1.Association between visceral fat area measured with quantitative CT and fatty liver in normal weight population
Qi QIAO ; Yang ZHOU ; Yongbing SUN ; Xin QI ; Yawei DU ; Zhonglin LI ; Zhi ZOU ; Xiaoling WU ; Jing ZHOU ; Gong ZHANG ; Min QU ; Xiaolin ZHANG ; Yong WANG ; Shewei DOU ; Hongming LIU ; Fengshan YAN ; Jiadong ZHU ; Yongli LI
Chinese Journal of Health Management 2024;18(2):120-126
Objective:To analyze the association between visceral fat area (VFA) and fatty liver based on quantitative CT (QCT) in people receiving health examination with normal body mass index (BMI).Methods:A cross-sectional study. A total of 1 305 physical examiners who underwent chest CT and QCT examination in the Department of Health Management of Henan Provincial People′s Hospital from January to December 2021 were retrospectively selected as subjects. The physical components at the central level of the lumbar two cone were measured with QCT, including subcutaneous fat area (SFA), VFA and liver fat content (LFC). And the metabolic indexes, such as blood lipids and blood glucose, were collected. The t-test and χ2 test were used to analyze the correlation between the detection rate of fatty live and LFCr and age and gender. According to level of VFA (<100 cm 2, 100-150 cm 2 and≥150 cm 2), the subjects were divided into three groups, and one-way ANOVA and χ2 test were used in comparison between groups. Multiple linear regression was used to analyze the correlation between VFA and metabolic indexes and LFC. Results:Of the 1 305 subjects, there were 634 males and 671 females. The detection rate of fatty liver in normal BMI population was 65.67%, and it was 72.71% and 59.02% respectively in men and women ( χ2=27.12, P<0.001), and the detection rate of fatty liver and LFC increased with age (both P<0.05). With the increase of VFA, the age, BMI, SFA, LFC, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), alanine aminotransferase (ALT), blood uric acid and prevalence of fatty liver increased (all P<0.05), and the low-density lipoprotein cholesterol (HDL-C) decreased ( P<0.001). Multiple linear regression analysis showed that after adjustment for age factors, regardless of male or female, LFC was independently positively related with VFA, BMI, and ALT (male β=0.206, 0.145, 0.174, female β=0.194, 0.150, 0.184; all P<0.05). FBG was positively correlated with male independently ( β=0.134; P<0.001). The indicators related to female independently were TC, TG, and blood uric acid ( β=-0.121, 0.145, 0.141, all P<0.05) Conclusion:In the population receiving health examination with normal BMI, the VFA measured by QCT technique is closely related to fatty liver.
2.Correlations of lumbar bone mineral density and metabolic syndrome in adult males
Xinbei LIN ; Yongbing SUN ; Zhi ZOU ; Xiaoling WU ; Zhonglin LI ; Ling WANG ; Jiadong ZHU ; Yongli LI ; Hao LI
Chinese Journal of Medical Imaging Technology 2024;40(10):1562-1566
Objective To explore the correlations of lumbar bone mineral density(BMD)and metabolic syndrome(MS)in adult males.Methods Data of low dose chest CT and quantitative CT of 13 490 adult males were retrospectively analyzed,and lumbar BMD were measured to judge whether MS existed and the degree of MS,and the correlations of lumbar BMD with MS or not and the degree of MS,as well as of lumbar BMD value and the related indicators of MS were assessed.Taken lumbar BMD as the dependent variable,the age,low density lipoprotein cholesterol(LDL-C),blood uric acid(BUA),hemoglobin(Hb)and MS or not were included in multiple linear regression analysis to observe the impact of MS and related indicators on lumbar BMD.Results Among 13 490 adult males,3 900 were found with MS(MS group),while 9 590 were found without MS(non-MS group).Significant difference of lumbar BMD was detected between groups(P=0.001).Lumbar BMD values were negatively correlated with MS(rs=-0.025,P=0.004)and the degree of MS(rs=-0.038,P<0.001),whereas positively correlated with abdominal obesity,high triglyceride and low HDL-C or not(rs=0.024,0.061,0.036,all P<0.001)but negatively correlated with hypertension and hyperglycemia or not(rs=-0.135,-0.104,both P<0.05).After adjustment of age,lumbar BMD of adult males was negatively correlated with MS or not as well as LDL-C(both P<0.05),but positively correlated with BUA and Hb(both P<0.001).Conclusion Lumbar BMD was associated with MS in adult males.
