Publications by authors named "Jianning Li"

43 Publications

: Database of 500 high-resolution healthy human skulls and 29 craniotomy skulls and implants.

Data Brief 2021 Dec 4;39:107524. Epub 2021 Nov 4.

Graz University of Technology (TU Graz), Graz, Styria, Austria.

In this article, we present a skull database containing 500 healthy skulls segmented from high-resolution head computed-tomography (CT) scans and 29 defective skulls segmented from craniotomy head CTs. Each healthy skull contains the complete anatomical structures of human skulls, including the cranial bones, facial bones and other subtle structures. For each craniotomy skull, a part of the cranial bone is missing, leaving a defect on the skull. The defects have various sizes, shapes and positions, depending on the specific pathological conditions of each patient. Along with each craniotomy skull, a cranial implant, which is designed manually by an expert and can fit with the defect, is provided. Considering the large volume of the healthy skull collection, the dataset can be used to study the geometry/shape variabilities of human skulls and create a robust statistical model of the shape of human skulls, which can be used for various tasks such as cranial implant design. The craniotomy collection can serve as an evaluation set for automatic cranial implant design algorithms.
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http://dx.doi.org/10.1016/j.dib.2021.107524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591340PMC
December 2021

MMP-12 siRNA improves the homeostasis of the small intestine and metabolic dysfunction in high-fat diet feeding-induced obese mice.

Biomaterials 2021 11 11;278:121183. Epub 2021 Oct 11.

State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China. Electronic address:

The changes of small intestinal homeostasis have been recognized to contribute essentially to the obese development. However, the core small intestinal regulator which mediates over-nutrient impacts on the homeostasis of the small intestines remains elusive. Here, we identify the MMP-12 as such a responsive factor in mouse small intestines. Taking advantages of the nano delivery system, we demonstrate that small intestine-specific MMP-12 knockdown alleviates high-fat diet feeding-induced metabolic disorders and improves intestinal homeostasis in mice, including a significant decrease in lipid transportation, bile acid reabsorption, and inflammation. In parallel, the small intestinal integrity is recovered and the gut microbiota composition is reversed towards that under normal diet feeding. Mechanistically, MMP-12, differing from its traditional elastolytic function, acts as a transcriptional factor to activate Fabp4 transcription through epigenetic modification. In translational medicine, clinical applications of our nanosystem and therapeutic interventions targeting MMP-12 will benefit patients with obesity and associated diseases.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121183DOI Listing
November 2021

A review on patient-specific facial and cranial implant design using Artificial Intelligence (AI) techniques.

Expert Rev Med Devices 2021 Oct 1;18(10):985-994. Epub 2021 Sep 1.

State Key Laboratory of Mechanical System and Vibration, School of Mechanical Engineering, Institute of Bio-medical Manufacturing and Life Quality Engineering, Shanghai Jiao Tong University, Shanghai, China.

Introduction: Researchers and engineers have found their importance in healthcare industry including recent updates in patient-specific implant (PSI) design. CAD/CAM technology plays an important role in the design and development of Artificial Intelligence (AI) based implants.The across the globe have their interest focused on the design and manufacturing of AI-based implants in everyday professional use can decrease the cost, improve patient's health and increase efficiency, and thus many implant designers and manufacturers practice.

Areas Covered: The focus of this study has been to manufacture smart devices that can make contact with the world as normal people do, understand their language, and learn to improve from real-life examples. Machine learning can be guided using a heavy amount of data sets and algorithms that can improve its ability to learn to perform the task. In this review, artificial intelligence (AI), deep learning, and machine-learning techniques are studied in the design of biomedical implants.

Expert Opinion: The main purpose of this article was to highlight important AI techniques to design PSIs. These are the automatic techniques to help designers to design patient-specific implants using AI algorithms such as deep learning, machine learning, and some other automatic methods.
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http://dx.doi.org/10.1080/17434440.2021.1969914DOI Listing
October 2021

Automatic skull defect restoration and cranial implant generation for cranioplasty.

Med Image Anal 2021 10 20;73:102171. Epub 2021 Jul 20.

Institute of Computer Graphics and Vision, Graz University of Technology, Inffeldgasse 16, Graz 8010, Austria; Department of Oral and Maxillofacial Surgery, Medical University of Graz, Auenbruggerplatz 2, Graz 8036, Austria; Computer Algorithms for Medicine Laboratory, Graz, Austria; BioTechMed-Graz, Mozartgasse 12/II, Graz 8010, Austria. Electronic address:

A fast and fully automatic design of 3D printed patient-specific cranial implants is highly desired in cranioplasty - the process to restore a defect on the skull. We formulate skull defect restoration as a 3D volumetric shape completion task, where a partial skull volume is completed automatically. The difference between the completed skull and the partial skull is the restored defect; in other words, the implant that can be used in cranioplasty. To fulfill the task of volumetric shape completion, a fully data-driven approach is proposed. Supervised skull shape learning is performed on a database containing 167 high-resolution healthy skulls. In these skulls, synthetic defects are injected to create training and evaluation data pairs. We propose a patch-based training scheme tailored for dealing with high-resolution and spatially sparse data, which overcomes the disadvantages of conventional patch-based training methods in high-resolution volumetric shape completion tasks. In particular, the conventional patch-based training is applied to images of high resolution and proves to be effective in tasks such as segmentation. However, we demonstrate the limitations of conventional patch-based training for shape completion tasks, where the overall shape distribution of the target has to be learnt, since it cannot be captured efficiently by a sub-volume cropped from the target. Additionally, the standard dense implementation of a convolutional neural network tends to perform poorly on sparse data, such as the skull, which has a low voxel occupancy rate. Our proposed training scheme encourages a convolutional neural network to learn from the high-resolution and spatially sparse data. In our study, we show that our deep learning models, trained on healthy skulls with synthetic defects, can be transferred directly to craniotomy skulls with real defects of greater irregularity, and the results show promise for clinical use. Project page: https://github.com/Jianningli/MIA.
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http://dx.doi.org/10.1016/j.media.2021.102171DOI Listing
October 2021

- Dataset for automatic cranial implant design and a benchmark for volumetric shape learning tasks.

