Publications by authors named "C Li"

53,947 Publications

Surface Plasmon Coupling Effects on the Förster Resonance Energy Transfer from Quantum Dot into Rhodamine 6G.

Nanotechnology 2021 Apr 13. Epub 2021 Apr 13.

Institute of Photonics and Optoelectronics and Department of Electrical Engineering, National Taiwan Univ., Taipei, TAIWAN.

Rhodamine 6G (R6G) molecules linked CdZnSeS/ZnS green-emitting quantum dots (QDs) are self-assembled onto Ag nanoparticles (NPs) for studying the surface plasmon (SP) coupling effect on the Förster resonance energy transfer (FRET) process from QD into R6G. SP coupling can enhance the emission efficiency of QD such that FRET has to compete with QD emission for transferring energy into R6G. It is found that FRET efficiency is reduced under the SP coupling condition. Although R6G emission efficiency can also be enhanced through SP coupling when it is directly linked onto Ag NP, the enhancement decreases when R6G is linked onto QD and then the QD-R6G complex is self-assembled onto Ag NP. In particular, R6G emission efficiency can be reduced through SP coupling when the number of R6G molecules linked onto a QD is high. A rate-equation model is built for resembling the measured photoluminescence decay profiles and providing us with more detailed explanations for the observed FRET and SP coupling behaviors.
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http://dx.doi.org/10.1088/1361-6528/abf775DOI Listing
April 2021

New insights into restoring microbial communities by side-stream supersaturated oxygenation to improve the resilience of rivers affected by combined sewer overflows.

Sci Total Environ 2021 Apr 6;782:146903. Epub 2021 Apr 6.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China. Electronic address:

Combined sewer overflows (CSOs) are a dominant contributor to urban river pollution. Therefore, reducing the environmental impacts of CSOs and improving the self-purification capacity of water bodies are essential. In this study, the side-stream supersaturation (SSS) oxygenation was applied to restore microbial function of rivers which are affected by CSOs to improve the self-purification capacity. The results showed that apart from the dissolved organic matter inputs from CSO event, the sediment had become an important contributor to pollution in the studied river. After the long-term (46 d) implementation of SSS oxygenation, dissolved oxygen and the oxidation-reduction potential of the river water increased by 98% and 238%, respectively, compared to emergency control measures implemented following individual CSO events. The NH-N concentrations and the chemical oxygen demand also decreased by 20% and 45%, respectively. In addition, the occurrence of microbial functions related to information storage and processing, and cellular process and signaling, increased by 1.87% and 0.82% in response to SSS oxygenation, respectively, and the Shannon index of the sediment microbial community increased by more than 15%. The frequencies of genes related to nitrification and sulfur oxidation also increased by 20-450% and >50%, respectively. This research provides new insights into the ecological restoration of rivers affected by CSOs.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146903DOI Listing
April 2021

Decreasing Surgical Management of Secondary Hyperparathyroidism in the United States.

J Surg Res 2021 Apr 10;264:444-453. Epub 2021 Apr 10.

Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address:

Background: Secondary hyperparathyroidism (SHPT) commonly occurs in end-stage renal disease (ESRD), leading to vascular calcification and increased mortality. For SHPT refractory to medical management, parathyroidectomy improves symptoms and decreases mortality. Medical management has changed with the release of new guidelines and advent of novel medications. We investigate recent national trends in parathyroidectomy for SHPT.

Materials And Methods: We used the National/Nationwide Inpatient Sample from 2004 to 2016 to identify hospitalizations including parathyroidectomy for SHPT and calculated parathyroidectomy rates utilizing data from the United States Renal Data System. Subgroup analysis was conducted by race. Risk factors for in-hospital mortality were identified with purposeful selection and multivariable logistic regression.

Results: From 2004 to 2016, the rate of parathyroidectomies for SHPT per 1000 ESRD patients decreased from 6.07 (95% CI: 4.83-7.32) to 3.67 (95% CI: 3.33-4.00). Black patients underwent parathyroidectomy for SHPT at a 1.8-fold higher rate than white and Hispanic patients (5.59 versus 3.04 and 3.07). Almost all tracked comorbidities increased in prevalence. In-hospital mortality trended lower (1.5% to 0.8%, P = 0.051). Risk factors for in-hospital mortality included weight loss (OR 4.19, 95% CI: 2.00-8.78) and cardiac arrhythmia (OR 3.38, 95% CI: 1.66-6.91), while additional calendar year (OR = 0.87, 95% CI: 0.80-0.95) was protective.