3.Correlation between body fat distribution measured by quantitative CT and body mass index in adults receiving physical examination
Yang ZHOU ; Yongbing SUN ; Qi QIAO ; Xin QI ; Yawei DU ; Zhonglin LI ; Zhi ZOU ; Xiaoling WU ; Jing ZHOU ; Min QU ; Xiaolin ZHANG ; Yong WANG ; Shewei DOU ; Hongming LIU ; Fengshan YAN ; Jiadong ZHU ; Yongli LI
Chinese Journal of Health Management 2024;18(5):354-360
Objective:To analyze the correlation between body fat distribution measured by quantitative CT (QCT) and body mass index in adults receiving physical examination.Methods:It was a cross-sectional study. From January to December 2021, 3 205 adults undergoing physical examination who met the inclusion criteria and underwent chest CT and QCT examination in the health management discipline of Henan Provincial People′s Hospital were selected as the research objects. The general data were collected; and the subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate were measured by QCT. According to body mass index, the subjects were divided into normal group (18.5-<24.0 kg/m 2, 1 343 cases), overweight group (24.0-<28.0 kg/m 2, 1 427 cases) and obesity group (≥28.0 kg/m 2, 435 cases). One-way analysis of variance and χ2 test were used to compare the differences of QCT indexes among the three groups. Pearson and Spearman correlation analysis were used to evaluate the correlation between QCT indexes and body mass index. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic effect of QCT on obesity and fatty liver. Results:Subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate in obese group were all significantly higher than those in overweight group and normal group [males, (147.60±46.44) vs (104.33±27.68), (73.46±22.65) cm 2; (297.46±54.70) vs (229.40±53.12), (159.57±49.68) cm 2; (445.06±70.24) vs (333.73±62.91), (233.02±61.87) cm 2; 11.30% (7.90%, 15.55%) vs 8.75% (6.50%, 11.70%), 6.60% (4.80%, 8.70%); 100.0% vs 96.0%, 64.0%; 92.9% vs 86.7%, 73.3%; females, (213.96±48.61) vs (155.85±35.31), (107.24±31.01) cm 2; (185.41±43.88) vs (142.48±41.75), (96.56±36.50) cm 2; (399.37±68.07) vs (298.33±56.86), (203.80±57.53) cm 2; 9.80% (6.90%, 13.30%) vs 7.30% (5.05%, 9.80%), 5.40%(3.50%, 7.20%); 96.4% vs 74.8%, 28.9%; 87.3% vs 75.6%, 56.5%], and were all positively correlated with body mass index (males, r/ rs=0.709, 0.738, 0.831, 0.402, 0.464, 0.225; females, r/ rs=0.798, 0.695, 0.841, 0.416, 0.605, 0.276) (all P<0.001). In both male and female subjects, the detection rates of obesity based on QCT were significantly higher than those based on body mass index (male, 86.9% vs 16.6%; female, 49.3% vs 8.9%), and the detection rates of fatty liver based on QCT were significantly higher than those based on ultrasound (male, 83.6% vs 57.1%; female, 65.2% vs 27.6%) (all P<0.001). ROC curve showed that when the visceral fat area of 142 cm 2 was used as the cut-off value for the diagnosis of obesity in male subjects, the sensitivity and specificity was 100% and 15.8%, respectively; and when the cut-off value of liver fat content 5.0% was used to diagnose fatty liver, the sensitivity and specificity was 88.9% and 25.1%, respectively. When the visceral fat area of 115 cm 2 was set as the cut-off value for the diagnosis of obesity in female subjects, the sensitivity and specificity was 96.4% and 55.3%, respectively; when the liver fat content of 5.0% was set as the cut-off value for the diagnosis of fatty liver, the sensitivity and specificity was 83.7% and 43.2%, respectively. Conclusions:The indexes of abdominal fat and liver fat measured by QCT in adults receiving physical examination are all positively correlated with body mass index. The effect of QCT in the diagnosis of obesity and fatty liver are both better than body mass index and ultrasound.
