Publications by authors named "Li Xiao"

3,469 Publications

  • Page 1 of 1

Direct and Indirect Costs of Influenza-Like Illness Treated with and Without Oseltamivir in 15 European Countries: A Descriptive Analysis Alongside the Randomised Controlled ALICE Trial.

Clin Drug Investig 2021 Jul 22. Epub 2021 Jul 22.

Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium.

Background And Objective: Influenza-like illness (ILI) leads to a substantial disease burden every winter in Europe; however, oseltamivir is not frequently prescribed to ILI patients in the primary-care setting. An open-label, multi-country, multi-season, randomised controlled trial investigated the effectiveness of oseltamivir for treating ILI in 15 European countries. We aimed to evaluate whether patients presenting with ILI in primary care and being managed with the addition of oseltamivir to usual care had lower average direct and indirect costs compared to patients with usual care alone.

Methods: Resource use data were extracted from participants' daily diaries. Itemised country-specific unit costs were collected through official tariffs, pharmacies or literature. Costs were converted to 2018 values. The null hypothesis was tested based on one-sided credible intervals (CrIs) obtained by bootstrapping. Base-case analysis estimated direct cost and productivity losses using itemised costed resource use and the human capital approach. Scenario analyses with self-reported spending rather than itemised costing were also performed.

Results: Patients receiving oseltamivir (N = 1306) reported fewer healthcare visits, medication uses, hospital attendances and paid-work hours lost than the other patients (N = 1298). Excluding the oseltamivir cost, the average direct costs were lower in patients treated with oseltamivir from all perspectives, but these differences were not statistically significant (perspective of patient: €17 [0-95% Crl: 16-19] vs. €24 [5-100% Crl: 18-29]; healthcare provider: €37 [28-67] vs. €44 [25-55]; healthcare payers: €54 [45-85] vs. €68 [45-81]; and society: €423 [399-478] vs. €451 [390-478]). Scenario and age-group analyses confirmed these findings, but with some between-country differences.

Conclusion: The average direct and indirect costs were consistently lower in patients treated with oseltamivir than in patients without from four perspectives (excluding the oseltamivir cost). However, these differences were not statistically significant.
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http://dx.doi.org/10.1007/s40261-021-01057-yDOI Listing
July 2021

Bioprinting of 3D Functional Tissue Constructs.

Int J Bioprint 2021 22;7(3):395. Epub 2021 Jun 22.

Engineering Product Development Pillar, Singapore University of Technology and Design, Singapore 487372, Singapore.

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http://dx.doi.org/10.18063/ijb.v7i3.395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287492PMC
June 2021

Coaxial Electrohydrodynamic Bioprinting of Pre-vascularized Cell-laden Constructs for Tissue Engineering.

Int J Bioprint 2021 4;7(3):362. Epub 2021 Jun 4.

State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

Recapitulating the vascular networks that maintain the delivery of nutrition, oxygen, and byproducts for the living cells within the three-dimensional (3D) tissue constructs is a challenging issue in the tissue-engineering area. Here, a novel coaxial electrohydrodynamic (EHD) bioprinting strategy is presented to fabricate thick pre-vascularized cell-laden constructs. The alginate and collagen/calcium chloride solution were utilized as the outer-layer and inner-layer bioink, respectively, in the coaxial printing nozzle to produce the core-sheath hydrogel filaments. The effect of process parameters (the feeding rate of alginate and collagen and the moving speed of the printing stage) on the size of core and sheath lines within the printed filaments was investigated. The core-sheath filaments were printed in the predefined pattern to fabricate lattice hydrogel with perfusable lumen structures. Endothelialized lumen structures were fabricated by culturing the core-sheath filaments with endothelial cells laden in the core collagen hydrogel. Multilayer core-sheath filaments were successfully printed into 3D porous hydrogel constructs with a thickness of more than 3 mm. Finally, 3D pre-vascularized cardiac constructs were successfully generated, indicating the efficacy of our strategy to engineer living tissues with complex vascular structures.
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http://dx.doi.org/10.18063/ijb.v7i3.362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287508PMC
June 2021

Sex Differences in Angiotensin II-Induced Hypertension and Kidney Injury: Role of AT1a Receptors in The Proximal Tubule of The Kidney.

Clin Sci (Lond) 2021 Jul 20. Epub 2021 Jul 20.

Tulane University School of Medicine, New Orleans, Louisiana, United States.

In the present study, we tested the hypothesis that there are significant sex differences in angiotensin II (Ang II)-induced hypertension and kidney injury using male and female wild-type and proximal tubule-specific AT1a receptor knockout mice (PT-Agtr1a-/-). Twelve groups (n=8-12 per group) of adult male and female wild-type and PT-Agtr1a-/- mice were infused with a pressor dose of Ang II via osmotic pump for 2 weeks (1.5 mg/kg/day, i.p.) and simultaneously treated with or without losartan (20 mg/kg/day, p.o.) to determine the respective roles of AT1a receptors in the proximal tubules versus systemic tissues. Basal systolic, diastolic, and mean arterial pressure were approximately 13 ± 3 mmHg lower (P<0.01), while basal 24 h urinary Na+, K+, and Cl- excretion were significantly higher in both male and female PT-Agtr1a-/- mice than wild-type controls (P<0.01) without significant sex differences between different strains. Both male and female wild-type and PT-Agtr1a-/- mice developed hypertension (P<0.01), and the magnitudes of the pressor responses to Ang II were similar between male and female wild-type and PT-Agtr1a-/- mice (n.s.). Likewise, Ang II-induced hypertension was significantly attenuated in both male and female PT-Agtr1a-/- mice (P<0.01). Furthermore, losartan attenuated the hypertensive responses to Ang II to similar extents in both male and female wild-type and PT-Agtr1a-/- mice. Finally, Ang II-induced kidney injury was attenuated in PT-Agtr1a-/- mice (P<0.01). In conclusion, the present study demonstrates that deletion of AT1a receptors in the proximal tubules of the kidney attenuates Ang II-induced hypertension and kidney injury without revealing significant sex differences.
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http://dx.doi.org/10.1042/CS20201574DOI Listing
July 2021

Rare Case of a Schwannoma of the Posterior Pharyngeal Wall in a Child.