Conclusions: The etiology of the declining parathyroidectomy rate for SHPT is unclear; possible factors include changing guidelines emphasizing medical management, widespread availability of cinacalcet, changing practice patterns, and inadequate surgical referral.
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http://dx.doi.org/10.1016/j.jss.2021.03.013DOI Listing
April 2021

Bone marrow-derived mesenchymal stem cells attenuate silica-induced pulmonary fibrosis by inhibiting apoptosis and pyroptosis but not autophagy in rats.

Ecotoxicol Environ Saf 2021 Apr 10;216:112181. Epub 2021 Apr 10.

Department of Occupational Health and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China. Electronic address:

This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on silica-induced lung fibrosis in a rat model. Thirty SD rats were randomly divided into three groups: control group, silica group, and BMSC group (n = 10 rats per group). BMSCs were injected successively into rats on the 14th, 28th, and 42nd days after silica exposure. All rats were sacrificed 56 days after silica exposure. We detected the pathological and fibrotic changes, apoptosis, autophagy, and pyroptosis in their lung tissue by histopathological examination, hydroxyproline content assays, real-time quantitative polymerase chain reactions, western blot assays, immunohistochemistry staining, immunofluorescence staining, and enzyme-linked immunosorbent assays. We found that BMSCs significantly relieved lung inflammatory infiltrates, collagen deposition, hydroxyproline content, and the mRNA and protein levels of collagen 1 and fibronectin. Compared to the silica group, in the BMSC group, apoptosis-associated proteins, including cleaved caspase 3 and Bax, were significantly downregulated, and Bcl-2/Bax was significantly upregulated; pyroptosis-related proteins, including Nlrp3, cleaved caspase 1, IL-1β, and IL-18, were significantly reduced. However, the BMSCs had no significant impact on autophagy-related proteins, including Beclin 1, P62, and LC3. In summary, BMSCs protected lung tissue against severe fibrosis by inhibiting apoptosis and pyroptosis but not autophagy.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112181DOI Listing
April 2021

Transfer mechanism and bioaccumulation risk of potentially toxic elements in soil-rice systems comparing different soil parent materials.

Ecotoxicol Environ Saf 2021 Apr 10;216:112214. Epub 2021 Apr 10.

No. 4 Geology Team of Guangxi Zhuang Autonomic Region, Nanning 530031, PR China.

Although the accumulation of potentially toxic elements in soil and crops has attracted widespread attention, the characteristics of the transfer and accumulation of potentially toxic elements in soil-crop systems with different soil parent materials are still not clear. Soil and crop samples were collected from agricultural regions with different soil parent materials in Guangxi, China. This study analyzed the concentrations of Cd, Zn, and Fe in the roots, straws, and seeds of rice (Oryza sativa L.) and soils with Quaternary sediments and clastic rocks as the parent materials. The concentration of several potentially toxic elements in rice tissue from the two areas followed the order of C> C> C. The transport capability of Cd and Zn from roots to straws is higher than straws to seeds, and Fe showed a strong capability for transport from straws to seeds. In general, the transfer capacity of potentially toxic elements in the soil-rice system in the Quaternary sediments area was stronger than that in the soil-rice system in the clastic rocks area. Soil pH and minerals, which were represented by major elements, were the main factors affecting the transfer of metals from soil to seeds. This approach could help to evaluate the bioaccumulation risk of potentially toxic elements in crops in different areas quantitatively.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112214DOI Listing
April 2021

Mettl14-mediated mA Modification Facilitates Liver Regeneration by Maintaining Endoplasmic Reticulum Homeostasis.

Cell Mol Gastroenterol Hepatol 2021 Apr 10. Epub 2021 Apr 10.

Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu, 610041, China; Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.

Background & Aims: N-methyladenosine (mA), the most prevalent and dynamic posttranscriptional methylation modification of mammalian mRNA, is involved in various biological processes, but its role in liver regeneration has not been characterized.

Methods: We first conducted transcriptome-wide mA mRNA sequencing (mA-seq) and characterized the expression pattern of mA in regenerating mouse liver. Next, we generated hepatocyte-specific Mettl3- or Mettl14-deficient mice and investigated their role in liver regeneration. A series of biochemical experiments in vitro and in vivo was further performed to investigate potential mechanisms.

