Publications by authors named "Wenming Wu"

124 Publications

Portable Heating System Based on a Liquid Metal Bath for Rapid PCR.

ACS Omega 2022 Aug 20;7(30):26165-26173. Epub 2022 Jul 20.

Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 516001, China.

With the outbreak of COVID-19 around the world, rapid and accurate detection of new coronaviruses is the key to stop the transmission of the disease and prevent and control the novel coronavirus, among which polymerase chain reaction (PCR) is the mainstream nucleic acid detection method. A temperature cycling device is the core of the PCR amplification micro-device. The precision of the temperature control and temperature change rate directly affect the efficiency of PCR amplification. This study proposes a new PCR method based on rapid PCR chip optimization of a liquid metal bath, which realizes precise and rapid temperature rise and fall control. We systematically explored the feasibility of using liquid metals with different melting points in the system and proposed a 47 °C bismuth-based liquid metal bath as the heat conduction medium of the system to optimize the system. The heat conduction properties of the thermally conductive silicone oil bath were compared. Compared with the thermally conductive silicone oil bath, thermal cycle efficiency is improved nearly 3 times. The average heating rate of the liquid metal bath is fast, and the temperature control stability is good, which can significantly reduce the hysteresis, and the temperature change curve is more gentle, which can greatly improve the efficiency of PCR amplification. The results of gene amplification using rat DNA as the template and SEC61A as the target also indicate that the system can be successfully used in PCR devices, and the types of PCR containers can be not limited to PCR tubes. Based on the experiment, we proved that the PCR method optimized by the liquid metal bath multi-gene rapid PCR chip can further improve the temperature response speed. It has the advantages of accurate data, fast response speed, low price, safety, and environmental protection and can effectively reduce the time of PCR and improve the application efficiency. As far as we know, this is the first international report on using a liquid metal bath to do rapid-cooling PCR.
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http://dx.doi.org/10.1021/acsomega.2c01824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352155PMC
August 2022

Early detection of pancreatic cancer: are we ready for prime time?

Authors:
Wenming Wu

Gastroenterology 2022 Aug 2. Epub 2022 Aug 2.

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2022.07.072DOI Listing
August 2022

Construction of dPCR and qPCR integrated system based on commercially available low-cost hardware.

Analyst 2022 Jul 22;147(15):3494-3503. Epub 2022 Jul 22.

Institute of biological and medical engineering, Guangdong Academy of Sciences, China.

Fluorescent quantitative PCR (qPCR) and digital PCR (dPCR) are two mainstream nucleic acid quantification technologies. However, commercial dPCR and qPCR instruments have a low integration, a high price, and a large footprint. To solve these shortcomings, we introduce a compound PCR system with both qPCR and dPCR functions. All the hardware used in this compound PCR system is commercially available and low-cost, and free software was used to realize the absolute quantification of nucleic acids. The compound PCR provides two working modes. In the qPCR mode, thermal cycling is realized by controlling the reciprocating motion of the axis. The heating rate is 1.25 °C s and the cooling rate is 1.75 °C s. We performed amplification experiments of the PGEM-3zf (+)1 gene. The performance level was similar to commercial qPCR instruments. In the dPCR mode, the heating rate is 0.5 °C s and the cooling rate is 0.6 °C s. We performed the UPE-Q gene amplification and used the sequential actions of the two-dimensional mechanical sliders to scan the reaction products and used the method of regional statistics and back-inference threshold to get test results. The result we got was 1208 copies per μL, which was similar to expectations.
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http://dx.doi.org/10.1039/d2an00694dDOI Listing
July 2022

Murine double minute 2 aggravates adipose tissue dysfunction through ubiquitin-mediated six-transmembrane epithelial antigen of prostate 4 degradation.

iScience 2022 Jul 7;25(7):104544. Epub 2022 Jun 7.

State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing 100005, China.

Healthy adipose tissue is crucial to maintain normal energy homeostasis. Little is known about the role of murine double minute 2 (MDM2), an E3 ubiquitin ligase and has been highlighted in oncopathology, in adipose tissue. Our results indicated that MDM2 expression was associated with nutritional status. adipocyte-specific knock-in (-AKI) mice exhibited exacerbated weight gain, insulin resistance, and decreased energy expenditure. Meanwhile, chronic high-fat diet (HFD) exposure caused obvious epididymal white adipose tissue (eWAT) dysfunction, such as senescence, apoptosis, and chronic inflammation, thereby leading to hepatic steatosis in -AKI mice. Mechanically, MDM2 could interact with six-transmembrane epithelial antigen of prostate 4 (STEAP4) and inhibit STEAP4 expression through ubiquitin-mediated STEAP4 degradation. Thereinto, the K18 and K161 sites of STEAP4 were ubiquitin-modificated by MDM2. Finally, STEAP4 restoration in eWAT of -AKI mice on a HFD rescued MDM2-induced adipose dysfunction, insulin resistance, and hepatic steatosis. Summary, the MDM2-STEAP4 axis in eWAT plays an important role in maintaining healthy adipose tissue function and improving hepatic steatosis.
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http://dx.doi.org/10.1016/j.isci.2022.104544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209722PMC
July 2022

An Optimized Thermal Feedback Methodology for Accurate Temperature Control and High Amplification Efficiency during Fluorescent qPCR.

Bioengineering (Basel) 2022 May 28;9(6). Epub 2022 May 28.

Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 510000, China.