4.Quantitative CT study of fat distribution in normal weight population
Yang ZHOU ; Qi QIAO ; Yongbing SUN ; Xin QI ; Yawei DU ; Zhonglin LI ; Zhi ZOU ; Xiaoling WU ; Jing ZHOU ; Min QU ; Xiaolin ZHANG ; Yong WANG ; Shewei DOU ; Hongming LIU ; Fengshan YAN ; Gong ZHANG ; Jiadong ZHU ; Yongli LI
Chinese Journal of Health Management 2024;18(6):410-415
Objective:To analyze the distribution of body fat with quantitative computed tomography (QCT) in people with normal body mass index (BMI).Methods:A cross-sectional study was conducted in the physical examination population who underwent chest CT and QCT examination in the Department of Health Management, Henan Provincial People′s Hospital from January to December in 2021, and 1 395 physical examination subjects who met the inclusion criteria were selected as the research subjects. The subjects were divided into five groups according to their age. The general data of the subjects were collected. The total abdominal fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), total abdominal muscle area (TMA) and muscle fat content (MFC) in the subjects were measured by QCT. One-way analysis of variance, Welch test and Kruskal-Wallis test were used to compare the above QCT measurement indexes between the two genders among different age groups with normal BMI. Pearson correlation analysis was used to analyze the correlation between VFA and sarcopenia indexes. Multivariate linear regression was used to analyze the relationship between VFA and linear correlation variables in the related indicators of sarcopenia.Results:There were significant differences in TFA, VFA, TMA and SMI among different age groups in subjects with normal BMI (all P<0.05). Pearson correlation analysis showed that VFA was negatively correlated with TMA in some age groups (male: 18-39 years group: r=-0.351; 40-49 years group: r=-0.278; 60-69 years group: r=-0.245; female:40-49 years group: r=-0.251; 50-59 years group: r=-0.270;≥70 years group: r=-0.391; all P<0.01); it was negatively correlated with SMI (male: 18-39 years group: r=-0.352; 40-49 years group: r=-0.340; 50-59 years group: r=-0.266; 60-69 years group: r=-0.316; female: 40-49 years group: r=-0.240; 50-59 years group: r=-0.284; all P<0.001); it was positively correlated with MFC (male: 18-39 years group: r=0.342; 40-49 years group: r=0.291; female: 50-59 years group: r=0.133; 60-69 years group: r=0.284; all P<0.05). Multivariate linear regression analysis showed that VFA was independently and negatively correlated with SMI in both men and women after adjusting for age interference factors (male B=-1.881, t=-6.025, P<0.001; female B=-0.603, t=-2.887, P=0.004), and it was independently positively correlated with MFC (male B=1.230, t=4.271, P<0.001;female B=0.893, t=3.836, P<0.001). There was an independent negative correlation between VFA and TMA in male subjects ( B=0.263, t=2.478, P=0.013). Conclusions:VFA is correlated with TMA, SMI and MFC in people with normal BMI. Regardless of gender, SMI has a negative effect on VFA, and MFC has a positive effect on VFA.
