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   Table of Contents - Current issue
Coverpage
5th October 2017
Volume 130 | Issue 19
Page Nos. 2269-2394

Online since Friday, September 22, 2017

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EDITORIAL  

Amyotrophic Lateral Sclerosis: Precise Diagnosis and Individualized Treatment Highly accessed article p. 2269
Qing-Qing Tao, Zhi-Ying Wu
DOI:10.4103/0366-6999.215323  PMID:28937029
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ORIGINAL ARTICLES Top

A De novo Mutation in Dystrophin Causing Muscular Dystrophy in a Female Patient Highly accessed article p. 2273
Hao Yu, Yu-Chao Chen, Gong-Lu Liu, Zhi-Ying Wu
DOI:10.4103/0366-6999.215338  PMID:28937030
Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive neuromuscular diseases resulting from dystrophin (DMD) gene mutations. It has been known that the carrier of DMD mutations may also have symptoms of the disease. While de novo mutation is quite common in BMD/DMD patients, it is rarely reported in the female carriers. Methods: Two sporadic Chinese patients with progressive muscular dystrophy and their familial members were recruited. The targeted next-generation sequencing (NGS) and the multiplex ligation-dependent probe analysis (MLPA) were performed in the proband. Blood tests, electrocardiography, echocardiography, and electromyography were also evaluated. Results: Two novel mutations of DMD gene were identified, c.7318C>T (p.Q2440*) in the male proband and c.4983dupA (p.A1662Sfs*24) in the female carrier. The MLPA analysis did not detect any large rearrangements. The haplotype analysis indicated that the two mutations were derived from de novo mutagenesis. Conclusions: We identified two novel de novo mutations of DMD gene in two Chinese pedigrees, one of which caused a female patient with muscular dystrophy. The mutational analysis is important for DMD patients and carriers in the absence of a family history. The NGS can help detect the mutations in MLPA-negative patients.
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A Novel AGRN Mutation Leads to Congenital Myasthenic Syndrome Only Affecting Limb-girdle Muscle Highly accessed article p. 2279
Ying Zhang, Yi Dai, Jing-Na Han, Zhao-Hui Chen, Li Ling, Chuan-Qiang Pu, Li-Ying Cui, Xu-Sheng Huang
DOI:10.4103/0366-6999.215332  PMID:28937031
Background: Congenital myasthenic syndromes (CMSs) are a group of clinically and genetically heterogeneous disorders caused by impaired neuromuscular transmission. The defect of AGRN was one of the causes of CMS through influencing the development and maintenance of neuromuscular transmission. However, CMS reports about this gene mutation were rare. Here, we report a novel homozygous missense mutation (c.5302G>C) of AGRN in a Chinese CMS pedigree. Methods: We performed a detailed clinical assessment of a Chinese family with three affected members. We screened for pathogenic mutations using a disease-related gene panel containing 519 genes associated with genetic myopathy (including 17 CMS genes). Results: In the family, the proband showed limb-girdle pattern of weakness with sparing of ocular, facial, bulbar, and respiratory muscles. Repetitive nerve stimulation showed a clear decrement of the compound muscle action potentials at 3 Hz only. Pathological analysis of the left tibialis anterior muscle showed predominance of type I fiber and the presence of scattered small angular fibers. The proband's two elder sisters shared a similar but more severe phenotype. By gene analysis, the same novel homozygous mutation (c.5302G>C, p. A1768P) of AGRN was identified in all three affected members, whereas the same heterozygous mutation was found in both parents, revealing an autosomal recessive transmission pattern. All patients showed beneficial responses to adrenergic agonists. Conclusions: This study reports a Chinese pedigree in which all three children carried the same novel AGRN mutation have CMS only affecting limb-girdle muscle. These findings might expand the spectrum of mutation in AGRN and enrich the phenotype of CMS.
