1.Role of TRPV1 in Cardiovascular Disease and the Related Progress of Traditional Chinese Medicine Research
Hongying LYU ; Mingshuang HOU ; Guanjun JIA ; Yushun KOU ; Mengyao LI ; Yongxiang LI ; Jing XU ; Qianqian CHEN ; Zhengjie TENG ; Lin YI
Chinese Journal of Modern Applied Pharmacy 2024;41(4):556-566
Transient receptor potential vanilloid-1(TRPV1) channel is a non-selective ligand-gated cationic channel with multiple activation mechanisms in the transient receptor potential subfamily. In recent years, a large number of studies have found that TRPV1 plays an important role in the field of cardiovascular diseases such as hypertension and atherosclerosis. With the in-depth study of traditional Chinese medicine, it has been found that Chinese medicine monomers and their active components can activate or inhibit TRPV1 channels, which has certain potential in the study of cardiovascular diseases. In this paper, the role of TRPV1 channel in cardiovascular diseases and the research progress of traditional Chinese medicine prevention and treatment of cardiovascular diseases based on TRPV1 channel are reviewed, in order to provide new ideas for prevention and treatment of cardiovascular system diseases.
2.Muscle Force Characteristics of Knee Joints in Taekwondo Roundhouse Kick
Mengyao JIA ; Yong MA ; Jun XIONG ; Lin LIU ; Qian PENG ; Shijie LIN ; Weitao ZHENG
Journal of Medical Biomechanics 2024;39(5):969-977
Objective To explore the muscle force characteristics of the knee joint during a Taekwondo roundhouse kick in Korea.Methods Kinematic and dynamic data from twelve elite Taekwondo athletes were collected using the DaeDo electronic scoring system,Vicon optical motion capture system,Kistler three-dimensional force plates.The OpenSim software was used to simulate these movements and calculate the muscle forces,joint torques,joint stiffness,and muscle coordination patterns of the knee.Results During the knee-lifting and striking phases,the coronal torque of the knee joint in the attacking leg was significant,and the sagittal torque peaked during the strike.For the supporting leg,the highest coronal torque of the knee joint occurred during knee lifting,with the sagittal torque reaching its peak during strike.In terms of muscle activity,the semimembranosus and long head of the biceps femoris in the attacking leg exerted greater force during the striking phase,whereas the semimembranosus and medial head of the gastrocnemius in the supporting leg were more active during the recovery phase.Five muscle synergy patterns were observed during the Taekwondo roundhouse kick.Conclusions Significant differences were found in the muscle forces and knee joint torques of the attacking and supporting legs when athletes performed the roundhouse kick,and there was a complex muscle synergy.
3.AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization.
Yue QIU ; Hongyang WANG ; Huaye PAN ; Jing GUAN ; Lei YAN ; Mingjie FAN ; Hui ZHOU ; Xuanhao ZHOU ; Kaiwen WU ; Zexiao JIA ; Qianqian ZHUANG ; Zhaoying LEI ; Mengyao LI ; Xue DING ; Aifu LIN ; Yong FU ; Dong ZHANG ; Qiuju WANG ; Qingfeng YAN
Journal of Zhejiang University. Science. B 2023;24(2):172-184
Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‒49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‒17.9%, which was significantly higher than that (6.9%‒7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans
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Apoptosis Inducing Factor/metabolism*
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NAD/metabolism*
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Dimerization
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Apoptosis
4.AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization
QIU YUE ; WANG HONGYANG ; PAN HUAYE ; GUAN JING ; YAN LEI ; FAN MINGJIE ; ZHOU HUI ; ZHOU XUANHAO ; WU KAIWEN ; JIA ZEXIAO ; ZHUANG QIANQIAN ; LEI ZHAOYING ; LI MENGYAO ; DING XUE ; LIN AIFU ; FU YONG ; ZHANG DONG ; WANG QIUJU ; YAN QINGFENG
Journal of Zhejiang University. Science. B 2023;24(2):172-184,中插22-中插31
Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%?49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%?17.9%, which was significantly higher than that (6.9%?7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
5.Exploration of the comparison between different biochemical detection systems based on sigma metrics
Jia LI ; Jia GAO ; Chanjuan CUI ; Mengyao YU ; Hao ZHANG ; Wei CUI
Chinese Journal of Laboratory Medicine 2022;45(5):536-542