Ear Nose Throat J 2021 Jul 19:1455613211031027. Epub 2021 Jul 19.

Department of Otorhinolaryngology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.

We present a rare case of a schwannoma which is localized on the posterior pharyngeal wall. It caused severe difficulty in swallowing and breathing in a 3-year-old child. Schwannomas of the posterior pharyngeal wall have been rarely reported in children. To our knowledge, only 7 cases of posterior pharyngeal wall schwannoma have been previously reported in the literature, but none of them is associated with a child. The tumor was removed with plasma radiofrequency excision via a transoral route. Computed tomography or magnetic resonance imaging examination showed no recurrence of the tumor up to 2 years. To our knowledge, for the first time, a case of posterior pharyngeal wall schwannoma has been reported in a 3-year-old child, and the schwannoma was removed via plasma radiofrequency transoral excision. This case study illustrates that schwannoma may occur in children, and it is safe to treat this disease through plasma radiofrequency transoral excision route.
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http://dx.doi.org/10.1177/01455613211031027DOI Listing
July 2021

3D Seed-Germination-Like MXene with In Situ Growing CNTs/Ni Heterojunction for Enhanced Microwave Absorption via Polarization and Magnetization.

Nanomicro Lett 2021 Jul 19;13(1):157. Epub 2021 Jul 19.

Laboratory of Advanced Materials, Shanghai Key Lab of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai, 200438, People's Republic of China.

Highlights: Benefiting from the possible "seed-germination" effect, the "seeds" Ni grow into "buds" Ni nanoparticles and "stem" carbon nanotubes (CNTs) from the enlarged "soil" of MXene skeleton. Compared with the traditional magnetic agglomeration, the MXene-CNTs/Ni hybrids exhibit the highly spatial dispersed magnetic architecture. 3D MXene-CNTs/Ni composites hold excellent microwave absorption performance (-56.4 dB at only 2.4 mm). TiCT MXene is widely regarded as a potential microwave absorber due to its dielectric multi-layered structure. However, missing magnetic loss capability of pure MXene leads to the unmatched electromagnetic parameters and unsatisfied impedance matching condition. Herein, with the inspiration from dielectric-magnetic synergy, this obstruction is solved by fabricating magnetic CNTs/Ni hetero-structure decorated MXene substrate via a facile in situ induced growth method. Ni ions are successfully attached on the surface and interlamination of each MXene unit by intensive electrostatic adsorption. Benefiting from the possible "seed-germination" effect, the "seeds" Ni grow into "buds" Ni nanoparticles and "stem" carbon nanotubes (CNTs) from the enlarged "soil" of MXene skeleton. Due to the improved impedance matching condition, the MXene-CNTs/Ni hybrid holds a superior microwave absorption performance of - 56.4 dB at only 2.4 mm thickness. Such a distinctive 3D architecture endows the hybrids: (i) a large-scale 3D magnetic coupling network in each dielectric unit that leading to the enhanced magnetic loss capability, (ii) a massive multi-heterojunction interface structure that resulting in the reinforced polarization loss capability, confirmed by the off-axis electron holography. These outstanding results provide novel ideas for developing magnetic MXene-based absorbers.
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http://dx.doi.org/10.1007/s40820-021-00680-wDOI Listing
July 2021

Genetic Diversity and Azole Resistance Among Natural Aspergillus fumigatus Populations in Yunnan, China.

Microb Ecol 2021 Jul 19. Epub 2021 Jul 19.

State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, and Key Laboratory for Southwest Microbial Diversity of the Ministry of Education, Yunnan University, Kunming, 650032, Yunnan, People's Republic of China.

The emergence and spread of azole resistance alleles in clinical and environmental isolates of Aspergillus fumigatus is a global human health concern and endangers the "One Health" approach in our fight against antifungal resistance (AFR) in this pathogen. A major challenge to combat AFR in A. fumigatus is the massive aerial dispersal ability of its asexual spores. Our recent fine-scale survey of greenhouse populations of A. fumigatus near Kunming, Yunnan, China, suggested that the use of azole fungicides for plant protection was likely a major driver of the high-frequency azole-resistant A. fumigatus (ARAF) in greenhouses. Here, we investigated the potential spread of those ARAF and the structure of geographic populations of A. fumigatus by analyzing 452 isolates from 19 geographic locations across Yunnan. We found lower frequencies of ARAF in these outdoor populations than those in greenhouses near Kunming, but there were abundant new alleles and new genotypes, including those associated with azole resistance, consistent with multiple independent origins of ARAF across Yunnan. Interestingly, among the four ecological niches, the sediments of a large lake near Kunming were found to have the highest frequency of ARAF (~ 43%). While most genetic variations were observed within the 19 local populations, statistically significant genetic differentiations were found between many subpopulations within Yunnan. Furthermore, similar to greenhouse populations, these outdoor populations of A. fumigatus in Yunnan were significantly different from those in other parts of the world. Our results call for increased attention to local and regional studies of this fungal pathogen to help develop targeted control strategies against ARAF.
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http://dx.doi.org/10.1007/s00248-021-01804-wDOI Listing
July 2021

Advances on (+)-nootkatone microbial biosynthesis and its related enzymes.

