1.Three new gallic acid sugaresters from Elaeagnus oxycarpa  Schlechtend leaves and their antioxidant and tyrosinase inhibitory activities
		                			
		                			Feng-zhen CUI ; Jian-hong FU ; Guo-yan XU ; AYEKABAYR·EKBAYR ; Chang-da MA
Acta Pharmaceutica Sinica 2025;60(2):434-441
		                        		
		                        			
		                        			 Five compounds were isolated and purified from the water extract of 
		                        		
		                        	
2.Early clinical outcomes of the domestic KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation: A single-arm, prospective, single-group target value clinical trial
Tong TAN ; Bingqi FU ; Peijian WEI ; Nianjin XIE ; Haozhong LIU ; Xiaoyi LI ; Shengwen WANG ; Haijiang GUO ; Jian LIU ; Jimei CHEN ; Jian ZHUANG ; Huiming GUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(02):269-275
		                        		
		                        			
		                        			Objective  To summarize and analyze the preliminary clinical outcomes of the KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation (DMR). Methods  This study was a single-arm, prospective, single-group target value clinical trial that enrolled patients who underwent the KokaclipTM transcatheter edge-to-edge repair (TEER) system for DMR in the Department of Heart Surgery of Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute from June 2022 to January 2023. Differences in the grade of mitral regurgitation (MR) during the perioperative and follow-up periods were compared, and the incidences of adverse events such as all-cause death, thoracotomy conversion, reoperation, and severe recurrence of MR during the study period were investigated. Results  The enrolled patient population consisted of 14 (50.0%) females with a mean age of 70.9±5.4 years. Twenty-eight (100.0%) patients were preoperatively diagnosed with typeⅡ DMR, with a prolapse width of 12.5 (11.0, 16.1) mm, a degree of regurgitation 4+ leading to pulmonary venous reflux, and a New York Heart Association cardiac function class≥Ⅲ. All patients completed the TEER procedure successfully, with immediate postoperative improvement of MR to 0, 1+, and 2+ grade in 2 (7.1%), 21 (75.0%), and 5 (17.9%) patients, respectively. Mitral valve gradient was 2.5 (2.0, 3.0) mm Hg. Deaths, thoracotomy conversion, or device complications such as unileaflet clamping, clip dislodgement, or leaflet injury were negative. Twenty-eight (100.0%) patients completed at least 3-month postoperative follow-up with a median follow-up time of 5.9 (3.6, 6.8) months, during which patients had a mean MR grade of 1.0+ (1.0+, 2.0+) grade and a significant improvement from preoperative values (P<0.001). There was no recurrence of ≥3+ regurgitation, pulmonary venous reflux, reoperation, new-onset mitral stenosis, or major adverse cardiovascular events. Twenty-two (78.6%) patients’ cardiac function improved to classⅠorⅡ. Conclusion  The domestic KokaclipTM TEER system has shown excellent preliminary clinical results in selected DMR patients with a high safety profile and significant improvement in MR. Additional large sample volume, prospective, multicenter studies, and long-term follow-up are expected to validate the effectiveness of this system in the future.
		                        		
		                        		
		                        		
		                        	
3.Stability study of umbilical cord mesenchymal stem cells formulation in large-scale production
Wang-long CHU ; Tong-jing LI ; Yan SHANGGUAN ; Fang-tao HE ; Jian-fu WU ; Xiu-ping ZENG ; Tao GUO ; Qing-fang WANG ; Fen ZHANG ; Zhen-zhong ZHONG ; Xiao LIANG ; Jun-yuan HU ; Mu-yun LIU
Acta Pharmaceutica Sinica 2024;59(3):743-750
		                        		
		                        			
		                        			 Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability. 
		                        		
