Publications by authors named "Jie Yuan"

569 Publications

Ultrasonography-guided radiofrequency ablation combined with lauromacrogol sclerotherapy for mixed thyroid nodules.

Am J Transl Res 2021 15;13(5):5035-5042. Epub 2021 May 15.

Department of Ultrasound, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine Shanghai City, China.

Objective: To evaluate the safety and effectiveness of ultrasonography-guided radiofrequency ablation combined with lauromacrogol foam sclerotherapy for the treatment of mixed thyroid nodules.

Methods: One hundred and nineteen patients with benign mixed thyroid nodules were included in this study. In all patients, radiofrequency ablation was performed on the solid components of nodules, and the cystic areas of nodules were treated with aspiration, irrigation with lauromacrogol injection and foam sclerotherapy. The nodule volume reduction ratio and thyroid-related laboratory tests were measured during operation and at 1, 3, 6, and 12 months after operation, and intraoperative and postoperative complications were recorded.

Results: A total of 136 mixed thyroid nodules from 119 patients all achieved complete ablation. At 1, 3, 6, and 12 months after treatment, the nodule volume decreased gradually while the volume reduction ratio increased gradually (P<0.05). The thyroid function of all patients returned to normal after operation, but 3 patients exhibited cyst recurrence. After the operation, no serious complications occurred.

Conclusion: Ultrasonography-guided radiofrequency ablation combined with lauromacrogol sclerotherapy is a safe and effective method for the treatment of mixed thyroid nodules with less surgical trauma and low incidence of complications.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205792PMC
May 2021

Developing MXenes from Wireless Communication to Electromagnetic Attenuation.

Nanomicro Lett 2021 Apr 27;13(1):115. Epub 2021 Apr 27.

School of Information Engineering, Minzu University of China, Beijing, 100081, People's Republic of China.

There is an urgent global need for wireless communication utilizing materials that can provide simultaneous flexibility and high conductivity. Avoiding the harmful effects of electromagnetic (EM) radiation from wireless communication is a persistent research hot spot. Two-dimensional (2D) materials are the preferred choice as wireless communication and EM attenuation materials as they are lightweight with high aspect ratios and possess distinguished electronic properties. MXenes, as a novel family of 2D materials, have shown excellent properties in various fields, owing to their excellent electrical conductivity, mechanical stability, high flexibility, and ease of processability. To date, research on the utility of MXenes for wireless communication has been actively pursued. Moreover, MXenes have become the leading materials for EM attenuation. Herein, we systematically review the recent advances in MXene-based materials with different structural designs for wireless communication, electromagnetic interference (EMI) shielding, and EM wave absorption. The relationship governing the structural design and the effectiveness for wireless communication, EMI shielding, and EM wave absorption is clearly revealed. Furthermore, our review mainly focuses on future challenges and guidelines for designing MXene-based materials for industrial application and foundational research.
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http://dx.doi.org/10.1007/s40820-021-00645-zDOI Listing
April 2021

A Nano-Micro Engineering Nanofiber for Electromagnetic Absorber, Green Shielding and Sensor.

Nanomicro Lett 2020 Nov 20;13(1):27. Epub 2020 Nov 20.

School of Information Engineering, Minzu University of China, Beijing, 100081, People's Republic of China.

Highlights: The role of electron transport characteristics in electromagnetic (EM) attenuation can be generalized to other EM functional materials. The integrated functions of efficient EM absorption and green shielding open the view of EM multifunctional materials. A novel sensing mechanism based on intrinsic EM attenuation performance and EM resonance coupling effect is revealed. It is extremely unattainable for a material to simultaneously obtain efficient electromagnetic (EM) absorption and green shielding performance, which has not been reported due to the competition between conduction loss and reflection. Herein, by tailoring the internal structure through nano-micro engineering, a NiCoO nanofiber with integrated EM absorbing and green shielding as well as strain sensing functions is obtained. With the improvement of charge transport capability of the nanofiber, the performance can be converted from EM absorption to shielding, or even coexist. Particularly, as the conductivity rising, the reflection loss declines from - 52.72 to - 10.5 dB, while the EM interference shielding effectiveness increases to 13.4 dB, suggesting the coexistence of the two EM functions. Furthermore, based on the high EM absorption, a strain sensor is designed through the resonance coupling of the patterned NiCoO structure. These strategies for tuning EM performance and constructing devices can be extended to other EM functional materials to promote the development of electromagnetic driven devices.
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http://dx.doi.org/10.1007/s40820-020-00552-9DOI Listing
November 2020

A Novel Study on Alar Mobility of HAN Female by 3dMD Dynamic Surface Imaging System.

Aesthetic Plast Surg 2021 Jun 11. Epub 2021 Jun 11.

Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Aim: The aim of this study is to conduct a quantitative analysis on alar mobility of HAN females and provided referenced materials for alar dynamic aesthetic.

Methods: One hundred and fifty healthy HAN females without rhinoplasty, nasal injury, nasal deformity and craniofacial deformity were included in this study. 3dMD surface imaging system was used for anthropometric analysis. All participants were instructed to perform the desired dynamic facial expression from rest to maximum smile without reveling teeth and recorded by 3dMD dynamic surface imaging system simultaneously. Two frames of rest status and alar maximum enlargement were selected for measuring alar width, alar base width and inner-canthal distance. The difference between two status represented alar mobility, which was generated through equation: [Formula: see text].

Results: Alar mobility consisted of alar flaring mobility and alar base mobility. The alar flaring mobility was (9.49 ± 4.90)%, reference range was(1.45, 17.53)% and regression equation between rest and maximum smile was Y = 7.953 + 0.886X (R = 0.641, p = 0.000); the alar base mobility was (17.94 ± 10.44)%, reference range was (0.88, 35.00)% and regression equation between rest and maximum smile was Y = 4.481 + 0.966X (R = 0.528, p = 0.000.