Results: We identified an overwhelming proportion of mA-modified genes with initially upregulated and subsequently downregulated mA levels as liver regeneration progressed. Loss of Mettl14 but not of Mettl3 resulted in markedly disrupted liver regeneration, and Mettl14-ablated hepatocytes were arrested in the G1 phase of the cell cycle. Most strikingly, the Mettl14-ablated regenerating liver exhibited extensive parenchymal necrosis. mRNA transcripts, such as Hsp90b1, Erp29, Stt3a, P4hb, and Lman1, encoding proteins involved in polypeptide processing and the endoplasmic reticulum (ER) stress response, were mA-hypomethylated, and their mRNA and protein levels were subsequently decreased, resulting in unresolved ER stress, hepatocyte death and inhibited proliferation.

Conclusion: We demonstrate the essential role of Mettl14 in facilitating liver regeneration by modulating polypeptide-processing proteins in the ER in an mA-dependent manner.
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http://dx.doi.org/10.1016/j.jcmgh.2021.04.001DOI Listing
April 2021

Donor cell memory confers a metastable state of directly converted cells.

Cell Stem Cell 2021 Apr 7. Epub 2021 Apr 7.

Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster 48149, Germany; Faculty of Medicine, University of Münster, Münster 48149, Germany. Electronic address:

Generation of induced oligodendrocyte progenitor cells (iOPCs) from somatic fibroblasts is a strategy for cell-based therapy of myelin diseases. However, iOPC generation is inefficient, and the resulting iOPCs exhibit limited expansion and differentiation competence. Here we overcome these limitations by transducing an optimized transcription factor combination into a permissive donor phenotype, the pericyte. Pericyte-derived iOPCs (PC-iOPCs) are stably expandable and functionally myelinogenic with high differentiation competence. Unexpectedly, however, we found that PC-iOPCs are metastable so that they can produce myelination-competent oligodendrocytes or revert to their original identity in a context-dependent fashion. Phenotypic reversion of PC-iOPCs is tightly linked to memory of their original transcriptome and epigenome. Phenotypic reversion can be disconnected from this donor cell memory effect, and in vivo myelination can eventually be achieved by transplantation of O4 pre-oligodendrocytes. Our data show that donor cell source and memory can contribute to the fate and stability of directly converted cells.
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http://dx.doi.org/10.1016/j.stem.2021.02.023DOI Listing
April 2021

High Transaldolase 1 expression predicts poor survival of patients with upper tract urothelial carcinoma.

Pathol Int 2021 Apr 13. Epub 2021 Apr 13.

Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Upper tract urothelial carcinoma (UTUC) is a rare tumor with an incidence that varies greatly between Eastern and Western countries. Transaldolase 1 (TALDO1) is a rate-limiting enzyme of the pentose phosphate pathway. In humans, aberrant TALDO1 activity has been implicated in various autoimmune diseases and malignancies; however, the function of TALDO1 in UTUC has not been previously investigated. Here we evaluated the clinical significance of TALDO1 expression in 115 paraffin-embedded tumor samples from patients with UTUC using immunohistochemistry. Our results demonstrated that there was an association between high TALDO1 expression and advanced stage (P = 0.011), tumor size (P = 0.005), tumor location (P = 0.047), distant metastases (P = 0.023), local recurrence (P = 0.002), and cancer death (P = 0.003). Using univariate and multivariate analyses, we found that chemotherapy was an independent factor for bladder recurrence-free survival. Late stage (III/IV) and high TALDO1 expression were independent prognostic factors for progression-free and cancer-specific survival. In summary, increased TALDO1 expression in UTUC was significantly correlated with late stage, tumor size, tumor location, distant metastases, local recurrence, and cancer death. Therefore, high TALDO1 expression could be a predictor of poor survival in patients with UTUC. Further studies are necessary to investigate the role of TALDO1 in UTUC development.
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http://dx.doi.org/10.1111/pin.13101DOI Listing
April 2021

Understanding Pixel-level 2D Image Semantics with 3D Keypoint Knowledge Engine.

IEEE Trans Pattern Anal Mach Intell 2021 Apr 13;PP. Epub 2021 Apr 13.

Pixel-level 2D object semantic understanding is an important topic in computer vision and could help machine deeply understand objects (e.g. functionality and affordance) in our daily life. However, most previous methods directly train on correspondences in 2D images, which is end-to-end but loses plenty of information in 3D spaces. In this paper, we propose a new method on predicting image corresponding semantics in 3D domain and then projecting them back onto 2D images to achieve pixel-level understanding. In order to obtain reliable 3D semantic labels that are absent in current image datasets, we build a large scale keypoint knowledge engine called KeypointNet, which contains 103,450 keypoints and 8,234 3D models from 16 object categories. Our method leverages the advantages in 3D vision and can explicitly reason about objects self-occlusion and visibility. We show that our method gives comparative and even superior results on standard semantic benchmarks.
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http://dx.doi.org/10.1109/TPAMI.2021.3072659DOI Listing
April 2021

Correction to: Inter-transformation between silver nanoparticles and Ag induced by humic acid under light or dark conditions.