J Ind Microbiol Biotechnol 2021 Jul 19. Epub 2021 Jul 19.

Key Laboratory of Environment Correlative Dietology, Ministry of Education, College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

(+)-Nootkatone is an important functional sesquiterpene and is comprehensively used in pharmaceutical, cosmetic, agricultural and food flavor industries. However, (+)-nootkatone is accumulated trace amounts in plants, and the demand for industry is mainly met by chemical methods which is harmful to the environment. The oxygen-containing sesquiterpenes prepared using microbial methods can be considered as 'natural'. Microbial transformation has the advantages of mild reaction conditions, high efficiency, environmental protection and strong stereoselectivity, and has become an important method for the production of natural spices. The microbial biosynthesis of (+)-nootkatone from the main precursor (+)-valencene is summarized in this paper. Whole-cell systems of fungi, bacteria, microalgae and plant cells have been employed. It was described that the enzymes involved in the microbial biosynthesis of (+)-nootkatone, including cytochrome p450 enzymes, laccase, lipoxygenase and so on. More recently, the related enzymes were expressed in microbial hosts to heterologous produce (+)-nootkatone, such as Escherichia coli, Pichia pastoris, Yarrowia lipolytica and Saccharomyces cerevisiae. Finally, the development direction of research for realizing industrialization of microbial transformation was summarized and it provided many options for future improved bioprocesses.
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http://dx.doi.org/10.1093/jimb/kuab046DOI Listing
July 2021

PGK1 Is a Key Target for Anti-Glycolytic Therapy of Ovarian Cancer: Based on the Comprehensive Analysis of Glycolysis-Related Genes.

Front Oncol 2021 1;11:682461. Epub 2021 Jul 1.

Department of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, China.

Reprogramming of energy metabolism is a key hallmark of cancer, which provides a new research perspective for exploring the development of cancer. However, the most critical target of anti-glycolytic therapy for ovarian cancer remains unclear. Therefore, in the present study, Oncomine, GEPIA, and HPA databases, combined with clinical specimens of different histological types of ovarian cancer were used to comprehensively evaluate the expression levels of glycolysis-related metabolite transporters and enzymes in ovarian cancer. We selected phosphoglycerate kinase 1 (), which showed the greatest prognostic value in the Kaplan-Meier Plotter database, for subsequent validation. Immunochemistry assays confirmed that PGK1 was highly expressed in ovarian cancer. The PGK1 expression level was an independent risk factor for the survival and prognosis of patients with ovarian cancer. Functional analysis showed that the expression level was positively correlated with the infiltration of neutrophils. Cell experiments confirmed that inhibiting PGK1 expression in ovarian cancer cells could reduce the epithelial-mesenchymal transition (EMT) process, resulting in loss of cell migration and invasion ability. The small molecule NG52 dose-dependently inhibited the proliferation of ovarian cancer cells. In addition, NG52 reduced the EMT process and reversed the Warburg effect by inhibiting PGK1 activity. Therefore, PGK1 is an attractive molecular target for anti-glycolytic therapy of ovarian cancer.
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http://dx.doi.org/10.3389/fonc.2021.682461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281930PMC
July 2021

A Novel Partitivirus That Confer Hypovirulence to the Plant Pathogenic Fungus .

Front Microbiol 2021 22;12:653809. Epub 2021 Jun 22.

Hunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Changsha, China.

Here, we report a novel double-stranded RNA virus designated Colletotrichum liriopes partitivirus 1 (ClPV1) from the plant pathogenic fungus ClPV1 genome has two double stranded RNAs (dsRNAs), named as dsRNA 1 and dsRNA 2, which in the lengths of 1,807 and 1,706 bp, respectively. The dsRNA 1 and dsRNA 2 encoded proteins showing significant amino acid (aa) sequence identity to the RNA-dependent RNA polymerase (RdRp) and coat protein (CP) of partitiviruses, respectively. Phylogenetic analysis using the aa sequences of RdRp and CP indicated that ClPV1 was grouped to members of the putative Epsilonpartitivirus genus in the family. Spherical viral particles in approximately 35 nm in diameter and packaging the ClPV1 genome were isolated. Virus elimination and virus transfection with purified viral particles, and biological comparison revealed that ClPV1 could reduce the virulence and conidia production of . To the best of our knowledge, this is the first report of mycovirus in fungus.
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http://dx.doi.org/10.3389/fmicb.2021.653809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262616PMC
June 2021

Protective effects of Nrf2 against sepsis-induced hepatic injury.

Life Sci 2021 Jul 7;282:119807. Epub 2021 Jul 7.

Jiangsu Center Pharmacodynamic Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China; Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, China. Electronic address:

Aim: This study was designed to investigate the changes of liver injury and Nrf2 signaling pathway in the process of sepsis. We also aimed to examine the role of Nrf2 in resisting oxidative stress and relieving inflammation in sepsis-induced hepatic injury.

Main Methods: By operating cecal ligation and puncture (CLP) on Nrf2 mice and wild type mice, a sepsis-induced hepatic injury model was established. We compared and contrasted the wild type mice with the Nrf2 mice during sepsis-induced hepatic injury, and evaluated the liver damage by biochemical analyses and staining hematoxylin-eosin (HE). Western blot or real-time PCR was performed to detect Nrf2 and its regulated genes NQO-1, GCLM and HO-1. Additionally, we detected the expressions and secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), IL-1β and anti-inflammatory cytokines IL-10. We assessed the oxidative stress through the levels of MDA and NO.