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Development and Standardization of a New Cognitive Assessment Test Battery for Chinese Aphasic Patients: A Preliminary Study p. 2283
Ji-Bao Wu, Zhi-Hong Lyu, Xiao-Jia Liu, Hai-Peng Li, Qi Wang
DOI:10.4103/0366-6999.215326  PMID:28937032
Background: Nonlinguistic cognitive impairment has become an important issue for aphasic patients, but currently there are few neuropsychological cognitive assessment tests for it. To get more information on cognitive impairment of aphasic patients, this study aimed to develop a new cognitive assessment test battery for aphasic patients, the Non-language-based Cognitive Assessment (NLCA), and evaluate its utility in Chinese-speaking patients with aphasia. Methods: The NLCA consists of five nonverbal tests, which could assess five nonlinguistic cognitive domains such as visuospatial functions, attention test, memory, reasoning, and executive functions of aphasic patients. All tests are modified from the nonverbal items of the current existed tests with some changes to the characteristics of Chinese culture. The NLCA was tested in 157 participants (including 57 aphasic patients, 50 mild cognitive impairment (MCI) patients, and 50 normal controls), and was compared with other well-established relative neuropsychological tests on the reliability, validity, and utility. Results: The NLCA was fully applicable in the MCI patients and the normal controls, almost working in the aphasic patients (57/62 patients, 91.9%). The NLCA scores were 66.70 ± 6.30, 48.67 ± 15.04, and 77.58 ± 2.56 for the MCI group, the aphasic group, and the control group, respectively , and a significant difference was found among three groups (F = 118.446, P < 0.001). The Cronbach's alpha of the NLCA as an index of internal consistency was 0.805, and the test-retest and interrater reliability was adequate (r=0.977 and r= 0.970, respectively). The correlations of the cognitive subtests and their validation instruments were between 0.540 and 0.670 (all P < 0.05). Spearman's correlation analysis indicated that the coefficient of internal consistency of each subtest itself was higher than other subtests. When choosing the Montreal Cognitive Assessment score of <26 as the diagnostic criteria of cognitive impairment, the area under the curve for all participants in the control and MCI groups was 0.942 (95% confidence interval: 0.895–0.989), and an optimal cutoff point of 75.00 seemed to provide the best balance between sensitivity and specificity. Age (r = −0.406, P < 0.001) was the main influence factor for the NLCA. Conclusions: The NLCA could efficiently differentiate the cognitive impairment patients from the normal controls and is a reliable and valid cognitive assessment test battery to specially find nonlinguistic cognitive function for aphasic patients.
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Transcranial Sonographic Alterations of Substantia Nigra and Third Ventricle in Parkinson's Disease with or without Dementia p. 2291
Zhi-Fen Dong, Cai-Shan Wang, Ying-Chun Zhang, Ying Zhang, Yu-Jing Sheng, Hua Hu, Wei-Feng Luo, Chun-Feng Liu
DOI:10.4103/0366-6999.215329  PMID:28937033
Background: Numerous studies have demonstrated that patients with Parkinson's disease (PD) have a higher prevalence of substantia nigra (SN) hyperechogenicity compared with controls. Our aim was to explore the neuroimaging characteristics of transcranial sonography (TCS) of patients with PD and those with PD with dementia (PDD). The correlation between the echogenicity of the SN and clinical symptoms in Chinese patients with PDD was also assessed. Methods: The ratios of SN hyperechogenicity (SN+), maximum sizes of SN+, and widths of third ventricle (TV) were measured using TCS for all the recruited patients. Data were analyzed using one-way analysis of variance, rank-sum test, Chi-square test, and receiver-operating characteristic (ROC) curve analysis. Results: The final statistical analysis included 46 PDD patients, 52 PD patients, and 40 controls. There were no significant differences in ratios of SN+ and maximum sizes of SN+ between PDD and PD groups (P > 0.05). TV widths were significantly larger in PDD group (7.1 ± 1.9 mm) than in PD group (6.0 ± 2.0 mm) and controls (5.9 ± 1.5 mm, P < 0.05); however, the ratios of enlarged TV did not differ among the three groups (P = 0.059). When cutoff value was set at 6.8 mm, the TV width had a relatively high sensitivity and specificity in discriminating between PDD and PD groups (P = 0.030) and between PDD group and controls (P = 0.003), based on ROC curve analysis. In PDD patients, SN+ was more frequently detected in akinetic-rigid subgroup, and patients with SN+ showed significantly higher Hoehn and Yahr stage and Nonmotor Symptoms Questionnaire scores (P < 0.05). Conclusions: Compared to Chinese patients with PD, patients with PDD had a wider TV, altered SN sonographic features, and more severe clinical symptoms. Our findings suggest that TCS can be used to assess brain atrophy in PD and may be useful in discriminating between PD with and without dementia.