Conclusion: Asian alar anatomy has great distinction from Caucasian, processing conspicuous alar movement and damaging alar aesthetic dynamically. This study novelly defined alar mobility by three-dimensional anthropometric analysis, providing objective references for alar dynamic aesthetic and arousing plastic surgeons' attention on keeping balance of static and dynamic aesthetic in rhinoplasty.

Level Of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-021-02386-1DOI Listing
June 2021

Large scale RNA-binding proteins/LncRNAs interaction analysis to uncover lncRNA nuclear localization mechanisms.

Brief Bioinform 2021 May 31. Epub 2021 May 31.

Department of Orthaepedics and Traumatology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Long non-coding RNAs (lncRNAs) are key regulators of major biological processes and their functional modes are dictated by their subcellular localization. Relative nuclear enrichment of lncRNAs compared to mRNAs is a prevalent phenomenon but the molecular mechanisms governing their nuclear retention in cells remain largely unknown. Here in this study, we harness the recently released eCLIP data for a large number of RNA-binding proteins (RBPs) in K562 and HepG2 cells and utilize multiple bioinformatics methods to comprehensively survey the roles of RBPs in lncRNA nuclear retention. We identify an array of splicing RBPs that bind to nuclear-enriched lincRNAs (large intergenic non-coding RNAs) thus may act as trans-factors regulating their nuclear retention. Further analyses reveal that these RBPs may bind with distinct core motifs, flanking sequence compositions, or secondary structures to drive lincRNA nuclear retention. Moreover, network analyses uncover potential co-regulatory RBP clusters and the physical interaction between HNRNPU and SAFB2 proteins in K562 cells is further experimentally verified. Altogether, our analyses reveal previously unknown factors and mechanisms that govern lincRNA nuclear localization in cells.
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http://dx.doi.org/10.1093/bib/bbab195DOI Listing
May 2021

[Preliminary study on memory function of Sorbus aucuparia suspension cell to biotic stress].

Zhongguo Zhong Yao Za Zhi 2021 May;46(10):2467-2473

School of Pharmacy, Nanjing University of Chinese Medicine Nanjing 210023, China China Academy of Chinese Medical Sciences Beijing 100700, China.

Plants have a memory function for the environmental stress they have suffered. When they are subjected to repeated environmental stress, they can quickly and better activate the response and adaptation mechanism to environmental stress, thus realizing long-term stable reproduction. However, most of the relevant studies are applied to crops and Arabidopsis thaliana rather than medicinal plants about the improvement of plant growth status and the effect on phytoalexin biosynthesis. In this study, yeast extract(YE) was used as an elicitor to simulate biotic stress, and the changes in biomass and the content of some secondary metabolites were measured by giving repeated stresses to Sorbus aucuparia suspension cell(SASC). The results showed that the accumulation levels of biomass and some secondary metabolites in SASC subjected to repeated stress are significantly increased at some time points compared with single stress. A phenomenon that SASC can memorize biotic stress is confirmed in this study and influences phytoalexin accumulation in SASC. Furthermore, the work laid the groundwork for research into the transgenerational stress memory mechanism of medicinal plant.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210123.103DOI Listing
May 2021

Association between meteorological factors and daily new cases of COVID-19 in 188 countries: A time series analysis.

Sci Total Environ 2021 Aug 23;780:146538. Epub 2021 Mar 23.

Department of Epidemiology and Biostatics, School of Public Health, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing 100191, China. Electronic address:

By 31 December 2020, Coronavirus disease 2019 (COVID-19) had been prevalent worldwide for one year, and most countries had experienced a complete seasonal cycle. The role of the climate and environment are essential factors to consider in transmission. We explored the association between global meteorological conditions (including mean temperature, wind speed, relative humidity and diurnal temperature range) and new cases of COVID-19 in the whole past year. We assessed the relative risk of meteorological factors to the onset of COVID-19 by using generalized additive models (GAM) and further analyzed the hysteresis effects of meteorological factors using the Distributed Lag Nonlinear Model (DLNM). Our findings revealed that the mean temperature, wind speed and relative humidity were negatively correlated with daily new cases of COVID-19, and the diurnal temperature range was positively correlated with daily new cases of COVID-19. These relationships were more apparent when the temperature and relative humidity were lower than their average value (21.07°Cand 66.83%). The wind speed and diurnal temperature range were higher than the average value(3.07 m/s and 9.53 °C). The maximum RR of mean temperature was 1.30 under -23°C at lag ten days, the minimum RR of wind speed was 0.29 under 12m/s at lag 24 days, the maximum RR of range of temperature was 2.21 under 28 °C at lag 24 days, the maximum RR of relative humidity was 1.35 under 4% at lag 0 days. After a subgroup analysis of the countries included in the study, the results were still robust. As the Northern Hemisphere enters winter, the risk of global covid-19 remains high. Some countries have ushered in a new round of COVID-19 epidemic. Thus, active measures must be taken to control the source of infection, block transmission and prevent further spread of COVID-19 in winter.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986348PMC
August 2021

Metagenomic NGS optimizes the use of antibiotics in appendicitis patients: bacterial culture is not suitable as the only guidance.

Am J Transl Res 2021 15;13(4):3010-3021. Epub 2021 Apr 15.

Department of General Surgery, Zhujiang Hospital, Southern Medical University Guangzhou 510280, Guangdong Province, China.

Background: Previous treatment guidelines have suggested that bacteria are associated with the severity of appendicitis, and the use of postoperative antibiotics should be guided according to the bacteria culture results derived from intraoperative samples. However, this approach has many limitations. Patients were commonly administrated antibiotics during the perioperative period, which can lead to inaccurate culture result.

Aim: To assess the relationship between pathogenic bacteria and appendicitis and optimize the process of antibiotic selection.