Key Findings: The results showed that Nrf2 expressions at mRNA and protein levels were increased 1 day after CLP, namely the early stage of sepsis. Compared with wild type mice after CLP, Nrf2 mice showed more severe liver injury, accompanied by higher expression of inflammatory cytokines and oxidative stress. Notably, Nrf2-regulated genes GCLM and NQO-1, were strongly downregulated in Nrf2 mice.

Significance: Nrf2 was probably implicated in decreasing inflammatory cytokine levels and counteracting oxidative stress to alleviate sepsis-induced hepatic injury, mainly through regulating GCLM and NQO-1 in the early stage after CLP.
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http://dx.doi.org/10.1016/j.lfs.2021.119807DOI Listing
July 2021

HtrA serine proteases in cancers: A target of interest for cancer therapy.

Biomed Pharmacother 2021 Jul 8;139:111603. Epub 2021 May 8.

Hepatobiliary/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Transplantation, Chinese Academy of Medical Sciences, Nanjing, China. Electronic address:

The HtrA protein family is composed by evolutionally-conserved serine proteases, which are homologous to the HtrA protein of the model bacterium Escherichia coli. They are widely distributed in organisms including humans, prokaryotes and eukaryotes. Moreover, HtrA family proteins are important regulators of a variety of human physiological processes, which contains the maintenance of mitochondrial homeostasis, cellular signal transduction and apoptosis regulation. The HtrA family has been found to be associated with cancer and could be used as a target for future cancer treatments. The purpose of this article is to review the relationship between these HtrA and cancer and to summarize the latest researches on HtrA and cancer.
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http://dx.doi.org/10.1016/j.biopha.2021.111603DOI Listing
July 2021

Prediction of Unbound Vancomycin Levels in Intensive Care Unit and Nonintensive Care Unit Patients: Total Bilirubin May Play an Important Role.

Infect Drug Resist 2021 2;14:2543-2554. Epub 2021 Jul 2.

Department of Clinical Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, People's Republic of China.

Background: The mean unbound vancomycin fraction and whether the unbound vancomycin level could be predicted from the total vancomycin level are still controversial, especially for patients in different groups, such as intensive care unit (ICU) versus non-ICU patients. Other relevant potential patient characteristics that may predict unbound vancomycin levels have yet to be clearly determined.

Methods: We enrolled a relatively large study population and included widely comprehensive potential covariates to evaluate the unbound vancomycin fractions in a cohort of ICU (n=117 samples) and non-ICU patients (n=73 samples) by using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.

Results: The mean unbound vancomycin fraction was 45.80% ± 18.69% (median, 46.01%; range: 2.13-99.45%) in the samples from the total population. No significant differences in the unbound vancomycin fraction were found between the ICU patients and the non-ICU patients (P=0.359). A significant correlation was established between the unbound and total vancomycin levels. The unbound vancomycin level can be predicted with the following equations: unbound vancomycin level=0.395×total vancomycin level+0.019×total bilirubin level+0.468 (R=0.771) for the ICU patients and unbound vancomycin level=0.526×total vancomycin level-0.527 (R=0.749) for the non-ICU patients. Overall, the observed-versus-predicted plots were acceptable.

Conclusion: A significant correlation between the total and unbound vancomycin levels was found, and measurement of the unbound vancomycin level seems to have no added value over measurement of the total vancomycin level. The study developed parsimonious equations for predicting the unbound vancomycin level and provides a reference for clinicians to predict the unbound vancomycin level in adult populations.
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http://dx.doi.org/10.2147/IDR.S311231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259942PMC
July 2021

Acceptance of overseas clinical trial data of medical devices for pre-market registration: general principles and considerations of the National Medical Products Administration.

Chin Med J (Engl) 2021 Jul 7. Epub 2021 Jul 7.

Department of Clinical and Biostatistics I, Center for Medical Device Evaluation National Medical Products Administrition, Beijing 100081, China Center for Medical Device Evaluation National Medical Products Administrition, Beijing 100081, China.

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http://dx.doi.org/10.1097/CM9.0000000000001595DOI Listing
July 2021

Current Perspectives on B Lymphocytes in the Immunobiology of Hepatocellular Carcinoma.

Front Oncol 2021 21;11:647854. Epub 2021 Jun 21.

Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Immune cells infiltrating tumors are capable of significantly impacting carcinogenesis through cancer promotion and anticancer responses. There are many aspects of hepatocellular carcinoma (HCC) related T lymphocytes that are undergoing extensive studies, whereas the effect exerted by B lymphocytes remains a less researched area. In this study, the latest research on the effect of B lymphocytes as they infiltrate tumors in relation to HCC is presented. Their prognosis-related importance is analyzed, along with their function in the tumor microenvironment (TME), as well as the way that B cell biology can be employed to help create a B cell therapy strategy for HCC.
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http://dx.doi.org/10.3389/fonc.2021.647854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256159PMC
June 2021

Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients.

Chin Med Sci J 2021 Jun;36(2):103-109

Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, China.

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus (T2DM). Previous researches report that methylenetetrahydrofolate reductase gene () polymorphisms might influence the occurrence of coronary heart disease (CHD) in T2DM patients. The purpose of this study was to evaluate whether C677T and A1298C mutations are associated with the risk of CHD in T2DM patients. Methods A total of 197 subjects with T2DM were studied, of which 95 patients with CHD. The genotypes of C677T and A1298C were analyzed by using dideoxy chain-termination method, and compared between patients with CHD and those without CHD. Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD (=0.011). However, there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD. Furthermore, the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine (Hcy) levels (≤15 μmol/L) (=0.006), while no effect of gene polymorphism on the incidence of CHD was found in patients with higher Hcy levels (>15 μmol/L) (=0.491). Conclusion The C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hcy levels.
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http://dx.doi.org/10.24920/003792DOI Listing
June 2021

The Downregulation of Placental Lumican Promotes the Progression of Preeclampsia.