Traditional qPCR instrument is combined with CMOS and a personal computer, and a photoelectric feedback automatic fluorescence detection system is designed to realize quantitative real-time PCR. The key to reaction efficiency lies in how to ensure that the temperature of the detection reagent completely matches the set temperature. However, for most traditional real-time fluorescent PCR systems, the temperature cycling is controlled by detecting the temperature of the heating well plate. It cannot directly measure the temperature in the reaction reagent PCR tube, which will cause the deviation in the actual temperature of the reagent to be as expected. Therefore, in this paper, we raise a method of directly detecting the temperature in the reaction tube of the reagent during the temperature cycling is adopted. According to the deviation from the expected value, the set temperature of the PCR instrument is adjusted to make the actual temperature of the reagent closer to the expected value. Through this method, we also realized the temperature calibration and optimization of the TEC circulation system we built. Experiments show that this low-cost, portable real-time quantitative PCR system can detect and analyze pathogens in situ.
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http://dx.doi.org/10.3390/bioengineering9060237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220086PMC
May 2022

Automatic bleeding detection in laparoscopic surgery based on a faster region-based convolutional neural network.

Ann Transl Med 2022 May;10(10):546

Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Background: Laparoscopic surgery has been in great demand over the past decades; it has also brought several obstacles, such as increasing difficulty in maintaining hemostasis, changes in surgical approach, and reduced field of vision. Locating the bleeding point can help surgeons to control bleeding quickly, however, to date, there have been no tools designed for automatic bleeding tracking in laparoscopic operations. Herein, we have proposed a spatiotemporal hybrid model based on a faster region-based convolutional neural network (RCNN) for bleeding point detection in laparoscopic surgery videos.

Methods: Laparoscopic videos performed at our hospital were retrieved and images containing bleeding events were extracted. Spatiotemporal features were extracted by using red-green-blue (RGB) frames and optical flow maps and a spatiotemporal hybrid model was developed based on the faster RCNN. The proposed model contributed to (I) providing real-time bleeding point detection which directly assist surgeons, (II) showing the blood's optical flow which improved bleeding point detection, and (III) detecting both arterial and venous bleeding.

Results: In this study, 12 different bleeding videos were included for deep learning model training. Compared with models containing a single RGB or a single optical flow map, our model combining RGB and optical flow achieved great detection results (precision rate of 0.8373, recall rate of 0.8034, and average precision of 0.6818).

Conclusions: Our approach performs well in bleeding point location and recognition, indicating its potential value in helping to maintain and re-establish hemostasis during operations.
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http://dx.doi.org/10.21037/atm-22-1914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201197PMC
May 2022

Analysis of 55 patients with multiple endocrine neoplasia type 1-associated insulinoma from a single center in China.

Orphanet J Rare Dis 2022 06 13;17(1):219. Epub 2022 Jun 13.

Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China.

Objective: To investigate the clinical characteristics of patients with multiple endocrine neoplasia type 1 (MEN1)-related insulinoma and their relationship with specific biochemical changes and to summarize the features of treatment options for the Chinese population with this disease and the impact on long-term prognosis.

Methods: "MEN1" and "insulinoma" were used when searching the Peking Union Medical College Hospital (PUMCH) medical record retrieval system to obtain clinical information about patients. We identified patients diagnosed with MEN1-associated insulinoma based on endocrinological, radiological, and pathological examinations, and subsequently analyzed their clinical data.

Results: A total of 55 patients with MEN1-associated insulinoma were included, including 29 (52.7%) men and 26 (47.3%) women. The parathyroid gland was the most commonly affected (78.2%), followed by the pituitary gland (69.1%) and adrenal gland (16.4%). Insulinoma was the first manifestation of MEN1 in at least 23.6% (13/55) of patients. Nineteen (34.5%) patients presented with initial symptoms of hypoglycemia before the age of 22 years. Among the 24 Patients with high serum calcium (Ca) had significantly lower serum insulin levels than those with normal serum Ca levels (p < 0.001) during hypoglycemic episodes. However, serum C-peptide level at 0.5 h and serum insulin level at 1 h was higher in patients with hypercalcemia than in patients with normal serum Ca levels in the oral glucose tolerance test (OGTT), although the differences were not statistically significant. Multifocal pancreatic neuroendocrine tumors (pNETs) were present in 38 (69.1%) patients; most of them (55.6%, 20/36) underwent multiple enucleations, and 45% (9/20) had a postoperative recurrence. Five patients (10%) who underwent distal pancreatectomy developed pancreatic insufficiency after an average of seven years. patients who underwent genetic testing, 23 (95.8%) were positive for MEN1 mutation, with mutations most commonly found in exons 2 (21.7%) and 3 (13%).

Conclusions: In our study, the rates of postoperative recurrence and long-term complications in patients with MEN1 with multifocal pNETs were significantly different from those in other international centers and might be related to the choice of surgical method. In addition, elevated serum Ca levels in patients with primary hyperparathyroidism may affect insulin secretion.
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http://dx.doi.org/10.1186/s13023-022-02370-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9195405PMC
June 2022

Low Cost Three-Dimensional Programmed Mini-Pump Used in PCR.

Micromachines (Basel) 2022 May 14;13(5). Epub 2022 May 14.

National Engineering Research Center for Healthcare Devices, Guangdong Provincial Key Laboratory of Medical Electronic Instruments and Polymer Material Products, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 510316, China.

Programmed mini-pumps play a significant role in various fields, such as chemistry, biology, and medicine, to transport a measured volume of liquid, especially in the current detection of COVID-19 with PCR. In view of the cost of the current automatic pipetting pump being higher, which is difficult to use in a regular lab, this paper designed and assembled a three-dimensional programmed mini-pump with the common parts and components, such as PLC controller, motor, microinjector, etc. With the weighting calibration before and after pipetting operation, the error of the pipette in 10 μL (0.2%), 2 μL (1.8%), and 1 μL (5.6%) can be obtained. Besides, the contrast test between three-dimensional programmed mini-pump and manual pipette was conducted with the ORF1ab and pGEM-3Zf (+) genes in qPCR. The results proved that the custom-made three-dimensional programmed mini-pump has a stronger reproducibility compared with manual pipette (ORF1ab: 24.06 ± 0.33 vs. 23.50 ± 0.58, = 0.1014; pGEM-3Zf (+): 11.83.06 ± 0.24 vs. 11.50 ± 0.34, = 0.8779). These results can lay the foundation for the functional, fast, and low-cost programmed mini-pump in PCR or other applications for trace measurements.
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http://dx.doi.org/10.3390/mi13050772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143699PMC
May 2022

Convergence between germline and somatic mutations in pancreatic neuroendocrine tumors.

