1.Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies.
Xiaopeng PENG ; Zhihao HU ; Limei ZENG ; Meizhu ZHANG ; Congcong XU ; Benyan LU ; Chengpeng TAO ; Weiming CHEN ; Wen HOU ; Kui CHENG ; Huichang BI ; Wanyi PAN ; Jianjun CHEN
Acta Pharmaceutica Sinica B 2024;14(2):533-578
Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.
2.Effect of Danshen Baoxin Cha on a Rat Model of Coronary Heart Disease Combined with Cognitive Impairment by Regulation of AMPK/OPA1 Pathway
Yi HUANG ; Yuxin DU ; Shuyue KANG ; Kairong ZHENG ; Guoyang ZHENG ; Shuiming HUANG ; Huafeng PAN ; Weirong LI ; Limei YAO
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(10):1542-1551
Objective To investigate the effect of Danshen Baoxin Cha (DBC) on a rat model of coronary heart disease combined with cognitive impairment. Methods Male Sprague-Dawley(SD) rats were randomly assigned to two groups:normal group and model group. Streptozotocin was injected into the bilateral ventricles of rats in the model group to establish cognitive impairment model,then isoproterenol hydrochloride was injected subcutaneously to model myocardial ischemia. Behavioral experiments were conducted to verify the success of the model of cognitive dysfunction. The rats of the model group were randomly divided into five groups:model control group,Tongxinluo Capsule group (TXL group,1.6 g·kg-1),and low-(4 g·kg-1),medium-(8 g·kg-1),and high-(16 g·kg-1) dose DBC groups. These groups were received the respective treatments continuously for two weeks. Subsequently,the Y-maze,novel object recognition and Morris water maze experiment were employed to assess the learning and memory abilities of rats. A kit was utilized to quantify the level of oxidative stress in the brain and the adenosine triphosphate (ATP) content in the brain and mitochondria. Hematoxylin-eosin (HE) staining and Nissl staining were employed to observe the pathological changes of neurons in hippocampus CA1 region. Electron microscopy was utilized to observe the pathological changes of mitochondria in hippocampal CA1 region. The expression levels of peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),glucose transporter type 4(GLUT4),and optic atrophy 1(OPA1) were quantified by real-time fluorescence quantitative polymerase chain reaction (PCR),and the expression of proteins related to the AMPK/OPA1 signaling pathway was determined by Western Blot analysis. Results Compared with the normal group,the spontaneous alternating reaction rate,the novel object recognition index,number of crossing the original platform,and distance ratio in the model group were obviously decreased (P<0.01). Neuronal density in the CA1 region of the hippocampus was decreased,Nissl bodies were decreased,and nucleus consolidation was increased. The ATP level in mitochondria,and the levels of ATP,SOD,and GSH-PX in brain were significantly decreased(P<0.05,P<0.01),as well as the content of ROS and MDA were significantly increased (P<0.05,P<0.01). The mitochondria of hippocampus in CA1 region were swollen,with sparse and vacuolated cristae. The mRNA expression levels of GLUT4,PGC-1α,and OPA1 were significantly decreased (P<0.01). The protein expression levels of GLUT4,SIRT1,PGC-1α and OPA1,and p-AMPK/AMPK ratio were significantly decreased (P<0.05,P<0.01). Compared with the model group,the behavioral indexes of rats in the DBC groups were significantly improved (P<0.05,P<0.01),the number of neurons in the hippocampal CA1 area,Nissl bodies and nucleus consolidation were improved. The ATP level in mitochondria and the levels of ATP,SOD,and GSH-PX in brain were significantly increased (P<0.05,P<0.01). The levels of ROS and MDA were significantly decreased (P<0.05,P<0.01). The structure of mitochondrial cristae in hippocampal CA1 region were relatively intact. The mRNA expression levels of GLUT4,PGC-1α and OPA1 were increased (P<0.05,P<0.01),and the expression of proteins related to the AMPK/OPA1 signaling pathway was significantly increased(P<0.05,P<0.01). Conclusion DBC can enhance learning and memory abilities,reduce neuronal damage in a rat model of coronary heart disease combined with cognitive impairment. The mechanism may be related to the reduction of oxidative stress damage in the brain,the activation of the AMPK/OPA1 signaling pathway,and the restoration of energy levels.