Methods: A nonconsecutive case series analysis was conducted from January to July 2017. Nineteen patients were divided into two groups according to their postoperative histological results (Non-perforated: phlegmonous/Perforated: gangrenous, n = 9/10) and postoperative bacterial culture results (Negative/Positive, n = 8/11). Patients were administrated same antibiotics during the perioperative period. During appendectomy, the diseased appendixes were collected, and whole metagenomic sequencing was used to identify the pathogenic bacteria in the specimens. Conventional technology was used to culture bacteria from appendix samples.

Results: We identified 361 species in the appendix samples. Six species in the appendix samples had relative abundances > 5%. No significant differences were observed in the bacterial composition of the two assayed groups. In particular, according to the grouping of culture results, the sequencing analysis results were completely different from those of the culture-based method.

Conclusion: In clinical practice, because patients are regularly administrated antibiotics during the perioperative period, these antibiotics inevitably affect the results of bacterial culture. Therefore, bacterial culture results are not suitable for exclusively guiding the use of antimicrobial agents after appendicitis. Next-generation sequencing has numerous advantages, such as precisely characterizing the profiles of microbiota and their antibiotic resistance in appendicitis patients. Based on the above results, we propose that a combination of bacterial culture and next-generation sequencing should be used to improve the efficacy of antibiotic therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129245PMC
April 2021

Necessity of facial contouring in feminization surgery for Chinese transgender females.

Ann Transl Med 2021 Apr;9(7):603

Department of Reconstructive and Plastic Surgery, Shanghai 9th People's Hospital, Shanghai Jiaotong University, Shanghai, China.

Background: An increasing number of transgender females are suffering from a critical gender dysphoria, which often presents as depression and self-destructive behavior. Facial feminization surgery (FFS) is an effective method to alleviate symptoms of gender dysphoria, which could be more important than genital reassignment surgery for Chinese. Facial contour surgery is perceived as an ordinary FFS for the Chinese women to improve their facial appearance. The zygoma and jaw are key areas for feminizing the facial contour. This study mainly emphasized the necessity of FFS and discussed the importance of facial contour surgery of Chinese individuals.

Methods: The differences of facial contour before and after FFS in terms of skeletal and soft tissue were analyzed. The pre- and postoperative images were evaluated for feminization. The results of the full suite of measurements were compared to reveal the effective change of FFS. Furthermore, a surgery satisfaction survey was conducted among these patients after recovery.

Results: All the patients expressed their satisfaction with the reduction in the intergonial width as well as the middle face prominence. All the facial contour ratios changed significantly after surgery in both hard tissue and soft tissue.

Conclusions: Facial contour surgery is crucial to changing one's facial appearance and sex impression, which significantly alleviates gender dysphoria.
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http://dx.doi.org/10.21037/atm-20-5887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105846PMC
April 2021

An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness.

Nat Commun 2021 05 11;12(1):2693. Epub 2021 May 11.

Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.

Notch signaling represents a key mechanism mediating cancer metastasis and stemness. To understand how Notch signaling is overactivated to couple tumor metastasis and self-renewal in NSCLC cells, we performed the current study and showed that RFC4, a DNA replication factor amplified in more than 40% of NSCLC tissues, directly binds to the Notch1 intracellular domain (NICD1) to competitively abrogate CDK8/FBXW7-mediated degradation of NICD1. Moreover, RFC4 is a functional transcriptional target gene of Notch1 signaling, forming a positive feedback loop between high RFC4 and NICD1 levels and sustained overactivation of Notch signaling, which not only leads to NSCLC tumorigenicity and metastasis but also confers NSCLC cell resistance to treatment with the clinically tested drug DAPT against NICD1 synthesis. Furthermore, together with our study, analysis of two public datasets involving more than 1500 NSCLC patients showed that RFC4 gene amplification, and high RFC4 and NICD1 levels were tightly correlated with NSCLC metastasis, progression and poor patient prognosis. Therefore, our study characterizes the pivotal roles of the positive feedback loop between RFC4 and NICD1 in coupling NSCLC metastasis and stemness properties and suggests its therapeutic and diagnostic/prognostic potential for NSCLC therapy.
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http://dx.doi.org/10.1038/s41467-021-22971-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113560PMC
May 2021

A Review on the Phytochemical and Pharmacological Properties of Rosa laevigata: A Medicinal and Edible Plant.

Chem Pharm Bull (Tokyo) 2021 ;69(5):421-431

Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine.

Rosa laevigata Michx., a medicinal and edible plant in China, has exerted a variety of medicinal values and health benefits. This present review aims to achieve a comprehensive and up-to-date investigation in the phytochemistry and pharmacology of R. laevigata. According to these findings in the literature, approximately 123 chemical ingredients covering triterpenoids, flavonoids, tannis, lignans and polysaccharides, have been characterized from various parts of this species. Among these isolates, 77 triterpenoids have been isolated and thus regarded as the primary and characteristic substance. Based on the chemical structures, most of the obtained triterpenoids can be classified into polyhydroxy triterpenoids and readily divided into four categories: ursane-type, oleanane-type, lupinane-type, as well as seco-triterpenoids. The crude extracts and the purified compounds have demonstrated various pharmacological effects in vitro and in vivo, such as antioxidant activity, immunomodulatory effect, anti-inflammatory effect, liver protection, kidney protection, cardiovascular protection, neuroprotective effect and improvement of diabetic cataract. Noticeably, these pharmacological results of R. laevigata provide evidences for its traditional uses. In addition, these different chemical ingredients existing in the title plant may have synergistic effects. In conclusion, the chemical profiles, including ingredients and structures, together with the modern pharmacological properties have been adequately summarized. These evidences have revealed this plant to be a valuable source for therapeutic foodstuff and more attention should be paid to a better utilization of this plant.
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http://dx.doi.org/10.1248/cpb.c20-00743DOI Listing
January 2021

Proteomics study of colorectal cancer and adenomatous polyps identifies TFR1, SAHH, and HV307 as potential biomarkers for screening.