Eur J Endocrinol 2022 May 19;187(1):85-90. Epub 2022 May 19.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

Objectives: The pancreatic neuroendocrine tumors (PanNETs) are a group of clinically heterogeneous neoplasms. Although previous studies illustrated the somatic mutation pattern for PanNETs, the germline mutation pattern is still unclear. Here, we comprehensively screened the underlying germline mutations in a cohort of multiple endocrine neoplasia type 1 (MEN1)-related and sporadic PanNETs to reveal the characteristics of germline mutation in PanNET patients.

Methods: Patients diagnosed with PanNETs by biopsy or surgical pathology were enrolled in this study. Peripheral blood samples were used for genomic DNA purification and subsequent sequencing. The following sequencing techniques were used and compared for validation: (1) targeted gene capture with a customized panel; (2) whole exome sequencing data from previous study.

Results: A total of 184 PanNET patients were enrolled, including 20 MEN1-related and 164 sporadic cases. In this study, MEN1 mutation rate in MEN1-related PanNETs was 60% (12/20), of which 50% were novel mutation sites. For sporadic PanNETs, the overall germline mutation rate was very low. Besides the rare MEN1 mutation, previously unreported germline variant in DAXX was found in one non-functional PanNET.

Conclusions: This study revealed distinctive germline mutation rates between MEN1-related and sporadic PanNETs. The novel MEN1 mutations contribute to revealing the spectrum of MEN1 mutations in PanNETs. The newly discovered germline variant of DAXX in sporadic PanNET implies a tendency of convergence between germline and somatic mutation genes.
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http://dx.doi.org/10.1530/EJE-21-0893DOI Listing
May 2022

Clustering of Multilayer Networks Using Joint Learning Algorithm With Orthogonality and Specificity of Features.

IEEE Trans Cybern 2022 Mar 14;PP. Epub 2022 Mar 14.

Complex systems in nature and society consist of various types of interactions, where each type of interaction belongs to a layer, resulting in the so-called multilayer networks. Identifying specific modules for each layer is of great significance for revealing the structure-function relations in multilayer networks. However, the available approaches are criticized undesirable because they fail to explicitly the specificity of modules, and balance the specificity and connectivity of modules. To overcome these drawbacks, we propose an accurate and flexible algorithm by joint learning matrix factorization and sparse representation (jMFSR) for specific modules in multilayer networks, where matrix factorization extracts features of vertices and sparse representation discovers specific modules. To exploit the discriminative latent features of vertices in multilayer networks, jMFSR incorporates linear discriminant analysis (LDA) into non-negative matrix factorization (NMF) to learn features of vertices that distinguish the categories. To explicitly measure the specificity of features, jMFSR decomposes features of vertices into common and specific parts, thereby enhancing the quality of features. Then, jMFSR jointly learns feature extraction, common-specific feature factorization, and clustering of multilayer networks. The experiments on 11 datasets indicate that jMFSR significantly outperforms state-of-the-art baselines in terms of various measurements.
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http://dx.doi.org/10.1109/TCYB.2022.3152723DOI Listing
March 2022

Pathological complete response in a patient with locally advanced pancreatic adenocarcinoma treated with neoadjuvant gemcitabine and S-1: a case report and literature review.

Gland Surg 2022 Feb;11(2):494-503

Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Radical resection is currently the only potential curative treatment. However, over 80% of patients present with unresectable tumor at the time of diagnosis. It is recommended that patients with unresectable pancreatic cancers be offered neoadjuvant treatment. A combination of gemcitabine and S-1 (GS-1) has been reported to be an effective regimen for unresectable pancreatic cancers, however, there have been no reports of pathological complete response up until now.

Case Description: Herein, we present a 67-year-old male who presented with a 4-month history of upper abdominal and back pain, as well as unintentional weight loss. Abdominal computed tomography (CT) confirmed a hypovascular mass in the pancreas neck consistent with unresectable pancreatic cancer. Positron emission tomography (PET)/CT also revealed a high fludeoxyglucose (FDG)-avid lesion in the pancreas neck without evidence of distant metastasis. Pancreatic adenocarcinoma was confirmed with ultrasound-guided fine-needle aspiration cytology. The patient was recommended to undergo treatment with gemcitabine and S-1. After 5 cycles of neoadjuvant chemotherapy, CT and PET/CT both revealed the disappearance of the lesion and a pancreaticoduodenectomy was offered as a potentially curative treatment. Histological assessment revealed no evidence of residual adenocarcinoma [ypT0N0 (0/38)]. The tumor marker cancer antigen (CA)125 increased one month after the surgery, resulting in two additional cycles of GS-1. This patient remained disease-free for 21 months after surgery.

Conclusions: This report is the first to present a case of a pathological complete response in a patient with locally advanced pancreatic cancer following GS-1 treatment, suggesting radical resection after GS-1 chemotherapy might be a potential curative treatment strategy for unresectable PDAC.
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http://dx.doi.org/10.21037/gs-22-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899423PMC
February 2022

Epidemiology and Antimicrobial Resistance Profiles of the Species in China, 2009 to 2021.

Microbiol Spectr 2022 04 2;10(2):e0156021. Epub 2022 Mar 2.

Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China.