Objective:To explore the feasibility of using the sigma metrics calculated with the data of internal quality control for the comparison of the analytical performance between different biochemical analyzers.Methods:The internal quality control results of twenty-five biochemical assays in the biochemical analyzers of the department of clinical laboratory in Cancer Hospital from February 1, 2021 to July 31, 2021 were collected. The formula sigma =( TEa- Bias)/ CV was used to calculate the sigma metrics of two different levels of the biochemical assays including albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, calcium, cholesterol, creatine kinase, chlorine, creatinine, γ- glutamyltranspeptidase, blood glucose, high density lipoprotein cholesterol, immunoglobulin A, immunoglobulin G, immunoglobulin M, potassium, lactate dehydrogenase, low density lipoprotein cholesterol, sodium, inorganic phosphorus, total bilirubin, triglyceride, total protein, urea, uric acid. The imprecision was obtained by the coefficient of variation of internal quality control. The bias was calculated by the deviation between the mean of internal quality control of the comparison instrument and the target instrument. The allowable total error ( TEa) was based on People's Republic of China Health Industry Standard (WS/T403-2012) or EQA standard of National Center for Clinical Laboratories (NCCL). Compared the sigma values of the comparison instrument relative to the target instrument with the average percentage bias obtained by the traditional comparison method. Quality goal index was used to analyze the causes of poor performance and judge the results of comparison. Results:Compared with the target instrument Beckman AU5800-3, the comparison instrument Beckman AU5800-1 had 10 assays with σ>6, accounting for 40%, 23 assays with σ>3, accounting for 92%, and only albumin and blood glucose showed σ<3. Through statostical analysis, the comparisons of all assays were passed. The comparison instrument Beckman AU5800-2 had 8 assays with σ>6, accounting for 32%, 20 assays with σ>3, accounting for 80%. Only alkaline phosphatase, calcium, lactate dehydrogenase, total protein and urea showed σ<3. Through statostical analysis, the comparisons of GGT and IgM failed. For the traditional comparison method, the percentage bias between the comparison instruments and the target instrument were all within the range of the evaluation standard. But there was no significant correlation between the σ value and the average bias of the traditional comparison method, and the biases were correlated.Conclusions:Using the sigma metrics calculated with the data of internal quality control for the comparison of different detection systems is a convenient and operable method. It can monitor the comparability between different detection systems in the laboratory at any time and be the supplement of the traditional comparison method.
6.Analysis of perioperative risk factors for seizures in children with congenital heart disease following cardiopulmonary bypass
Mengyao LI ; Yanqin CUI ; Shuyao NING ; Xinxin CHEN ; Jia LI
Chinese Journal of Applied Clinical Pediatrics 2021;36(1):14-18
Objective:To examine the occurrence of seizures and perioperative risk factors in children after obtaining cardiopulmonary bypass (CPB).Methods:Electroencephalograph (EEG) and cerebral oxygen saturation (ScO 2) were monitored in 87 patients (aged 3 days-110 months, with the median at 4.4 months) and they were admitted to the Cardiac Intensive Care Unit (CICU) from May 2018 to April 2019, with 77 patients for 72 h after CPB and 10 cases with clinical seizures after CICU discharge for 8-180 h. Clinical data were recorded every 4 hours, including blood pressure, central venous pressure (CVP), temperature, arterial blood gases, lactate, doses of Dopamine, Milrinone, and Adrenalin, and daily C-reaction protein (CRP) and N-terminal pro-brain natriuretic peptide(NT-proBNP). Demographic data, the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery(STAT) mortality classification and clinical outcomes (duration of mechanical ventilation, CICU and hospital stay, and death) were recorded. Results:Seizures occurred in 24 patients (27.6%) within 48 h after CPB.EEG seizures appeared in 7 patients, both EEG and clinical seizures in 7 patients, and clinical seizures in 10 patients.Three patients developed epilepsy.There were 2 hospital deaths and both had EEG seizures.Patients with seizures had higher STAT categories, longer operative time and worse clinical outcomes (all P<0.05). Univariate regression revealed that the occurrence of seizures was positively related to adrenalin, temperature, lactate level (all P<0.01), blood pressure, CVP (all P<0.05) and CRP ( P<0.1), and negatively correlated with arterial carbon dioxide tension[ pa(CO 2)], ScO 2 and dose of Milrinone (all P<0.05). In multivariate regression, only dose of Adrenalin ( P<0.001) and lactate level ( P<0.01) remained significant. Conclusions:The incidence of seizures was high in children after CPB.Numerous perioperative factors that were related to seizures were identified.The most significant risk factors were higher dose of adrenaline and lactate level.Studies on neurological injury after CPB are urgently needed in China in order to reduce brain injury and improve neurodevelopmental outcomes.