		                        		
		                        		
		                        	
4.Efficacy of arthroscopic superior capsular reconstruction using composite autologous patch graft combined with tenodesis of the long head of the biceps tendon in the treatment of irreparable massive rotator cuff tears
Yuncong JI ; Jian XU ; Yunkang KANG ; Wenzhi BI ; Wei MA ; Dongqiang YANG ; Honglin CUI ; Pengfei FU ; Yijun LIU ; Jinxiang TIAN ; Biao GUO
Chinese Journal of Trauma 2024;40(3):236-242
		                        		
		                        			
		                        			Objective:To investigate the efficacy of arthroscopic superior capsular reconstruction using composite autologous patch graft combined with tenodesis of the long head of the biceps tendon in the treatment of irreparable massive rotator cuff tears (IMRCT).Methods:A retrospective case series study was performed on 11 IMRCT patients who were admitted to Affiliated Fuyang Hospital of Bengbu Medical University (Fuyang People′s Hospital) from May 2020 to June 2022, including 7 males and 4 females, aged 54-74 years [(62.6±7.3)years]. All the patients were treated with arthroscopic superior capsular reconstruction using composite patch graft combined with tenodesis of the long head of the biceps tendon. The Visual Analogue Scale (VAS), Acromiohumeral Distance (AHD), Constant-Murley score and University of California Los Angeles (UCLA) score and active range of motion of the shoulder joint before, at 6 months after surgery and at the last follow-up were compared. At the last follow-up, the integrity of reconstructed superior capsule and the long head of the biceps tendon was evaluated using MRI of the shoulder joint. Postoperative complications were observed.Results:All the patients were followed up for 13-39 months [16(13, 36)months]. The VAS score, AHD, Constant-Murley score, and UCLA score were 2(2, 3)points, (9.1±1.1)mm, (56.1±5.4)points, and (19.7±2.8)points respectively at 6 months after surgery, which were all significantly improved from those before surgery [6(5, 7)points, (5.1±1.2)mm, (37.9±2.2)points, and (11.8±1.2)points] ( P<0.05). The VAS score, AHD, Constant-Murley score, and UCLA score were 0(0, 1)points, (8.4±0.9)mm, (83.6±3.8)points, and (28.2±2.3)points respectively at the last follow-up, which were all significantly improved from those before surgery ( P<0.05). At the last follow-up, the VAS score or AHD were not significantly improved from those at 6 months after surgery ( P>0.05); Constant-Murley score and UCLA score were both significantly improved from those at 6 months after surgery ( P<0.05). At 6 months after surgery, shoulder active ranges of motion in forward flexion, abduction and external rotation were (134.6±13.5)°, (124.6±18.6)° and 45(40, 50)° respectively, which were all significantly improved compared with those before surgery [(63.2±36.1)°, (65.0±23.1)°, and [30(20, 40)°] ( P<0.05). At the last follow-up, shoulder active ranges of motion in forward flexion, abduction and external rotation were (144.1±12.6)°, (139.6±15.4)° and 60(45, 65)° respectively, which were all significantly improved compared with those before surgery ( P<0.05). There were no significant differences in active range of motion of the shoulder in forward flexion, abduction and external rotation between 6 months after surgery and the last follow-up ( P>0.05). At the last follow-up, MRI revealed integrity of the reconstructed superior joint capsule and the long head of the biceps tendon in 10 patients. One patient developed resorption of the greater tuberosity and 1 showed a partial tear of the supraspinatus tendon at 1 year after surgery. Conclusion:Arthroscopic superior capsular reconstruction using composite autologous patch graft combined with tenodesis of the long head of the biceps tendon can relieve shoulder pain, decrease upward displacement of the humerus head, improve the function and range of motion of the shoulder joint, and reduce complications in the treatment of IMRCT.
		                        		
		                        		
		                        		
		                        	
5.Clinical outcomes and bone resection analysis of unilateral double-channel endoscopic technique in treating lumbar disc herniation
Qing-Yun XIN ; Wen-Zheng LI ; Jun-Jian HAN ; Qi-Tao LIU ; Chao FENG ; Xiu-Sheng GUO ; Jie WEI ; Jie-Fu SONG ; De-An QIN ; Deng-Jun ZHANG
China Journal of Orthopaedics and Traumatology 2024;37(3):222-227
		                        		