J Proteomics 2021 Jul 26;243:104246. Epub 2021 Apr 26.

BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China; BGI Genomics, BGI-Shenzhen, Shenzhen 518083, China; BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, Guangzhou 510006, China. Electronic address:

Colorectal cancer (CRC) is a malignant tumour with high morbidity and mortality worldwide. Efficient screening strategies for CRC and pre-cancerous lesions can promote early medical intervention and treatment, thereby reducing morbidity and mortality. Proteins are generally considered key biomarkers of cancer. Herein, we performed a quantitative, original-tissue proteomics study in a cohort of ninety patients from pre-cancerous to cancerous conditions via liquid chromatography-tandem mass spectrometry. In total, 134,812 peptides, 8697 proteins, 2355 union differentially expressed proteins (DEPs), and 409 shared DEPs (compared with adjacent tissues) were identified. The number of DEPs indicated a positive correlation with increasing severity of illness. The union and shared DEPs were both enriched in the KEGG pathway of focal adhesion, metabolism of xenobiotics by cytochrome P450, and drug metabolism by cytochrome P450. Among the 2355 union DEPs, 32 were selected for identification and validation by multiple reaction monitoring from twenty plasma specimens. Of these, three proteins, transferrin receptor protein 1 (TFR1), adenosylhomocysteinase (SAHH), and immunoglobulin heavy variable 3-7 (HV307), were significantly differentially expressed and displayed the same expression pattern in plasma as observed in the tissue data. In conclusion, TFR1, SAHH, and HV307 may be considered as potential biomarkers for CRC screening. SIGNIFICANCE: Although CRC is a malignant tumour with high morbidity and mortality worldwide, efficient screening strategies for CRC and pre-cancerous lesions can play an important role in addressing these issues. Screening of molecular biomarkers provide a non-invasive, cost-effective, and efficient approach. Proteins are generally considered key molecular biomarkers of cancer. Our study reports a quantitative proteomics analysis of protein biomarkers for colorectal cancer (CRC) and adenomatous polyps, and identifies TFR1, SAHH, and HV307 as potential biomarkers for screening. This research makes a significant contribution to the literature as although mass spectrometry-based proteomics research has been widely used for clinical research, its application to clinical translation as parallel specimens ranging from pre-cancerous to cancerous tissues-according to the degree of disease progression-has not been readily assessed.
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http://dx.doi.org/10.1016/j.jprot.2021.104246DOI Listing
July 2021

Low-Frequency Magnetic Stimulation of Shenmen Acupoint Reduces Blood Oxygen Levels in the Prefrontal Cortex of Healthy Subjects: A Near-Infrared Brain Functional Imaging Study.

Chin J Integr Med 2021 Apr 21. Epub 2021 Apr 21.

Department of Encephalopathy, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, 710003, China.

Objective: To explore the effect of low-frequency magnetic stimulation at Shenmen (HT 7) acupoint on blood oxygen levels in the prefrontal cortex of healthy subjects.

Methods: Functional near-infrared spectroscopy (fNIRS) technology was used to collect real-time data of oxygenated hemoglobin (oxy-Hb) in the prefrontal cortex of 16 healthy subjects at resting state and low-frequency magnetic stimulation of Shenmen. The mean and integral values of blood oxygen concentration were analyzed.

Results: Compared with the resting state, the mean and integral values of blood oxygen concentration were decreased during the task period, recovery period, and the whole process in the magnetic stimulation of Shenmen acupoint (P<0.05). In particular, the difference was statistically significant in the recovery period (P<0.01).

Conclusions: The prefrontal cortex was widely activated and produced an immediate effect by reducing the local blood oxygen concentration at low-frequency magnetic stimulation of Shenmen acupoint, which verifies the sedative effect of Shenmen acupoint.
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http://dx.doi.org/10.1007/s11655-021-3291-zDOI Listing
April 2021

Accuracy and Prognosis Value of the Sequential Organ Failure Assessment Score Combined With C-Reactive Protein in Patients With Complicated Infective Endocarditis.

Front Med (Lausanne) 2021 25;8:576970. Epub 2021 Mar 25.

Department of Health Management, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.

This study aimed to evaluate the accuracy and prognostic value of the sequential organ failure assessment (SOFA) score combined with C-reactive protein (CRP) in patients with complicated infective endocarditis (IE). A total of 246 consecutive patients with complicated IE were included in the multicentric prospective observational study. These patients were divided into four groups depending on the SOFA score and CRP optimal cutoff values (≥5 points and ≥17.6 mg/L, respectively), which were determined using the receiver operating characteristic analysis: low SOFA and low CRP ( = 83), low SOFA and high CRP ( = 87), high SOFA and low CRP ( = 25), and high SOFA and high CRP ( = 51). The primary endpoint was in-hospital death, and the secondary endpoint was long-time mortality, defined as subsequent readmission and 3-years mortality in the follow-up period. High SOFA score and high CRP were associated with approximately 29.410% (15/51) of higher incidence of in-hospital death with an area under the curve of 0.872. Multivariate analyses showed that age [odds ratio (OR) = 2.242, 1.142-4.401], neurological failure (Glasgow Coma Scale ≤ 12) (OR = 2.513, 1.041-4.224), (OR = 2.151, 1.252-4.513), SOFA ≥ 5 (OR = 9.320, 3.621-16.847), and surgical treatment (OR = 0.121, 0.031-0.342) were clinical predictors for in-hospital death. On following up for 12-36 months, SOFA ≥ 5 ( = 0.000) showed higher mortality. A high SOFA score combined with increased CRP levels is associated with in-hospital mortality. Also, SOFA score, but not CRP, predicts long-term mortality in complicated IE.
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http://dx.doi.org/10.3389/fmed.2021.576970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044865PMC
March 2021

Changes in Maxillary Sinus Mucosal Thickening following the Extraction of Teeth with Advanced Periodontal Disease: A Retrospective Study Using Cone-Beam Computed Tomography.

