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Review
An overview of studies on psychological well-being in children born following assisted reproductive technologies
Qi-tao Zhan, Pei-pei Pan, Xiang-rong Xu, Hang-ying Lou, Yi-yun Lou, Fan Jin
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(11): 947-960.   https://doi.org/10.1631/jzus.B1300101
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Over the course of the past 35 years, assisted reproductive technologies (ARTs) have been increasingly used worldwide, while debates on their safety have been generated. Birth defects and imprinting disorders were reported in previous research. Thus, the psychological development of children born following ARTs has become a major concern nowadays. This review gives a systematic view of psychological well-being of children conceived by different types of ART, including in vitro fertilization, intracytoplasmic sperm injection (ICSI), preimplantation genetic diagnosis/screening, and in vitro maturation. The previous studies are analyzed in three sections: (1) cognitive, motor, and language developments, (2) behavior problems and socio-emotional development, and (3) parent-child relationship. We conclude that although the majority of the studies on cognitive, motor, and language developments reported comparable achievements in the ART group vs. the naturally conceived group, lower intelligence quotient (IQ) scores, worse visual-motor ability or locomotor development, and delayed receptive language competence were found in the ART group. The results on the socio-emotional development were reassuring. As for the behavior problems, a higher prevalence of behavior problems existed in ART children; moreover, ICSI children were found to be at a higher risk of autism than the general population. Meanwhile, ART parents tended to have positive parental attitudes and be more protective of their children. Some suggestions for further research are also given in this review.
Articles
Menstrual blood-derived mesenchymal stem cells differentiate into functional hepatocyte-like cells
Xiao-zhou Mou, Jian Lin, Jin-yang Chen, Yi-fei Li, Xiao-xing Wu, Bing-yu Xiang, Cai-yun Li, Ju-ming Ma, Charlie Xiang
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(11): 961-972.   https://doi.org/10.1631/jzus.B1300081
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Orthotopic liver transplantation (OLT) is the only proven effective treatment for both end-stage and metabolic liver diseases. Hepatocyte transplantation is a promising alternative for OLT, but the lack of available donor livers has hampered its clinical application. Hepatocyte-like cells (HLCs) differentiated from many multi-potential stem cells can help repair damaged liver tissue. Yet almost suitable cells currently identified for human use are difficult to harvest and involve invasive procedures. Recently, a novel mesenchymal stem cell derived from human menstrual blood (MenSC) has been discovered and obtained easily and repeatedly. In this study, we examined whether the MenSCs are able to differentiate into functional HLCs in vitro. After three weeks of incubation in hepatogenic differentiation medium containing hepatocyte growth factor (HGF), fibroblast growth factor-4 (FGF-4), and oncostain M (OSM), cuboidal HLCs were observed, and cells also expressed hepatocyte-specific marker genes including albumin (ALB), α-fetoprotein (AFP), cytokeratin 18/19 (CK18/19), and cytochrome P450 1A1/3A4 (CYP1A1/3A4). Differentiated cells further demonstrated in vitro mature hepatocyte functions such as urea synthesis, glycogen storage, and indocyanine green (ICG) uptake. After intrasplenic transplantation into mice with 2/3 partial hepatectomy, the MenSC-derived HLCs were detected in recipient livers and expressed human ALB protein. We also showed that MenSC-derived HLC transplantation could restore the serum ALB level and significantly suppressed transaminase activity of liver injury animals. In conclusion, MenSCs may serve as an ideal, easily accessible source of material for tissue engineering and cell therapy of liver tissues.
Partial least squares based identification of Duchenne muscular dystrophy specific genes
Hui-bo An, Hua-cheng Zheng, Li Zhang, Lin Ma, Zheng-yan Liu
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(11): 973-982.   https://doi.org/10.1631/jzus.B1300060
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Large-scale parallel gene expression analysis has provided a greater ease for investigating the underlying mechanisms of Duchenne muscular dystrophy (DMD). Previous studies typically implemented variance/regression analysis, which would be fundamentally flawed when unaccounted sources of variability in the arrays existed. Here we aim to identify genes that contribute to the pathology of DMD using partial least squares (PLS) based analysis. We carried out PLS-based analysis with two datasets downloaded from the Gene Expression Omnibus (GEO) database to identify genes contributing to the pathology of DMD. Except for the genes related to inflammation, muscle regeneration and extracellular matrix (ECM) modeling, we found some genes with high fold change, which have not been identified by previous studies, such as SRPX, GPNMB, SAT1, and LYZ. In addition, downregulation of the fatty acid metabolism pathway was found, which may be related to the progressive muscle wasting process. Our results provide a better understanding for the downstream mechanisms of DMD.