Data Brief 2021 Apr 24;35:106902. Epub 2021 Feb 24.

Brno University of Technology (BUT), Brno, Czech Republic.

The article introduces two complementary datasets intended for the development of data-driven solutions for cranial implant design, which remains to be a time-consuming and laborious task in current clinical routine of cranioplasty. The two datasets, referred to as the SkullBreak and SkullFix in this article, are both adapted from a public head CT collection (http://headctstudy.qure.ai/dataset) with license. The SkullBreak contains 114 and 20 complete skulls, each accompanied by five defective skulls and the corresponding cranial implants, for training and evaluation respectively. The SkullFix contains 100 triplets (complete skull, defective skull and the implant) for training and 110 triplets for evaluation. The SkullFix dataset was first used in the MICCAI 2020 AutoImplant Challenge (https://autoimplant.grand-challenge.org/) and the ground truth, i.e., the complete skulls and the implants in the evaluation set are held private by the organizers. The two datasets are not overlapping and differ regarding data selection and synthetic defect creation and each serves as a complement to the other. Besides cranial implant design, the datasets can be used for the evaluation of volumetric shape learning algorithms, such as volumetric shape completion. This article gives a description of the two datasets in detail.
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http://dx.doi.org/10.1016/j.dib.2021.106902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100897PMC
April 2021

AutoImplant 2020-First MICCAI Challenge on Automatic Cranial Implant Design.

IEEE Trans Med Imaging 2021 09 31;40(9):2329-2342. Epub 2021 Aug 31.

The aim of this paper is to provide a comprehensive overview of the MICCAI 2020 AutoImplant Challenge. The approaches and publications submitted and accepted within the challenge will be summarized and reported, highlighting common algorithmic trends and algorithmic diversity. Furthermore, the evaluation results will be presented, compared and discussed in regard to the challenge aim: seeking for low cost, fast and fully automated solutions for cranial implant design. Based on feedback from collaborating neurosurgeons, this paper concludes by stating open issues and post-challenge requirements for intra-operative use. The codes can be found at https://github.com/Jianningli/tmi.
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http://dx.doi.org/10.1109/TMI.2021.3077047DOI Listing
September 2021

Synthetic skull bone defects for automatic patient-specific craniofacial implant design.

Sci Data 2021 01 29;8(1):36. Epub 2021 Jan 29.

Institute for Computer Graphics and Vision, Graz University of Technology, Inffeldgasse 16c/II, 8010, Graz, Austria.

Patient-specific craniofacial implants are used to repair skull bone defects after trauma or surgery. Currently, cranial implants are designed and produced by third-party suppliers, which is usually time-consuming and expensive. Recent advances in additive manufacturing made the in-hospital or in-operation-room fabrication of personalized implants feasible. However, the implants are still manufactured by external companies. To facilitate an optimized workflow, fast and automatic implant manufacturing is highly desirable. Data-driven approaches, such as deep learning, show currently great potential towards automatic implant design. However, a considerable amount of data is needed to train such algorithms, which is, especially in the medical domain, often a bottleneck. Therefore, we present CT-imaging data of the craniofacial complex from 24 patients, in which we injected various artificial cranial defects, resulting in 240 data pairs and 240 corresponding implants. Based on this work, automatic implant design and manufacturing processes can be trained. Additionally, the data of this work build a solid base for researchers to work on automatic cranial implant designs.
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http://dx.doi.org/10.1038/s41597-021-00806-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846796PMC
January 2021

Augmented Reality for Head and Neck Carcinoma Imaging: Description and Feasibility of an Instant Calibration, Markerless Approach.

Comput Methods Programs Biomed 2021 Mar 20;200:105854. Epub 2020 Nov 20.

Institute of Computer Graphics and Vision, Graz University of Technology, Inffeldgasse 16, 8010 Graz, Austria; Department of Oral and Maxillofacial Surgery, Medical University of Graz, Auenbruggerplatz 5, 8036 Graz, Austria; Computer Algorithms for Medicine Laboratory, Graz, Austria; BioTechMed-Graz, Mozartgasse 12/II, 8010 Graz, Austria. Electronic address:

Background And Objective: Augmented reality (AR) can help to overcome current limitations in computer assisted head and neck surgery by granting "X-ray vision" to physicians. Still, the acceptance of AR in clinical applications is limited by technical and clinical challenges. We aim to demonstrate the benefit of a marker-free, instant calibration AR system for head and neck cancer imaging, which we hypothesize to be acceptable and practical for clinical use.

Methods: We implemented a novel AR system for visualization of medical image data registered with the head or face of the patient prior to intervention. Our system allows the localization of head and neck carcinoma in relation to the outer anatomy. Our system does not require markers or stationary infrastructure, provides instant calibration and allows 2D and 3D multi-modal visualization for head and neck surgery planning via an AR head-mounted display. We evaluated our system in a pre-clinical user study with eleven medical experts.

Results: Medical experts rated our application with a system usability scale score of 74.8 ± 15.9, which signifies above average, good usability and clinical acceptance. An average of 12.7 ± 6.6 minutes of training time was needed by physicians, before they were able to navigate the application without assistance.

Conclusions: Our AR system is characterized by a slim and easy setup, short training time and high usability and acceptance. Therefore, it presents a promising, novel tool for visualizing head and neck cancer imaging and pre-surgical localization of target structures.
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http://dx.doi.org/10.1016/j.cmpb.2020.105854DOI Listing
March 2021

[Synergistic role of JAK/STAT5 and PI3K/AKT signaling pathways in regulating eIF4B in acute leukemia].