Authors:
Zheng Cao Jie Yuan

Biomed Res Int 2021 23;2021:6688634. Epub 2021 Mar 23.

Dental Clinic of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China.

Objectives: To explore the alterations in maxillary sinus mucosal thickening after extracting teeth with severe periodontal disease using cone-beam computed tomography (CBCT).

Methods: 30 patients with severe periodontal disease of maxillary posterior teeth that needed to be extracted and who were radiographically diagnosed with mucosal thickening (MT) in the maxillary sinus participated in the study. CBCT scans were taken before tooth extraction and 2-29 months after tooth extraction. The postextraction follow-up time was divided into two groups: group 1 (<4 months) and group 2 (≥4 months). Dimensions of maxillary sinus MT, including the MT zone length (SL) and the maximum thickness of the MT zone (ST), were evaluated preextraction and postextraction; the residual ridge height (RRH) was evaluated at the sites of extracted and nonextracted teeth.

Result: Of the 24 patients with unilateral tooth extraction, there was a statistically significant difference in MT between the extraction and nonextraction sides ( < 0.05). The RRH at the site of the extracted teeth was significantly lower than that of the nonextracted teeth ( < 0.05). MT decreased significantly after tooth extraction on the extraction side but not on the nonextraction side. There was no significant difference between group 1 and group 2 regarding the reduction in mucosal thickness over time.

Conclusions: Severe periodontitis can cause MT in the maxillary sinus. The RRH was lower at the sites of extracted teeth. MT reduced quickly by a thorough debridement after tooth extraction in 4 months. MT will not decrease further over time.
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http://dx.doi.org/10.1155/2021/6688634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009702PMC
May 2021

VEGF-C/VEGFR-3/iNOS Signaling in Osteosarcoma MG63 Cells Mediates Stimulatory Effects on Human Umbilical Vein Endothelial Cell Proliferation.

Chin Med Sci J 2021 Mar;36(1):35-42

Department of Orthopaedics, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.

Objective To assess the effects of vascular endothelial growth factor-C (VEGF-C)/vascular endothelial growth factor receptor-3 (VEGFR-3) signaling on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in human osteosarcoma MG63 cells and the subsequent impact on the proliferation of human umbilical vein endothelial cells (HUVECs). MethodsMG63 cells were treated with VEGF-C alone (VEGF-C group), VEGF-C + iNOS inhibitor aminoguanidine (AG; AG group), and VEGF-C + VEGFR-3 inhibitor MAZ51 (MAZ51 group); untreated MG63 cells were used as controls. NO production was evaluated by a colorimetric method involving nitrate reductase. Meanwhile, mRNA and protein levels of iNOS were examined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. To explore the effect of VEGF-C/VEGFR-3/iNOS signaling of MG63 cells on proliferation of HUVECs, we set up six groups: HUVECs, HUVECs+MG63, HUVECs+VEGF-C, HUVECs+MG63+VEGF-C, HUVECs+MG63+VEGF-C+AG, and HUVECs+MG63+VEGF-C+MAZ51 groups. The proliferation of HUVEC cells was assessed by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, and proliferating cell nuclear antigen (PCNA) expression quantitation. ResultsVEGF-C treatment enhanced iNOS expression at both gene and protein levels (mRNA: LSD-=4.152, ; protein: LSD-=3.486, ) and increased NO release of MG63 cells (LSD-=3.774, ); treatment with either AG or MAZ51 decreased these effects (mRNA: LSD-=9.183, <0.001; LSD-=8.639, <0.001; protein: LSD-=5.170, <0.001; LSD-=7.255, <0.001; NO production:LSD-=10.326, <0.001; LSD-=10.540, <0.001). Interestingly, co-incubation of HUVECs with MG63 cells and/or VEGF-C significantly promoted HUVEC proliferation (EdU: LSD-=5.374, 0.001; LSD-=2.984, 0.05; LSD-=8.526, 0.001; PCNA: LSD-=9.267, <0.001; LSD-=5.515, 0.001; LSD-=14.873, 0.001).The proliferation effects of HUVEC induced by MG63 cells and VEGF-C attenuated by the treatment of AG (EdU: LSD-=10.770, 0.001; PCNA: LSD-=19.940, <0.001) or MAZ51 (EdU: LSD-=6.950, 0.001; PCNA: LSD-=14.001, <0.001). ConclusionIn human osteosarcoma MG63 cells, activation of VEGFR-3 by VEGF-C promotes iNOS expression and NO production, which subsequently induces HUVEC proliferation.
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http://dx.doi.org/10.24920/003753DOI Listing
March 2021

Dual-Stimulus Responsive Near-Infrared Reversible Ratiometric Fluorescent and Photoacoustic Probe for Tumor Imaging.

Anal Chem 2021 04 22;93(13):5420-5429. Epub 2021 Mar 22.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China.

Tumor-specific imaging is a major challenge in clinical tumor resection. To overcome this problem, several activatable probes have been developed for use in tumor imaging. However, most of these probes are activated based on a single-factor stimulation and are irreversible. Therefore, false signals that make tumor-specific imaging difficult are easily generated. We have developed a new dual-stimulus responsive near-infrared (NIR) reversible adenosine 5'-triphosphate (ATP)-pH probe for fluorescence and photoacoustic ratiometric imaging of tumors. Since the H and ATP content is significantly higher in the tumor microenvironment than that in normal tissues, the Förster resonance energy transfer-based probe ATP-pH was constructed with silicon rhodamine as the donor, CS dye as the acceptor, and ATP/H recognition units that could only be activated when both H and ATP were connected to the acceptor. The ATP-pH probe is reversibly activated by both the H and ATP, which effectively reduces the cumulative response of the probe in circulation after intravenous injection. Further, the NIR ratiometric property of the probe makes it suitable for imaging. Finally, our probe was successfully utilized in ratiometric photoacoustic and fluorescence tumor imaging and ratiometric fluorescence imaging-guided tumor resection.
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http://dx.doi.org/10.1021/acs.analchem.0c04804DOI Listing
April 2021

[Size Distribution of Aerosol Hygroscopic Growth Factors in Winter in Tianjin].