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Effect of Cordyceps sinensis on the Treatment of Experimental Autoimmune Encephalomyelitis: A Pilot Study on Mice Model p. 2296
Shan-Shan Zhong, Ya-Juan Xiang, Pen-Ju Liu, Yang He, Ting-Ting Yang, Yang-Yang Wang, A Rong, Jun Zhang, Guang-Zhi Liu
DOI:10.4103/0366-6999.215335  PMID:28937034
Background: As a traditional Chinese medicine, Cordyceps sinensis (CS) possesses a variety of immunoregulatory properties. This study aimed to explore the therapeutic potential of CS in a mice model of multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE). Methods: Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein35–55to induce EAE, followed by an instant intragastric feeding with a low dosage of CS (low-CS group, n = 5), high dosage of CS (high-CS group, n = 5), or the same volume of normal saline (control group, n = 5). All the mice were observed for clinical assessment. Over the 30 days of CS treatment, flow cytometry was used to detect the frequency of helper T-cell (Th) subsets, Th1 and Th17, and CD4+ CD25+ regulatory T cells in the spleen and lymph nodes. Meanwhile, pathological changes in brain were determined using both hematoxylin-eosin and luxol fast blue staining. Data were analyzed using the one-way analysis of variance (ANOVA). Results: Over the 15 and 30 days of CS treatment, the clinical assessment for EAE demonstrated that both high-CS group (2.51 ± 0.31 and 2.26 ± 0.39 scores, respectively) and low-CS group (2.99 ± 0.40 and 2.69 ± 0.46, respectively) had lower disease severity scores than those of control group (3.57 ± 0.53 and 3.29 ± 0.53, all P < 0.01, respectively). Meanwhile, after 15 and 30 days, the high-CS group (19.18 ± 1.34 g and 20.41 ± 1.56 g, respectively) and low-CS group (18.07 ± 1.18 g and 19.48 ± 1.69 g, respectively) had a lower body weight, as compared with control group (16.85 ± 1.15 g and 18.22 ± 1.63 g, all P < 0.01, respectively). At 30 days post-CS treatment, there was a lower Th1 frequency in the lymph nodes (2.85 ± 1.54% and 2.77 ± 1.07% vs. 5.35 ± 1.34%, respectively; P < 0.05) and spleens (3.96 ± 1.09% and 3.09 ± 0.84% vs. 5.07 ± 1.50%, respectively; P < 0.05) and less inflammatory infiltration and demyelination in the brain of CS-treated mice than that of control group. Conclusions: Our preliminary study demonstrated that CS efficiently alleviated EAE severity and EAE-related pathology damage and decreased the number of Th1s in the periphery, indicating its effectiveness in the treatment of murine EAE. Thus, our findings strongly support the therapeutic potential of this agent as a new traditional Chinese medicine approach in MS treatment.
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Effects of Pinealectomy and Gonadectomy on Olfactory Bulb Dopaminergic Neurons in Rats p. 2302
Yan Li, Jian Zhu, Ying Wang, Lei Guo, Lei Li, Dong Wang
DOI:10.4103/0366-6999.215336  PMID:28937035
Background: Olfactory disorder is an early manifestation of Parkinson's disease (PD), likely to be associated with abnormalities of the dopaminergic neurons in the olfactory bulb (OB); however, the causes of olfactory disorder in PD are not entirely clear. Some studies showed that melatonin (MT) and androgens (mainly testosterone, T) might participate in the pathogenesis of PD. The research aimed to investigate effects of MT or T deficiency on OB dopaminergic neurons in rats. Methods: One hundred and twenty normal male Wistar rats were randomly divided into the control, sham operation pinealectomy (PX), sham operation gonadectomy (GDX), PX, GDX, and PX + GDX groups. After 60 days, glial cell hyperplasia and neuronal apoptosis were examined with hematoxylin and eosin and the TUNEL method; the expression levels of tyrosine hydroxylase (TH), Bax, and Bcl-2 were measured using immunohistochemistry (IH) by the streptavidin peroxidase conjugated method. Comparison among multiple sets used analysis of variance and LSD method or Kruskal-Wallis test and Nemenyi method. Results: There were no significant differences between the sham operation groups and the control group; thus, they were merged into Group A. There was no significant glial cell hyperplasia (P > 0.05) or change in shape in any of the groups after PX or GDX. The number of apoptotic cells in Groups A (1.41 ± 0.56), PX (12.31 ± 4.68), GDX (20.52 ± 5.13), and PX + GDX (30.23 ± 5.25) successively significantly increased (P < 0.05). The number of TH (+) cells in Groups A (42.62 ± 5.63), PX (37.31 ± 4.32), GDX (31.07 ± 4.21), and PX + GDX (25.22 ± 3.66) was successively significantly decreased (P < 0.05). The gray value of TH (+) cells and fibers in Groups A (98.51 ± 10.36), PX (108.96 ± 13.01), GDX (119.02 ± 12.98), and PX + GDX (128.99 ± 13.39) was successively significantly increased (P < 0.05). The results of Bax staining were as follows: Group A+, Group PX++, Group GDX++, and Group PX+ GDX+++, the results of Bcl-2 in all groups were +. Conclusions: PX or GDX could lead to OB neurotoxicity in the following groups of rats in the following order: PX < GDX < PX + GDX. PX or GDX increased the ratio of Bax/Bcl-2. The effect of PX and GDX was equal, but both were less than that of PX + GDX. Neurotoxicity as a result of PX or GDX was not related to inflammation.