Sheng Wu Gong Cheng Xue Bao 2020 Nov;36(11):2413-2423

Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Human acute leukemia (AL) is a clonal malignancy with abnormal hematopoietic stem cells. Clinically, AL is very difficult to cure due to its sudden onset and short course of disease progression. Previous studies have shown that eukaryotic initiation factor 4B (eIF4B) plays a critical role in the development of chronic leukemia. However, the involvement of eIF4B in human acute leukemia is still largely unknown. Therefore, we studied eIF4B function and its regulatory mechanism in human acute leukemia. We found that phosphorylation levels of eIF4B in acute leukemia cells were significantly reduced in response to treatment with either LY294002 (PI3K inhibitor), AKTi (AKT inhibitor) or SMI-4A (Pim inhibitor). Co-treatment with inhibitors targeting JAK/STAT5/Pim and PI3K/AKT/mTOR signaling dramatically promoted apoptosis of acute leukemia cells by downregulating eIF4B phosphorylation. Furthermore, in vitro and in vivo functional experiments showed that eIF4B played an important anti-apoptosis role in the acute leukemia cells by regulating the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL. In contrast, silencing eIF4B inhibited the growth of acute leukemia cells as engrafted tumors in nude mice. Taken together, our results indicate the synergistic role of JAK/STAT5/Pim and PI3K/AKT/mTOR signaling pathways in regulating eIF4B phosphorylation in acute leukemia, and highlight eIF4B as a candidate therapeutic target for treatment of acute leukemia.
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http://dx.doi.org/10.13345/j.cjb.200015DOI Listing
November 2020

Exosomal miR-199a-5p promotes hepatic lipid accumulation by modulating MST1 expression and fatty acid metabolism.

Hepatol Int 2020 Dec 10;14(6):1057-1074. Epub 2020 Oct 10.

School of Basic Medical Sciences, Ningxia Medical University, Xingqing District, 692 Shengli St, Yinchuan, 75004, China.

Background And Aims: Non-alcoholic fatty liver disease (NAFLD) and its complications has become an expanding health problem worldwide with limited therapeutic approaches. The current study was aiming to identify novel microRNA in the regulation of hepatic lipid metabolism in NAFLD.

Approches And Results: Systematic screening of microRNA expression by high-throughput small RNA sequencing demonstrated that microRNA 199a-5p (miR-199a-5p) was significantly upregulated in high fat diet-induced steatosis mouse model, with the most abundant expression in adipose tissue. MST1 was further identified as the target gene for miR-199a with specific recognition at the 3' untranslated region with dural luciferase reporter assay. Delivery of miR-199a-5p with exosomes into mice aggravated liver lipid accumulation in hepatocytes, accompanied by down-regulation of hepatic MST1 expression and modulation of hepatic lipogenesis and lipolysis, including SREBP-1c, AMPK signaling cascades and the down-stream CPT1α and FASN. Conversely, administration of exosome containing anti-miR-199a-5p resulted in attenuated steotosis in mice fed on high fat diet. Importanly, miR-199a-5p-induced abnormal cellular lipid accumulation could be markedly reversed by overexpression of MST1.

Conclusion: miR-199a-5p might be an essentail regulator for hepatic lipid metabolism, possibly through its interction with MST1 and the subsequent signaling cascade. Thus, miR-199a-5p may serve as an important therapeutic target in the treatment of NAFLD.
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http://dx.doi.org/10.1007/s12072-020-10096-0DOI Listing
December 2020

Detection, segmentation, simulation and visualization of aortic dissections: A review.

Med Image Anal 2020 10 7;65:101773. Epub 2020 Jul 7.

Institute of Computer Graphics and Vision, Graz University of Technology, Inffeldgasse 16, 8010 Graz, Austria; Computer Algorithms for Medicine Laboratory, Graz, Austria; BioTechMed-Graz, Mozartgasse 12/II, 8010 Graz, Austria; Department of Oral and Maxillofacial Surgery, Medical University of Graz, Auenbruggerplatz 2, 8036 Graz, Austria; Shanghai Jiao Tong University, School of Mechanical Engineering, 800 Dong Chuan Road, Shanghai 200240, China. Electronic address:

Aortic dissection (AD) is a condition of the main artery of the human body, resulting in the formation of a new flow channel, or false lumen. The disease is usually diagnosed with a computed tomography angiography scan during the acute phase. A better understanding of the causes of AD requires knowledge of the aortic geometry (segmentation), including the true and false lumina, which is very time-consuming to reconstruct when performed manually on a slice-by-slice basis. Hence, different automatic and semi-automatic medical image analysis approaches have been proposed for this task over the last years. In this review, we present and discuss these computing techniques used to segment dissected aortas, also in regard to the detection and visualization of clinically relevant information and features from dissected aortas for customized patient-specific treatments.
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http://dx.doi.org/10.1016/j.media.2020.101773DOI Listing
October 2020

Angiogenesis in primary colorectal cancer and matched metastatic tissues: Biological and clinical implications for anti-angiogenic therapies.

Oncol Lett 2020 May 6;19(5):3558-3566. Epub 2020 Mar 6.

Department of Gastrointestinal Cancer Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China.

Metastasis remains a notable issue in patients with newly diagnosed colorectal carcinomas (CRC). Although anti-angiogenic therapies target metastatic diseases, hypoxia-inducible factor-1 α (HIF-1α) and vascular endothelial growth factor (VEGF) status are routinely evaluated in primary tumors as metastatic sites are infrequently biopsied. The present study aimed to investigate the expression and significance of HIF-1α, VEGF and microvascular density (MVD) in primary tumors and corresponding metastatic CRC tissues. HIF-1α, VEGF and CD34 status were analyzed via immunohistochemistry analysis in 46 patients who underwent surgical resection of primary CRC (35 colon and 11 rectum) and matched metastases (lymph node and liver metastases) in Shandong Cancer Hospital. The association between selected biomarker status and clinicopathological characteristics was analyzed, and expression levels in primary tumors and corresponding metastases were compared. A total of 46 paired colorectal primary tumor and synchronous metastases samples were acquired for analysis using a standardized HIF-1α, VEGF and CD34 immunohistochemical procedure. The results demonstrated that the positive rates of HIF-1α and VEGF in primary CRC were 70 and 73.9%, respectively. HIF-1α (60.9%) and VEGF (58.7%) expression decreased in the lymph metastatic samples compared with primary CRC. Conversely, the level of MVD in primary tumors was significantly higher compared with metastatic tumors. No significant differences were demonstrated between HIF-1α and VEGF expression and the different clinicopathological features in primary CRC and corresponding metastases. Primary carcinomas and matched metastatic tissues demonstrated a moderate level of consistent immunoreactivity for HIF-1α and VEGF. HIF-1α, VEGF and CD34 were expressed in both primary tumors and corresponding metastases of CRC, suggesting that they may be involved in the development of metastasis. HIF-1α and VEGF expression in primary sites was consistent with that observed in metastases; however, it varied from that exhibited in MVD. The current analysis will improve the current understanding of the metastasis models and provide further evidence for evaluating the response to HIF-1α and VEGF inhibitors.
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http://dx.doi.org/10.3892/ol.2020.11450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115125PMC
May 2020