Huan Jing Ke Xue 2021 Feb;42(2):574-583

China Meteorological Administration-Nankai University Cooperative Laboratory for Atmospheric Environment-Health Research, State Environmental Protection Key Laboratory of Urban Ambient Air Particulate Matter Pollution Prevention and Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China.

Aerosol hygroscopic growth factors[(RH)] are key for evaluating aerosol light extinction and direct radiative forcing. The hygroscopic tandem differential mobility analyzer (HTDMA) was utilized to measure the size-resolved (RH) under different polluted conditions in winter in Tianjin. Furthermore, based on the size distribution of aerosol water-soluble ions, the (RH) across a wide size range (60 nm to 9.8 μm) was estimated using the -Köhler theory, which provides a basis for the estimation of aerosol optical parameters and direct radiative forcing under ambient conditions. Under clean conditions, ultrafine particles (<100 nm) were more hygroscopic and (RH=80%) was higher than 1.30 due to the active photolysis reaction. However, under severely polluted conditions, the proportion of water-soluble ions in aerosols increased with the increasing size; (RH) increased with particle size, where (RH=80%) and (RH=85%) for 300 nm particles was 1.39 and 1.46, respectively. For a wide size range (60 nm to 9.8 μm), the aerosols in the accumulation mode were more hygroscopic and aerosols in the Aitken mode were less hygroscopic, with coarse mode aerosols being the least hygroscopic. During the polluted period, the particulate size notably increased, and the mass fraction of NO and SO in the accumulation mode aerosols was significantly higher than during the clean period. Accordingly, the hygroscopicity of accumulation mode aerosols was strongly enhanced during the polluted period[(RH)=1.3-1.4] and aerosols in the 0.18-3.1 μm size range all had a strong hygroscopicity. On polluted days, the synergistic effect of the increase in particle size, water-soluble ions, and aerosol hygroscopicity results in the considerable deterioration of visibility.
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http://dx.doi.org/10.13227/j.hjkx.202007273DOI Listing
February 2021

Global disassortative rewiring strategy for enhancing the robustness of scale-free networks against localized attack.

Phys Rev E 2021 Feb;103(2-1):022313

School of Electronic Science and Engineering, Nanjing University, Nanjing 210023, China.

The robustness of complex networks against attack has been an important issue for decades. Most of the previous studies focused on targeted attack (TA) and random attack (RA), while recently localized attack (LA) has drawn the attention of researchers. However, the existing studies related to LA mainly aim to reveal the properties on various network topologies so that the strategy to enhance network robustness against LA is still not well studied. In this paper, we propose a global disassortative rewiring strategy to enhance the robustness of scale-free networks against LA without changing the degree distribution. The validations are conducted on simulated scale-free networks and two real-life networks. As global disassortative rewiring strategy outperforms the other strategies, it can be proved effective in enhancing network robustness against LA and may contribute to future network risk reduction. In addition, by avoiding calculating and comparing the localized-robustness measurement within each rewire operation, our strategy offers a significant advantage in computational efficiency.
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http://dx.doi.org/10.1103/PhysRevE.103.022313DOI Listing
February 2021

No difference in hepatocellular carcinoma risk in chronic hepatitis B patients treated with tenofovir vs entecavir: evidence from an updated meta-analysis.

Aging (Albany NY) 2021 02 26;13(5):7147-7165. Epub 2021 Feb 26.

Graduate School, Chongqing Medical University, Chongqing, China.

Whether tenofovir disoproxil fumarate (TDF) is superior to entecavir in reducing hepatocellular carcinoma (HCC) risk among treatment-naïve chronic hepatitis B (CHB) patients remains controversial. We aimed to clarify this controversy. Several databases, including PubMed and Embase, were retrieved through November 2020. Cohort studies comparing the effectiveness of TDF and entecavir in reducing HCC incidence among treatment-naïve CHB patients were included if they reported multivariable-adjusted or propensity-score-matched risk estimates. A random-effects model was used to pool hazard ratios (HRs). Thirteen cohort studies, involving 4097 HCC cases and 80202 CHB patients, were included. Multivariable-adjusted meta-analysis revealed no significant difference in HCC incidence between TDF and entecavir groups (HR 0.86, 95% confidence interval 0.72-1.04), which was consistent with propensity-score-matched meta-analysis (HR 0.83, 95% confidence interval 0.66-1.03). Subgroup analysis showed that the observed similarity of TDF to entecavir for HCC prevention persisted in studies with follow-up length of ≥4 years but not in those with follow-up length of <4 years (<0.01). In conclusion, TDF is similar to entecavir in reducing HCC incidence among treatment-naïve CHB patients. Heterogeneous results of included studies may result from their disparity in follow-up length. Our findings should be treated with caution and need to be further confirmed.
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http://dx.doi.org/10.18632/aging.202573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993671PMC
February 2021

Anticoagulation and Transjugular Intrahepatic Portosystemic Shunt for the Management of Portal Vein Thrombosis in Cirrhosis: A Prospective Observational Study.

Am J Gastroenterol 2021 Feb 25. Epub 2021 Feb 25.

Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Centre for Digestive Diseases and Xi'an International Medical Center Hospital of Digestive Diseases, Northwestern University, Xi'an, China; Department of Liver Diseases and Interventional Radiology, Xi'an International Medical Center Hospital of Digestive Diseases, Northwestern University, Xi'an, China; Department of Ultrasound, National Clinical Research Centre for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China; State Key Laboratory of Cancer Biology, National Clinical Research Centre for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.