3.Exploring the Mechanism of Action of Danshen Baoxin Cha on Depressed Mice with Coronary Heart Disease Based on Network Pharmacology and NLRP3 Inflammatory Pathway
Di ZHAO ; Yi HUANG ; Wenxuan CHEN ; Guoyang ZHENG ; Kairong ZHENG ; Limei YAO ; Huafeng PAN ; Weirong LI
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(10):1552-1561
Objective To explore the mechanism of action of Danshen Baoxin Cha(DBC) on depressed mice with coronary heart disease (CHD) based on network pharmacology and NLRP3 inflammatory pathway. Methods (1) TCMSP and BATMAN-TICAM databases were used to screen the DBC active ingredients and targets. The targets of CHD with depression were screened using the OMIM and Genecards databases. The targets of DBC active ingredients and related targets of CHD with depression were imported into Venny 2.1 online platform to obtain the intersection targets,which was the potential target of DBC in the treatment of CHD with depression. Protein-protein interaction (PPI) analysis was performed on the intersection targets using the STRING platform to screen the key targets. A "drug-active ingredients-disease-targets" network was created to select the main active ingredients and core targets of DBC for the treatment of CHD with depression. Thereafter,the primary targets were examined by GO function and KEGG pathway enrichment using the Metascape database.(2)Kunming mice were split into six groups of eight mice each at random:the control group,the model group,the positive control group (metoprolol tartrate 5.14 mg·kg-1+sertraline hydrochloride 10.3 mg·kg-1),and the DBC high-,middle-,and low-dose groups (30.8,15.4 and 7.7 g·kg-1·d-1). Chronic unpredictable mild stimulation (CUMS)and subcutaneous injection of isoprenaline hydrochloride (ISO) were used to induce a mice model of CHD with depression. Mice were treated orally with the corresponding drug once a day for 18 consecutive days. Behavioral experiments involving forced swimming test,tail suspension test,and open-field test were applied to detect depression levels of mice. Histopathological alterations in hippocampus tissues were noted using HE and Nissl staining. qPCR was used to determine the mRNA expression levels of IL-6,TNF-α,NLRP3,IL-1β,IL-10,and Caspase-1 in hippocampus tissues. Results(1) Sixty-five active components in Salvia and seven active components in green tea were screened out. A total of 1042 potential targets and 2116 CHD complicated with depression-related targets were obtained. The intersection of the targets of active components and disease-related targets was performed by Venny 2.1.0 platform to obtain 299 potential targets (common targets) of DBC in the treatment of CHD with depression. The core targets including IL-1β,AKT1,TNF-α,IL-6,VEGFA,CASP3 and IL-10 were screened through PPI network analysis of potential targets. Key active ingredients including vitamin B,luteolin,salvianolic acid,tanshinone ⅡA and catechin,as well as key targets,such as PTGS2、IL-1β、IL-6、TNF-α and IL-10,were obtained by network analysis of "drugs-active ingredients-disease-targets". The potential targets were correlated with biological processes such as inflammation response,regulation of tumour necrosis factor (TNF),glucocorticoid regulation,regulation of nuclear factor kappa B(NF-κB) transcription factor,as well as major pathways including PI3K-Akt signaling pathway,TNF signaling pathway,apoptosis signaling pathway,and NF-κB signaling pathway.(2) Compared with the control group,mice in the model group showed a significant decrease in the total and center distance of the open field (P<0.01) and a significant increase in the time of forced swimming and immobility time of tail suspension test (P<0.01). The mRNA expression of IL-6,TNF-α,NLRP3,IL-1β,and Caspase-1 was significantly up-regulated(P<0.01) in the hippocampus tissues,but IL-10 mRNA expression was down-regulated (P<0.05). Compared with the model group,the total and center distance in DBC high-,middle-,and low-dose groups were significantly up-regulated(P<0.05,P<0.01),and the time of forced swimming and immobility time of tail suspension test were significantly down-regulated (P<0.01). The mRNA expression of IL-6,TNF-α,NLRP3,IL-1β and Caspase-1 of the DBC high-,middle-,and low-dose groups were significantly down-regulated(P<0.01),IL-10 mRNA expression in mice hippocampus tissue of DBC high-and middle-dose groups was up-regulated (P<0.01). Conclusion The intervention effect of DBC on depressed mice with CHD may be achieved by active ingredients including luteolin,tanshinone,salvianolic acid and catechin acting on the key targets,such as IL-6,TNF-α,IL-1β and IL-10,to regulate the NLRP3 inflammatory signaling pathway.
