To assess the potential of transient expression of recombinant human plasminogen activator (rhPA) in plants as a cost-effective approach for recombinant rhPA production.
METHODS:
Tobacco mosaic virus-based expression vector pTMV rhPA-NSK and plant binary expression vector pJ Zera-rhPA were constructed by sequence synthesis and subcloning. The two vectors were inoculated on either or leaves agroinfiltration. The expression of recombinant rhPA in leaves was examined using Western blotting and ELISA, and the fibrinolysis activity of plant-produced rhPA was assessed by fibrin agarose plate assay (FAPA).
RESULTS:
Five to nine days after infiltration with an inoculum containing pTMV rhPA-NSK, necrosis appeared in the infiltrated area on the leaves of both plants, but intact recombinant rhPA was still present in the necrotic leaf tissues. The accumulation level of recombinant rhPA in infiltrated leaves was significantly higher than that in leaves ( < 0.05). The yield of recombinant rhPA was up to 0.6% of the total soluble protein (or about 60.0 μg per gram) in the fresh leaf biomass at 7 days post-inoculation. The plant-derived rhPA was bioactive to convert inactive plasminogen to active plasmin. No necrosis occurred in pJ Zera-rhPA-infiltrated leaves. The Zera-rhPA protein was partially cleaved between the site of Zera tag and rhPA sequence in both leaves. We speculated that the formation of Zera tags-induced particles in the plant cells was a dynamic process of progressive aggregation in which some of the soluble polypeptides were encapsulated in these particles.
CONCLUSIONS
Enzymatically active recombinant rhPA can be rapidly expressed in tobacco plants using the plant viral ampliconbased system, which offers a promising alternative for cost-effective production of recombinant rhPA.
Humans
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Plant Leaves
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Plants, Genetically Modified
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Plasminogen
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Plasminogen Activators
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metabolism
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Recombinant Proteins
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Tobacco
5.Trilogy of drug repurposing for developing cancer and chemotherapy-induced heart failure co-therapy agent.
Xin CHEN ; Xianggang MU ; Lele DING ; Xi WANG ; Fei MAO ; Jinlian WEI ; Qian LIU ; Yixiang XU ; Shuaishuai NI ; Lijun JIA ; Jian LI
Acta Pharmaceutica Sinica B 2024;14(2):729-750
Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.