Ecotoxicology 2021 Apr 13. Epub 2021 Apr 13.

Soil and Fertilizer Institute of Hunan Province, Hunan Academy of Agricultural Sciences, 401125, Changsha, China.

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http://dx.doi.org/10.1007/s10646-021-02412-7DOI Listing
April 2021

The CXCL12/CXCR7 signalling axis promotes proliferation and metastasis in cervical cancer.

Med Oncol 2021 Apr 13;38(5):58. Epub 2021 Apr 13.

Department of Gynecology, The First Hospital of Huai'an Affiliated to Nanjing Medical University, West Beijing Road, Huai'an, 223300, Jiangsu, China.

C-X-C chemokine receptor 7 (CXCR7), a novel receptor of C-X-C motif chemokine ligand 12 (CXCL12), is associated with the occurrence and metastasis of various malignant tumours. However, the role, function and underlying mechanisms of CXCR7 expression in cervical cancer remain undefined. The expression level of CXCR7 was evaluated in cervical cancer samples by immunohistochemistry and real-time PCR analyses. Western blot analysis was used to examine the expression level of CXCR7 in cervical cancer cell lines. HeLa cells were genetically silenced or pharmacologically inhibited for CXCR7 or CXCR4. Transwell and CCK-8 assays were used to examine cell migration and proliferation. The expression levels of MMP2, MMP9, TIMP-1 and TIMP-2 in HeLa cells were assessed by western blot or real-time PCR. HeLa cells silenced for CXCR7 were subcutaneously injected into nude mice to form tumours. The expression of CXCR7 in nude mice was investigated by immunohistochemical staining. Tumour volumes and weights were measured. The in vivo expression levels of MMP2, MMP9, TIMP-1 and TIMP-2 were determined by western blot analysis and real-time PCR. CXCR7 was overexpressed in cervical cancer tissues and cell lines. CXCL12 was highly expressed in cervical cancer lines. CXCR7 silencing or CCX733 treatment rather than CXCR4 silencing or AMD3100 treatment suppressed the proliferation, migration and invasion of cervical cancer cells stimulated by CXCL12. In a xenograft tumour model, CXCR7 silencing or CCX733 treatment inhibited the volumes and weights of xenograft tumours. In addition, downregulation of CXCR7 decreased the expression levels of MMP2 and MMP9 but increased the expression levels of TIMP-1 and TIMP-2 in vivo. These data support the finding that the downregulation of CXCR7 suppresses the proliferation and metastasis of cervical cancer cells. Inhibition of CXCR7 may be a potential targeted therapy for cervical cancer.
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http://dx.doi.org/10.1007/s12032-021-01481-2DOI Listing
April 2021

Analgesic comparison of dezocine plus propofol versus fentanyl plus propofol for gastrointestinal endoscopy: A meta-analysis.

Medicine (Baltimore) 2021 Apr;100(15):e25531

Department of Geriatrics.

Introduction: As the adjunctive anesthesia to propofol, both dezocine and fentanyl showed some potential for gastrointestinal endoscopy. This meta-analysis aimed to compare their efficacy and safety.

Methods: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of dezocine versus fentanyl for the anesthesia of patients undergoing gastrointestinal endoscopy were included.

Results: Five RCTs involving 677 patients were included in the meta-analysis. Overall, compared with fentanyl plus propofol for gastrointestinal endoscopy, dezocine plus propofol resulted in the reduction in propofol dose(mean difference [MD] = -11.72; 95% confidence interval [CI] = -22.83 to -0.61; P = .04), awakening time (std. MD = -1.79; 95% CI = -3.31 to -0.27; P = .02) and hypopnea (risk ratio [RR] = 0.16; 95% CI = 0.06-0.41; P = .0002), but had no remarkable effect on induction time (MD = 1.20; 95% CI = -0.98 to 3.39; P = .28), postoperative pain score (MD = -0.38; 95% CI = -1.00 to 0.24; P = .24), nausea or vomiting (RR = 0.45; 95% CI = 0.10-1.98; P = .29).