Influence of injection of Chinese botulinum toxin type A on the histomorphology and myosin heavy chain composition of rat gastrocnemius muscles
Bin Hong, Min Chen, Xing-yue Hu
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(11): 983-992.   https://doi.org/10.1631/jzus.B1300021
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Background and objective: Botulinum toxin type A (BoNT/A) is a metalloprotease that blocks synaptic transmission via the cleavage of a synaptosomal-associated protein of 25 kDa (SNAP-25). It has gained widespread use as a treatment for cerebral palsy and skeletal muscle hypertrophy. In China, Chinese botulinum toxin type A (CBTX-A), a type of BoNT/A, is in widespread clinical use. However, the changes in the morphological and biochemical properties of treated muscles and in remote muscles from the CBTX-A injection site are relatively unknown. Therefore, we investigated the changes in histomorphology and myosin heavy chain (MyHC) isoform composition and distribution in rat gastrocnemius muscles after intramuscular injection of CBTX-A. Methods: The weakness of the injected muscles was assessed periodically to identify their functional deficiency. Muscle slices were stained with hematoxylin-eosin (HE) and adenosine triphosphatase (ATPase). MyHC isoform composition was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to uncover changes in morphological and biochemical properties. Results: Our findings demonstrate that following injection of CBTX-A 5 U into rat gastrocnemius muscles, shifts in MyHC isoform composition emerged on the third day after injection and peaked in the fourth week. The composition remained distinctly different from that of the control group after the twelfth week. More specifically, there was a decrease in the proportion of the type IIb isoform and an increase in the proportions of type IIx, type IIa, and type I isoforms. Conclusions: Data revealed that CBTX-A led to a shift in MyHC composition towards slower isoforms and that the MyHC composition remained far from normal six months after a single injection. However, no noticeable remote muscle weakness was induced.
In vivo application of poly-3-hydroxyoctanoate as peripheral nerve graft
D. Burcu Hazer, Ercan Bal, Gülay Nurlu, Kemal Benli, Serdar Balci, Feral ?ztürk, Baki Hazer
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(11): 993-1003.   https://doi.org/10.1631/jzus.B1300016
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Objective: This study aims to investigate the degree of biocompatibility and neuroregeneration of a polymer tube, poly-3-hydroxyoctanoate (PHO) in nerve gap repair. Methods: Forty Wistar Albino male rats were randomized into two groups: autologous nerve gap repair group and PHO tube repair group. In each group, a 10-mm right sciatic nerve defect was created and reconstructed accordingly. Neuroregeneration was studied by sciatic function index (SFI), electromyography, and immunohistochemical studies on Days 7, 21, 45 and 60 of implantation. Biocompatibility was analyzed by the capsule formation around the conduit. Biodegradation was analyzed by the molecular weight loss in vivo. Results: Electrophysiological and histomorphometric assessments demonstrated neuroregeneration in both groups over time. In the experimental group, a straight alignment of the Schwann cells parallel to the axons was detected. However, autologous nerve graft seems to have a superior neuroregeneration compared to PHO grafts. Minor biodegradation was observed in PHO conduit at the end of 60 d. Conclusions: Although neuroregeneration is detected in PHO grafts with minor degradation in 60 d, autologous nerve graft is found to be superior in axonal regeneration compared to PHO nerve tube grafts. PHO conduits were found to create minor inflammatory reaction in vivo, resulting in good soft tissue response.
Neuroprotective effects of flavonoids extracted from licorice on kainate-induced seizure in mice through their antioxidant properties
Ling-hui Zeng, Hua-dan Zhang, Cai-ju Xu, Yu-jia Bian, Xue-jiao Xu, Qiang-min Xie, Rong-hua Zhang
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(11): 1004-1012.   https://doi.org/10.1631/jzus.B1300138
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A relationship between status epilepticus (SE) and oxidative stress has recently begun to be recognized. To explore whether the flavonoids extracted from licorice (LFs) have any protective effect on kainate (KA)-induced seizure in mice, we treated mice with LFs before and after KA injection. In KA-treated mice, we found that superoxide dismutase (SOD) activity decreased immediately after the onset of seizure at 1 h and then increased at 6 h. It returned to baseline 1 d after seizure and then increased again at 3, 7, and 28 d, while malondialdehyde (MDA) content remained at a high level at 1 h, 6 h, 3 d, 7 d, and 28 d, indicating a more oxidized status related to the presence of more reactive oxygen species (ROS). Treatment with LFs before KA injection reversed the seizure-induced change in SOD activity and MDA content at 1 h, 6 h, 3 d, 7 d, and 28 d. Treatment with LFs after seizure decreased KA-induced SOD activity and MDA content at 7 and 28 d. Also, LF pre- and post-KA treatments decreased seizure-induced neuronal cell death. Subsequently, Morris water maze tests revealed that the escape latency was significantly decreased and the number of target quadrant crossings was markedly increased in the LF-treated groups. Thus, our data indicate that LFs have protective effects on seizure-induced neuronal cell death and cognitive impairment through their anti-oxidative effects.