		                        			
		                        			Objective To explore clinical outcomes and bone resection of interlaminar fenestration decompression and u-nilateral biportal endoscopic(UBE)technique in treating lumbar disc herniation(LDH).Methods A retrospective study was performed on 105 patients with single-level LDH treated from December 2019 to December 2021.Fifty-four patients in UBE group,including 32 males and 22 females,aged from 18 to 50 years old with an average of(38.7±9.3)years old,were treated with UBE,29 patients withL4.5and 25 patients with L5S1.There were 51 patients in small fenestration group,including 27 males and 24 females,aged from 18 to 50 years old with an average of(39.9±10.0)years old,were treated with small fenestra-tion,25 patients with L4.5 and 26 patients with L5S1.Perioperative indexes,such as operation time,postoperative time of getting out of bed and hospital stay were observed and compared between two groups.Visual analogue scale(VAS)and Oswestry dis-ability index(ODI)were compared between two groups before operation and 1,3,6 and 12 months after operation,respective-ly;and modified MacNab evaluation criteria was used to evaluate clinical efficacy.Amount of bone resection and retention rate of inferior articular process laminoid complex were compared between two groups.Results All 105 patients were successfully completed operation.Both of two groups were followed up from 6 to 12 months with an average of(10.69±2.49)months.Oper-ation time,postoperative time of getting out of bed and hospital stay were(58.20±5.54)min,(2.40±0.57)dand(3.80±0.61)d in UBE group,and(62.90±7.14)min,(4.40±0.64)d and(4.40±0.64)d in small fenestrum group,respectively;and had sta-tistically difference between two groups(P<0.05).Postoperative VAS of low back and leg pain and ODI in both groups were significantly lower than those before surgery(P<0.05).VAS of lumbar pain in UBE group(1.37±0.49)score was lower than that of small fenestration group(2.45±0.64)score,and had statistically difference(t=9.745,P<0.05).Postoperative ODI in UBE group at 1 and 3 months were(28.54±3.31)%and(22.87±3.23)%,respectively,which were lower than those in small fenestra group(36.31±9.08)%and(29.90±8.36)%,and the difference was statistically significant(P<0.05).There were no significant difference in VAS and ODI between two groups at other time points(P>0.05).According to the modified MacNab evaluation criteria at the latest follow-up,49 patients got excellent result,3 good,and 2 fair in UBE group.In small fenestration group,35 patients got excellent,12 good,and 4 fair.In UBE group,amount of bone resection on L4,5 segment was(0.45±0.08)cm3 and(0.31±0.08)cm3 on the segment of L5S1.In small fenestration group,amount of bone resection on L4.5 segment was(0.57±0.07)cm3 and(0.49±0.04)cm3 on the segment of L5S1,and amount of bone resection of lower articular process laminar complex on the same segment in UBE group was less than that in small fenestration group(P<0.05).In UBE group,retention rate of laminoid complex on L4,5 segment was(0.73±0.04)and L5S1 segment was(0.83±0.03),whileL4,5segment was(0.68± 0.06)and L5S1 segment was(0.74±0.04)in small fenestration group,the lower articular process laminar complex retention rate in UBE group was higher than that in small fenestration group(P<0.05).Conclusion Both unilateral double-channel endoscopy and small fenestration of laminae could achieve good clinical results in treating LDH,but UBE has advantages of less trauma,higher eficiency,faster postoperative recovery and less damage to bone structure.
		                        		
		                        		
		                        		
		                        	
6.Effect and complication among different kinds of spinal endoscopic surgery for lumbar disc herniation
Kang CHEN ; Fu-Guo YANG ; Yuan-Chao LUO ; Ren-Jian HE
China Journal of Orthopaedics and Traumatology 2024;37(3):228-234
		                        		