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Socioeconomic and Environmental Determinants to Preterm Birth in Tibetan Women: An Analysis Based on the Hierarchically Conceptual Frame p. 2307
Xiao-Jing Fan, Jian-Min Gao, Yi-Jun Kang, Shao-Nong Dang, Wei-Hua Wang, Hong Yan, Duo-Lao Wang
DOI:10.4103/0366-6999.215341  PMID:28937036
Background: Preterm birth is a common cause of death in newborns and may result from many determinants, but evidence for the socioeconomic and environmental determinants of preterm birth in Tibetan women of childbearing age is limited. The aim of this study was to understand the current status of preterm birth in native Tibetan women and investigate the socioeconomic and environmental determinants. Methods: Data were drawn from a cohort study which was conducted from August 2006 to August 2012 in rural Lhasa, Tibet, China. A total of 1419 Tibetan pregnant women were followed from 20 weeks' gestation until delivery; the loss to follow-up rate was 4.69%. The incidence of preterm birth was estimated to show the status of preterm births in Tibet. Logistic regression models for longitudinal data were established, and odds ratios (ORs) together with 95% confidence intervals (CIs) were used to evaluate the association between the occurrence of preterm birth and 16 selected potential determinants based on the hierarchical conceptual frame. Results: The incidence of preterm birth was 4.58% (95% CI = 3.55–5.80%). After adjusting for health-related variables of the mothers and newborns, socioeconomic and environmental determinants associated with preterm birth included season (spring: OR = 0.28, 95% CI = 0.09–0.84; autumn: OR = 0.21, 95% CI = 0.06–0.69; and winter: OR = 0.31, 95% CI = 0.12–0.82) and calendar year of delivery (2010: OR = 5.03, 95% CI = 1.24–20.35; 2009: OR = 6.62, 95% CI = 1.75–25.10; and 2007–2008: OR = 5.93, 95% CI = 1.47–23.90). Conclusions: The incidence of preterm birth among native Tibetan women was low and there was a decreasing trend in recent years; however, it is still essential to strengthen seasonal maternal care, extend the spacing between pregnancies, and reinforce adequate maternal nutrition.
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CORRIGENDUM Top

Corrigendum: Chinese Guidelines for the Diagnosis and Management of Tumefactive Demyelinating Lesions of Central Nervous System p. 2315

DOI:10.4103/0366-6999.215346  PMID:28937037
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Factors Related to Ventricular Size and Valvular Regurgitation in Healthy Tibetans in Lhasa p. 2316
Ying Yang, Yun-Dai Chen, Bin Feng, Zha-Xi-Duo Ji, Wei Mao, Guang Zhi
DOI:10.4103/0366-6999.215327  PMID:28937038
Background: Lhasa is the main residence of Tibetans and one of the highest cities in the world. Its unique geography and ethnic population provide the chance to investigate the interactions among high altitude, ethnicity, and cardiac adaptation. Meanwhile, echocardiographic data about healthy Tibetans on a large scale are not available. This study aimed to analyze physiological factors related to ventricular size and valvular function in healthy Tibetans in Lhasa. Methods: A representative sample of residents in Tibet was recruited using a multistage cluster random sampling method. Two-dimensional echocardiographic measurements and Doppler evaluation for valvular function were performed. Healthy Tibetans in Lhasa constituted the study population. Associations between physiological parameters and ventricular dimensions in healthy Tibetans were analyzed by canonical correlation analysis. Factors related to valvular regurgitations were determined by logistic regression analysis. Results: The 454 healthy Tibetans (340 females and 114 male) in Lhasa were included in the final analysis. Canonical correlation analysis revealed that weight was positively correlated with the proximal right ventricular outflow diameter and the basal left ventricular linear dimension in both genders. Weight and pulse were negatively related to mild tricuspid regurgitation. Age was a positive factor for pulmonary and aortic regurgitations. The same was found between systolic blood pressure and mitral regurgitation. Conclusions: Weight is associated with ventricular size and valvular regurgitation in healthy Tibetans. It should be of more concern in research of high altitude population.