Improvement of enamel bond strengths for conventional and resin-modified glass ionomers: acid-etching vs. conditioning
Ling Zhang, Tian Tang, Zhen-liang Zhang, Bing Liang, Xiao-miao Wang, Bai-ping Fu
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(11): 1013-1024.   https://doi.org/10.1631/jzus.B1300034
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Objective: This study deals with the effect of phosphoric acid etching and conditioning on enamel micro-tensile bond strengths (μTBSs) of conventional and resin-modified glass ionomer cements (GICs/RMGICs). Methods: Forty-eight bovine incisors were prepared into rectangular blocks. Highly-polished labial enamel surfaces were either acid-etched, conditioned with liquids of cements, or not further treated (control). Subsequently, two matching pre-treated enamel surfaces were cemented together with one of four cements [two GICs: Fuji I (GC), Ketac Cem Easymix (3M ESPE); two RMGICs: Fuji Plus (GC), RelyX Luting (3M ESPE)] in preparation for μTBS tests. Pre-treated enamel surfaces and cement-enamel interfaces were analyzed by scanning electron microscopy (SEM). Results: Phosphoric acid etching significantly increased the enamel μTBS of GICs/RMGICs. Conditioning with the liquids of the cements produced significantly weaker or equivalent enamel μTBS compared to the control. Regardless of etching, RMGICs yielded stronger enamel μTBS than GICs. A visible hybrid layer was found at certain enamel-cement interfaces of the etched enamels. Conclusions: Phosphoric acid etching significantly increased the enamel μTBSs of GICs/RMGICs. Phosphoric acid etching should be recommended to etch the enamel margins before the cementation of the prostheses such as inlays and onlays, using GICs/RMGICs to improve the bond strengths. RMGICs provided stronger enamel bond strength than GICs and conditioning did not increase enamel bond strength.
Effects of orthodontic load on the periodontium of autogenously transplanted teeth in beagle dogs
Lu Lu, Hui-fang Sun, Han Xue, Jing Guo, Yang-xi Chen
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(11): 1025-1032.   https://doi.org/10.1631/jzus.B1300062
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Objective: To observe the periodontal healing of autogenously transplanted teeth loaded orthodontically after autotransplantation in Beagle dogs. Methods: Forty-eight teeth were autogenously transplanted, 24 of which were loaded postoperatively with orthodontic force at different time points and for different durations. Periodontal healing was evaluated by probing pocket depth (PPD), the expression of relevant proteins, and histomorphometric analyses. Results: The dental pockets of loaded and non-loaded teeth were both much deeper after the first postoperative week than before transplantation (P<0.05). Later, the PPD, which was measured after postoperative weeks 1, 3, 5, 9 and 13, gradually became shallow. The expressions of alkaline phosphatase (ALP) and basic fibroblast growth factor (bFGF) were higher in loaded teeth than in non-loaded teeth (P<0.05), and in groups subjected to two weeks duration of loading than in other groups at the same load time point (P<0.05). For the same load duration, the expressions of ALP and bFGF in teeth loaded after postoperative week 4 were higher than those of other treatments (P<0.05). According to histomorphometric analyses, an orthodontic force on transplanted teeth applied after postoperative weeks 4 or 8 for two weeks duration should be favorable for periodontal healing. Conclusions: It is advisable to apply an appropriate magnitude of force on autotransplanted teeth, such as orthodontic force, at appropriate time points and for a suitable duration, to achieve the optimal clinical prognosis following autogenous tooth transplantation. These results may serve as a basis for subsequent studies in humans so as to make clinical improvements.