Introduction: Current guidelines recommend anticoagulation as the mainstay of portal vein thrombosis (PVT) treatment in cirrhosis. However, because of the heterogeneity of PVT, anticoagulation alone does not always achieve satisfactory results. This study aimed to prospectively evaluate an individualized management algorithm using a wait-and-see strategy (i.e., no treatment), anticoagulation, and transjugular intrahepatic portosystemic shunt (TIPS) to treat PVT in cirrhosis.

Methods: Between February 2014 and June 2018, 396 consecutive patients with cirrhosis with nonmalignant PVT were prospectively included in a tertiary care center, of which 48 patients (12.1%) were untreated, 63 patients (15.9%) underwent anticoagulation, 88 patients (22.2%) underwent TIPS, and 197 patients (49.8%) received TIPS plus post-TIPS anticoagulation. The decision of treatment option mainly depends on the stage of liver disease (symptomatic portal hypertension or not) and degree and extension of thrombus.

Results: During a median 31.7 months of follow-up period, 312 patients (81.3%) achieved partial (n = 25) or complete (n = 287) recanalization, with 9 (3.1%) having rethrombosis, 64 patients (16.2%) developed major bleeding (anticoagulation-related bleeding in 7 [1.8%]), 88 patients (22.2%) developed overt hepatic encephalopathy, and 100 patients (25.3%) died. In multivariate competing risk regression models, TIPS and anticoagulation were associated with a higher probability of recanalization. Long-term anticoagulation using enoxaparin or rivaroxaban rather than warfarin was associated with a decreased risk of rethrombosis and an improved survival, without increasing the risk of bleeding. However, the presence of complete superior mesenteric vein thrombosis was associated with a lower recanalization rate, increased risk of major bleeding, and poor prognosis.

Discussion: In patients with cirrhosis with PVT, the individualized treatment algorithm achieves a high-probability recanalization, with low rates of portal hypertensive complications and adverse events.
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http://dx.doi.org/10.14309/ajg.0000000000001194DOI Listing
February 2021

The KbvR Regulator Contributes to Capsule Production, Outer Membrane Protein Biosynthesis, Antiphagocytosis, and Virulence in Klebsiella pneumoniae.

Infect Immun 2021 Apr 16;89(5). Epub 2021 Apr 16.

Biomedical Research Institute, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China

is an opportunistic pathogen that mostly affects patients with weakened immune systems, but a few serotypes (especially K1 and K2) are highly invasive and result in systemic infection in healthy persons. The ability to evade and survive the components of the innate immune system is critical in infection. To investigate the role and mechanism of transcription regulator KP1_RS12260 (KbvR) in virulence and defense against the innate immune response, deletion mutant and complement strains were constructed. The animal infection assay and antiphagocytosis assay demonstrate KbvR is an important regulator that contributes to virulence and the defense against phagocytosis of macrophages. The transcriptome analysis and phenotype experiments demonstrated that deletion of decreased production of capsular polysaccharide (CPS) and biosynthesis of partly outer membrane proteins (OMPs). The findings suggest that KbvR is a global regulator that confers pathoadaptive phenotypes, which provide several implications for improving our understanding of the pathogenesis of .
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http://dx.doi.org/10.1128/IAI.00016-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091090PMC
April 2021

Technical note: On the actuator rate limit effect in reaction curves.

ISA Trans 2021 Feb 6. Epub 2021 Feb 6.

Mechatronics, Embedded Systems and Automation Lab, University of California, Merced, CA 95343, USA. Electronic address:

While actuator rate limit is common and counted in practical engineering, it has not drawn enough attention in control synthesis especially system identification. In this note, it aims to construct a new identification framework for first-order plus time-delay (FOPTD) systems affected by actuator rate limit. It is found that the rate limit can lead to an illusory delay in system reaction curves. Furthermore, necessary quantitative analyses are given to validate that excessively estimated or illusory delay significantly influences estimation accuracy of other parameters and subsequently degrades control performance. Two illustrative examples and experimental results are provided to demonstrate the adverse effect of actuator rate limit on system identification and the effectiveness of the proposed model structure on control performance.
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http://dx.doi.org/10.1016/j.isatra.2021.01.061DOI Listing
February 2021

MitoQ alleviates LPS-mediated acute lung injury through regulating Nrf2/Drp1 pathway.

Free Radic Biol Med 2021 Mar 1;165:219-228. Epub 2021 Feb 1.

Department of Anesthesiology and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong, Shanghai, 200120, China. Electronic address:

Lipopolysaccharide (LPS) has been known to cause alveolar epithelial cell (AEC) apoptosis and barrier breakdown that characterize acute lung injury (ALI) and acute respiratory distress syndrome. We aimed to investigate whether mitoquinone (MitoQ), a mitochondria-targeted antioxidant, could alleviate LPS-induced AEC damage in ALI and its underlying mechanisms. In vitro studies in AEC A549 cell line, we noted that LPS could induce dynamin-related protein 1 (Drp1)-mediated mitochondrial fission, AEC apoptosis and barrier breakdown, which could be reversed with MitoQ and mitochondrial division inhibitor 1 treatment. Moreover, the protective role of MitoQ was attenuated with Drp1 overexpression. Nuclear factor E2-related factor 2 (Nrf2) downregulation could block the effect of MitoQ by decreasing the expression of Nrf2 target genes in LPS-treated AEC, such as heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). Nrf2 gene knockdown in LPS-treated A549 cells prevented the protective effect of MitoQ from decreasing Drp1-mediated mitochondrial fission, AEC apoptosis and barrier breakdown. The lung protective effect of MitoQ by regulating the Drp1-mediated mitochondrial fission, AEC apoptosis and barrier breakdown was further confirmed in vivo with LPS-induced ALI mouse model. Additionally, the protective effect of MitoQ was inhibited by Nrf2 inhibitor ML385. We therefore conclude that MitoQ exerts ALI-protective effects by preventing Nrf2/Drp1-mediated mitochondrial fission, AEC apoptosis as well as barrier breakdown.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.01.045DOI Listing
March 2021

Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy.