4.Impact of patient-centered care services on the treatment compliance among patients with multidrug-resistant or rifampicin-resistant pulmonary tuberculosis
Jingjing PAN ; Hui ZHOU ; Linmei QIAN ; Limei ZHU ; Qiao LIU
Chinese Journal of Schistosomiasis Control 2024;36(5):494-501
Objective To examine the effect of patient-centered care services on compliance to treatment among patients with multidrug-resistant (MDR) or rifampicin-resistant (RR) pulmonary tuberculosis (PTB), so as to provide the scientific evidence for promoting the widespread application of the appropriate nursing process of MDR/RR-PTB patients in the hospital. Methods The MDR/RR-PTB patients that were definitely diagnosed at the Sixth People’s Hospital of Nantong City during the period from January 2017 to October 2020 were enrolled. The patients with confirmed diagnosis of MDR/RR-PTB during the period January 2017 to December 2018 served as controls, who were given routine care in the hospital, and those with confirmed diagnosis of MDR/RR-PTB during the period January 2019 to October 2020 served as the care group, who were given patient-centered personalized care services, including one-to-one consultations, periodic group activities, informatization case management, and personal reminder for return visits. The proportion of inclusion into treatment, loss to follow-up, return visits and sputum examinations were compared between the care and control groups. Results A total of 104 MDR/RR-PTB patients were included, including 54 cases in the control group and 50 cases in the care group. There was no significant difference in gender and age distribution between the two groups (χ2 = 3.013, 1.336, P > 0.05). The proportion of inclusion into treatment was higher in the care group (100.00%, 50/50) than in the control group (87.04%, 47/54) (P = 0.013), and the proportion of loss to follow-up was lower in the care group (0, 0/43) than in the control group (19.05%, 8/42) (P = 0.002). In addition, the overall proportion of return visits was higher in the care group (93.09%, 377/405) than in the control group (83.56%, 371/444) (χ2 = 18.345, P < 0.001), and the proportion of sputum examinations was higher in the care group was (83.70%, 339/405) than in the control group (79.28%, 352/444) (χ2 = 2.737, P = 0.098). Conclusion Patient-centered care services facilitate the improvements in the proportion of inclusion into treatment and compliance to treatment and reduction in the proportion of loss to follow-up among MDR/RR-PTB patients, which deserves widespread applications.
5.Consistency evaluation of antinuclear antibody indirect immunofluorescence kit
Xiupan GAO ; Zhaoxing CHEN ; Junxiang ZENG ; Limei GAO ; Youyou YU ; Xiujun PAN
Chinese Journal of Clinical Laboratory Science 2024;42(11):816-820
Objective To evaluate the agreement of four common HEp-2 indirect immunofluorescence assay(IFA)kits in the patients with antinuclear antibody(ANA)-associated rheumatic immune diseases(AARD)and the patients with non-autoimmune diseases(NAD).Methods The experiment in this study included two stages.In stage 1,the serum samples were randomly selected from 134 patients,and ANAs were detected by IFA at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from Janu-ary to June 2023.All of the samples were tested using four kinds of HEp-2 IFA kits,and the consistency of qualitative results was eval-uated by statistical analysis.The kit exhibited highest positive rate was defined as Kit X.In the stageⅡ,a total of 554 serum samples(from 218 AARD and 336 NAD patients)with positive results detected by initial screening of reagent X were selected during the same period,and then the samples were tested by the other three HEp-2 IFA kits.The patterns and titers of ANA were recorded,and a semi-quantitative evaluation system was established.The reproducibility of different patterns of ANA and the consistency of the results among varying clinical characteristics,fluorescence reaction intensities and positive reaction sites in nucleus was statistically analyzed.Results There were no significant differences of qualitative results among the results from four kits(P>0.05).The highest positive rate ap-peared in the kit m(45.86%)which was deemed as the initial screening kit X.Significant differences in the consistency of ANA pat-terns were observed.The reproducibility scores of centromeric pattern and granular pattern were higher than those of homogeneous pat-tern,dense fine speckled pattern,nuclear cytoplasmic mixed pattern and other mixed pattern with significant difference(P<0.05).The reproducibility score of simple pattern was higher than that of mixed patterns(P<0.05).In the nucleoplasmic region,the consistency score of the AARD group was higher than that of NAD group(P<0.01).The consistency scores of each reaction site increased with the rise of the intensity of reaction.In the three reaction parts(nucleoplasm,nucleolus and equatorial plate),the scores between the weak and strong fluorescence reaction intensity groups showed significant differences(P<0.001).The lowest consistency score occurred in cytoplasmic region.Conclusion The clinical interpretation for IFA ANA reports should be more cautious for the results showing weak fluorescence intensity,mixed patterns,and staining positive cytoplasmic sites.For the choice for reagents,the clinical laboratories should be also mindful of the impacts of fluorescent secondary antibodies of anti-human immunoglobulin on the test results.The develop-ment of standardized official guidelines for the manufacture of HEp-2 IFA kits should be crucial initiative for enhancing the consistency of ANA detection and promoting mutual recognition for the results between laboratories.