A Robust Algorithm for Selecting Optimal Regularization Parameter Based on Bilateral Accumulative Area.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:4893-4896

The choice of regularization parameters is very important for the reconstruction result in the inverse problem of electrocardiology. In this study, the bilateral accumulative area detector is introduced to estimate the optimal parameter points of the L-curve and Generalized Cross-Validation method to Tikhonov regularization and truncated singular value decomposition. The experimental results suggest that this method can achieve high validity and high robustness for the estimation of regularization parameters compared to conventional methods.
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http://dx.doi.org/10.1109/EMBC.2019.8856865DOI Listing
July 2019

Structural Analysis of Complex Atrial Intramural Microstructure from A Multi-layer Model Based on Siamese Network.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:294-297

Quantitative analysis of complex atrial intramural microstructure is a crucial step towards understanding the mechanism behind atrial fibrillation (AF) maintenance. Siamese network was adopted to extract features from computationally simulated multi-layer fibrosis structure. Through analysis of the features produced by the feature extractor, the difference between Non-sustained and Sustained simulations was comprehended intuitively and electrophysiologically. Complex conduction pathway marked by the feature extractor might be an indicator for AF radio-frequency ablation clinically.
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http://dx.doi.org/10.1109/EMBC.2019.8857276DOI Listing
July 2019

Evidence updating with static and dynamical performance analyses for industrial alarm system design.

ISA Trans 2020 Apr 9;99:110-122. Epub 2019 Sep 9.

School of Automation, Hangzhou Dianzi University, Hangzhou 100084, China.

In the Dempster-Shafer theory (DST) of evidence, the alarm evidence updating-based method can effectively deal with the uncertainty of the monitored process variable so as to significantly reduce the false alarm rates (FAR) and missed alarm rates (MAR) of the industrial alarm system. But the price of the decrease of FAR and MAR is the increase of the averaged alarm delay (AAD). In order to obtain better comprehensive performance, besides the accuracy indices (FAR and MAR), the sensitivity index (AAD) should be considered simultaneously in the alarm system parameter optimization design. In the framework of DST, firstly, this paper defines the static and dynamical performance indices in the alarm evidence space which are compatible with FAR/MAR/AAD in the process variable space. But the former can measure the performance of the DST-based alarm systems more naturally and elaborately than the latter; secondly, a systematic parameter optimization design procedure for the alarm system is investigated by using these new indices and the tradeoff among them. Finally, two typical numerical experiments and an industrial case are provided to illustrate the effectiveness of the static and dynamical indices for improving the comprehensive performance of the DST-based alarm systems.
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http://dx.doi.org/10.1016/j.isatra.2019.09.006DOI Listing
April 2020

Short-term efficacy and safety of MR-guided focused ultrasound surgery for analgesia in children with metastatic bone tumors.

Oncol Lett 2019 Sep 18;18(3):3283-3289. Epub 2019 Jul 18.

Ultrasonic Diagnostic Laboratory, Shandong Medical Imaging Research Institute, Jinan, Shandong 250001, P.R. China.

Short-term efficacy and safety of magnetic resonance-guided focused ultrasound surgery (MRgFUS) for analgesia in children with metastatic bone tumors were studied. Thirty children with pediatric bone metastases admitted to Jinan Maternity and Child Care Hospital from March 2015 to March 2018 and who received MRgFUS treatment of the bone metastasis lesions were collected. The postoperative efficacy was assessed. The observation indicators included the Numerical Rating Scale (NRS) scores, European Organization for Research and Treatment of Cancer (EORTC) and Quality of Life Questionnaire (QLQ) scores before surgery, and 1 week, 1, 2, and 3 months after surgery and the Karnofsky Performance Status (KPS) scores before surgery, and 1 week and 3 months after surgery. The adverse reactions and medications of the children after the surgery were also under observation. NRS and VAS scores of all different observation time-points after surgery were statistically lower than those before surgery (P<0.05), and the NRS scores and Visual Analog Scale (VAS) scores 3 months after surgery were lower than those 1 week after surgery (P<0.05). Compared with the preoperative conditions, the QLQ-C30 scores of terms like physical function, cognitive function, nausea and vomiting, and degree of pain 1 week, 1, 2, and 3 months after surgery were decreased, and the clinical symptoms of the children were relieved (P<0.05). There was a statistical difference between the total QLQ-C30 scores 3 months after operation and the total QLQ-C30 scores 3 months before operation (P<0.05). No serious adverse reactions related to treatment were reported, and the application of analgesics was reduced. MRgFUS relieves bone metastasis pain in children with good curative effect and high safety.
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http://dx.doi.org/10.3892/ol.2019.10628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676446PMC
September 2019

Diagnostic value of echocardiography in fetal cardiac malformation and clinical classification.

Exp Ther Med 2019 Sep 3;18(3):1595-1600. Epub 2019 Jul 3.

Department of Ultrasound, Jinan Maternity and Child Care Hospital, Jinan, Shandong 250001, P.R. China.