Theranostics 2021 19;11(7):3502-3511. Epub 2021 Jan 19.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R China.

Photodynamic therapy (PDT) has emerged as one of the most up-and-coming non-invasive therapeutic modalities for cancer therapy in rencent years. However, its therapeutic effect was still hampered by the short life span, limited diffusion distance and ineluctable depletion of singlet oxygen (O), as well as the hypoxic microenvironment in the tumor tissue. Such problems have limited the application of PDT and appropriate solutions are highly demand. Herein, a programmatic treatment strategy is proposed for the development of a smart molecular prodrug (), which comprise a two-photon photosensitizer and a hypoxia-activated chemotherapeutic prodrug. A rhodamine dye was designed to connect them and track the drug release by the fluorescent signal generated through azo bond cleavage. The prodrug () can stay on the cell membrane and enrich at the tumor site. Upon light irradiation, the therapeutic effect was enhanced by a stepwise treatment: (i) direct generation of O on the cell membrane induced membrane destruction and promoted the uptake; (ii) deep tumor hypoxia caused by two-photon PDT process further triggered the activation of the chemotherapy prodrug. Both and experiments, have exhabited excellent tumor treatment effect. The innovative treatment strategy provides new strategy for the design of follow-up anticancer drugs.
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http://dx.doi.org/10.7150/thno.55014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847693PMC
January 2021

Biomedical Photoacoustic Imaging with Unknown Spatially Distributed Ultrasound Sensor Array.

IEEE Trans Biomed Eng 2021 Feb 3;PP. Epub 2021 Feb 3.

Objective: With the growth of interest in different medical study on biological function, non-invasive photoacoustic imaging of biological tissue attracts the interests for researchers. To eliminate the limited angle effect of photoacoustic imaging based on ultrasound linear array, spatially distributed ultrasound sensor array is applied. The accurate sensor array position determines the quality of the imaging results. In this study, we proposed three methods based on photoacoustic and ultrasound signals to enhance the imaging quality using a 256-element full-ring array.

Methods: Groups of photoacoustic and ultrasound signals are used to regress the position of each element sensor.

Result: In phantom study and mouse brain study, photoacoustic imaging results can both yield details clearly with average error rate of less than 1% (50 μm).

Conclusion: The performance of our three methods have proved that they can be potentially applied to other ultrasound-based medical imaging studies with unknown distributed positions of sensor array to enhance the imaging quality.

Significance: The proposed methods can contribute to precise biomedical imaging with unknown distributed positions of sensor array in different application scenarios.
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http://dx.doi.org/10.1109/TBME.2021.3056715DOI Listing
February 2021

A novel p.Pro871Leu missense mutation in SPECC1L gene causing craniosynostosis in a patient.

Orthod Craniofac Res 2021 Feb 1. Epub 2021 Feb 1.

Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Introduction: Craniosynostosis is one of the most common craniofacial abnormalities. It involves premature closure of one or more cranial sutures. Mutations in many genes have been and continue to be identified in patients.

Settings And Sample Population: Whole blood samples were collected from the patient and family members.

Material And Methods: Whole exome sequencing was performed to identify potential mutations in the patient. The results were verified by Sanger sequencing by comparing SPECC1L gene sequence of blood samples from 100 unrelated population-matched controls.

Results: The patient presented with craniosynostosis with fusion of the bicoronal and sagittal sutures. A novel missense mutation (c.2612C>T, p.Pro871Leu) in the SPECC1L gene was identified. Gene analysis showed a missense mutation in exon1 of SPECC1L that led to an amino acid substitution in the region between coiled-coil domain 3 and calponin homology domain.

Conclusion: Our observations expand the molecular spectrum of gene mutations in craniosynostosis and emphasize the importance of gene testing in the diagnosis of craniosynostosis. The observations also reinforce the characteristics of SPECC1L-related cranial disorders.
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http://dx.doi.org/10.1111/ocr.12473DOI Listing
February 2021

Development and Validation of a Nomogram to Predict Type 2 Diabetes Mellitus in Overweight and Obese Adults: A Prospective Cohort Study from 82938 Adults in China.

Int J Endocrinol 2020 7;2020:8899556. Epub 2020 Dec 7.

Department of Cardiology of People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China.

Background: The twin epidemic of overweight/obesity and type 2 diabetes mellitus (T2DM) is a major public health problem globally, especially in China. Overweight/obese adults commonly coexist with T2DM, which is closely related to adverse health outcomes. Therefore, this study aimed to develop risk nomogram of T2DM in Chinese adults with overweight/obesity.

Methods: We used prospective cohort study data for 82938 individuals aged ≥20 years free of T2DM collected between 2010 and 2016 and divided them into a training ( = 58056) and a validation set ( = 24882). Using the least absolute shrinkage and selection operator (LASSO) regression model in training set, we identified optimized risk factors of T2DM, followed by the establishment of T2DM prediction nomogram. The discriminative ability, calibration, and clinical usefulness of nomogram were assessed. The results were assessed by internal validation in validation set.

Results: Six independent risk factors of T2DM were identified and entered into the nomogram including age, body mass index, fasting plasma glucose, total cholesterol, triglycerides, and family history. The nomogram incorporating these six risk factors showed good discrimination regarding the training set, with a Harrell's concordance index (C-index) of 0.859 [95% confidence interval (CI): 0.850-0.868] and an area under the receiver operating characteristic curve of 0.862 (95% CI: 0.853-0.871). The calibration curves indicated well agreement between the probability as predicted by the nomogram and the actual probability. Decision curve analysis demonstrated that the prediction nomogram was clinically useful. The consistent of findings was confirmed using the validation set.

Conclusions: The nomogram showed accurate prediction for T2DM among Chinese population with overweight and obese and might aid in assessment risk of T2DM.
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http://dx.doi.org/10.1155/2020/8899556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775153PMC
December 2020