6.Quantitative evaluation of left and right atrial function and its difference in normal fetus during middle and late pregnancy using two-dimensional speckle tracking echocardiography
Limei ZHOU ; Bowen ZHAO ; Mei PAN ; Xiaohui PENG ; Ran CHEN ; Mingming MA ; Yuanshi TIAN ; Yan DENG
Chinese Journal of Ultrasonography 2024;33(8):659-666
Objective:To explore the potential application of two-dimensional speckle tracking echocardiography (2D-STE) in terms of quantification and evaluating left and right atrial function in normal fetuses, and to investigate the relevant factors affecting left and right atrial function in normal fetuses as well as differences between both atrial function.Methods:A total of 100 single fetuses underwent fetal echocardiography in the Department of Diagnostic Ultrasound & Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine from January 2019 to October 2022 were retrospectively enrolled. The standard basal or apical four-chamber view clips were obtained, and the left and right atrial function were quantitatively analyzed using TomTec-ARENA off-line cardiac analysis software for quantitative assessment of both atrial strain measurements including left atrial reservoir phase longitudinal strain (LASr), left atrial ductal phase longitudinal strain (LAScd), left atrial systolic phase longitudinal strain (LASct), right atrial reservoir phase longitudinal strain (RASr), right atrial ductal phase longitudinal strain (RAScd), right atrial systolic phase longitudinal strain (RASct), and the ratio of systolic longitudinal strain to conduit longitudinal strain in left and right atrial systolic display groups were calculated which was denoted as Sct/Scd.Routine fetal obstetric ultrasound measurements and fetal echocardiographic parameters in the two groups were obtained including fetal heart rate (FHR), left atrial end-systolic length (LAESL), left atrial end-systolic diameter (LAESD), left atrial end-systolic area (LAESA), left ventricular end-diastolic transverse diameter (LVEDD), right atrial end-systolic length (RAESL), right atrial end-systolic diameter (RAESD), right atrial end-systolic area (RAESA), right ventricular end-diastolic transverse diameter (RVEDD), peak blood flow velocity of mitral valve and tricuspid valve in early and late diastolic period (E, A), peak ratio of E and A: E/A (MV), E/A (TV), and the difference between the left and right atrial strain indices and the routine fetal obstetric ultrasound and fetal echocardiographic parameters, as well as the correlation between the above parameters and gestational age were analyzed. The repeatability tests were performed using the intra-class correlation coefficientt (ICC).Results:Significant differences were found in LASr and RASr, LAScd and RAScd, LASct and LAScd, Sct/Scd between the left atrium and right atrium, E/A (MV) and E/A (TV), LAESD and RAESD, LAESL and RAESL (all P<0.05), there was significant difference in FHR between the left atrial contraction display group and the no atrial contraction display group ( P=0.011), no significant difference in other parameters (all P>0.05). Correlation analysis showed that, LASr, LASct, RASr, and RASct showed moderate negative correlation with gestational age ( rs=-0.570, -0.601, -0.469, -0.568; all P<0.001). While LAScd, RAScd, E/A (MV), E/A (TV) were moderately positively related with gestational age ( rs=0.310, 0.350, 0.330, 0.343; all P<0.05). LAESL, LAESD, LAESA, RAESL, RAESD, RAESA, LVEDD and RVEDD were significantly positively related with gestational age ( rs=0.662, 0.768, 0.792, 0.728, 0.828, 0.822, 0.838, 0.802, all P<0.001). The inter-examiner ICC of fetal LASr and RASr were 0.89 and 0.84 (both P<0.05) and the intra-examiner ICC of fetal RASr and LASr both were 0.80 (both P<0.05), with good consistency. Conclusions:2D-STE is highly feasible and reproducible in assessing fetal atrial function. The corresponding variation values of fetal atria at different gestational weeks were obtained in this study, which provides a new reference index for us to further study normal fetal atria as well as comparative analysis of fetal cardiac function under prenatal pathological conditions.