		                        			
		                        			Objective To compare clinical efficacy and complication rate of percutaneous endoscopic transforaminal discec-tomy(PETD),percutaneous endoscopic interlaminar discectomy(PEID)and unilateral biportal endoscopic(UBE)in treating single-segment lumbar disc herniation(LDH).Methods From October 2019 to August 2021,121 LDH patients with single-segment treated by spinal endoscopy were retrospectively analyzed and divided into three groups.In PETD group,there were 48 patients,including 19 males and 29 females,aged from 18 to 72 years old with an average of(44.0±13.9)years old;3 patients with L3,4 segments,27 patients with L4,5 segments,and 18 patients with L5S1 segments.In PEID group,there were 43 patients,including 23 males and 20 females,aged from 20 to 69 years old with an average of(40.1±12.1)years old;1 patient with L3.4 segments,15 patients with L4.5 segments,and 27 patients with L5S1 segments.In UBE group,there were 30 patients,including 12 males and 18 females,agedfrom29 to 72 years old with an average of(41.2±15.0)years old;1 patient with L3,4 segments,18 patients with L4,5 segments,and 11 patients with L5S1 segments.Operation time,blood loss,fluoroscopy times and complica-tions among three groups were observed and compared.Before opertaion,3 months after operation and at the latest follow-up,visual analogue scale(VAS)was used to evaluate low back pain and lower extremity pain,Oswestry disfunction index(ODI)was used to evaluate lumbar function,and modified MacNab was used to evaluate clinical efficacy at the latest follow-up.Re-sults All patients were performed endoscopic spinal surgery completely and were followed up for at least 12 months.One patient occurred dural sac rupture both in PETD and PEID group,and dural sac rupture was small,and there was no obvious discomfort after operation.Two patients were occurred intraoperative rupture of dural sac in UBE group.One patient was occurred cere-brospinal fluid leakage after operation,and was improved after rest in supine position and fluid rehydration.One patient without no significant postoperative discomfort.(1)There were no significant difference in operating time,blood loss and hospital stay between PETD and PEID group(P>0.05),while UBE group was higher than those of PETD and PEID group(P<0.05).There was no statistical significance in fluoroscopy times between PEID and UBE group(P>0.05),but PETD group was higher than that of PEID and UBE group(P<0.05).(2)VAS of low back pain at 3 months after operation in UBE group was higher than that in PETD and PEID group(P<0.05),but there was no significant difference between PETD and PEID group(P>0.05).At the latest follow-up,there was no significant difference in VAS of low back pain among three groups(P>0.05).(3)Lower ex-tremity pain of VAS and ODI among 3 groups after operation were significantly improved at all time points compared with those before opertaion(P<0.05),and there were no statistical significance between groups(P>0.05),and there were no statistical significance in interaction between different time points and operation groups(P>0.05).(4)At the latest follow-up,according to the modified MacNab standard,the results of PETD group were excellent in 27 patients,good in 16 patients,moderate in 4 patients,poor in 1 patient;in PEID group,27 patients got excellent result,12 good,3 moderate,and 1 poor;in UBE group,16 patients got excellent,10 good,2 moderate,and 2 poor.There was no significant difference among three groups(x2=0.308,P>0.05).Recurrence of lumbar disc herniation occurred in 1 patient among each three groups,symptoms were improved in 2 pa-tients after symptomatic treatment,and 1 patient was treated in other hospitals.Conclusion PETD,PEID and UBE techniques could achieve good early clinical effects in treating lumbar disc herniation with similar complication rates.Both of PETD and PEID are single-channel minimally invasive surgery,with mild intraoperative tissue damage and quick postoperative recovery;while intraoperative fluoroscopy of PETD was relatively more frequent,and PEID was more suitable for L5S1 segment;UBE is a two-channel surgery,in which the intraoperative soft tissue damage is more severe,but exposure is broad,which is more suit-able for complex cases.
		                        		
		                        		
		                        		
		                        	
7.Two kinds of percutaneous endoscopic lumbar decompression in the treatment of single level lumbar lateral recess stenosis
Kang CHEN ; Yuan-Chao LUO ; Fu-Guo YANG ; Ren-Jian HE
China Journal of Orthopaedics and Traumatology 2024;37(4):338-344
		                        		