5.Effects of thinned anterolateral thigh perforator flaps combined with finger splitting and webplasty in sequential treatment of degloving destructive wound of total hand
Shanqing YIN ; Feng ZHU ; Yaopeng HUANG ; Jiadong PAN ; Dongchao XIAO ; Linhai LIU ; Xueyuan LI ; Xin WANG
Chinese Journal of Burns 2024;40(11):1052-1058
Objective:To investigate the effects of thinned anterolateral thigh perforator flaps combined with finger splitting and webplasty in sequential treatment of degloving destructive wound of total hand.Methods:This study was a retrospective observational study. From January 2012 to January 2023, a total of 15 cases who met the inclusion criteria with degloving destructive wound of total hand were admitted to Ningbo No.6 Hospital, including 10 males and 5 females, aged 17-75 years. The wounds were all combined with exposed bones or tendon. Emergency debridement and vacuum sealing drainage were performed in all cases before flap transplantation in stage Ⅰ. After thorough debridement, the wound area was 11.0 cm×3.0 cm-23.0 cm×13.5 cm. One or both anterolateral thigh perforator flaps with size of 12.5 cm×5.0 cm-25.0 cm×15.5 cm were designed, cut, and thinned to repair the skin and soft tissue defects of the hand. The donor site was sutured directly or repaired with medium-thickness skin graft from the opposite thigh. As needed, the flap was reconstructed by finger splitting and webplasty once or more times every 3 months after stage Ⅰoperation. The survival and complications of flap and wound healing at the donor site were observed after stage Ⅰoperation. The appearance of flap, two-point discrimination distance, and hand function were observed during the follow-up. At the final follow-up, the function of the affected hand was evaluated by the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association.Results:After the operation of stage Ⅰ, all the flaps of 15 cases of patients survived completely, including 1 case that had arterial crisis of flap but survived completely after exploration and re-anastomosis of blood vessels; all the wounds at the donor site healed. During the follow-up period of 6 to 18 months after stage Ⅰ, the flap was slightly swollen, with a little pigmentation, and the two-point discrimination distance in the finger flap was 8-11 mm. The fingers could complete the basic life actions such as flexion, extension, pinch, and grip. At the final follow-up, 3 cases were excellent, 9 cases were good, and 3 cases were acceptable in function evaluation of the affected hand.Conclusions:For degloving destructive wound of total hand, free transplantation of one or both thinned anterolateral thigh perforator flaps is used for repair in stage Ⅰ, and finger splitting and webplasty are used to reconstruct the flaps in the later stage, which can basically restore the pinch and grip function of the affected hand that is required for daily life, and is worthy of clinical promotion.
6.Somatostatin-Positive Neurons in the Rostral Zona Incerta Modulate Innate Fear-Induced Defensive Response in Mice.
Shan LIN ; Meng-Yue ZHU ; Meng-Yu TANG ; Mi WANG ; Xiao-Dan YU ; Yi ZHU ; Shi-Ze XIE ; Dan YANG ; Jiadong CHEN ; Xiao-Ming LI
Neuroscience Bulletin 2023;39(2):245-260
Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival. The zona incerta (ZI) has been demonstrated to play important roles in fear learning and fear memory, as well as modulating auditory-induced innate defensive behavior. However, whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown. Here, we found that somatostatin (SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus. Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus. Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia. In addition, we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens (Re) mediated fear-like defensive behavior. Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus (SC) that projected to the Re-projecting SST-positive neurons in the rostral ZI (SC-ZIrSST-Re pathway). Together, our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.
Mice
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Animals
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Zona Incerta/metabolism*
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Neurons/metabolism*
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Fear/physiology*
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Somatostatin/metabolism*
7.Correlation between body fat distribution measured by quantitative CT and blood lipids in overweight and obese individuals undergoing physical examinations
Yongbing SUN ; Yang ZHOU ; Xin QI ; Zhonglin LI ; Zhi ZOU ; Xiaoling WU ; Jing ZHOU ; Min QU ; Xiaolin ZHANG ; Yong WANG ; Shewei DOU ; Hongming LIU ; Fengshan YAN ; Jiadong ZHU ; Yongli LI
Chinese Journal of Health Management 2023;17(9):698-704