7.Quantitative evaluation of left atrial function in fetuses with left ventricular outflow tract obstruction using two-dimensional speckle tracking echocardiography
Limei ZHOU ; Bowen ZHAO ; Mei PAN ; Xiaohui PENG ; Ran CHEN ; Yuanshi TIAN ; Mingxuan ZHANG ; Min DI
Chinese Journal of Ultrasonography 2024;33(9):767-775
Objective:To explore the potential application of two-dimensional speckle tracking echocardiography (2D-STE) in terms of quantification and evaluating left atrial function in normal fetuses and fetuses with left ventricular outflow tract obstruction (LVOTO).Methods:A total of 32 fetuses diagnosed with LVOTO, who underwent fetal echocardiography at Sir Run Run Shaw Hospital, Zhejiang University College of Medicine between May 2020 to June 2022, were selected as the case group, and 100 pregnant women with normal singleton fetuses between January 2019 to October 2022 were chosen as the control group. The standard basal or apical four-chamber view clips were obtained and were quantitatively analyzed using TomTec-Arena off-line cardiac analysis software to obtain the left atrial strain parameters of the two groups of fetuses including left atrial reservoir phase longitudinal strain(LASr), left atrial ductal phase longitudinal strain(LAScd), left atrial systolic phase longitudinal strain (LASct), as well as the routine obstetric ultrasound measurements and fetal echocardiographic parameters of the two groups: biparietal diameter (BPD), femur length (FL), aortic annulus end-systolic inner diameter (AO), pulmonary annulus end-systolic inner diameter (PA), left atrial end-systolic long length (LAESL), left atrial end-systolic transverse diameter (LAESD), right atrial end-systolic long length (RAESL), right atrial end-systolic transverse diameter (RAESD), left ventricular end-diastolic transverse diameter (LVEDD) and right ventricular diastole end-diastolic transverse diameter (RVEDD). The ratio of right ventricular end-diastolic transverse diameter to left ventricular end-diastolic transverse diameter (RVd/LVd) and the ratio of pulmonary annulus diameter to aortic annulus diameter (PA/AO) were calculated. The differences of strain parameters between the two groups were compared, and the correlation between strain parameters and gestational age, RVd/LVd and other conventional measurement parameters were analyzed. ROC curve was used to compare the specificity and sensitivity of LASr and RVd/LVd in evaluating fetal cardiac dysfunction with LVOTO.Results:There were significant differences in LASr, LAScd, LASct, MAPSE, AO, LAESL, LVEDD, RVd/LVd and PA/AO between the two groups (all P<0.05), there were no significant differences in other parameters (all P>0.05). Correlation analysis showed that LASr was negatively correlated with RVd/LVd in LVOTO group ( rs=-0.394, P=0.025), and LASct was negatively correlated with RVd/LVd ( rs=-0.626, P=0.004). In the control group, LASr was negatively correlated with gestational age, AO and PA ( r/ rs=-0.570, -0.440, -0.493; all P<0.001), and LASct was negatively correlated with gestational age, AO and PA ( r/ rs=-0.601, -0.532, -0.568; all P<0.001). LAScd was positively correlated with gestational age, AO and PA ( r/ rs=0.310, 0.370, 0.314; all P<0.05). There were no significant correlations between the other parameters (all P>0.05). ROC curve analysis showed that the area under the curve(AUC) in LASr evaluation of fetal cardiac dysfunction with LVOTO was 0.890 (0.826, 0.953) and the AUC in RVd/LVd evaluation of fetal cardiac dysfunction with LVOTO was 0.742 (0.637, 0.846), there were significant differences between them( P<0.05). Conclusions:2D-STE is highly feasible and reproducible in assessing fetal left atrial function. Evaluation of fetal left atrial function by 2D-STE provides a new reference index for quantitative analysis of fetal cardiac dysfunction.