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Safety and Necessity of Antiplatelet Therapy on Patients Underwent Endovascular Aortic Repair with Both Stanford Type B Aortic Dissection and Coronary Heart Disease p. 2321
Rui-Xia He, Lei Zhang, Tie-Nan Zhou, Wen-Jie Yuan, Yan-Jie Liu, Wen-Xia Fu, Quan-Min Jing, Hai-Wei Liu, Xiao-Zeng Wang
DOI:10.4103/0366-6999.215330  PMID:28937039
Background: Acute aortic dissection is known as the most dangerous aortic disease, with management and prognosis determined as the disruption of the medial layer provoked by intramural bleeding. The objective of this study was to evaluate the safety and necessity of antiplatelet therapy on patients with Stanford Type B aortic dissection (TBAD) who underwent endovascular aortic repair (EVAR). Methods: The present study retrospectively analyzed 388 patients with TBAD who underwent EVAR and coronary angiography. The primary outcomes were hemorrhage, death, endoleak, recurrent dissection, myocardial infarction, and cerebral infarction in patients with and without aspirin antiplatelet therapy at 1 month and 12 months. Results: Of those 388 patients, 139 (35.8%) patients were treated with aspirin and 249 (64.2%) patients were not treated with aspirin. Patients in the aspirin group were elderly (57.0 ± 10.3 years vs. 52.5 ± 11.9 years, respectively, χ2 = 3.812, P < 0.001) and had more hypertension (92.1% vs. 83.9%, respectively, χ2 = 5.191, P = 0.023) and diabetes (7.2% vs. 2.8%, respectively, χ2 = 4.090, P = 0.043) than in the no-aspirin group. Twelve patients (aspirin group vs. no-aspirin group; 3.6% vs. 2.8%, respectively, χ2 = 0.184, P = 0.668) died at 1-month follow-up, while the number was 18 (4.6% vs. 5.0%, respectively, χ2 = 0.027, P = 0.870) at 12-month follow-up. Hemorrhage occurred in 1 patient (Bleeding Academic Research Consortium [BARC] Type 2) of the aspirin group, and 3 patients (1 BARC Type 2 and 2 BARC Type 5) in the no-aspirin group at 1-month follow-up (χ2 = 0.005, P = 0.944). New hemorrhage occurred in five patients in the no-aspirin group at 12-month follow-up. Three patients in the aspirin group while five patients in the no-aspirin group had recurrent dissection for endoleak at 1-month follow-up (2.3% vs. 2.2%, respectively, χ2 = 0.074, P = 0.816). Four patients had new dissection in the no-aspirin group at 12-month follow-up (2.3% vs. 3.8%, respectively, χ2 = 0.194, P = 0.660). Each group had one patient with myocardial infarction at 1-month follow-up (0.8% vs. 0.4%, respectively, χ2 = 0.102, P = 0.749) and one more patient in the no-aspirin group at 12-month follow-up. No one had cerebral infarction in both groups during the 12-month follow-up. In the percutaneous coronary intervention (PCI) subgroup, 44 (31.7%) patients had taken dual-antiplatelet therapy (DAPT, aspirin + clopidogrel) and the other 95 (68.3%) patients had taken only aspirin. There was no significant difference in hemorrhage (0% vs. 1.1%, respectively, χ2 = 0.144, P = 0.704), death (4.8% vs. 4.5%, respectively, χ2 = 0.154, P = 0.695), myocardial infarction (2.4% vs. 0%, respectively, χ2 = 0.144, P = 0.704), endoleak, and recurrent dissection (0% vs. 3.4%, respectively, χ2 = 0.344, P = 0.558) between the two groups at 12-month follow-up. Conclusions: The present study indicated that long-term oral low-dose aspirin was safe for patients with both TBAD and coronary heart disease who underwent EVAR. For the patients who underwent both EVAR and PCI, DAPT also showed no increase in hemorrhage, endoleak, recurrent dissection, death, and myocardial infarction.
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Elevated Levels of Very Low-density Lipoprotein Cholesterol Independently Associated with In-stent Restenosis in Diabetic Patients after Drug-eluting Stent Implantation Highly accessed article p. 2326
Zheng Qin, Fang-Wu Zheng, Chuang Zeng, Kuo Zhou, Yu Geng, Jian-Long Wang, Yue-Ping Li, Qing-Wei Ji, Yu-Jie Zhou
DOI:10.4103/0366-6999.213575  PMID:28836572
Background: High rate of in-stent restenosis (ISR) remained an unsolved clinical problem in clinical practice, especially among patients with diabetes mellitus (DM). Diabetic patients often had hypertriglyceridemia with elevated levels of very low-density lipoprotein cholesterol (VLDL-C). Increasing evidence suggested that VLDL-C was known as a significant risk factor for atherosclerosis and had been recommended as a treatment target by current dyslipidemia guidelines. However, the role of VLDL-C in the occurrence and development of ISR in coronary artery disease (CAD) patients with DM had not been studied. The aim of this study was to evaluate the association between the elevated levels of VLDL-C and the risk of ISR in CAD patients with DM. Methods: A total of 1390 diabetic patients, who underwent coronary drug-eluting stent (DES) implantation at Beijing Anzhen Hospital and followed up by angiography within 6–24 months, were consecutively enrolled. Patients' demographic and clinical characteristics, including age, gender, CAD risk factors, family history, life style, medical history, and coronary angiographic information, were collected carefully at baseline percutaneous coronary intervention and follow-up angiography. Multivariate Cox's proportional hazards regression modeling using the step-wise method (entry, 0.05; removal, 0.05) was used to determine the independent risk associated with ISR in diabetic patients. Results: Finally, 1206 of patients were included in this study. ISR occurred in 132/1206 diabetic patients (10.9%) by follow-up angiography. Patients with ISR had elevated median serum VLDL-C levels compared with those without ISR (0.65 mmol/L vs. 0.52 mmol/L, P = 0.030). The multivariate regression analysis showed that VLDL-C was significantly associated with the risk of ISR in diabetic CAD patients (hazard ratio [HR] = 1.15, 95% confidence interval [CI]: 1.03–1.29, P = 0.017). The HR for the risk of ISR associated with VLDL-C level ≥0.52 mmol/L was 3.01 (95% CI: 1.24–7.34, P = 0.015). Conclusion: The elevated level of serum VLDL-C was a significant and independent risk factor for ISR in diabetic CAD patients after coronary DES implantation.