Objective:To analyze the correlation between quantified body fat distribution measured by computed tomography (CT) and blood lipids in overweight and obese individuals undergoing physical examinations.Methods:In this retrospective cohort study, a total of 3 463 physical examination subjects who underwent chest CT combined with quantified CT examination in the Department of Health Management at Henan Provincial People′s Hospital from January to December 2021 were selected using a comprehensive sampling method. The subjects were divided into three groups: normal group (1, 424 cases), overweight group (1, 531 cases), and obese group (508 cases) based on their body mass index: 18.5 to <24.0 kg/m 2, 24.0 to <28.0 kg/m 2, and≥28.0 kg/m 2, respectively. General information, blood lipid parameters, and different body fat distributions measured by quantified CT (subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, muscle fat content) were collected in the three groups. One-way analysis of variance was used to compare differences in body fat distribution and blood lipid parameters, and Pearson correlation analysis was performed to evaluate the correlation between body fat distribution and blood lipids. Results:In the obese group, compared to the normal and overweight groups, subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, muscle fat content, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were significantly higher [males: (152.80±49.27) vs (72.94±22.68), (103.79±28.30) cm 2; (287.95±57.55) vs (156.36±49.40), (224.67±53.10) cm 2; (440.75±72.44) vs (229.31±62.01), (328.46±62.77) cm 2; (12.92±8.61)% vs (6.82±3.31)%, (9.39±4.88)%; (9.06±9.34)% vs (4.55±5.06)%, (6.70±6.73)%; (6.52±0.94) vs (4.87±1.03), (6.27±0.96) mmol/L; (3.05±0.76) vs (2.92±0.86), (2.97±0.77) mmol/L; (2.34±1.42) vs (1.53±0.82), (1.99±1.28) mmol/L; females: (213.82±46.87) vs (104.69±30.62), (155.05±34.90) cm 2; (184.88±46.54) vs (90.67±34.09), (138.92±42.06) cm 2; (398.71±71.28) vs (195.37±55.32), (293.97±57.05) cm 2; (11.36±6.34)% vs (5.51±3.02)%, (7.98±4.77)%; (7.44±7.60)% vs (3.70±3.90)%, (5.56±5.94)%; (5.27±0.96) vs (5.04±0.86), (5.11±0.96) mmol/L; (3.26±0.84) vs (2.92±0.79), (3.01±0.74) mmol/L; (1.74±0.69) vs (1.27±0.65), (1.57±0.77) mmol/L], while high-density lipoprotein cholesterol (HDL-C) was significantly lower [males: (1.17±0.19) vs (1.38±0.28), (1.25±0.25) mmol/L; females: (1.36±0.22) vs (1.59±0.32), (1.42±0.27) mmol/L] (all P<0.001). In males, the visceral fat area and total abdominal fat area in the overweight group were positively correlated with triglycerides ( r=0.175, 0.113) and negatively correlated with HDL-C ( r=-0.125, -0.113), while liver fat content was positively correlated with total cholesterol, LDL-C, and triglycerides ( r=0.083, 0.075, 0.206) and negatively correlated with HDL-C ( r=-0.093) (all P<0.05). In the obese group, the liver fat content was positively correlated with triglycerides ( r=0.170) and negatively correlated with HDL-C ( r=-0.166) in males (both P<0.05). In females, the visceral fat area and total abdominal fat area in the overweight group were positively correlated with total cholesterol, LDL-C, and triglycerides (visceral fat area: r=0.129, 0.160, 0.348; total abdominal fat area: r=0.121, 0.130, 0.283) and negatively correlated with HDL-C ( r=-0.264, -0.173), while liver fat content was positively correlated with triglycerides ( r=0.352) and negatively correlated with HDL-C ( r=-0.195) (all P<0.05). In the obese group, the visceral fat area was positively correlated with triglycerides ( r=0.213) and negatively correlated with HDL-C ( r=-0.223) in females (both P<0.05). Conclusion:Blood lipids are correlated with body fat distribution in overweight and obese individuals undergoing physical examinations, and the degree of correlation varies between different genders and body regions, with triglycerides showing the strongest correlation with liver fat content.
8.Pathological Networks Involving Dysmorphic Neurons in Type II Focal Cortical Dysplasia.
Yijie SHAO ; Qianqian GE ; Jiachao YANG ; Mi WANG ; Yu ZHOU ; Jin-Xin GUO ; Mengyue ZHU ; Jiachen SHI ; Yiqi HU ; Li SHEN ; Zhong CHEN ; Xiao-Ming LI ; Jun-Ming ZHU ; Jianmin ZHANG ; Shumin DUAN ; Jiadong CHEN
Neuroscience Bulletin 2022;38(9):1007-1024
Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. Dysmorphic neurons are the major histopathological feature of type II FCD, but their role in seizure genesis in FCD is unclear. Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients. Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in type II FCD, including an enlarged soma, aberrant dendritic arbors, increased current injection for rheobase action potential firing, and reduced action potential firing frequency. Intriguingly, the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na+-K+-Cl- cotransporter. In addition, we found a depolarizing shift of the GABA reversal potential in the CamKII-cre::PTENflox/flox mouse model of drug-resistant epilepsy, suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons. Thus, imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in type II FCD.