		                        			
		                        			Objective To prospectively compare the clinical efficacy and radiographic outcomes between interlaminar per-cutaneous endoscopic lumbar decompression(IL-PELD)and transforaminar percutaneous endoscopic lumbar decompression(TF-PELD)in the treatment of single-segment lumbar lateral recess stenosis.Methods From April 2018 to July 2021,85 pa-tients with single-segment lumbar lateral recess stenosis underment percutaneous endoscopic lumbar decompression.There were 44 males and 41 females,aged from 49 to 81 years old with an average of(65.5±8.3)years old,duration of lumbar lateral re-cess stenosis ranging from 3 to 83 months with an average of(26.7±16.5)months.They were divided into IL-PELD group and TF-PELD group according to the different operation methods.There were 47 patients in the IL-PELD group,including 28 males and 19 females aged from 50 to 80 yeaes old with an average age was(66.7±9.3)years old.The disease duration ranged from 3 to 65 months with an average of(25.7±15.0)months.There were 38 patients in the TF-PELD group,including 16 males and 22 females,aged from 51 to 78 years old with an average of(64.1±7.6)years old.The disease duration ranged from 4 to 73 months with an average of(27.9±18.3)months The operation time,intraoperative blood loss,intraoperative fluoroscopy,hospi-talization day and complications of the two groups were recorded.Visual analogue scale(VAS)to evaluate low back pain and lower limb pain,Oswestry disability index(ODI)to evaluate lumbar function in preoperative and postoperative period(1 month,6 months and last follow-up)were recorded.the sagittal diameter of the lateral recess of the responsible intervertebral space in preoperative and 1 week after the operation were recorded.Results The operation was successfully completed in both groups without serious complications such as vascular injury,dural sac tear and nerve injury.The operation time in IL-PED group(69.3±19.3)min was significantly longer than that in TF-PELD group(57.5±14.5)min(P<0.05).There was no significant dif-ference in the intraoperative blood loss between the two groups(P>0.05).The number of intraoperative fluoroscopy in TF-PELD group(8.8±2.6)times was significantly higher than that in IL-PED group(4.8±1.2)times(P<0.05).The hospitalization days of the two groups were not statistically significant(P>0.05).VAS for low back and lower extremity pain and ODI were(5.1±2.2),(6.9±1.3)scores and(71.4±12.6)%in IL-PELD group,and(4.7±1.8),(6.9±1.3)scores and(68.4±13.9)%in TF-PELD group.In the IL-PELD group,the VAS of low back pain was(2.4±1.5),(1.6±0.8),(1.4±0.9)scores,and the VAS of lower extremity pain was(3.0±1.2),(1.6±0.7),(1.5±1.0)scores,ODI was(32.6±11.9)%,(17.4±6.5)%,(19.3±9.3)%;In TF-PELD group,the VAS of low back pain was(2.6±1.4),(1.5±0.6),(1.4±1.0)scores,and the VAS of lower extremity pain was(2.8±1.2),(1.6±0.6),(1.5±1.2)scores,The ODI was(32.0±11.2)%,(15.0±6.1)%,and(20.0±11.3)%.The VAS and ODI of the two groups at each time point after operation were significantly improved compared with those before operation(P<0.05),but there was no statistically significant difference between the groups(P>0.05),and there was no statistically sig-nificant difference in the interaction between different time points and groups(P>0.05).At 1 week after operation,the sagittal diameter of lateral recess in both groups was significantly increased compared with that before operation(P<0.05),but there was no significant difference between the two groups at each time point(P>0.05).According to the modified Macnab criteria,IL-PELD group was rated as excellent in 24 cases,good in 19 cases and fair in 4 cases.In TF-PELD group the results were ex-cellent in 19 cases,good in 15 cases,fair in 3 cases and poor in 1 case.There was no significant difference between the two groups(P>0.05).Conclusion IL-PELD and TF-PELD can expand the lateral recess in the treatment of single level lumbar lateral recess stenosis,and have achieved good clinical effects.
		                        		
		                        		
		                        		
		                        	
8.Multi-parametric MRI radiomics-based nomogram model for predicting the lymphovascular space invasion of endometrial endometrioid adenocarcinoma
Xiao-Liang MA ; Min-Hua SHEN ; Feng-Hua MA ; Guo-Fu ZHANG ; Jian-Jun ZHOU ; Meng-Su ZENG ; Jin-Wei QIANG
Fudan University Journal of Medical Sciences 2024;51(3):306-314,322
		                        		
