1.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
2.The Causes of Platelet Aggregation in Version 6.4 Trima Accel Automated Blood Collection System and the Comparison of Two Intervention Measures
Shu-Ming HUANG ; Xiao-Mei LIN ; Hui-Wei TANG ; Jia ZENG
Journal of Experimental Hematology 2024;32(4):1207-1211
Objective:To explore the causes of platelet aggregation in version 6.4 Trima Accel automated blood collection system and the effect of 2 intervention measures.Methods:The data on platelet aggregation(n=61)and non-aggregation(n=323)of 61 donors in 2020 were collected and the causes of aggregation were analyzed.Then the 72 donors with platelet aggregation in 2021 were randomized into intervention group A(increasing the anticoagulant-to-blood ratio)and intervention group B(wrapping the donor's arm with an electric blanket to keep warm and improve the blood flow speed).The collection time,average blood flow speed,number of machine alarms,anticoagulant usage,deaggregation and citrate reaction of the two groups were compared.Results:Platelet aggregation was negatively correlated with the average blood flow speed(r=-0.394)and positively correlated with the collection time(r=0.458).The equations for predicting aggregation and non-aggregation were constructed based on Bayesian and Fisher discriminant analysis,and the predicted accuracy was 77.1%.The comparison of the effects of two intervention measures showed that the average blood flow speed in group B was higher than that in group A;the collection time,number of machine alarms,anticoagulant usage and proportion of citrate reaction in blood donors in group B were all lower than those in Group A,all these differences were significant(P<0.05).In the entire cohort in 2021,90.28%of the products were immediately deaggregated after collection,and 9.72%of the products were deaggregated within 4 hours.There was no statistically significant difference in deaggregation between the two intervention groups(P>0.05).Conclusion:During apheresis platelet collection,the predictive equations for aggregation and non-aggregation can be used to predict the occurrence probability of aggregation,and the intervention can be made in advance.Both intervention measures are effective in reducing platelet aggregation,however,measure B has the advantages of improving the speed of blood collection,shortening the collection time,reducing the alarm frequency and the anticoagulant usage,and reducing the incidence of citrate reaction in blood donors.
3.Ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa by activating the sonic hedgehog factor signaling pathway
Mei-Yan ZENG ; Meng XIONG ; Hou-Pan SONG ; Chen OU ; Chao-Jun FU ; Qing-Hua PENG ; Yu-Hui QIN
Chinese Traditional Patent Medicine 2024;46(8):2551-2561
AIM To explore the ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa(RP)and the possible mechanism.METHODS The RP transgenic mice(rd10)were randomly divided into the model group,the Leding group(0.15 g/kg)and the low and high dose Ziyin Mingmu Pills groups(4.50,9.00 g/kg),in contrast to the C57BL/6 mice of the normal group,with 12 mice in each group.The mice had their retinal pathological changes detected by HE staining;their visual function detected by electroretinogram(ERG);their fundus conditions and retinal thickness detected by optical coherence tomography(OCT);their retinal blood perfusion detected by laser speckle blood flow technique;their mRNA expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA detected by digital PCR;and their protein expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin detected by immunofluorescence staining.RESULTS Compared with the normal group,the model group displayed pathological changes in the fundus and retina and decreased amplitudes of ERG a wave and b wave(P<0.01);decreased retinal thickness(P<0.01);decreased retinal blood perfusion(P<0.01);and decreased retinal expressions of Shh,Ptc,Smo,Gli1,N-myc,Cyclin mRNA and protein(P<0.01).Compared with the model group,the groups intervened with Ziyin Mingmu Pills or Leding shared improved pathological changes in the fundus and retina tissue,and increased retinal thickness(P<0.01);increased retinal blood flow(P<0.01);increased amplitudes of ERG a wave and b wave(P<0.01);and increased retinal Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA and protein expressions(P<0.01).CONCLUSION Ziyin Mingmu Pills can improve the fundus pathological changes and visual function to delay RP in mice because of their efficacy in ameliorating retinal thickness and blood flow possibly by activating Shh signaling pathway.