7.Feasibility study of ultrasound-guided percutaneous endomyocardial septal cryoablation of isolated porcine hearts
Xiaonan LU ; Jin HE ; Jia ZHAO ; Jing LI ; Lei ZUO ; Mengyao ZHOU ; Rui HU ; Xiaoli ZHU ; Liwen LIU
Chinese Journal of Ultrasonography 2021;30(5):436-440
Objective:To investigate the feasibility of ultrasound-guided percutaneous endomyocardial septal cryoablation of in vitro porcine hearts and to compare its effect with the percutaneous endomyocardial radiofrequency ablation.Methods:Experiment 1: Six in vitro porcine hearts were divided into 1 min ( n=2), 3 min ( n=2) and 5 min ( n=2) groups according to the cryoablation time, and all were subjected to ultrasound-guided percutaneous intra-myocardial septal cryoablation at 100% power respectively. After cryoablation, ultrasound images, the size of the solid dissection of the ice ball, and the size of the necrotic area after melting of the frozen ice ball were measured. Experiment 2: The in vitro porcine hearts were divided into cryoablation group ( n=3) and radiofrequency ablation group ( n=3), and ultrasound-guided percutaneous endomyocardial septal cryoablation and radiofrequency ablation were performed with 100% cryo power and 40 W radiofrequency power, and the extent of complete necrotic area and incomplete necrotic area were compared between the two ablation methods after 1 min. Results:Experiment 1: In the 1 min cryoablation time group ( n=2), the short diameter of the puck measured by ultrasound was (8.00±0.84)mm, the short diameter of the puck measured by solid was (8.38±1.19)mm, and the short diameter of the necrotic zone measured by solid was (8.35±0.83)mm; in the 3 min group ( n=2), the short diameter of the puck measured by ultrasound was (19.4±0.28)mm, and the short diameter of the puck measured by solid was (19.03±0.33)mm, solid measurement of the short diameter of the necrotic zone was (19.16±0.25)mm; in the 5 min group ( n=2), the short diameter of the puck measured under ultrasound was (26.4±2.54)mm, solid measurement of the short diameter of the puck was (26.01±0.24)mm, and solid measurement of the short diameter of the necrotic zone was (24.82±0.25)mm. Randomized blocks analysis of variance was performed on this data and the difference of block Factor b (freezing time: 1 min, 3 min, 5 min) among the three groups was statistically significant( F=505.884, P<0.001). The SNK- q test showed that all three groups differed from each other(all P<0.05). The analysis results for the treatment factors K (measurement modality-ultrasound image measurements, solid anatomical measurements of the puck, and measurements of the necrotic area after melting of the frozen puck) was not statistically significant ( F=0.470, P=0.635). Experiment 2: In the RF ablation group ( n=3), the ratio of incomplete necrotic zone to the radius of the RF ablation area was 0.64±0.01; in the cryoablation group ( n=3), the ratio of incomplete necrotic zone to the radius of the ablation area was 0.26±0.02. The difference was statistically significant( P=0.002) and it can be considered that the incomplete necrotic zone of cryoablation was smaller than that of RF ablation. Conclusions:Percutameous intramyocardial septal cryoablation is controllable in scope, ultrasound image evaluation of ablation area is more accurate and incomplete necrosis area is small, which may have potential applications in cardiac ablation.
8.Clinical analysis of nine cases of neuroimmune disease with antibodies against glutamic acid decarboxylase 65
Mengyao ZHANG ; Yu JIA ; Huifang WANG ; Yuping WANG
Chinese Journal of Neurology 2021;54(9):908-913
Objective:To explore the clinical features, auxiliary examinations, therapies and prognoses of patients with antibodies targeting glutamic acid decarboxylase 65 (GAD65).Methods:The nine patients with anti-GAD65 neuroimmune disease, admitted to Xuanwu Hospital, Capital Medical University from October 2018 to October 2020, were analyzed, retrospectively.Results:The onset age of nine cases was 17-68 (43.6±20.5) years old, and six cases were female. Two cases had preceding infection. The data of initial symptoms were collected and analyzed, including epileptic onset in four cases, memory impairment in two cases, dizziness in two cases and limb stiffness in one case. As the disease continued to advance, one case developed cerebellar ataxia, one case presented with isolated epilepsy, five cases suffered from limbic encephalitis, one case had stiffman syndrome, one case had brainstem encephalitis. Five cases had antibodies against thyroid peroxidase. Brain magnetic resonance imaging scan showed abnormal signals of T 2/fluid attenuated inversion recovery sequences in four cases, mainly involved bilateral temporal lobes or hippocampus. Epileptiform discharges of frontal or temporal regions of electroencephalography were observed in six cases. All cases received immunotherapy and long-term follow-up was performed in seven cases. Four cases benefited from the immunotherapy. Among the four patients, one fully recovered and returned to work, the other three cases developed neurologic sequelae, including seizures (two cases), and short-term memory loss (one case). The remaining three patients were unresponsive to treatment. Conclusions:GAD65 antibody-mediated neuroimmune disease is a rare neurological disorder, presenting with various syndromes including limbic encephalitis or stiffman syndrome, which is more susceptible to young female. The clinical manifestations included epileptic onset, limb stiffness, cognitive impairment and cerebellar ataxia, etc. Detection of GAD65 antibody in serum or cerebrospinal fluid was gold standard. Early immunotherapy contributed to improving the prognosis of patients, especially for those patients with epileptic onset as the main symptom.