The genus Nocardia includes ubiquitous environmental saprophytes and the most frequently isolated aerobic actinomycete human pathogen responsible for localized or disseminated infection. Herein, the species distribution and antimicrobial susceptibility profiles of 441 nonrepetitive Nocardia strains are reported, collected from 21 provinces/cities in China over 13 years (from 2009 to 2021). These isolates were identified to species level by mass spectrometry or targeted DNA sequencing. The susceptibility profiles of Nocardia species for 15 antibiotics were determined by the broth microdilution method. Among these Nocardia isolates, Nocardia farcinica was the most commonly isolated species (39.9%, 176 of 441), followed by Nocardia cyriacigeorgica (28.6%, 126), Nocardia abscessus (6.6%, 29), and Nocardia otitidiscaviarum (5.9%, 26). Furthermore, 361 Nocardia strains (81.9%) were collected from lower respiratory tract (sputum, lung tissue, and bronchoalveolar lavage fluid), 50 (11.3%) were collected from skin and soft tissues, 9 were collected from blood, 9 were collected from eye, 4 were collected from cerebrospinal fluid and brain abscesses, and 2 were collected from pleural effusion. All of the Nocardia strains were susceptible to linezolid, followed by amikacin (99.3%) and trimethoprim-sulfamethoxazole (TMP-SMX) (99.1%). The antibiotic resistance profiles of other antibiotics varied tremendously among different Nocardia species. This demonstrated that accurate species identification and/or antibiotic susceptibility testing should be performed before the usage of these antibiotics. In summary, this is the largest study on the species and antibiotic resistance profiles of the genus Nocardia circulating in China, and our data will contribute to a better understanding of clinical nocardiosis. The genus Nocardia has the potential to cause nocardiosis, which might be underrecognized and underdiagnosed. Herein, the demographical features of 441 nonrepetitive nocardiosis cases and species distribution of their Nocardia strains in China, 2009 to 2021, are summarized. The susceptibility profiles for 15 antibiotics against all of the above Nocardia strains were also determined by the broth microdilution method. To date, this is the largest study on the genus Nocardia contributing to nocardiosis in China. Our study will be helpful for understanding the species diversity of Nocardia isolates distributed in China and for decision-making in the context of nocardiosis diagnosis and treatment.
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http://dx.doi.org/10.1128/spectrum.01560-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045199PMC
April 2022

Novel technologies in cfDNA analysis and potential utility in clinic.

Chin J Cancer Res 2021 Dec;33(6):708-718

Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.

The profiling of plasma cell-free DNA (cfDNA) is becoming a valuable tool rapidly for tumor diagnosis, monitoring and prognosis. Diverse plasma cfDNA technologies have been in routine or emerging use, including analyses of mutations, copy number alterations, gene fusions and DNA methylation. Recently, new technologies in cfDNA analysis have been developed in laboratories, and potentially reflect the status of epigenetic modification, the immune microenvironment and the microbiome in tumor tissues. In this review, the authors discuss the principles, methods and effects of the current cfDNA assays and provide an overview of studies that may inform clinical applications in the near future.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2021.06.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742177PMC
December 2021

Mutant Kras co-opts a proto-oncogenic enhancer network in inflammation-induced metaplastic progenitor cells to initiate pancreatic cancer.

Nat Cancer 2021 01 2;2(1):49-65. Epub 2020 Nov 2.

Tsinghua University School of Medicine, Beijing, China.

Kras-activating mutations display the highest incidence in pancreatic ductal adenocarcinoma. Pancreatic inflammation accelerates mutant Kras-driven tumorigenesis in mice, suggesting high selectivity in the cells that oncogenic Kras transforms, although the mechanisms dictating this specificity are poorly understood. Here we show that pancreatic inflammation is coupled to the emergence of a transient progenitor cell population that is readily transformed in the presence of mutant KrasG12D. These progenitors harbor a proto-oncogenic transcriptional program driven by a transient enhancer network. KrasG12D mutations lock this enhancer network in place, providing a sustained Kras-dependent oncogenic program that drives tumors throughout progression. Enhancer co-option occurs through functional interactions between the Kras-activated transcription factors Junb and Fosl1 and pancreatic lineage transcription factors, potentially accounting for inter-tissue specificity of oncogene transformation. The pancreatic ductal adenocarcinoma cell of origin thus provides an oncogenic transcriptional program that fuels tumor progression beyond initiation, accounting for the intra-tissue selectivity of Kras transformation.
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http://dx.doi.org/10.1038/s43018-020-00134-zDOI Listing
January 2021

Incidence and prognosis of thyroid cancer in children: based on the SEER database.

Pediatr Surg Int 2022 Mar 29;38(3):445-456. Epub 2022 Jan 29.

College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, No.28 Fuxing Road, Haidian District, Beijing, 100853, China.

Objective: To update the recognition of the trends in the incidence of childhood thyroid cancer (TC) and its prognosis.

Methods: A large-scale sample based on long time-line public database was recruited. Join-point regression model was used to analyze the incidence trend of childhood TC. Univariable and multivariable Cox regression model analyses were applied to explore the survival situation and prognostic factors.

Results: The incidence rate of childhood TC increased between 1975 and 2016 from 3.8/million (95% CI 2.6-5.5) to 11.5/million (95% CI 9.2-14.1), AAPC = 2.38% (95% CI 1.98-9.65) and could be divided into two stages of increasing trends. The incidence rate of Trend1 (1975-2005) increased slowly (APC = 1.08%, 95% CI 0.38-1.82) while Trend2 (2005-2016) increased dramatically (APC = 6.77%, 95% CI 4.30-9.28). Annual incidence rate of small size tumor (< 4 cm) and local stage childhood TC increased significantly. The overall cumulative survival rate for childhood TC was high up to 97-99%. Males, black race, MTC type, distant metastasis, tumor size ≥ 4 cm, non-primary cancer were the independent risk factors of childhood TC prognosis.