		                        			
		                        			Objective To investigate the feasibility and value of a multi-parametric MRI radiomics-based nomogram model for pretreatment predicting the lymphovascular space invasion(LVSI)of endometrial endometrioid adenocarcinoma(EEA).Methods Preoperative MRI and baseline clinical characteristics of 205 EEA patients were prospectively collected from Oct 2020 to Jan 2022 in the Obstetrics and Gynecology Hospital,Fudan University,and randomly divided into training set(n=123)and validation set(n=82)in a 6∶4 ratio.The whole-tumor region of interest was manually drawn on T2-weighted imaging,diffusion-weighted imaging(apparent diffusion coefficient),and dynamic contrast-enhanced MRI,respectively,for radiomics features extraction.In the training set,univariate and multivariate Logistic regression analysis were used to select independent clinical predictors of LVSI(+)and construct the clinical model.The least absolute shrinkage and selection operator(LASSO)regression and multivariate Logistic regression analysis were used to select optimal radiomics features to form a radiomics signature.A combined nomogram model was established by integrating clinical independent predictors and the radiomics signature,and validated in the validation set.The predicting performance and clinical net benefit were evaluated by using the area under the receiver operating characteristic curve(AUC)and clinical decision curve analysis,respectively.Results Of the 205 EEA cases,144 cases were LVSI(-)and 61 cases were LVSI(+).Menopausal status,CA125,and CA199 were independent clinical predictors for the LVSI(+),and contributing to a clinical model with AUCs of 0.714(training)and 0.731(validation).From 8 240 extracted radiomics features,five were selected to construct a MRI radiomics signature after de-redundancy and LASSO dimensionality reduction,yielding AUCs of 0.860(training)and 0.759(validation).The combined nomogram model showed AUCs of 0.887(training)and 0.807(validation),outperforming others and achieving maximum clinical benefit in a large range of threshold probability in both training and validation sets.Conclusion The multi-parametric MRI-based nomogram model has the potential for pretreatment predicting the LVSI status of EEA,providing valuable information for clinical management decision-making and improving patient's clinical benefits.
		                        		
		                        		
		                        		
		                        	
9.The role and mechanism of miR-34a/SIRT1 in intensive care unit acquired weakness
Zheng-Xiao LIN ; Zhao-Xia XU ; Juan CHEN ; Jian HU ; Guo-Yun ZHU ; Zhong-Li ZHU ; Jian FENG ; Fu-Xiang LI
Medical Journal of Chinese People's Liberation Army 2024;49(7):796-803
		                        		