Influence of HbA1c on short-term blood pressure variability in type 2 diabetic patients with diabetic nephropathy
Fang Liu, Min Wu, Yan-huan Feng, Hui Zhong, Tian-lei Cui, You-qun Huang, Ya-ping Liang, Yong-shu Diao, Li Zang, Ling Li, Jing Zang, Hong-yu Qiu, Song-min Huang, Ping Fu
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(11): 1033-1040.   https://doi.org/10.1631/jzus.B1300030
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The aim of this study was to understand the characteristics of blood pressure (BP) variability in subjects with diabetic nephropathy (DN), and identify the probable predictors affecting BP variability. Fifty-one chronic kidney disease (CKD)-hypertensive patients without diabetes (NDN group) and sixty type 2 diabetic patients with overt DN (DN group) were enrolled in this study. The values of short-term BP variability were obtained from 24 h ambulatory BP monitoring (ABPM). Variance analysis or nonparametric analysis revealed that 24-h systolic BP variability and nighttime systolic BP variability of the DN group were significantly higher than those of the NDN group [(12.23±3.66) vs. (10.74±3.83) mmHg, P<0.05; (11.23±4.82) vs. (9.48±3.69) mmHg, P<0.05]. Then the patients of the DN group were divided into two groups according to glycated hemoglobin (HbA1c) level: Group A (HbA1c<7%) and Group B (HbA1c≥7%), and the t-test showed that patients in Group B had larger 24-h diastolic, daytime diastolic, and nighttime systolic/diastolic BP variability compared with Group A. In the DN group, partial correlation analysis revealed that HbA1c exhibited a strong association with 24-h diastolic, daytime diastolic, nighttime systolic and diastolic BP variability (P<0.001, P<0.001, P<0.05, and P<0.001, respectively). Taken together, larger short-term BP variability was detected in hypertensive type 2 diabetic patients with overt nephropathy and renal insufficiency. It may imply that the optimal BP variability level could benefit from a better glycaemic control.
An approach to optimize the batch mixing process for improving the quality consistency of the products made from traditional Chinese medicines
Bin-jun Yan, Hai-bin Qu
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(11): 1041-1048.   https://doi.org/10.1631/jzus.B1300059
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The efficacy of traditional Chinese medicine (TCM) is based on the combined effects of its constituents. Variation in chemical composition between batches of TCM has always been the deterring factor in achieving consistency in efficacy. The batch mixing process can significantly reduce the batch-to-batch quality variation in TCM extracts by mixing them in a well-designed proportion. However, reducing the quality variation without sacrificing too much of the production efficiency is one of the challenges. Accordingly, an innovative and practical batch mixing method aimed at providing acceptable efficiency for industrial production of TCM products is proposed in this work, which uses a minimum number of batches of extracts to meet the content limits. The important factors affecting the utilization ratio of the extracts (URE) were studied by simulations. The results have shown that URE was affected by the correlation between the contents of constituents, and URE decreased with the increase in the number of targets and the relative standard deviations of the contents. URE could be increased by increasing the number of storage tanks. The results have provided a reference for designing the batch mixing process. The proposed method has possible application value in reducing the quality variation in TCM and providing acceptable production efficiency simultaneously.
Letters
Effect of a pain diary use on recovery from acute whiplash injury: a cohort study
Robert Ferrari, Deon Louw
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(11): 1049-1053.   https://doi.org/10.1631/jzus.B1300022
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Objectives: The objective of the current study was to examine the effect of a daily pain diary on recovery from acute whiplash injury. Design: Cohort-controlled study. Setting: Primary care clinic. Participants: A total 56 of 60 initially-recruited subjects were seen in follow-up three months post-injury, 27 in the Diary group and 29 in the Control group. Summary of Background Data: Symptom diaries are often recommended to or used by patients suffering with acute whiplash injury. Diaries have been shown to be associated, however, with symptom amplification in healthy subjects. The effect of diary use on recovery from injury is unknown. Interventions: Subjects with acute whiplash injury were randomly assigned to one of two groups: a Diary group and Control group. Primary outcome measures: Data was gathered within one week of injury on gender, age, and Whiplash Disability Questionnaire scores. The Diary group was asked then to keep a record of their overall pain experience, rating their pain on a scale of 1–10 on a daily basis for four weeks. Results: At the outset, both groups had similar mean age, gender distribution, and mean Whiplash Disability Questionnaire scores. After four weeks of pain diary use, fewer Diary group subjects reported recovery at three months compared to the Control group (59% versus 86%, respectively, p<0.05). Conclusions: The use of a pain diary for four weeks in acute whiplash-injured subjects is associated with a reduced rate of recovery.
Open wedge re-correction high tibial osteotomy in an elderly patient with a varus angulated non-united dome-shaped high tibial osteotomy
Steffen Schr?ter, Lukas Konstantinidis, Tobias M. Kraus, Fabian Stuby, Ulrich St?ckle, Thomas Freude
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(11): 1054-1058.   https://doi.org/10.1631/jzus.B1300050
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Objective: Non-union is a well-known complication after high tibial osteotomy. Non-union may result in a loss of correction or failed implants. Methods: Revision surgery of failed dome-shaped HTO with a re-corrective open wedge HTO has not been described to date. Here, the case of a 74-year-old woman with a varus angulated non-union (mechanical tibiofemoral angle of −28°C) after a dome-shaped osteotomy is presented. Results: Revision surgery was performed with the TomofixTM plate. Conclusions: Even in elderly patients, the clinical result that is achieved without a total knee arthroplasty can be satisfactory.
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