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Surgical Outcomes of Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery in Children: An Echocardiography Follow-up p. 2333
Yan Gao, Jing Zhang, Guo-Ying Huang, Xue-Cun Liang, Bing Jia, Xiao-Jing Ma
DOI:10.4103/0366-6999.215334  PMID:28937040
Background: Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare but potentially life-threatening congenital heart defect. A retrospective analysis was carried out to elucidate the surgical outcomes of ALCAPA in infants and children using follow-up echocardiography. Methods: From September 2008 to March 2017, 26 children diagnosed with ALCAPA underwent left coronary re-implantation. All surviving patients received echocardiography during follow-up. Results: The mortality rate after the operation was 11.5%. Before repair, twenty patients (76.9%) presented with left ventricular (LV) dysfunction. The mean Z-score of the preoperative LV end-diastolic diameter was 4.42 ± 2.09. Mitral regurgitation (MR) was present in all patients. Two patients (7.7%), both with mitral valve prolapse, underwent mitral valve repair at the time of ALCAPA repair. Two children required postoperative extracorporeal membrane oxygenation. LV function normalized at a median time of 5.3 months (range: 0.5–36.0 months). The Z-score of the LV end-diastolic diameter decreased simultaneously. The degree of MR gradually decreased in all surviving patients. All patients had patency of the proximal left coronary artery confirmed by echocardiography at the most recent follow-up. Six patients (26.1%) showed supravalvar pulmonary stenosis and seven patients (30.4%) showed right pulmonary stenosis during follow-up. Conclusions: Coronary re-implantation was effective for rebuilding a dual coronary system in patients with ALCAPA and resulted in progressive improved LV function and reduced functional MR. Echocardiography was valuable for evaluating the outcomes. LV function, the degree of MR, and possible complications could be detected with follow-up echocardiography.
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Evaluation of Circulating Endometrial Cells as a Biomarker for Endometriosis p. 2339
Ying Chen, Hong-Lan Zhu, Zhe-Wen Tang, Kuang Hong Neoh, Dong-Fang Ouyang, Heng Cui, Hong-Yan Cheng, Rui-Qiong Ma, Xue Ye, Ray PS Han, Xiao-Hong Chang
DOI:10.4103/0366-6999.215325  PMID:28937041
Background: Circulating endometrial cells (CECs) have been reported to be present in the peripheral blood of women with endometriosis (EM), providing clear and specific evidence of the presence of ectopic lesions. In this study, we established a method with a high detection rate of CECs, assessed the diagnostic value of CECs for EM and compared with serum CA125, and proposed a hypothesis for the pathogenesis of EM from the new perspective of CECs. Methods: The participants were enrolled prospectively from October 2015 to July 2016. The peripheral blood samples were collected from 59 participants, and the blood cells were isolated for immunofluorescence staining via microfluidic chips. The cells that were positive for vimentin/cytokeratin and estrogen/progesterone receptor and negative for CD45 were identified as CECs. The serum CA125 level was tested with electrochemiluminescence immunoassay. Results: The detection rate of CECs reached 89.5% (17/19) in the EM group, which was significantly higher than that of the control group (15.0% [6/40], P < 0.001) and was independent of menstrual cycle phases. Furthermore, a positive CEC assay detected 4/5 cases of Stage I–II EM. In contrast, a positive CA125 test had limited value in detecting EM (13/19, 68.4%) and detected only one case of Stage I–II EM. Conclusion: CECs are promising biomarkers for EM with great potential for a noninvasive diagnostic assay.