		                        			
		                        			Objective To investigate the role and underlying mechanisms of miR-34a/SIRT1 in intensive care unit acquired weakness(ICU-AW).Methods(1)C2C12 mouse skeletal muscle cells were induced to differentiate into myotubes,and were divided into two groups:model group[ICU-AW group,treated with lipopolysaccharides(LPS)for 12 hours]and normal control group(treated with the same amount of sterile water for 12 hours).Western blotting was used to detect the protein expression level of Muscle ring finger 1(MuRF-1),atrophy gene 1(Atrogin-1)and Sirtuin-1(SIRT1).RT-qPCR was used to assess the mRNA expression level of microRNA-34a(miR-34a),MuRF-1,Atrogin-1 and SIRT1,and light microscope was used to observe the growth and differentiation of C2C12 skeletal muscle cells in each group.(2)ICU-AW cells were further subdivided into control group(treated with siRNA transfection agent intervention),Scra siRNA group(treated with transfection agent and non-specific siRNA),miR-34a siRNA group(treated with transfection agent and specific siRNA intervention),vehicle group(treated with agonist solvent dimethyl sulfoxide)and SRT1720 group(treated with SIRT1 agonist SRT1720).Western blotting was used to detect the protein expression level of SIRT1,Atrogin-1 and MuRF-1 in each group.RT-qPCR was used to detect the miR-34a and the mRNA expression level of SIRT1,Atrogin-1 and MuRF-1 in each group.(3)In addition,another group of ICU-AW cells were divided into control group(treated with siRNA transfection),miR-34a siRNA group(treated with transfection agent and specific siRNA intervention),miR-34a siRNA+vehicle group(treated with transfection agent,specific siRNA and Dimethyl sulfoxide intervention)and miR-34a siRNA+EX-527 group(treated with transfection agent,specific siRNA and SIRT1 inhibitor EX-527).Western blotting was used to detect the protein expression level of Atrogin-1 and MuRF-1.RT-qPCR was used to assess the mRNA expression level of Atrogin-1 and MuRF-1.Results Myotube differentiation was observed on the 4th day.Compared with control group,myotube atrophy was obvious in ICU-AW group.RT-qPCR and Western blotting results revealed that,compared with normal control group,in ICU-AW group,the mRNA and protein expression levels of Atrogin-1 and MuRF-1 significantly increased(P<0.05),and the expression level of miR-34a significantly increased(P<0.05),while the mRNA and protein expression levels of SIRT1 significantly decreased(P<0.05).RT-qPCR results showed that,compared with control group(treated with siRNA transfection agent intervention)and Scra siRNA group,the expression of miR-34a and mRNA expression of Atrogin-1 and MuRF-1 in miR-34a siRNA group significantly decreased(P<0.05),while the mRNA expression of SIRT1 significantly increased(P<0.05),meanwhile the protein expression of Atrogin-1 and MuRF-1 decreased significantly(P<0.01),and the protein expression of SIRT1 significantly increased(P<0.05).RT-qPCR results also showed that,compared with vehicle group,the mRNA expression of Atrogin-1 and MuRF-1 in SRT1720 group decreased significantly(P<0.05),while SIRT1 increased significantly(P<0.05).Western blotting results demonstrated that,compared with control group and Scra siRNA group,the protein expression of Atrogin-1 and MuRF-1 in miR-34a siRNA group decreased significantly(P<0.05),while SIRT1 increased significantly(P<0.05).RT-qPCR and Western blotting results indicated that,compared with miR-34a siRNA+vehicle group,the mRNA and protein expression of Atrogin-1 and MuRF-1 in miR-34a siRNA+EX-527 group increased significantly(P<0.05).Conclusion Overactivation of miR-34a in ICU-AW contributes to skeletal muscle atrophy by inhibiting the expression of SIRT1,which may play an important role in the pathogenesis of ICU-AW.
		                        		
		                        		
		                        		
		                        	
10.Ricolinostat reduces X-ray induced myocardial fibrosis and drives disassembly of primary cilia
Cheng-Xu MA ; Xiao-Ni MA ; Li-Hua MA ; Song-Bo FU ; Jian-Guo CHENG
Chinese Pharmacological Bulletin 2024;40(10):1844-1849
		                        		
		                        			
		                        			Aim To evaluate the effect of ricolinostat on X-ray induced myocardial fibrosis and damage to primary cilia in myocardial fibroblasts.Methods Wistar rats were subjected to a single dose of 8 Gy whole-body irradiation,followed by intraperitoneal in-jection of ricolinostat.Serum troponinT(TnT)and brain natriuretic peptide(BNP)levels were measured using ELISA.The degree of myocardial tissue fibrosis was measured using HE and Masson staining.Type Ⅰcollagen and primary cilia were detected using immuno-fluorescence.The gene and protein levels of histone deacetylase 6(HDAC6)in myocardial tissue and cells were detected using PCR and Western blot.Results Compared with the control group,X-ray radiation in-creased type Ⅰ collagen content and promoted the pro-liferation of myocardial fibroblasts in rat myocardial tis-sue.X-ray radiation slightly up-regulated the expres-sion of HDAC6 in myocardial fibroblasts(P>0.05),and significantly increased the formation of primary cil-ia in myocardial tissue and myocardial fibroblasts.Af-ter treatment with ricolinostat,the expression of HDAC6 and primary cilia formation decreased in myo-cardial tissue and myocardial fibroblasts(P<0.05),and acetylation in the cytoplasm significantly in-creased.The arrangement of collagen fibers in myocar-dial tissue was slightly neat,collagen volume fraction was reduced,and the levels of TnT(P<0.01)and BNP decreased.Conclusions Ricolinostat can miti-gate X-ray induced myocardial fibrosis via the disas-sembly of primary cilia,with potential value for trea-ting radiation-induced myocardial fibrosis.
		                        		
		                        		
		                        		
		                        	
            
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