Reprod Sci 2021 Jul 6. Epub 2021 Jul 6.

College of Pharmacy, Jining Medical University, Rizhao, Shandong, China.

Multiple pieces of evidence illustrate that impaired trophoblast function results in preeclampsia (PE), and migration/invasion of human trophoblast cells is stringently regulated by extracellular matrix (ECM) components. Many studies have indicated abnormal expressions of placental ECM components are associated with preeclampsia. However, the change and influence of lumican, a vital member of extracellular matrix (ECM) molecules, on trophoblast cells during preeclampsia remain unclear. This study examines the possibility that the roles of lumican in trophoblast cells contribute to PE. To address this issue, the expression of lumican in human placental tissues was observed using immunohistochemistry, fluorescence quantitative PCR, and Western blot technology. After the HTR-8/SVneo cell line was transfected with pcDNA3.1-human lumican, pGPU6-human lumican shRNA, and their negative controls, the impact of lumican on the HTR-8/SVneo cell line was investigated. Lumican was expressed in human placental tissues. Compared with the control group, its expression was significantly lower in PE placentas. Lumican downregulation inhibited cell proliferation significantly and reduced Bcl-2 expression, but increased P53 expression. These results indicate that the downregulation of placental lumican may drive PE development via promoting the downregulation of Bcl-2 expression and upregulation of P53.
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http://dx.doi.org/10.1007/s43032-021-00660-wDOI Listing
July 2021

[Revealing the mechanisms underlying the therapeutic effects of acupuncture on migraine using neuroimaging: a narrative review].

Sheng Li Xue Bao 2021 Jun;73(3):433-445

Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.

Migraine is a neurological disorder characterized by attacks of moderate or severe headache and various neurological symptoms. Acupuncture, as a commonly used non-pharmacological therapy, has the advantage of obvious therapeutic effect and few side effects in the prevention and treatment of migraine. But the underlying mechanism of acupuncture on migraine remains unclear. Recently, advances in neuroimaging technology have helped to objectively assess the effect of acupuncture on treating migraine and offered new opportunities to explore the central mechanism of acupuncture on treating migraine. In order to better understand the current status of neuroimaging studies on the therapeutic mechanism of acupuncture on migraine and shed light on future research, this review aims to overview the neuroimaging studies in recent 10 years from two aspects: (1) Central mechanism of acupuncture on treating acute migraine attack; (2) Central mechanism of acupuncture on preventing migraine attack.
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June 2021

Genome-wide analysis of genomic imprinting in the endosperm and allelic variation in flax.

Plant J 2021 Jul 6. Epub 2021 Jul 6.

Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China.

Genomic imprinting is an epigenetic phenomenon that causes biased expression of maternally and paternally inherited alleles. In flowering plants, genomic imprinting predominantly occurs in the triploid endosperm and plays a vital role in seed development. In this study, we identified 248 candidate imprinted genes including 114 maternally expressed imprinted genes (MEGs) and 134 paternally expressed imprinted genes (PEGs) in flax (Linum usitatissimum L.) endosperm using deep RNA sequencing. These imprinted genes were neither clustered in specific chromosomal regions nor well conserved among flax and other plant species. MEGs tended to be expressed specifically in the endosperm, whereas the expression of PEGs was not tissue-specific. Imprinted single nucleotide polymorphisms differentiated 200 flax cultivars into the oil flax, oil-fiber dual purpose flax and fiber flax subgroups, suggesting that genomic imprinting contributed to intraspecific variation in flax. The nucleotide diversity of imprinted genes in the oil flax subgroup was significantly higher than that in the fiber flax subgroup, indicating that some imprinted genes underwent positive selection during flax domestication from oil flax to fiber flax. Moreover, imprinted genes that underwent positive selection were related to flax functions. Thirteen imprinted genes related to flax seed size and weight were identified using a candidate gene-based association study. Therefore, our study provides information for further exploration of the function and genomic variation of imprinted genes in the flax population.
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http://dx.doi.org/10.1111/tpj.15411DOI Listing
July 2021

Somatostatin receptor 5 is critical for protecting intestinal barrier function in vivo and in vitro.

Mol Cell Endocrinol 2021 Jul 2;535:111390. Epub 2021 Jul 2.

Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China. Electronic address:

Somatostatin receptor 5 (SSTR5) is involved in intestinal barrier protection during colitis through modulating tight junction (TJ) proteins, but the mechanisms of SSTR5 in TJ regulation are largely unknown. Therefore, the present study was designed to illuminate how SSTR5 modulated intestinal barrier function and TJ proteins. In this study, activation of SSTR5 by its special agonist L817,818 effectively ameliorated impaired intestinal barrier function in TNF-α-pretreated cells and mice with colitis. Restoration of intestinal barrier function was dependent on upregulation of claudin-4 and ZO-1. Suppression of SSTR5 signaling through specific siRNA or the antagonist BIM23056 markedly exacerbated TNF-α-induced claudin-4 and ZO-1 damage. L817,818 treatment markedly suppressed TNF-α-induced NF-κB p65 phosphorylation, myosin light chain kinase (MLCK) upregulation and myosin light chain (MLC) phosphorylation. Exposure to a NF-κB inhibitor (QNZ) or MLCK inhibitor (ML-7) effectively inhibited compromised claudin-4 and ZO-1 induced by BIM23056/TNF-α. These observations indicate that activation of SSTR5 protects intestinal barrier function by upregulating claudin-4 and ZO-1 expression, which is mediated by NF-κB-MLCK-MLC signaling. Taken together, our findings suggest that SSTR5 might represent a promising target for colitis therapy.
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http://dx.doi.org/10.1016/j.mce.2021.111390DOI Listing
July 2021

Hydrophobic magnetic nanoparticle assisted catanionic surfactant supramolecular solvent microextraction of multiresidue antibiotics in water samples.