4.Classification and minimally invasive management of ureteroileal bladder anastomotic stricture after radical cystectomy
Ruibao CHEN ; Jiang MEI ; Yisheng YIN ; Hui ZHOU ; Yue CHE ; Shurong LI ; Yiqun TIAN ; Ying ZHAN ; Xiaoyong ZENG
Chinese Journal of Urology 2023;44(4):265-269
Objective:To discuss the classification and treatment of ureteroileal anastomotic stricture (UAS) after radical cystectomy.Methods:The clinical data of 34 patients with UAS after radical cystectomy in the Department of Urology of Tongji Hospital from January 2017 to January 2022 were reviewed and analyzed. There were 25 males and 9 females. The average age was (66.3±7.7)years, including 2 cases of bilateral hydronephrosis and 32 cases of unilateral hydronephrosis. The average time of UAS was detected (14.7±6.5)months after radical cystectomy. There were 32 patients of unilateral hydronephrosis and 2 patients of bilateral hydronephrosis. Two patients had undergone nephrostomy in an external hospital. Three patients had elevated leukocytes in blood routine. Among them, two patients had fever. First, nephrostomy on the hydronephrosis side and anti-infection treatment were performed. After routine blood tests showed that the white blood cells were normal and antibiotics were stopped for 24 hours without fever, the operation was performed. 34 patients had preoperative hydronephrosis of (2.7±0.6) cm. Of the 34 cases in this group, 5 cases were injected with methylene blue through a preoperative nephrostomy tube, and 29 were injected with methylene blue through the renal pelvis using an 18G puncture needle under ultrasound guidance. Using a ureteroscope to observe in the ileal bladder, methylene blue was seen in 4 cases. Methylene blue was used to guide the search for the stenosis and a super smooth guide wire was inserted. Among them, 3 cases were dilated with a 5 mm ureteral dilation balloon catheter, 1 case was dilated with a F14 ureteral access sheath, and then a F6 single J stent was inserted. Methylene blue was not seen in the ileal conduit in 30 cases, of which 16 cases were treated with a flexible ureteroscope through the nephrostomy to locate the stenosis, incised with a 30 W holmium laser. 9 cases were treated with 5 mm ureteral dilation balloon catheter, and 7 cases were treated with a F14 ureteral access sheath, and then an F6 single J stent was inserted. 14 cases were unable to find the stenosis by antegrade method. According to the operation time and patient's condition, it was decided to perform immediate or second stage dual endoscope surgery. Through the nephrostomy, a flexible ureteroscope was used to enter the stenosis along the super slide guide wire. A rigid ureteroscope was used to observe the stenosis through the ileal conduit, and the stenosis was found. The stenosis was found in 10 cases and incised with a 30 W holmium laser. 8 cases were treated with 5 mm ureteral dilation balloon catheter, and 2 cases were treated with a F14 ureteral access sheath, and then an F6 single J stent was inserted. 4 cases were still unable to accurately locate the stenosis using the dual endoscope surgery(one case was bilateral stenosis, and one side was relieved), and continued indwelling nephrostomy. The definition of successful removal of stricture in this study is that an F6 single J stent can be inserted into the ureter.Results:UAS were classified into four types based on the severity of the intraoperative findings: Type Ⅰ, the narrow ureteral lumen is more than 50% narrower than the normal ureteral lumen, but methylene blue can pass through in strands; Type Ⅱ, needle like stricture of the ureteral lumen, allowing only methylene blue filaments to pass through; Type Ⅲ, membranous atresia of the ureter, with a narrow segment of 1 to 3 mm in length, and methylene blue cannot pass through; Type Ⅳ, long segment stenosis. Of the 34 cases in this group, 4 cases were type Ⅰ, and the stenosis was dredged by retrograde method; 16 cases were type Ⅱ, and the stenotic segments were dredged by antegrade method; 10 cases were type Ⅲ, and the stenosis was dredged by the dual endoscope surgery; Four cases were of type Ⅳ (one case was of bilateral UAS, one side was of type Ⅲ, and the other side was of type Ⅳ, which was classified as type Ⅳ). The stenotic segment could not be solved through the above methods. Among the 34 patients, 30 patients were successfully relieved of anastomotic obstruction, and 1 patient with bilateral obstruction was unilaterally relieved of anastomotic obstruction. In the other 3 cases, because the stenosis segment was too long, 2 cases were changed to nephrostomy, and 1 case was changed to open surgery, with a success rate of 88.2%. UAS was classified into 4 types based on the severity of UAS seen during surgery. No serious complications occurred during and after the operation. During the follow-up of 6-24 months, the imaging evaluation of 4 patients showed that hydronephrosis was aggravated, with an average increase in creatinine of (32.5±10.9)μmol/L, requiring replacement of a single J tube. The imaging evaluation of the remaining 26 patients showed that the postoperative hydronephrosis was 0.9 ± 0.6 cm less than the preoperative hydronephrosis 2.6 ± 0.6 cm, with a statistically significant difference ( P<0.01). The quality of life score at 3 months after surgery was (1.9±0.6), which was significantly improved compared to the preoperative indwelling nephrostomy period (5.2±0.7), with a statistically significant difference ( P<0.01) Conclusions:The treatment of UAS after radical cystectomy with retrograde, antegrade, and dual endoscope surgery has a high success rate, which can help some patients avoid the inconvenience of indwelling external drainage tubes and the risk of open surgery. Choosing an appropriate surgical method can achieve the goal of treating UAS with minimal trauma.
5.Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model.
Rong YUAN ; Zi-Han LI ; Mei-Wen HUANG ; Peng-Qi LI ; Yu MIAO ; Hui MO ; Li ZENG ; Zhen-Yu JU ; Qi-Qi XIN ; Wei-Hong CONG
China Journal of Chinese Materia Medica 2023;48(14):3890-3903
This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA_07227 and circRNA_11464 in the aorta of AS model and circRNA expression(such as circRNA_11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS_00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.