Conclusion: A contribution of overdetection to rising pediatric TC rates might not be able to rule out. For clinical implications, screening TC in children with potential specific risk factors is feasible. Over-treatment to small size and local stage TC in children should be avoided.
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http://dx.doi.org/10.1007/s00383-022-05069-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831364PMC
March 2022

Network-based integrative analysis of single-cell transcriptomic and epigenomic data for cell types.

Brief Bioinform 2022 03;23(2)

School of Computer Science and Technology, Xidian University, Xi an, 710071, China.

Advances in single-cell biotechnologies simultaneously generate the transcriptomic and epigenomic profiles at cell levels, providing an opportunity for investigating cell fates. Although great efforts have been devoted to either of them, the integrative analysis of single-cell multi-omics data is really limited because of the heterogeneity, noises and sparsity of single-cell profiles. In this study, a network-based integrative clustering algorithm (aka NIC) is present for the identification of cell types by fusing the parallel single-cell transcriptomic (scRNA-seq) and epigenomic profiles (scATAC-seq or DNA methylation). To avoid heterogeneity of multi-omics data, NIC automatically learns the cell-cell similarity graphs, which transforms the fusion of multi-omics data into the analysis of multiple networks. Then, NIC employs joint non-negative matrix factorization to learn the shared features of cells by exploiting the structure of learned cell-cell similarity networks, providing a better way to characterize the features of cells. The graph learning and integrative analysis procedures are jointly formulated as an optimization problem, and then the update rules are derived. Thirteen single-cell multi-omics datasets from various tissues and organisms are adopted to validate the performance of NIC, and the experimental results demonstrate that the proposed algorithm significantly outperforms the state-of-the-art methods in terms of various measurements. The proposed algorithm provides an effective strategy for the integrative analysis of single-cell multi-omics data (The software is coded using Matlab, and is freely available for academic https://github.com/xkmaxidian/NIC ).
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http://dx.doi.org/10.1093/bib/bbab546DOI Listing
March 2022

Advances in Filament Structure of 3D Bioprinted Biodegradable Bone Repair Scaffolds.

Int J Bioprint 2021 13;7(4):426. Epub 2021 Oct 13.

School of Railway Tracks and Transportation, Wuyi University, Jiangmen 529020, China.

Conventional bone repair scaffolds can no longer meet the high standards and requirements of clinical applications in terms of preparation process and service performance. Studies have shown that the diversity of filament structures of implantable scaffolds is closely related to their overall properties (mechanical properties, degradation properties, and biological properties). To better elucidate the characteristics and advantages of different filament structures, this paper retrieves and summarizes the state of the art in the filament structure of the three-dimensional (3D) bioprinted biodegradable bone repair scaffolds, mainly including single-layer structure, double-layer structure, hollow structure, core-shell structure and bionic structures. The eximious performance of the novel scaffolds was discussed from different aspects (material composition, ink configuration, printing parameters, etc.). Besides, the additional functions of the current bone repair scaffold, such as chondrogenesis, angiogenesis, anti-bacteria, and anti-tumor, were also concluded. Finally, the paper prospects the future material selection, structural design, functional development, and performance optimization of bone repair scaffolds.
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http://dx.doi.org/10.18063/ijb.v7i4.426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600304PMC
October 2021

Evaluation on absorption risks of amentoflavone after oral administration in rats.

Biopharm Drug Dispos 2021 Nov 23;42(9):435-443. Epub 2021 Oct 23.

Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China.

The present study was aimed to systemically assess the absorption risks of amentoflavone (AMF). Physicochemical properties of AMF were evaluated using in vitro assays including water solubility and stability in both simulated gastric and intestinal fluids, as well as logD, pka and permeability studies in a monolayer Caco-2 model. The results together suggested that AMF was a compound with moderate intestinal absorption and the poor solubility was the key rate-limiting step for the oral absorption of AMF, and PVP-K30 were thus used as a solubilizer to improve its solubility and oral bioavailability. Furthermore, studies on pharmacokinetics and biliary excretion of AMF with tween 80 or PVP-K30 were performed after oral administration, and the results showed that the percentage of AMF conjugates in bile was determined up to be 96.73% and no AMF conjugates were detected in rat plasma. The above results revealed that the poor oral absorption of AMF may probably be attributed to the low solubility, high level of metabolism and hepatic first-pass effects. The relative bioavailability of AMF solubilized by PVP-K30 was about 2-fold than that of AMF suspended in 1% tween 80. The present study may help provide scientific insights to guide the rational design of AMF into more efficient formulation systems.
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http://dx.doi.org/10.1002/bdd.2304DOI Listing
November 2021

Expression and related mechanisms of miR-330-3p and S100B in an animal model of cartilage injury.

J Int Med Res 2021 Sep;49(9):3000605211039471

Lirimax (Tianjin) Medical Technical Co., Ltd, Tianjin, China.

Objective: To investigate the roles of and relationship between microRNA (miR)-330-3p and S100 calcium-binding protein B (S100B) in an animal model of cartilage injury.

Methods: This study included 30 New Zealand male rabbits randomly divided into three groups: an intervention group, a model group and a sham surgery control group. Modelling was performed in the intervention and model groups, but in the sham surgery group, only the skin was cut. After modelling, the intervention and model groups were injected with the miR-330-3p overexpression vector GV268-miR-330-3p or the control GV268-N-ODN vector, respectively, twice a week for 7 weeks.

Results: Levels of interleukin-1β and tumour necrosis factor-α in the synovial fluid were significantly higher in the model group than in the intervention and control groups. The level of miR-330-3p in the cartilage tissue was significantly higher in the control group than in the model group but it was significantly lower compared with the intervention group. Levels of S100B, fibroblast growth factor receptor 1 and fibroblast growth factor-2 in the cartilage tissue of rabbits in the model group were significantly higher compared with the control and intervention groups.