Diagnostic value of echocardiography in fetal cardiac malformation and clinical classification was investigated. In total, 206 high-risk parturients, who received a screening of prenatal fetal cardiac malformation in Jinan Maternity and Child Care Hospital from January 2015 to June 2017, were retrospectively analyzed, among those parturients, the results of labor induction or newborns of 141 parturients were diagnosed as cardiac malformation, the fetuses of 65 parturients were diagnosed as non-cardiac malformation, the detection of fetal cardiac malformation of all the parturients was carried out by two-dimensional ultrasound and four-dimensional ultrasound during gestation period, presence or absence of congenital cardiac malformation of the fetuses and clinical classification were estimated. The sensitivity of two-dimensional ultrasound diagnosis combined with four-dimensional ultrasound diagnosis was significantly higher than that of two-dimensional ultrasound diagnosis and four-dimensional ultrasound diagnosis (P<0.05). In addition, the sensitivity of four-dimensional ultrasound diagnosis was significantly higher than that of two-dimensional ultrasound diagnosis (P<0.05). The specificity and positive predictive value of four-dimensional ultrasound diagnosis were significantly higher than those of two-dimensional ultrasound diagnosis and two-dimensional ultrasound diagnosis combined with four-dimensional ultrasound diagnosis (P<0.05). The diagnostic coincidence rates of four-dimensional ultrasound diagnosis and two-dimensional ultrasound diagnosis combined with four-dimensional ultrasound diagnosis were significantly higher than that of two-dimensional ultrasound diagnosis (P<0.05). The negative predictive values of the combined ultrasound diagnosis and four-dimensional ultrasound diagnosis were significantly higher than that of two-dimensional ultrasound diagnosis (P<0.05). The diagnostic efficiency of two-dimensional ultrasound combined with four-dimensional ultrasound was good in the diagnosis of fetal cardiac malformation in prenatal period of pregnant women, it could improve detection rate of fetal cardiac malformation and is worthy of being generalized in clinic.
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http://dx.doi.org/10.3892/etm.2019.7732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676119PMC
September 2019

The effect of complex intramural microstructure caused by structural remodeling on the stability of atrial fibrillation: Insights from a three-dimensional multi-layer modeling study.

PLoS One 2018 28;13(11):e0208029. Epub 2018 Nov 28.

Institute of Biomedical Engineering, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China.

Background: Recent researches have suggested that the complex three-dimensional structures caused by structural remodeling play a key role in atrial fibrillation (AF) substrates. Here we aimed to investigate this hypothesis using a multi-layer model representing intramural microstructural features.

Methods: The proposed multi-layer model was composed of the endocardium, connection wall, and epicardium. In the connection wall, intramural fibrosis was simulated using fibrotic patches randomly scattered in the myocardial tissue of fibrotic layers, while endo-epicardial dissociation was simulated using myocardial patches randomly scattered in the fibrotic tissue of isolation layers. Multiple simulation groups were generated to quantitatively analyze the effects of endo-epicardial dissociation and intramural fibrosis on AF stability, including a stochastic group, interrelated groups, fibrosis-degree-controlled groups, and dissociation-degree-controlled groups.

Results: 1. Stable intramural re-entries were observed to move along complete re-entrant circuits inside the transmural wall in four of 65 simulations in the stochastic group. 2. About 21 of 23 stable simulations in the stochastic group were distributed in the areas with high endo-epicardial dissociation and intramural fibrosis. 3. The difference between fibrosis-degree-controlled groups and dissociation-degree-controlled groups suggested that some distributions of connection areas may affect AF episodes despite low intramural fibrosis and endo-epicardial dissociation. 4. The overview of tracking phase singularities revealed that endo-epicardial dissociation played a visible role in AF substrates.

Conclusion: The complex intramural microstructure is positively correlated with critical components of AF maintenance mechanisms. The occurrence of intramural re-entry further indicates the complexity of AF wave-dynamics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208029PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261624PMC
May 2019

Interaction of Abl Tyrosine Kinases with SOCS3 Impairs Its Suppressor Function in Tumorigenesis.

Neoplasia 2018 11 18;20(11):1095-1105. Epub 2018 Sep 18.

Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China. Electronic address:

Suppressor of cytokine signaling 3 (SOCS3) is involved in Bcr-Abl-induced tumorigenesis. However, how SOCS3 interacts with Bcr-Abl and is regulated by Abl kinases remains largely unknown. Since c-Abl plays a critical role in tumorigenesis, we asked whether SOCS3 is regulated by c-Abl-dependent phosphorylation. Here, we found that SOCS3 interacted with all three Abl kinases (Bcr-Abl, v-Abl, and c-Abl), and SH1 domain of the Abl kinases was critically required for such interaction. Furthermore, the SH2 domain of SOCS3 was sufficient to pull down the SH1 domain but not the full length of Bcr-Abl. Importantly, SOCS3 was highly tyrosine phosphorylated by c-Abl, leading to impairment of its ability to suppress JAK8+72 activity. In addition, disrupting the tyrosine phosphorylation of SOCS3 promoted apoptosis of c-Abl-expressing cells and impeded xenograft growth of these tumor cells in nude mice. The results demonstrate that SOCS3 is highly tyrosine phosphorylated by c-Abl and that tyrosine phosphorylation of SOCS3 is required for the survival and tumorigenesis of certain cells. Our findings provide novel insights into complicated mechanisms underlying the oncogenic function of Abl kinases.
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http://dx.doi.org/10.1016/j.neo.2018.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143717PMC
November 2018

Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient receiving tamoxifen: A case report and literature review.

Medicine (Baltimore) 2018 Jun;97(23):e10900

Department of General Surgery, Huzhou Central Hospital, Huzhou The Central Sterile Supply Department, Affiliated Hospital of Shandong Academy of Medical Sciences School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences The Fourth Surgical Department, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan Department of Clinical Laboratory, Zhucheng People's Hospital of Shandong Province, Zhucheng, China.