8.Quantitative evaluation of right atrial function in fetuses with moderate to severe tricuspid regurgitation by two-dimensional speckle tracking echocardiography
Limei ZHOU ; Bowen ZHAO ; Mei PAN ; Zusheng DU ; Zhen ZHANG ; Xiaohui PENG ; Ran CHEN
Chinese Journal of Ultrasonography 2023;32(7):600-607
Objective:To explore the application value of two-dimensional speckle tracking echocardiography (2D-STE) in measuring the global longitudinal peak strain of the right atrium (PRAGLS) in normal fetuses and evaluating PRAGLS in assessing right atrial function in fetuses with moderate and severe tricuspid regurgitation (TR).Methods:A total of 25 fetuses diagnosed with moderate and severe TR, who underwent fetal echocardiography at Run Run Shaw Hospital, Zhejiang University College of Medicine between October 2020 and May 2022, were selected as the case group. Their gestational age ranged from 25.00(24.00, 30.00)weeks. Additionally, 100 normal singleton fetuses were chosen as the control group, with a gestational age of 25.83(23.00, 28.75)weeks. Standard basal or apical four-chamber clips were acquired and inputted into TOMTEC-ARENA offline cardiac analysis software for analysis. The fetal PRAGLS values of the two groups were obtained, as well as the routine obstetric ultrasound measurements and fetal echocardiographic parameters of both groups: fetal heart rate (FHR), biparietal diameter (BPD), femur length (FL), aortic annulus inner diameter (AO), pulmonary annulus inner diameter (PA), PA/AO ratio, right atrial end-systolic length (RAESL), right atrial end-systolic diameter (RAESD), right atrial end-systolic area (RAESA), right ventricular end-diastolic diameter (RVEDD), and tricuspid annular plane systolic excursion (TAPSE). The peak TR velocity and pressure gradient were simultaneously measured in the case group.The differences in fetal PRAGLS and other parameters between the two groups were compared and analyzed. The correlation between fetal PRAGLS and gestational age (GA) and routine measurements was assessed for both groups. Intra- and inter-observer repeatability tests were conducted using the intragroup correlation coefficient (ICC).Results:A significant difference in PRAGLS was observed between the two groups ( t=11.55, P<0.01). The TAPSE difference between the two groups was also statistically significant ( Z=3.45, P=0.01). Notable differences were found in AO, PA, PA/AO, RAESL, RAESD, and RAESA between the two groups (all P<0.05), but no significant differences were identified in age, GA, FHR, BPD, FL, and RVEDD between the two groups (all P>0.05). PRAGLS in the control group exhibited a moderate negative correlation with GA ( r=-0.47, P<0.01) and were correlated with BPD, FL, AO, PA, RAESL, RAESD, RAESA, and RVEDD ( r=-0.50, -0.46, -0.39, -0.43, -0.45, -0.36, -0.43, -0.32, all P<0.05). No significant correlation was observed with maternal age, FHR, PA/AO, and TAPSE (all P>0.05). No significant correlation between PRAGLS and GA or other conventional parameters was found in the case group (all P>0.05). The inter-measurer and intra-measurer ICC of PRAGLS in the control group were 0.87 and 0.79, respectively, while the inter-measurer and intra-measurer ICC of PRAGLS in the case group were 0.94 and 0.97, respectively, demonstrating good consistency. Conclusions:2D-STE exhibits strong feasibility and reproducibility in assessing fetal atrial function.Fetuses with moderate and severe TR display decreased PRAGLS, suggesting impaired right atrial reservoir function. Right atrial strain introduces a novel method for evaluating fetal cardiac function.