Conclusion: These findings demonstrate that the upregulation of miR-330-3p can inhibit the expression of S100B.
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http://dx.doi.org/10.1177/03000605211039471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489778PMC
September 2021

Risk factors and prevention of postoperative pancreatic fistula after insulinoma enucleation:a retrospective study from a high-volume center.

Pancreatology 2021 Jun 5. Epub 2021 Jun 5.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China. Electronic address:

Background/objectives: Enucleation is an effective surgical method to treat pancreatic insulinoma, however, the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) is high. We aim to investigate the risk factors for CR-POPF which have not been well characterized and develop effective methods to prevent CR-POPF after enucleation.

Methods: This retrospective cohort study included 161 patients diagnosed with insulinoma from June 2016 to July 2020 in Peking Union Medical College Hospital. The risk factors for CR-POPF were evaluated and the role of prophylactic pre-operative pancreatic stent to prevent the occurrence of CR-POPF after enucleation of pancreatic insulinoma were explored.

Results: A cohort of 161 insulinoma cases were reviewed. The CT or MRI imaging reports could be tracked in 108 cases. A total of 96 patients underwent surgery, while 81 experienced pancreatic enucleation. Univariate and multivariate analyses showed that the distance from insulinoma to the main pancreatic duct (MPD) ≤2 mm was an independent risk factor for CR-POPF (p = 0.003, OR = 6.011, 95% Cl 1.852-19.512). The pre-operative pancreatic stent substantially reduced the incidence of CR-POPF in patients with tumor located in proximity to (distance ≤2 mm) the MPD (CR-POPF of the stented group vs the non-stented group: 37.5% vs 71.4%, p = 0.028).

Conclusions: The distance from insulinoma to MPD ≤2 mm is a predictive factor for CR-POPF after enucleation. Pancreatic duct stenting may benefit patients with insulinoma in proximity to the MPD by enabling a lower CR-POPF rate, so it should be considered before the enucleation of the insulinoma in proximity to the MPD (distance ≤2 mm).
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http://dx.doi.org/10.1016/j.pan.2021.06.001DOI Listing
June 2021

Interleukin-17 activates and synergizes with the notch signaling pathway in the progression of pancreatic ductal adenocarcinoma.

Cancer Lett 2021 06 10;508:1-12. Epub 2021 Mar 10.

Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China. Electronic address:

Interleukin (IL)-17 is a prominent cytokine that promotes pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) and is associated with the oncogenic pathways in tumor progression. However, the mechanism and therapeutic value of the IL-17 axis remain unclear. In this study, we verified the activation of the IL-17 and Notch pathways in PanIN/PDAC via complementary approaches and validated their pro-tumor effects on tumor progression. Additionally, we found a positive correlation between IL-17 and Notch; the IL-17 axis can upregulate Notch activity via the canonical NF-κB pathway in vitro, thus synergistically promoting PanIN/PDAC. Furthermore, we observed that the co-inhibition of IL-17 and the Notch pathway can enhance the therapeutic effect by restricting tumor growth in vivo. Our study highlights the synergistic effect of the IL-17 axis and Notch pathway in promoting PanIN/PDAC and further suggests that IL-17-Notch co-inhibition is a novel therapeutic strategy with superior potential in treating PDAC.
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http://dx.doi.org/10.1016/j.canlet.2021.03.003DOI Listing
June 2021

jSRC: a flexible and accurate joint learning algorithm for clustering of single-cell RNA-sequencing data.

Brief Bioinform 2021 09;22(5)

School of Computer Science and Technology, Xidian University, Xi'an, 710071, China.

Single-cell RNA-sequencing (scRNA-seq) explores the transcriptome of genes at cell level, which sheds light on revealing the heterogeneity and dynamics of cell populations. Advances in biotechnologies make it possible to generate scRNA-seq profiles for large-scale cells, requiring effective and efficient clustering algorithms to identify cell types and informative genes. Although great efforts have been devoted to clustering of scRNA-seq, the accuracy, scalability and interpretability of available algorithms are not desirable. In this study, we solve these problems by developing a joint learning algorithm [a.k.a. joints sparse representation and clustering (jSRC)], where the dimension reduction (DR) and clustering are integrated. Specifically, DR is employed for the scalability and joint learning improves accuracy. To increase the interpretability of patterns, we assume that cells within the same type have similar expression patterns, where the sparse representation is imposed on features. We transform clustering of scRNA-seq into an optimization problem and then derive the update rules to optimize the objective of jSRC. Fifteen scRNA-seq datasets from various tissues and organisms are adopted to validate the performance of jSRC, where the number of single cells varies from 49 to 110 824. The experimental results demonstrate that jSRC significantly outperforms 12 state-of-the-art methods in terms of various measurements (on average 20.29% by improvement) with fewer running time. Furthermore, jSRC is efficient and robust across different scRNA-seq datasets from various tissues. Finally, jSRC also accurately identifies dynamic cell types associated with progression of COVID-19. The proposed model and methods provide an effective strategy to analyze scRNA-seq data (the software is coded using MATLAB and is free for academic purposes; https://github.com/xkmaxidian/jSRC).
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http://dx.doi.org/10.1093/bib/bbaa433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953970PMC
September 2021

Surgical Treatment for Postprandial Hypoglycemia After Roux-en-Y Gastric Bypass: a Literature Review.

Obes Surg 2021 Apr 1;31(4):1801-1809. Epub 2021 Feb 1.

Department of General Surgery, Peking Union Medical College Hospital, Beijing, 100730, China.