Rationale: Small cell carcinoma of the ovary (SCCO) is a rare and aggressive extra-pulmonary variant of small cell tumors of uncertain histogenesis. The pathogenesis and optimal treatment of SCCO is unclear. We present a very rare case of a synchronous primary ovarian small cell carcinoma and endometrioid adenocarcinoma of the uterus in a patient after 2 years of tamoxifen treatment for breast cancer. This is the first such report in the English literature.

Patient Concerns: A 46-year-old woman had a history of left breast cancer that was treated with a simple mastectomy and sentinel lymph node biopsy in 2013. The post-operative pathology was invasive ductal carcinoma of the left breast. she had been taking tamoxifen for 2 years. The patient underwent an exploratory laparotomy to reduce the tumor burden, improve bowel compression symptoms, and promote defecation in 2015. The post-operative pathology revealed a rare, simultaneous occurrence of two tumors (endometrial adenocarcinoma and SCCO [pulmonary type]).

Diagnoses: Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient.

Interventions: The patient received 3 courses of chemotherapy after operation. The effect was not apparent and the general health status was poor.

Outcomes: The patient died of progressive disease 7 months post-operatively.

Lessons: The present case suggests that tamoxifen use might be among many etiologic factors in SCCO development. Despite its rarity, SCCO requires a high degree of attention in clinical work because it is an aggressive tumor that has a poor prognosis.
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http://dx.doi.org/10.1097/MD.0000000000010900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999514PMC
June 2018

Lycium barbarum polysaccharide attenuates high-fat diet-induced hepatic steatosis by up-regulating SIRT1 expression and deacetylase activity.

Sci Rep 2016 11 8;6:36209. Epub 2016 Nov 8.

Department of Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China.

In this study, we aimed to investigate the protective effects and underlying mechanism of Lycium barbarum polysaccharide (LBP) on high-fat-induced nonalcoholic fatty liver disease (NAFLD). Recently, sirtuin 1 (SIRT1) has been shown to play an important role in the regulation of hepatocellular lipid metabolism. Here, we demonstrated that LBP up-regulates SIRT1 deacetylase activity and protein expression by enhancing the NAD/NADH ratio. Subsequently, LBP promoted LKB1 deacetylation and AMPK phosphorylation via SIRT1-dependent signalling. We also found that LBP increases acetyl-CoA carboxylase (ACC) phosphorylation and adipose triglyceride lipase (ATGL) protein expression and decreases fatty acid synthase (FAS) by activating the SIRT1/LKB1/AMPK pathway in vitro and in vivo. However, SIRT1 small interfering RNA (siRNA)-mediated knockdown reversed the LBP-mediated effects on ACC, FAS and ATGL. Moreover, LBP elevated carnitine palmitoyltransferase-1 alpha (CPT-1α) expression by suppressing malonyl-CoA accumulation. Taken together, our data indicate that LBP plays a vital role in the regulation of hepatic lipid metabolism and that pharmacological activation of SIRT1 by LBP may be a strategy for the prevention of NAFLD.
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http://dx.doi.org/10.1038/srep36209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099939PMC
November 2016

[Primary study of corneal exposure ratio measured by Photoshop pixel method].

Zhonghua Zheng Xing Wai Ke Za Zhi 2016 May;32(3):170-4

Objective: To investigate the role of corneal exposure ratio in eyelid aesthetic assessment through the measurement by Photoshop pixel method in beauties and patients with double eyelid blepharoplasty.

Methods: 30 cases of female beauties and 43 cases with double eyelid blepharoplasty(23 cases with suture method and 20 cases with incision method) underwent measurement of corneal exposure ratio by Photoshop pixel method before operation and half a year after operation. The results were analyzed by SPSS 16.0 and compared between different sides or between pre-and post-operation.

Results: The corneal exposure ratio was (87.34±4.15)% on the left side and (87.22±3.77)% on the right side in the beauties. In the 23 cases with suture method, the pre-and post-operation results were (83.02 ± 4.05)% and (83.32 ±3.74)% on the left side,(82.93 ±3.75)% and (83.85±3.65)% on the right side. In the 20 cases with incision method, the pre-and post-operation results were (64.05 ±4.53) % and(84.93±2.39)% on the left side,(64.44 ±4.86)% and (85.09 ±2.77)% on the right side.

Conclusions: Corneal exposure ratio plays an important role in the eyelid aesthetic assessment. The measurement of Photoshop pixel method can provide an objective and precise assessment parameter for double eyelid blepharoplasty.
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May 2016

A Healthy Dietary Pattern Reduces Lung Cancer Risk: A Systematic Review and Meta-Analysis.

Nutrients 2016 Mar 4;8(3):134. Epub 2016 Mar 4.

Department of Surgical Oncology, Shandong Cancer Hospital and Institute, No. 440 Jiyan Road, Jinan 250117, China.

Background: Diet and nutrients play an important role in cancer development and progress; a healthy dietary pattern has been found to be associated with several types of cancer. However, the association between a healthy eating pattern and lung cancer risk is still unclear.

Objective: Therefore, we conducted a systematic review with meta-analysis to evaluate whether a healthy eating pattern might reduce lung cancer risk.

Methods: We identified relevant studies from the PubMed and Embase databases up to October 2015, and the relative risks were extracted and combined by the fixed-effects model when no substantial heterogeneity was observed; otherwise, the random-effects model was employed. Subgroup and publication bias analyses were also performed.

Results: Finally, eight observational studies were included in the meta-analysis. The pooled relative risk of lung cancer for the highest vs. lowest category of healthy dietary pattern was 0.81 (95% confidence interval, CI: 0.75-0.86), and no significant heterogeneity was detected. The relative risks (RRs) for non-smokers, former smokers and current smokers were 0.89 (95% CI: 0.63-1.27), 0.74 (95% CI: 0.62-0.89) and 0.86 (95% CI: 0.79-0.93), respectively. The results remained stable in subgroup analyses by other confounders and sensitivity analysis.