Anal Methods 2021 Jul 5. Epub 2021 Jul 5.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China.

A novel extraction technique i.e. hydrophobic magnetic nanoparticle (MNP)-assisted in situ supramolecular solvent (SUPRAS) microextraction was proposed, and it was applied for the analysis of sulfonamides (SAs) and fluoroquinolones (FQs) in aqueous samples, coupled with high performance liquid chromatography-UV detection (HPLC-UV). In this extraction method, hexafluoroisopropanol-mediated salt-free catanionic surfactant based SUPRAS in situ microextraction was initially carried out; then, the SUPRAS was quickly adsorbed by the hydrophobic magnetic nanoparticles and gathered by an external magnetic field. This can greatly shorten the separation time and overcome the dependence on centrifugation, and also perform a secondary extraction of free analytes (not extracted by SUPRAS) from water samples. The magnetic separation ability of different hydrophobic MNPs was evaluated by adsorbing supramolecular aggregates from the water sample. The effective parameters affecting the extraction efficiency of the analytes were investigated and optimized using the one variable at a time method. About 3 min was required to realize the extraction of analytes with an enrichment factor (EF) of 12-53 for SAs and 79-118 for FQs. Compared with the centrifugation-assisted SUPRAS microextraction, the hydrophobic MNP-assisted SUPRAS microextraction obtained much better extraction and preconcentration efficiency. The proposed novel extraction method with HPLC-UV provided LODs of 0.21-0.76 ng mL-1 for SAs and 0.10-0.18 ng mL-1 for FQs. Good linearity was obtained with correlation coefficients ranging from 0.9962 to 0.9999. The intra- and inter-day recoveries of the target antibiotics were in the range of 92.0-111.3% with RSD% below 10.4%. The method was successfully applied to determine SAs and FQs in real water samples, such as lake water, river water, reservoir water, and wastewater.
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http://dx.doi.org/10.1039/d1ay00525aDOI Listing
July 2021

Coronary artery calcification and risk of mortality and adverse outcomes in patients with COVID-19: a Chinese multicenter retrospective cohort study.

Chin J Acad Radiol 2021 Jun 28:1-9. Epub 2021 Jun 28.

Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nanjing, 210002 Jiangsu Province People's Republic of China.

Background: Coronary artery calcification (CAC) is an independent risk factor of major adverse cardiovascular events; however, the impact of CAC on in-hospital death and adverse clinical outcomes in patients with coronavirus disease 2019 (COVID-19) remains unclear.

Objective: To explore the association between CAC and in-hospital mortality and adverse events in patients with COVID-19.

Methods: This multicenter retrospective cohort study enrolled 2067 laboratory-confirmed COVID-19 patients with definitive clinical outcomes (death or discharge) admitted from 22 tertiary hospitals in China between January 3, 2020 and April 2, 2020. Demographic, clinical, laboratory results, chest CT findings, and CAC on admission were collected. The primary outcome was in-hospital death and the secondary outcome was composed of in-hospital death, admission to intensive care unit (ICU), and requiring mechanical ventilation. Multivariable Cox regression analysis and Kaplan-Meier plots were used to explore the association between CAC and in-hospital death and adverse clinical outcomes.

Results: The mean age was 50 years (SD,16) and 1097 (53.1%) were male. A total of 177 patients showed high CAC level, and compared with patients with low CAC, these patients were older (mean age: 49 vs. 69 years,  < 0.001) and more likely to be male (52.0% vs. 65.0%,  = 0.001). Comorbidities, including cardiovascular disease (CVD) ([33.3%, 59/177] vs. [4.7%, 89/1890],  < 0.001), presented more often among patients with high CAC, compared with patients with low CAC. As for laboratory results, patients with high CAC had higher rates of increased D-dimer, LDH, as well as CK-MB (all  < 0.05). The mean CT severity score in high CAC group was also higher than low CAC group (12.6 vs. 11.1,  = 0.005). In multivariable Cox regression model, patients with high CAC were at a higher risk of in-hospital death (hazard ratio [HR], 1.731; 95% CI 1.010-2.971,  = 0.046) and adverse clinical outcomes (HR, 1.611; 95% CL 1.087-2.387,  = 0.018).

Conclusion: High CAC is a risk factor associated with in-hospital death and adverse clinical outcomes in patients with confirmed COVID-19, which highlights the importance of calcium load testing for hospitalized COVID-19 patients and calls for attention to patients with high CAC.

Supplementary Information: The online version contains supplementary material available at 10.1007/s42058-021-00072-4.
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http://dx.doi.org/10.1007/s42058-021-00072-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237549PMC
June 2021

Th17/1-Biased Inflammatory Environment Involved in the Response of Epithelial Cells to Antigen Stimuli in Nasal Polyps.

J Immunol Res 2021 9;2021:5531606. Epub 2021 Jun 9.

Medical College of China Three Gorges University, China.