Animals
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Drug Resistant Epilepsy/surgery*
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Epilepsy/pathology*
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Malformations of Cortical Development/pathology*
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Malformations of Cortical Development, Group I
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Mice
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Neurons/pathology*
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Seizures/pathology*
9.Mako:A Graph-based Pattern Growth Approach to Detect Complex Structural Variants
Lin JIADONG ; Yang XIAOFEI ; Kosters WALTER ; Xu TUN ; Jia YANYAN ; Wang SONGBO ; Zhu QIHUI ; Ryan MALLORY ; Guo LI ; Zhang CHENGSHENG ; The Human Genome Structural Variation Consortium ; Lee CHARLES ; E.Devine SCOTT ; E.Eichler EVAN ; Ye KAI
Genomics, Proteomics & Bioinformatics 2022;20(1):205-218
Complex structural variants(CSVs)are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural variants.How-ever,detecting the compounded mutational signals of CSVs is challenging through a commonly used model-match strategy.As a result,there has been limited progress for CSV discovery com-pared with simple structural variants.Here,we systematically analyzed the multi-breakpoint con-nection feature of CSVs,and proposed Mako,utilizing a bottom-up guided model-free strategy,to detect CSVs from paired-end short-read sequencing.Specifically,we implemented a graph-based pattern growth approach,where the graph depicts potential breakpoint connections,and pattern growth enables CSV detection without pre-defined models.Comprehensive evaluations on both simulated and real datasets revealed that Mako outperformed other algorithms.Notably,validation rates of CSVs on real data based on experimental and computational validations as well as manual inspections are around 70%,where the medians of experimental and computational breakpoint shift are 13 bp and 26 bp,respectively.Moreover,the Mako CSV subgraph effectively characterized the breakpoint connections of a CSV event and uncovered a total of 15 CSV types,including two novel types of adjacent segment swap and tandem dispersed duplication.Further analysis of these CSVs also revealed the impact of sequence homology on the formation of CSVs.Mako is publicly available at https://github.com/xjtu-omics/Mako.
10.Phosphorylated TDP-43 Staging of Primary Age-Related Tauopathy.
Xiaoling ZHANG ; Bing SUN ; Xing WANG ; Hui LU ; Fangjie SHAO ; Annemieke J M ROZEMULLER ; Huazheng LIANG ; Chong LIU ; Jiadong CHEN ; Manli HUANG ; Keqing ZHU
Neuroscience Bulletin 2019;35(2):183-192
Primary age-related tauopathy (PART) is characterized by tau neurofibrillary tangles (NFTs) in the absence of amyloid plaque pathology. In the present study, we analyzed the distribution patterns of phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) in the brains of patients with PART. Immunohistochemistry and immunofluorescence double-labeling in multiple brain regions was performed on brain tissues from PART, Alzheimer's disease (AD), and aging control cases. We examined the regional distribution patterns of pTDP-43 intraneuronal inclusions in PART with Braak NFT stages > 0 and ≤ IV, and a Thal phase of 0 (no beta-amyloid present). We found four stages which indicated potentially sequential dissemination of pTDP-43 in PART. Stage I was characterized by the presence of pTDP-43 lesions in the amygdala, stage II by such lesions in the hippocampus, stage III by spread of pTDP-43 to the neocortex, and stage IV by pTDP-43 lesions in the putamen, pallidum, and insular cortex. In general, the distribution pattern of pTDP-43 pathology in PART cases was similar to the early TDP-43 stages reported in AD, but tended to be more restricted to the limbic system. However, there were some differences in the distribution patterns of pTDP-43 between PART and AD, especially in the dentate gyrus of the hippocampus. Positive correlations were found in PART between the Braak NFT stage and the pTDP-43 stage and density.
Aged
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Aged, 80 and over
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Aging
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metabolism
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pathology
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Brain
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metabolism
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pathology
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DNA-Binding Proteins
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metabolism
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Disease Progression
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Female
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Humans
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Immunohistochemistry
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Inclusion Bodies
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pathology
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Male
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Middle Aged
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Neurofibrillary Tangles
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metabolism
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pathology
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Neurons
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metabolism
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pathology
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Severity of Illness Index
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Tauopathies
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metabolism
;
pathology

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