9.Normal reference and regional variation of spinal bone mineral density under the quantitative CT in Chinese male population
Liuping CHEN ; Jian ZHAI ; Limei RAN ; Yongli LI ; Lü YINGRU ; Yan WU ; Shaolin LI ; Hanqi WANG ; Yaling PAN ; Tongtong CHEN ; Lü HAIYING ; Kaiping ZHAO ; Yuqin ZHANG ; Xiao MA ; Jing LU ; Xigang XIAO ; Xiangyang GONG ; Zehong YANG ; Wei CHEN ; Jianbo GAO ; Yuehua LI ; Xia DU ; Zhenlin LI ; Qiang ZENG ; Xiaoguang CHENG ; Shuang CHEN ; Jing WU ; Yong LU
Chinese Journal of Health Management 2022;16(9):604-609
Objective:To investigate the normal reference values of spinal bone mineral density measured by quantitative computed tomography (QCT) and the differences of bone mineral density (BMD) in different regions of in Chinese adult males.Methods:Men who underwent low-dose CT lung scan for cancer screening in regions of Northeast, North, East, South, Central and Southwest of China from January 2018 to December 2019 were selected. And the lumbar vertebrae BMD values in the male subjects were measured by the QCT system (Mindways Software, Inc.). The mean BMD values and their decline rates were calculated at an age interval of 10 years, and the prevalence of osteoporosis was calculated according to the American College of Radiology spine QCT osteoporosis diagnostic criteria.Results:A total of 50 682 males with a mean age of (50.22±12.79) years (ranged 20 to 98 years) were included in this study. The peak BMD of (173.11±28.56) mg/cm 3 in the healthy Chinese adult male population appeared in the age group of 20 to 29 years and then declined with age. Before the age of 70 years, the BMD was relatively higher in males in South China, and it was lower in Central China and Southwest China, and it was intermediate in Northeast, North and East of China, with statistically significant differences. There was no significant differences in BMD in the males in the two age groups of 70 to 79 years and 80 and older among the regions in China. The overall decline rate of spinal BMD in Chinese males under QCT was about 46.92% over the lifetime, and it declined obviouslyin the 40-49 age group. The overall prevalence of osteoporosis in Chinese male population aged 50 years and above was approximately 11.42%, with the highest prevalence in Southwest China and Central China (14.72% and 13.87%, respectively) and the lowest in North China and South China (8.53% and 7.71%, respectively). Conclusions:A reference of lumbar spine BMD values for healthy males in China based on QCT is established. BMD values were highest in South China and Lowest in Central China.
10.Isolation, Screening, and Identification of Actinomycetes with Antifungaland Enzyme Activity Assays against Colletotrichum dematium ofSarcandra glabra
Lisha SONG ; Ni JIANG ; Shugen WEI ; Zuzai LAN ; Limei PAN
Mycobiology 2020;48(1):37-43
A serious leaf disease caused by Colletotrichum dematium was found during the cultivationof Sarcandra glabra in Jingxi, Rong’an, and Donglan Counties in Guangxi Province, whichinflicted huge losses to plant productivity. Biological control gradually became an effectivecontrol method for plant pathogens. Many studies showed that the application of actinomycetesin biological control has been effective. Therefore, it may be of great significance tostudy the application of actinomycetes on controlling the diseases caused by S. glabra.Strains of antifungal actinomycetes capable of inhibiting C. dematium were identified, isolatedand screened from healthy plants tissues and the rhizospheres in soils containing S.glabra. In this study, 15 actinomycetes strains were isolated and among these, strains JT-2F,DT-3F, and JJ-3F, appeared to show antagonistic effects against anthracnose of S. glabra.The strains JT-2F and DT-3F were isolated from soil, while JJ-3F was isolated from plantstems. The antagonism rate of strain JT-2F was 86.75%, which was the highest value amongthe three strains. Additionally, the JT-2F strain also had the strongest antagonistic activitywhen the antagonistic activities were tested against seven plant pathogens. Strain JT-2F isable to produce proteases and cellulase to degrade the protein and cellulose componentsof cell walls of C. dematium, respectively. This results in mycelia damage which leads toinhibition of the growth of C. dematium. Strain JT-2F was identified as Streptomyces tsukiyonensisbased on morphological traits and 16S rDNA sequence analysis.

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