Several studies showed that IL-17A was significantly increased in nasal polyps (NPs). However, the source and characteristics of IL-17A-producing cells in NPs were not fully understood. We isolated mononuclear cells from NPs and uncinate tissues and analyzed them using flow cytometry. The results indicated that IL-17A was increased in NP tissues compared to uncinate tissues. The main IL-17A-expressing cells were CD3 T cells in NP tissues, including Th17 cells, Tc17 cells, and T17 cells. Not similar to those in uncinate tissues, the majority of Th17 cells highly coexpressed IFN- in NP tissues, such as Th17/1 cells, which highly expressed CXCR3, CCR6, RORt, and T-bet. Furthermore, Th17/1-biased environment increased the response of nasal epithelial cells to bacterial and viral stimuli, implying that Th17/1 cells play a greater role in the pathological development of NPs than Th17 or Th1 cells.
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http://dx.doi.org/10.1155/2021/5531606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211518PMC
June 2021

Diagnostic Value of the Fimbriae Distribution Pattern in Localization of Urinary Tract Infection.

Front Med (Lausanne) 2021 18;8:602691. Epub 2021 Jun 18.

Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

Urinary tract infections (UTIs) are one of the most common infectious diseases. UTIs are mainly caused by uropathogenic (UPEC), and are either upper or lower according to the infection site. Fimbriae are necessary for UPEC to adhere to the host uroepithelium, and are abundant and diverse in UPEC strains. Although great progress has been made in determining the roles of different types of fimbriae in UPEC colonization, the contributions of multiple fimbriae to site-specific attachment also need to be considered. Therefore, the distribution patterns of 22 fimbrial genes in 90 UPEC strains from patients diagnosed with upper or lower UTIs were analyzed using PCR. The distribution patterns correlated with the infection sites, an XGBoost model with a mean accuracy of 83.33% and a mean area under the curve (AUC) of the receiver operating characteristic (ROC) of 0.92 demonstrated that fimbrial gene distribution patterns could predict the localization of upper and lower UTIs.
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http://dx.doi.org/10.3389/fmed.2021.602691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249706PMC
June 2021

Sitagliptin on carotid intima-media thickness in type 2 diabetes and hyperuricemia patients: a subgroup analysis of the PROLOGUE study.

Ther Adv Chronic Dis 2021 22;12:20406223211026993. Epub 2021 Jun 22.

Department of General practice, The Second Affiliated Hospital of Chongqing Medical University, No 76 Linjiang Road, Chongqing, 400010, China.

Background And Aims: Studies have shown that dipeptidyl peptidase-4 (DDP-4) inhibitors have anti-atherosclerotic effects. However, in the PROLOGUE study, sitagliptin failed to slow the progression of carotid intima-media thickness (CIMT) relative to conventional therapy. We conducted a analysis of the PROLOGUE study and compared the effects of sitagliptin and conventional therapy on changes in CIMT in subgroups with or without hyperuricemia.

Methods: The PROLOGUE study was a randomized controlled trial of 442 patients with type 2 diabetes mellitus (T2DM). Patients were randomized to receive sitagliptin added therapy or conventional therapy. Based on the serum uric acid levels of all study populations in the PROLOGUE study, we divided them into hyperuricemia subgroup ( = 104) and non-hyperuricemia subgroup ( = 331). The primary outcome was changed in carotid intima-media thickness (CIMT) parameters compared with baseline during the 24 months treatment period.

Results: In the hyperuricemia subgroup, compared with the conventional therapy group, the changes in the mean internal carotid artery (ICA)-IMT and max ICA-IMT at 24 months were significantly lower in the sitagliptin group [-0.233 mm, 95% confidence interval (CI) (-0.419 to 0.046),  = 0.015 and -0.325 mm, 95% CI (-0.583 to -0.068),  = 0.014], although there was no significant difference in the common carotid artery CIMT.

Conclusion: The results of our analysis indicated that sitagliptin attenuated the progression of CIMT than conventional therapy in T2DM and hyperuricemia patients.
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http://dx.doi.org/10.1177/20406223211026993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221703PMC
June 2021

Preparation, characterization of PLGA/chitosan nanoparticles as a delivery system for controlled release of DHA.

Int J Biol Macromol 2021 Jun 30;185:782-791. Epub 2021 Jun 30.

College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China. Electronic address:

In this work, a novel DHA-loaded nanoparticle with PLGA and chitosan (PCSDNP) was successfully prepared. The structure of PCSDNP and DHA-loaded PLGA nanoparticles was measured by transmission electron microscope, scanning electron microscope, and differential scanning calorimeter. The interaction strength between DHA, PLGA, and chitosan was evaluated through Fourier transform infrared spectroscopy. The curves of controlled DHA release and stabilities for different environmental factors of two NPs were evaluated. Importantly, two NPs were almost regularly spherical and the interactions were hydrogen bonds and electrostatic interactions between PLGA and chitosan. These NPs had a good encapsulation rate (80.45%) and high-water solubility than the free DHA molecule. In simulated gastrointestinal fluid, two NPs showed a controlled-release pattern. Overall, PCSDNP had better stability and controlled-release effect with the synergy between CS and PLGA under the conditions of pH (2- 7), ionic strength (0- 500 mM), storage time (0- 42 d), and temperature (30- 80 °C).
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.190DOI Listing
June 2021

A Novel Model for the RNase MRP-Induced Switch between the Formation of Different Forms of 5.8S rRNA.

Int J Mol Sci 2021 Jun 22;22(13). Epub 2021 Jun 22.

Department of Biological Sciences, University of Maryland Baltimore County (UMBC), 1000 Hilltop Circle, Baltimore, MD 21250, USA.