Roux-en-Y gastric bypass (RYGB) is an effective treatment for severe obesity and obesity-related comorbidities. Postprandial hypoglycemia may occur as a long-term complication after RYGB. This study reviews the literature on surgical treatment for intractable post-RYGB hypoglycemia to provide updated information. A search was performed in Embase and PubMed, and 25 papers were identified. Thirteen papers on reversal were included. Resolution of postprandial hypoglycemic symptoms occurred in 42/48 (88%) patients after reversal. Twelve papers on pancreatectomy were included. Resolution occurred in 27/50 (54%) patients after pancreatectomy. The optimal surgical treatment for intractable post-RYGB hypoglycemia has not been defined, but reversal of RYGB seems to be more effective than other treatments. Further research on etiology and long-term evaluation of surgical outcomes may refine treatment options.
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http://dx.doi.org/10.1007/s11695-021-05251-xDOI Listing
April 2021

User-Friendly Microfabrication Method for Complex Topological Structure and Three-Dimensional Microchannel with the Application Prospect in Polymerase Chain Reaction (PCR).

Anal Chem 2021 01 16;93(3):1523-1528. Epub 2020 Dec 16.

State Key Laboratory of Applied Optics, Changchun Institute of Optics, Fine Mechanics and Physics (CIOMP), Chinese Academy of Sciences, Changchun 130033, China.

One of the most important challenges in the field of microfluidics is the rapid fabrication of microchips with complex topologies. Although the processing method of microfluidic chips has made brilliant achievements in the past 20 years, almost all traditional processing methods still face huge obstacles in the production of complex topologies and three-dimensional microchannel. Nowadays, the main methods of manufacturing microfluidic chips such as numerical control microprocessing, laser ablation, inkjet printing, photolithography, dry etching, and lithography, galvanoformung and abformung (LIGA) technology are not only inapplicable to the complex topological structure and the rapid processing of three-dimensional microfluidic chips but also rely on expensive processing equipment, complex manufacturing process, and low yield. To solve the problems of these traditional processing methods, we propose a low-cost methodology to obtain a microfluidic chip by sewing the chip pipe to the substrate with an embroidery machine as low as $6. Compared with the above-mentioned traditional microprocessing technologies, the new chip processing technology proposed by us does not involve professional microprocessing equipment and professional skills. Therefore, this new chip processing technology can significantly improve the efficiency of microprocessing.
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http://dx.doi.org/10.1021/acs.analchem.0c03827DOI Listing
January 2021

Compressed Air-Driven Continuous-Flow Thermocycled Digital PCR for HBV Diagnosis in Clinical-Level Serum Sample Based on Single Hot Plate.

Molecules 2020 Nov 30;25(23). Epub 2020 Nov 30.

State Key Laboratory of Applied Optics, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, China.

We report a novel compressed air-driven continuous-flow digital PCR (dPCR) system based on a 3D microfluidic chip and self-developed software system to realize real-time monitoring. The system can ensure the steady transmission of droplets in long tubing without an external power source and generate stable droplets of suitable size for dPCR by two needles and a narrowed Teflon tube. The stable thermal cycle required by dPCR can be achieved by using only one constant temperature heater. In addition, our system has realized the real-time detection of droplet fluorescence in each thermal cycle, which makes up for the drawbacks of the end-point detection method used in traditional continuous-flow dPCR. This continuous-flow digital PCR by the compressed air-driven method can meet the requirements of droplet thermal cycle and diagnosis in a clinical-level serum sample. Comparing the detection results of clinical samples (hepatitis B virus serum) with commercial instruments (CFX Connect; Bio Rad, Hercules, CA, USA), the linear correlation reached 0.9995. Because the system greatly simplified the traditional dPCR process, this system is stable and user-friendly.
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http://dx.doi.org/10.3390/molecules25235646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731400PMC
November 2020

Application of multiomics sequencing and advances in the molecular mechanisms of pancreatic neuroendocrine neoplasms.

Cancer Lett 2021 02 24;499:39-48. Epub 2020 Nov 24.

Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China. Electronic address:

The incidence of pancreatic neuroendocrine neoplasms (PanNENs) has gradually increased. PanNENs comprise two subtypes with different clinical manifestations and molecular mechanisms: functional PanNENs and nonfunctional PanNENs. Excessive hormones and tumor progression severely affect the quality of life of patients or are even life threatening. However, the molecular mechanisms of hormone secretion and tumor progression in PanNENs have not yet been fully elucidated. At present, advancements in sequencing technologies have led to the exploration of new biological markers and an advanced understanding of molecular mechanisms in PanNENs. Multiomics sequencing could reveal differences and similarities in molecular features in different fields. However, sequencing studies of PanNENs are booming and should be summarized to integrate the current findings. In this review, we summarize the current status of multiomics sequencing in PanNENs to further guide its application. We explore mainly advancements in the genome, transcriptome, and DNA methylation fields. In addition, the cell origin of PanNENs, which has been a hot issue in sequencing research, is described in multiple fields.
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http://dx.doi.org/10.1016/j.canlet.2020.11.012DOI Listing
February 2021

Risk factors for new-onset diabetes mellitus after distal pancreatectomy.

BMJ Open Diabetes Res Care 2020 10;8(2)

Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.

Introduction: Several previous studies have reported the incidence of new-onset diabetes mellitus (NODM) after pancreatectomy. Nevertheless, the results were inconsistent. The true rate of NODM after distal pancreatectomy (DP) is still unknown.

Research Design And Methods: The aim of this study was to investigate the incidence of and the risk factors for NODM after DP. This study enrolled patients who underwent DP between January 2004 and February 2016 at Peking Union Medical College Hospital. Patients with preoperative diabetes mellitus or diagnosed with pancreatic cancer were excluded. The primary outcome was NODM.