Animals
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Male
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Mice
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Atherosclerosis/genetics*
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Lipids
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Mice, Inbred C57BL
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Myocardial Infarction/genetics*
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RNA, Circular/genetics*
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RNA, Long Noncoding/genetics*
6.Cidan Capsule in Combination with Adjuvant Transarterial Chemoembolization Reduces Recurrence Rate after Curative Resection of Hepatocellular Carcinoma: A Multicenter, Randomized Controlled Trial.
Dong-Hai ZHENG ; Jia-Mei YANG ; Jian-Xiong WU ; Shu-Qun CHENG ; Shao-Geng ZHANG ; Dong WU ; Ai-Jun LI ; Xiao-Hui FU ; Xun LI ; Fu-Chen QI ; Wei-Hong DUAN ; Jun-Hui CHEN ; Zhi-Ying YANG ; Lu LIANG ; Jin-Xiong ZENG ; Wei-da ZHENG ; Meng-Chao WU
Chinese journal of integrative medicine 2023;29(1):3-9
OBJECTIVE:
To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC).
METHODS:
A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded.
RESULTS:
As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug.
CONCLUSIONS
Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).
7.Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity.
Can-Chao JIA ; Ling-Jie LI ; Zhi-Hao ZENG ; Rui-Yin TANG ; De-Zheng JIA ; Min-Juan YANG ; Jin-Yan QIU ; Dong-Mei LI ; Can-Hui XIE ; Guang-Ying WU ; Yang-Xue LI ; Jie-Yi JIANG ; Hong HUANG ; Guan-Lin XIAO ; Da-Ke CAI ; Xiao-Li BI
China Journal of Chinese Materia Medica 2023;48(16):4421-4428
This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans
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Chromatography, High Pressure Liquid
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Drugs, Chinese Herbal/chemistry*
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Asteraceae/chemistry*
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Lung Neoplasms/drug therapy*
9.Expert consensus on the prevention and treatment of adverse reactions in subcutaneous immunotherapy(2023, Chongqing).
Yu Cheng YANG ; Yang SHEN ; Xiang Dong WANG ; Yan JIANG ; Qian Hui QIU ; Jian LI ; Shao Qing YU ; Xia KE ; Feng LIU ; Yuan Teng XU ; Hong Fei LOU ; Hong Tian WANG ; Guo Dong YU ; Rui XU ; Juan MENG ; Cui Da MENG ; Na SUN ; Jian Jun CHEN ; Ming ZENG ; Zhi Hai XIE ; Yue Qi SUN ; Jun TANG ; Ke Qing ZHAO ; Wei Tian ZHANG ; Zhao Hui SHI ; Cheng Li XU ; Yan Li YANG ; Mei Ping LU ; Hui Ping YE ; Xin WEI ; Bin SUN ; Yun Fang AN ; Ya Nan SUN ; Yu Rong GU ; Tian Hong ZHANG ; Luo BA ; Qin Tai YANG ; Jing YE ; Yu XU ; Hua Bin LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(7):643-656
10.Preliminary application of transesophageal echocardiography in transapical mitral valve repair with Memoclip
Haixia LIU ; Xun CHEN ; Ju MEI ; Min TANG ; Jianbing HUANG ; Yi MENG ; Fanqiang ZENG ; Yu CHEN ; Linyi RAO ; Hui WANG ; Yunxia ZHANG
Chinese Journal of Ultrasonography 2023;32(6):501-507
Objective:To explore the value of transapical catheter of mitral valve repair (MVR) with Memoclip device in the management of moderate to severe and severe mitral regurgitation (MR) guided by transesophageal echocardiography (TEE).Methods:Fifteen patients with moderate to severe and severe MR in Hefei High-tech Cardiovascular Hospital from December 2021 to October 2022 were prospectively selected. Mitral valve morphology and length, regurgitation severity, left ventricular ejection fraction and pulmonary venous Doppler spectra were carefully evaluated before MVR by TEE.Intraprocedural TEE was performed to guide the MVR including transseptal catheterization, alignment of the clip delivery system, assessment of leaflet capture, clip deployment, post-clip deployment assessment, and withdrawal of the clip delivery system. The position and coaptation length of the clips, the mitral orifice morphology, residual mitral valve regurgitation and pressure gradient were evaluated after MVR.Meanwhile, the complications were monitored throughout the procedure.Results:Among the 15 patients, 12 were implanted with 1 clip and 3 were implanted with 2 clips, respectively. No complications occurred. There were 13 patients with mild regurgitation and 2 showed to moderate mitral regurgitation 1 month later after MVR, and 13 remained mild and 2 maintained moderate regurgitation 3 months later. Significant differences were found in maximal MR area (MRA-max), maximal and mean mitral valve pressure gradient (MVPG-max, MVPG-mean) and mitral valve area (MVA) among the 5 observation time points (all P<0.05). MRA-max, MVA and MVPG-mean were significantly decreased immediately and 3 months after the procedure ( P<0.001). No significant stenosis was found in mitral valve after MVR. Conclusions:MVR with Memoclip is safe, effective, easy to operate in treating patients with moderate to severe and severe MR. TEE plays a key role in perioperative MVR with Memoclip through apical catheterization.

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