Processing of the RNA polymerase I pre-rRNA transcript into the mature 18S, 5.8S, and 25S rRNAs requires removing the "spacer" sequences. The canonical pathway for the removal of the ITS1 spacer involves cleavages at the 3' end of 18S rRNA and at two sites inside ITS1. The process can generate either a long or a short 5.8S rRNA that differs in the number of ITS1 nucleotides retained at the 5.8S 5' end. Here we document a novel pathway to the long 5.8S, which bypasses cleavage within ITS1. Instead, the entire ITS1 is degraded from its 5' end by exonuclease Xrn1. Mutations in RNase MRP increase the accumulation of long relative to short 5.8S rRNA. Traditionally this is attributed to a decreased rate of RNase MRP cleavage at its target in ITS1, called A3. However, results from this work show that the MRP-induced switch between long and short 5.8S rRNA formation occurs even when the A3 site is deleted. Based on this and our published data, we propose that the link between RNase MRP and 5.8S 5' end formation involves RNase MRP cleavage at unknown sites elsewhere in pre-rRNA or in RNA molecules other than pre-rRNA.
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http://dx.doi.org/10.3390/ijms22136690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268776PMC
June 2021

In silico prediction of chemical-induced hematotoxicity with machine learning and deep learning methods.

Mol Divers 2021 Jul 1. Epub 2021 Jul 1.

Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China.

Chemical-induced hematotoxicity is an important concern in the drug discovery, since it can often be fatal when it happens. It is quite useful for us to give special attention to chemicals which can cause hematotoxicity. In the present study, we focused on in silico prediction of chemical-induced hematotoxicity with machine learning (ML) and deep learning (DL) methods. We collected a large data set contained 632 hematotoxic chemicals and 1525 approved drugs without hematotoxicity. Computational models were built using several different machine learning and deep learning algorithms integrated on the Online Chemical Modeling Environment (OCHEM). Based on the three best individual models, a consensus model was developed. It yielded the prediction accuracy of 0.83 and balanced accuracy of 0.77 on external validation. The consensus model and the best individual model developed with random forest regression and classification algorithm (RFR) and QNPR descriptors were made available at https://ochem.eu/article/135149 , respectively. The relevance of 8 commonly used molecular properties and chemical-induced hematotoxicity was also investigated. Several molecular properties have an obvious differentiating effect on chemical-induced hematotoxicity. Besides, 12 structural alerts responsible for chemical hematotoxicity were identified using frequency analysis of substructures from Klekota-Roth fingerprint. These results should provide meaningful knowledge and useful tools for hematotoxicity evaluation in drug discovery and environmental risk assessment.
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http://dx.doi.org/10.1007/s11030-021-10255-xDOI Listing
July 2021

Real-time Alerting System for COVID-19 Using Wearable Data.

medRxiv 2021 Jun 21. Epub 2021 Jun 21.

Early detection of infectious disease is crucial for reducing transmission and facilitating early intervention. We built a real-time smartwatch-based alerting system for the detection of aberrant physiological and activity signals (e.g. resting heart rate, steps) associated with early infection onset at the individual level. Upon applying this system to a cohort of 3,246 participants, we found that alerts were generated for pre-symptomatic and asymptomatic COVID-19 infections in 78% of cases, and pre-symptomatic signals were observed a median of three days prior to symptom onset. Furthermore, by examining over 100,000 survey annotations, we found that other respiratory infections as well as events not associated with COVID-19 (e.g. stress, alcohol consumption, travel) could trigger alerts, albeit at a lower mean period (1.9 days) than those observed in the COVID-19 cases (4.3 days). Thus this system has potential both for advanced warning of COVID-19 as well as a general system for measuring health via detection of physiological shifts from personal baselines. The system is open-source and scalable to millions of users, offering a personal health monitoring system that can operate in real time on a global scale.
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http://dx.doi.org/10.1101/2021.06.13.21258795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240687PMC
June 2021

The feasibility of ultrasound Graf method in screening infants and young children with congenital hip dysplasia and follow-up of treatment effect.

Transl Pediatr 2021 May;10(5):1333-1339

Department of Pediatric Surgery, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Congenital hip dysplasia is a common limb deformity in infants and young children. This study aimed to clarify the feasibility of ultrasound Graf method in screening congenital hip dysplasia of infants and young children, and its application value in follow-up treatment.

Methods: A total of 1,313 infants and young children with clinically suspected congenital hip dysplasia in our hospital from December 2016 to January 2018 were selected as the participants and were examined by ultrasound Graf method. The acetabulum shape and the measured values of α and β angles of the participants were observed. The development of the hip joint and distribution of congenital hip dysplasia were analyzed, and the treatment effect was followed up.

Results: Among 1,313 infants and young children with suspected congenital hip dysplasia, the positive rate of congenital hip dysplasia was 6.02% (79/1,313). The lesions were located on both sides in 14 cases, on the left side in 67 cases, and on the right side in 26 cases. The α angle of cases with congenital hip dysplasia was significantly lower than that of normal cases, and the β angle was significantly higher than that of normal cases (P<0.05). Ultrasound follow-up results showed that out of 24 cases who underwent hip abduction exercises, 22 (91.67%) returned to normal, and the remaining 2 returned to normal after Pavlik sling treatment. Among 46 cases treated with Pavlik sling, 42 (91.30%) returned to normal, and the remaining 4 cases returned to normal after closed reduction and plaster fixation. A total of 9 participants underwent plaster fixation after closed reduction, all of which returned to normal.

Conclusions: Ultrasound Graf method can be used as the first choice for screening infants and young children with congenital hip dysplasia. It can be followed up to observe the clinical treatment effect, and it has high clinical application value.
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http://dx.doi.org/10.21037/tp-21-137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192991PMC
May 2021
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