9. Exploration and practice of the combination of pluralistic teaching and process assessment in the clinical biochemical teaching
Jia GAO ; Jia LI ; Chanjuan CUI ; Mengyao YU ; Hao ZHANG ; Jianjun MU ; Wei CUI
Chinese Journal of Laboratory Medicine 2019;42(12):1078-1080
Clinical biochemical examination is an important part of medical laboratory, and it is also the key and difficult point of all kinds of examinations.However,the teaching of clinical biochemistry is easily to enter the misunderstanding of "focusing only on the instrument operation, while others depend on self-study". There is even confusion that teachers don′t know what to teach and students don′t know what to learn.In this paper, the teaching experience of the clinical biochemical laboratory is described,formulated a scientific block training program, adopted the teaching mode of combining tutorial responsibility with daily teaching,flexibly used a variety of teaching methods and procedural examinations, and greatly improved the teaching quality.
10.Study on Synthesis and Anti-tumor Activity of 6 Kinds of Tectorigenin Mannich Base Derivatives
Shuai CHEN ; Chongjun YUAN ; Sen LUO ; Mengyao YU ; Jia WANG
China Pharmacy 2019;30(21):2937-2941
OBJECTIVE: To conduct structural modification of tectorigenin to search for new compounds with anti-tumor activity. METHODS: Tectorigenin was used as a lead compound, and then added into amine reagents as ethanolamine, methylamine, ethylamine, dimethylamine, diethylamine, n-propylamine and formaldehyde solution. Tectorigenin Mannich base derivatives were synthesized by mannich reaction with as the lead compound. The structures of the derivatives were identified according to IR, UV, MS and NMR data. Solubility of tectorigenin and its derivatives were investigated by solubility test method. MTT assay was used to investigate the inhibitory effects of tectorigenin and its derivatives on the proliferation of human colon cancer cell line HCT116, human lung cancer cell line A549 and human hepatoma cell line HepG2, and half inhibitory concentration (IC50) was calculated. The inhibition rate of tectorigenin and its derivatives (100 mg/kg) on H22 hepatoma-bearing mice in vivo was studied. RESULTS: Totally of 6 kinds of tectorigenin mannich base derivatives were synthesized, such as 8-(N-hydroxyethyl)-methyleneamino-5,7,4′-trihydroxy-6-methoxyisoflavone, 8-(N-methyl)-methyleneamino-5,7,4′-trihydroxy-6- methoxyisoflavone, 8-(N, N-diethyl)-methyleneamino-5,7,4′-trihydroxy-6-methoxyisoflavone, 8-(N, N-dimethyl)-methyleneamino- 5,7,4′-trihydroxy-6-methoxyisoflavone, 8-(N-ethyl)-methyleneamino-5,7,4′-trihydroxy-6-methoxyisoflavone, 8-(N-propyl)- methyleneamino-5,7,4′-trihydroxy-6-methoxyisoflavone (compounds 1-6 in turn). Compared with tectorigenin, the water solubility of six derivatives was significantly improved, and the solubility was 5-20 times higher than that of tectorigenin. IC50 of compounds 1, 3 and 5 to HCT116 cells were (34.82±3.27), (16.21±4.13), (33.12±3.25) μmol/L, which were stronger than that of tectorigenin [(45.23±5.74) μmol/L]; IC50 of compounds 1, 3 and 5 to A549 cells were (37.05±5.74), (26.88±4.52), (30.13±6.23) μmol/L, which were stronger than that of tectorigenin [(53.24±6.34) μmol/L]; IC50 of compounds 1, 3 and 5 to HepG2 cells were (23.74±1.45), (18.96±2.34), (30.95±2.87) μmol/L, which were stronger than that of tectorigenin [(48.98±2.58) μmol/L]. Compounds 1, 3 and 5 showed higher inhibition rates (55.51%, 57.20% and 49.15%) than tectorigenin (33.05%) on H22 hepatoma-bearing mice, respectively. The other three compounds had no obvious advantage over tectorigenin in anti-tumor activity. CONCLUSIONS: In this study, compounds 1, 3 and 5 of six tectorigenin mannich base derivatives synthesized in this study have stronger antitumor activity than tectorigenin.


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