Conclusions: The results of our meta-analysis suggest that a healthy dietary pattern is associated with a lower lung cancer risk, and they provide more beneficial evidence for changing the diet pattern in the general population.
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http://dx.doi.org/10.3390/nu8030134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808863PMC
March 2016

[Preparation and application of rabbit antiserum against structural protein VP2 of canine bocavirus].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2016 Feb;32(2):253-7

Department of Biochemistry and Molecular Biology, School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, China. *Corresponding author, E-mail:

Objective: To prepare the rabbit polyclonal antibody against canine bocavirus (CBV) structural protein VP2 and identify its specificity.

Methods: The target sequence of gene fragment encoding VP2 C-terminal region (300 AA) was amplified from CBV infection clone. After the restriction enzyme digestion and nucleotide sequencing, the target gene was successfully inserted into pET32a(+) prokaryotic expression vector to form recombinant plasmid pET-32a(+)-VP2. Then pET-32a(+)-VP2 was transferred into E.coli (BL21), and VP2-his fusion protein was induced under the optimized induction of isopropyl β-D-thiogalactopyranoside (IPTG). The products were identified and analyzed by SDS-PAGE. The purified fusion protein was inoculated into adult rabbits to develop polyclonal antibody. After the titer of the antiserum was detected by ELISA, Western blotting and immunofluorescence staining were performed to evaluate the features of the prepared antiserum.

Results: Restriction enzyme digestion and sequencing showed that prokaryotic expression vector pET-32a(+)-VP2 was successfully constructed. The soluble recombinant protein was highly expressed in E.coli BL21 as expected. After purification and inoculation into adult rabbits, the high-titer polyclonal antibody was prepared and the titer was 1:6 400 000. Western blotting and immunohistochemistry demonstrated that the specificity of the prepared polyclonal antibody was perfect.

Conclusion: The polyclonal antibody against CBV structural protein VP2 has been successfully prepared.
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February 2016

eIF4B is a convergent target and critical effector of oncogenic Pim and PI3K/Akt/mTOR signaling pathways in Abl transformants.

Oncotarget 2016 Mar;7(9):10073-89

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.

Activation of eIF4B correlates with Abl-mediated cellular transformation, but the precise mechanisms are largely unknown. Here we show that eIF4B is a convergent substrate of JAK/STAT/Pim and PI3K/Akt/mTOR pathways in Abl transformants. Both pathways phosphorylated eIF4B in Abl-transformed cells, and such redundant regulation was responsible for the limited effect of single inhibitor on Abl oncogenicity. Persistent inhibition of one signaling pathway induced the activation of the other pathway and thereby restored the phosphorylation levels of eIF4B. Simultaneous inhibition of the two pathways impaired eIF4B phosphorylation more effectively, and synergistically induced apoptosis in Abl transformed cells and inhibited the growth of engrafted tumors in nude mice. Similarly, the survival of Abl transformants exhibited a higher sensitivity to the pharmacological inhibition, when combined with the shRNA-based silence of the other pathway. Interestingly, such synergy was dependent on the phosphorylation status of eIF4B on Ser422, as overexpression of eIF4B phosphomimetic mutant S422E in the transformants greatly attenuated the synergistic effects of these inhibitors on Abl oncogenicity. In contrast, eIF4B knockdown sensitized Abl transformants to undergo apoptosis induced by the combined blockage. Collectively, the results indicate that eIF4B integrates the signals from Pim and PI3K/Akt/mTOR pathways in Abl-expressing leukemic cells, and is a promising therapeutic target for such cancers.
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http://dx.doi.org/10.18632/oncotarget.7164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891105PMC
March 2016

Gallbladder perforation: a rare complication of postoperative chemotherapy of gastric cancer.

World J Surg Oncol 2015 Aug 15;13:245. Epub 2015 Aug 15.

Department of Colorectal Cancer Surgery, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, 250117, China.

A middle-aged man presented 1 day after being discharged from hospital with completing the first course of postoperative chemotherapy. He suffered a sudden persistent high fever and chills. It was noted that he had a history of a total gastrectomy (with D2 lymphadenectomy) 1 month ago. His admission bloods revealed total bilirubin was 142.2 umol/L, indirect bilirubin of 107.6 umol/L and white cell count of 20.05×10(9)/L. A color doppler ultrasound scan confirmed fluid and gas around liver and hilus lienis while the gallbladder cannot be detected. During Computed Tomography (CT) guided puncture positioning technology and setting a three-channel tube, about 400 ml of foul smell hazel turbid liquid was drained out. He was diagnosed as gallbladder perforation and he was underwent conservative treatment consist of drainage, banning diet, total parenteral nutrition and intravenous antibiotics. Then he recovered well within the subsequent 10 days and was discharged.
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http://dx.doi.org/10.1186/s12957-015-0659-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536862PMC
August 2015

Microsurgery in 46 cases with total hand degloving injury.

Asian J Surg 2015 Oct 14;38(4):205-9. Epub 2015 Mar 14.

Department of Orthopaedics, Ruihua Hospital Affiliated to Soochow University, Suzhou 215104, China. Electronic address:

Objective: To summarize the characteristics of total hand degloving injury and investigate the curative effect of microsurgery.

Methods: A total of 46 patients with total hand degloving injury were enrolled in this study. The injury classification and treatment methods were as follows: Type I (11 cases), treated by replantation of the gloved skin; Type II (6 cases), treated by reconstruction using thumb wrap-around flap and second toe; Type III (4 cases), treated by reconstruction using bilateral second toe with dorsal foot flap; Type IV (9 cases), treated by replantation in situ or reconstruction; Type V (16 cases), treated by replantation or abdominal flap reconstruction.

Results: Of the patients who received Type I treatment, five completely survived, whereas eight had finger necrosis. In Type II, both the reconstructed fingers and hand flaps survived. For four patients who received Type III treatment, eight reconstructed fingers survived. In Type IV, two patients with reconstructed fingers survived, whereas the six with replantation in situ had necrosis of the partial palmar or hand dorsum skin. In Type V, nine patients with reconstructed fingers survived, and five cases with abdominal skin flap reconstruction and one case with anterolateral femoral flap survived. The restoration of hand appearance and function was the best in patients who received replantation. For reconstruction cases, however, the hand function was recovered to the basic self-care level. In cases with abdominal flap reconstruction, the hand function showed poor recovery.