Results: A total of 485 patients were enrolled. The median (IQR) of follow-up duration was 30.95 (9.26-180.30) months. The accumulative incidence of NODM was 8.9% at postoperative 6 months, 14.0% at postoperative year one, 22.3% at year three, 27.1% at year five, and 35.5% at year ten. Multivariate analysis showed that the risk of postoperative NODM was positively correlated with age (HR 1.029 (1.013-1.045), p<0.001), preoperative body mass index (BMI) (HR 1.042 (1.003-1.083), p=0.001), operative blood loss (HR 1.0003 (1.0002-1.0010), p<0.001), and length of resected pancreas (HR 1.079 (1.013-1.148), p0.017). Moreover, concomitant splenectomy (HR 2.001 (1.202-3.331), p=0.008) was associated with significantly higher risk of postoperative NODM.

Conclusion: NODM incidence increased with postoperative time progression. Age, BMI, surgical blood loss, length of resected pancreas and splenectomy were independent risk factors for NODM after DP.

Trial Registration Number: NCT03030209.
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http://dx.doi.org/10.1136/bmjdrc-2020-001778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597507PMC
October 2020

A digital PCR system based on the thermal cycled chip with multi helix winding capillary.

Sci Rep 2020 10 20;10(1):17824. Epub 2020 Oct 20.

State Key Laboratory of Applied Optics, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun, 130033, China.

This paper presents a digital PCR system based on a novel thermal cycled chip, which wraps microchannels on a trapezoidal structure made of polydimethylsiloxane (PDMS) in a multi-helix manner for the first time. It is found that compared to the single helix chip commonly used in previous reports, this kind of novel multi-helix chip can make the surface temperature in the renaturation zone more uniform, and even in the case of rapid fluid flow, it can improve the efficiency of the polymerase chain reaction. What's more, the winding method of multi helix (such as double helix, six helix and eight helix) can obtain better temperature uniformity than the winding of odd helix (such as single helix and three helix). As a proof of concept, the temperature-optimized double-helical chip structure is applied to continuous-flow digital PCR and there is no need to add any surfactant to both the oil phase and reagent. In addition, we successfully analyzed the fluorescence signal of continuous-flow digital PCR by using CMOS camera. Finally, this method is applied for the absolute quantification of the clinical serum sample infected by HBV. The accuracy of the test results has been confirmed by commercial instruments.
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http://dx.doi.org/10.1038/s41598-020-74711-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576587PMC
October 2020

Comparison of minimal invasive versus open radical antegrade modular pancreatosplenectomy (RAMPS) for pancreatic ductal adenocarcinoma: a single center retrospective study.

Surg Endosc 2021 07 8;35(7):3763-3773. Epub 2020 Oct 8.

Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China.

Introduction: Radical antegrade modular pancreatosplenectomy (RAMPS) was proposed a decade ago with the aim to achieve higher R0 tangential margin and radical N1 lymph node resection for left-sided pancreatic adenocarcinoma (PDAC), which has been widely accepted worldwide at present. Laparoscopic RAMPS (Lap-RAMPS) has been attempted for PDAC during last several years, however, no outcomes evaluation by comparison between laparoscopic vs open RAMPS has been reported yet.

Materials And Methods: From August, 2012 to March, 2018, patients undergoing open or lap-RAMPS for the diagnosis of left-sided PDAC were reviewed from a prospective database. Patients excluded if they were related with combined organs or vessels resection, systematic metastasis as well as conversion from open RAMPS to lap RAMPS. The surgical and oncologic outcomes were compared.

Results: A total of 48 PDAC patients were enrolled (25 underwent lap-RAMPS and 23 underwent open-RAMPS). There were no significant differences in demographic or perioperative morbidity. In the lap-RAMPS group, R0 transection margin and retroperitoneal margin were both achieved in 23 of 25 patients (92%). In the open RAMPS group, R0 transection margin was achieved in 21 of 23 patients (91.3%), R0 retroperitoneal margin was 22 of 23 patients (95.65%). There were no differences in pathological examinations. The number of lymph node (LN) retrieved between lap-RAMPS and open- RAMPS group was not significant difference (15.84 vs 18.22; P = 0.268). Median disease-free survival (DFS) was analogous in two groups (18.11 m vs 20.00 m, P = 0.999). Median overall survival (OS) was 24.53 m in lap-RAMPS group and 28.73 m in the open-RAMPS group (P = 0.633).

Conclusions: Lap-RAMPS is technically feasible, and has comparable long-term oncological outcome with open-RMAPS.
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http://dx.doi.org/10.1007/s00464-020-07938-1DOI Listing
July 2021

[Retrospective analysis of primary parapharyngeal space tumors].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2020 Aug;34(8):743-747

College of Otorhinolaryngology Head and Neck Surgery,PLA General Hospital,Chinese PLA Medical School.

To explore the clinical feature and surgical treatment of patients with parapharyngeal space tumors. A retrospective review of 214 cases with parapharygeal space tumors treated. The data on clinical manifestations, imaging examinations, pathological types, surgical approach, and postoperative complications were reviewed. Of the 214 cases, the tumor was benign in nature in 135 cases(63.1%) and malignant in 79 cases(36.9%). There was no gender difference in the incidence of benign tumors, and the ratio of male to female was 1:1. The incidence of malignant tumors was higher in males than in females, and the ratio was 3.3:1. Regardless of benign and malignant tumors, the high incidence age is 40-59. Two-thirds of cases of parapharyngeal space tumors had different degrees of peripheral structural invasion. The most common cases involving the skull base were 76 cases(35.5%), followed by blood vessels and nerves, 24 cases(11.2%) and 16 cases(7.5%),respectively. Complications occurred in 65 patients(31.4%), the most common complications were hoarseness caused by X-cranial nerve palsy. There are various pathological types of parapharyngeal space tumors, and surgery is the first choice for parapharyngeal space tumors. The surgical plan should be made according to the imaging examinations, lesions, and the pathology et al. The risk of complications should be fully informed before the operation, and the cooperation of the patients should be obtained.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2020.08.015DOI Listing
August 2020
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