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Sirtuin 1 Mediates Hydrogen Sulfide-induced Cytoprotection Effects in Neonatal Mouse Cardiomyocytes p. 2346
Ai-Jun Liu, Bin Li, Ming Yang, Yang Liu, Ying-Long Liu, Jun-Wu Su
DOI:10.4103/0366-6999.215328  PMID:28937042
Background: Current knowledge indicates that oxidative damage and the following inflammation is pivotal pathway for myocardial cell death. In recent decades, hydrogen sulfide (H2S) has been identified as a novel endogenous vasodilator and neuromodulator due to its antioxidation capacity. However, whether H2S pretreatment in neonatal mouse cardiomyocytes is a protection effect against oxidative stress remains elusive. Methods: Primary neonatal mouse cardiomyocytes were isolated and cultured, subsequently, pretreated with the H2S donor, sodium hydrosulfide (NaHS). Cell viability, lactate dehydrogenase (LDH) release, and reactive oxygen species (ROS) production are evaluated. The levels of superoxide dismutase (Sod2) and Sirtuin 1 (Sirt1), a deacetylation enzyme, were detected by Western blotting. The statistics was performed using independent-sample t-test. Results: NaHS (100 μmol/L) had no toxicity to primary neonatal mouse cardiomyocytes. Furthermore, NaHS pretreatment significantly improved neonatal mouse cardiomyocytes survival after H2O2-induced cell death, indicated by the decrease in LDH release (40.00 ± 2.65% vs. 65.33 ± 4.33%, P < 0.01) and ROS production (1.90 ± 0.33 vs. 4.56 ± 0.56, P < 0.05), and that the salubrious effect was accompanied by the upregulation of Sod2 expression. In addition, the study showed that NaHS pretreatment improved mitochondrial DNA number in neonatal mouse cardiomyocyte. Furthermore, the result demonstrated NaHS increased the expression of Sirt1 in neonatal mouse cardiomyocyte. Ex 527, an inhibitor of Sirt1, could attenuate these effects of NaHS-induced Sod2 expression and mtDNA number increase, furthermore, abrogate the cytoprotective effects of NaHS for neonatal mouse cardiomyocytes. Conclusion: Sirt1 mediated H2S-induced cytoprotection effects in neonatal mouse cardiomyocytes.
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Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion p. 2354
Yu Zou, Xin He, Qian-Yi Peng, Qu-Lian Guo
DOI:10.4103/0366-6999.215333  PMID:28937043
Background: The CD38/cyclic ADP-ribose (cADPR) pathway plays a role in various central nervous system diseases and in morphine tolerance, but its role in local anesthetic intoxication is unknown. The aim of this study was to determine the role of the CD38/cADPR pathway in ropivacaine-induced convulsion. Methods: Forty male Sprague-Dawley rats were randomly divided into five groups (n = 8 per group): sham group, ropivacaine group, ropivacaine+8-Br-cADPR (5 nmol) group, ropivacaine+8-Br-cADPR (10 nmol) group, and ropivacaine+8-Br-cADPR (20 nmol) group (no rats died). Rats were intracerebroventricularly injected with normal saline or 8-Br-cADPR 30 min before receiving an intraperitoneal injection of ropivacaine. Electroencephalography and convulsion behavior scores were recorded. The hippocampus was harvested from each group and subjected to nicotinamide adenine dinucleotide and cADPR assays, Western blotting analysis, and malondialdehyde (MDA) and superoxide dismutase (SOD) assays. Results: Intraperitoneal injection of ropivacaine (33.8 mg/kg) induced convulsions in rats. CD38 and cADPR levels increased significantly following ropivacaine-induced convulsion (P = 0.031 and 0.020, respectively, compared with the sham group). Intraventricular injection of 8-Br-cADPR (5, 10, and 20 nmol) significantly prolonged convulsion latency (P = 0.037, 0.034, and 0.000, respectively), reduced convulsion duration (P = 0.005, 0.005, and 0.005, respectively), and reduced convulsion behavior scores (P = 0.015, 0.015, and 0.000, respectively). Intraventricular injection of 8-Br-cADPR (10 nmol) also increased the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein ratio (P = 0.044) and reduced cleaved Caspase 3/Caspase 3 ratio, inducible nitric oxide synthase, MDA and SOD levels (P = 0.014, 0.044, 0.001, and 0.010, respectively) compared with the ropivacaine group. Conclusions: The CD38/cADPR pathway is activated in ropivacaine-induced convulsion. Inhibiting this pathway alleviates ropivacaine-induced convulsion and protects the brain from apoptosis and oxidative stress.