Conclusion: Total hand degloving injury can be classified into different types according to the injury degree. The appropriate microsurgical treatment based on these types can produce better curative effect.
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http://dx.doi.org/10.1016/j.asjsur.2015.01.004DOI Listing
October 2015

[Efficacy of suture ligation combined with super-wet tumescent techniques in resection of peripheral arteriovenous malformations of head and neck].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2014 Nov;28(11):1385-8

Objective: To evaluate the feasibility and effectiveness of suture ligation combined with super-wet tumescent technique to replace embolization before surgical resection of peripheral arteriovenous malformations (AVMs) of the head and neck.

Methods: Between July 2007 and November 2010, 9 patients with peripheral AVMs of the head and neck were treated, including 4 males and 5 females with a median age of 21 years (range, 8 months to 55 years). The causes were congenital malformation in 6 cases, trauma in 2 cases, and unknown origin in 1 case. The lesions were located at the frontotemporal region in 2 patients, cheek in 2 patients, occipitocervical region in 2 patients, temporoparietal region in 1 patient, upper lip in 1 patient, and lower lip in 1 patient. The size of the AVMs lesions ranged from 2.2 cm x 1.2 cm to 13.0 cm x 10.0 cm. Of 9 cases, 8 were classified as Schobinger grade II and I as grade III. The AVMs involved 2 to 7 main nutrient arteries, with a diameter range of 1.7-3.1 mm. At one-stage operation, AVMs was removed and direct suture, skin graft or flaps were used for repair in 6 cases; the skin was expanded at one-stage operation, and then AVMs removal and repair were performed at two- stage operation in 3 cases. Before resection of AVMs, No.7 silk suture was used to ligate the main nutrient vessels, and then annular interrupted suture of soft tissue was performed with the silk sutures around the lesions, at least two rings. Tumescent anesthetic solution was injected into lesions, and super wet end-point achieved.

Results: Partial incision dehiscence occurred in 1 patient; the flaps and grafting skin survived, and primary healing of incision was obtained in the other patients. The mean operation time was 136 minutes (range, 42-367 minutes). The mean intraoperative blood loss was 268 mL (range, 15-1,000 mL). Only 1 patient received 3 units of blood transfusion. All patients were followed up for 4.2 years on average (range, 2 years to 6 years and 6 months); there was no recurrence case. The self-assessment cosmetic results were excellent or good in 5 cases and fair in 4 cases.

Conclusion: Intensive suture ligation followed by super-wet tumescent techniques might partially substitute preoperative embolization to facilitate surgical resection of peripheral AVMs of the head and neck, due to simple operation and less bleeding.
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November 2014

[Establishment of a canine WRD cell line with stable p53 knockdown by lentivirus-mediated p53 silencing].

Nan Fang Yi Ke Da Xue Xue Bao 2014 Dec;34(12):1721-7

Deptartment of Respiratory Medicine, General Hospital of Ningxia Medical University, Yinchuan 750004, China.E-mail:

Objective: To establish a canine cell line with p53 gene knockdown by lentivirus- mediated RNA interference (RNAi).

Methods: Four pairs of oligonucleotide sequences of p53 gene were synthesized and cloned into the pGMLV-SC5 RNAi vector. Following confirmation by PCR and DNA sequencing, the recombinant pGMLV-p53 plasmids and packaging mix vectors were packaged into mature lentivirus to infect 293T cells. The supernatant of the infected cells was harvested to infect WRD cells, in which p53 expression was detected using Western blotting and real-time PCR. The lentivirus with the strongest p53⁻ silencing effect was packaged for infecting WRD cells at the optimal multiplicity of infection (MOI) to establish a stably infected cell line (WRD/p53⁻) screened using puromycin.

Results: The lentivirus carrying p53 shRNA was constructed successfully and a virus titer of 1 × 10⁹ TU/ml. The 4 pGMLV-p53 plasmids all produced strong p53 interference affects, and pGMLV- p53A1 with the strongest effect. The stably infected cells line WRD/p53⁻ was established successfully using pGMLV-p53A1 plasmid.

Conclusion: The canine cell line WRD/p53⁻ with stable lentivirus-mediated p53 silencing has been established successfully.
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December 2014

Robotic versus laparoscopic right colectomy: a meta-analysis.

World J Surg Oncol 2014 Aug 28;12:274. Epub 2014 Aug 28.

Department of Colorectal Cancer Surgery, Shandong cancer hospital, 440 Jiyan Road, Jinan 250117, China.

Background: The objective of this meta-analysis was to compare the clinical safety and efficacy of robotic right colectomy (RRC) with conventional laparoscopic right colectomy (LRC).

Methods: A literature search was performed for comparative studies reporting perioperative outcomes of RRC and LRC. The methodological quality of the selected studies was assessed. Depending on statistical heterogeneity, the fixed effects model or the random effects model were used for the meta-analysis. Operative time, estimated blood loss, length of hospital stay, conversion rates to open surgery, postoperative complications, and related outcomes were evaluated.

Results: Seven studies, including 234 RRC cases and 415 conventional LRC cases, were analyzed. The meta-analysis showed that RRC had longer operative times (P < 0.00001), lower estimated blood losses (P = 0.0002), lower postoperative overall complications (P = 0.02), and significantly faster bowel function recovery (P < 0.00001). There were no differences in the length of hospital stay (P = 0.12), conversion rates to open surgery (P = 0.48), postoperative ileus (P = 0.08), anastomosis leakage (P = 0.28), and bleeding (P = 0.95).

Conclusions: Compared to LRC, RRC was associated with reduced estimated blood losses, reduced postoperative complications, longer operative times, and a significantly faster recovery of bowel function. Other perioperative outcomes were equivalent.
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http://dx.doi.org/10.1186/1477-7819-12-274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158068PMC
August 2014
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