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REVIEW ARTICLES Top

Priming of the Cells: Hypoxic Preconditioning for Stem Cell Therapy p. 2361
Zheng Z Wei, Yan-Bing Zhu, James Y Zhang, Myles R McCrary, Song Wang, Yong-Bo Zhang, Shan-Ping Yu, Ling Wei
DOI:10.4103/0366-6999.215324  PMID:28937044
Objective: Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues. Data Sources: This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords: “stem cells,” “hypoxic preconditioning,” “ischemic preconditioning,” and “cell transplantation.” Study Selection: Original articles and critical reviews on the topics were selected. Results: Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified. Conclusions: In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications.
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Carotid Atherosclerosis and Cognitive Impairment in Nonstroke Patients p. 2375
Wei-Hong Chen, Wei Jin, Pei-Yuan Lyu, Yang Liu, Rui Li, Ming Hu, Xiang-Jian Xiao
DOI:10.4103/0366-6999.215331  PMID:28937045
Objective: As a vascular risk factor, carotid atherosclerosis is crucial to cognitive impairment. While carotid intima-media thickness, carotid artery plaque, and carotid stenosis can reflect carotid atherosclerosis in different stages, this review aimed to explore researches on the role of carotid intima-media thickness, carotid artery plaque, and carotid stenosis in the progress of cognitive impairment in nonstroke patients and tried to illustrate the possible mechanisms. Data Sources: We searched the PubMed database for recently published research articles up to July 2017, with the key words of “carotid atherosclerosis,” “carotid intima-media thickness,” “carotid plaque,” “carotid stenosis,” “nonstroke,” and “cognitive impairment.” Study Selection: Articles were obtained and reviewed to analyze the role of carotid atherosclerosis such as carotid intima-thickness, carotid plaque, and carotid stenosis in the progress of cognitive impairment in nonstroke patients and the possible mechanisms. Results: In recent years, most studies proved that by evaluating carotid atherosclerosis with ultrasonography, carotid atherosclerosis accounts for the development of cognitive decline in nonstroke patients. Carotid atherosclerosis not only impairs the subtle general cognitive function but also decreases the specific domains of cognitive function, such as memory, motor function, visual perception, attention, and executive function. But, it is still controversial. The possible mechanisms of cognitive impairment in nonstroke patients with carotid atherosclerosis can be classified as systemic global cerebrovascular function, small-vessel diseases, and the mixed lesions. Conclusions: Carotid atherosclerosis can be used to predict the risk of cognitive impairment. Furthermore, diagnosing and treating carotid atherosclerosis at early stage might help clinicians prevent and treat vascular cognitive impairment in nonstroke patients.
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IDEAS AND OPINIONS Top

Curriculum of Interventional Radiology for Clinical Medical Undergraduates p. 2380
Zhong-Bao Tan, Huan-Jing Wang, Rong Zou, Xue-Qun Mao, Jian Zhang, Qing-Qing Wang, Zhen-Hai Di, Peng-Hua Lyu
DOI:10.4103/0366-6999.215344  PMID:28937046
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CLINICAL OBSERVATION Top

Atrial Septal Defect, Neuromuscular Junction and Skeletal Abnormalities in Spinal Muscular Atrophy Type III p. 2382
Xing-Hua Luan, Jun Liu
DOI:10.4103/0366-6999.215339  PMID:28937047
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Extraperitoneal Rectal Laceration Secondary to Blunt Trauma: Successful Transanal Endoscopic Repair with Hemoclips p. 2384
Koo-Yong Hahn, Soon-Young Ko, Woo-Surng Lee, Yong-Hun Kim
DOI:10.4103/0366-6999.215342  PMID:28937048
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Congenital Giant Epignathus with Intracranial Extension in a Fetal p. 2386
Ai-Chun Wang, Yi-Qun Gu, Xiu-Yun Zhou
DOI:10.4103/0366-6999.215343  PMID:28937049
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CLINICAL CHALLENGE Top

Preoperative Evaluation for Complex Female Genital Tract Malformation Using Three-dimensional Printing Technology p. 2388
Shu Wang, Shan Deng, Lan Zhu, Jing-Jing Lu, Yue Wang, Jing-He Lang
DOI:10.4103/0366-6999.215337  PMID:28937050
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CLINICAL PICTURE Top

Cardiac Lymphoma: After the Hurricane p. 2391
Marijana Tadic, Sabine Haßfeld, Burket Pieske, Martin Genger
DOI:10.4103/0366-6999.215345  PMID:28937051
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CORRESPONDENCE Top

Atypical Infantile-onset Pompe Disease with Hypertrophic Cardiomyopathy p. 2393
Jun-Jun Quan, Ling-Juan Liu, Tie-Wei Lyu, Xu-Pei Huang, Jie Tian
DOI:10.4103/0366-6999.215340  PMID:28937052
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