Conclusion: Dezocine plus propofol may be better for the anesthesia of gastrointestinal endoscopy than fentanyl plus propofol.
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http://dx.doi.org/10.1097/MD.0000000000025531DOI Listing
April 2021

Myocardial strain features by 2D-STE during the course of fulminant myocarditis: Correlation with characteristics by CMR and clinical implications.

Medicine (Baltimore) 2021 Apr;100(15):e25050

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.

Abstract: Myocardial strain analysis by 2D speckle tracking echocardiography could determine the left ventricular function. Our purpose is to investigate the global longitudinal strain (GLS) changes during the course of fulminant myocarditis (FM) and evaluate their correlation with cardiac magnetic resonance (CMR).Patients with clinical diagnosis of FM from June 30, 2017 to June 30, 2019 were screened prospectively. 18 survived patients (mean age 34 ± 18 years) who had two scans of transthoracic echocardiography and underwent CMR were included.All patients had severely impaired left ventricular ejection fraction and GLS value at admission that improved significantly before discharge. The patients in the healed stage revealed elevated global native T1 and T2 relaxation time and extracellular volume fraction as well, which were 1408.3 ± 88.3ms, 46.56 ± 5.23ms, and 0.35 ± 0.09, respectively. GLS from the second transthoracic echocardiography in the healed stage correlated significantly with global native T1 relaxation time (r =-0.574, P = .013) and with extracellular volume fraction (r = -0.582, P = .011), but not global native T2 relaxation time (r = -0.31, P = .211) and not with late gadolinium enhancement mass (r = 0.084, P = .743). In comparison, GLS at admission were not correlated with CMR parameters of fibrosis and oedema in the healed stage.GLS by 2D-STE may emerge as a new tool to monitor inflammatory myocardial injuries during the course of FM. FM in the acute healed stage has the presence of both chronic fibrosis and oedema which are correlated with GLS, but GLS at admission can't predict the early recovery of myocardial inflammation.
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http://dx.doi.org/10.1097/MD.0000000000025050DOI Listing
April 2021

[Retracted] Daidzein exerts anticancer activity towards SKOV3 human ovarian cancer cells by inducing apoptosis and cell cycle arrest, and inhibiting the Raf/MEK/ERK cascade.

Int J Mol Med 2021 Jun 13;47(6). Epub 2021 Apr 13.

Department of Gynecology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that several figures contained data that bore striking similarities to data published in other papers; notably, the western blot data shown in Fig. 6 appeared to have been presented in other studies, notably in Fig. 7B of another paper published around the same time and written by different authors based at different research institutions [Li P, Zhang Z, Zhang F, Zhou H and Sun W: Effects of 3‑tetrazolyl methyl‑3‑hydroxy‑oxindole hybrid (THOH) on cell proliferation, apoptosis, and G2/M cell cycle arrest occurs by targeting platelet‑derived growth factor D (PDGF‑D) and the MEK/ERK signaling pathway in human lung cell lines SK‑LU‑1, A549, and A‑427. Med Sci Monit 24: 4547‑4554, 2018]. Furthermore, cellular images featured in Fig. 2A and B of the above paper appeared in Fig. 2 of the following paper, albeit the data were presented in a different field of view: Yu L, Zhou G‑Q and Li D‑C: MiR‑136 triggers apoptosis in human gastric cancer cells by targeting AEG‑1 and BCL2. Eur Rev Med Pharmacol Sci 22: 7251‑7256, 2018. After having conducted an independent investigation in the Editorial Office, the Editor of has determined that this article should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published on 41, 3485-3492, 2018; DOI: 10.3892/ijmm.2018.3531].
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http://dx.doi.org/10.3892/ijmm.2021.4929DOI Listing
June 2021

Length of stay in the ward following a preeclamptic pregnancy.

J Hum Hypertens 2021 Apr 12. Epub 2021 Apr 12.

Department of Obstetrics & Gynaecology, The University of Auckland, Auckland, New Zealand.

To date, data on postpartum management of preeclampsia including the optimal time for discharge are limited. The aims of this study were to investigate the appropriate time for discharge after delivery, and factors that could affect the time for discharge. Data on 210 preeclamptic women including the severity or time of onset and days in the ward after delivery were collected and analysed. In total, 167 (73%) patients were followed up for at least 16 months and none of them developed any complications after delivery. The mean days in the ward after delivery in preeclamptic women with vaginal delivery or with caesarean section was 3.4 or 5.8 days, respectively. After adjusting for delivery modes and parity, women with severe or early onset preeclampsia or preeclamptic women complicated with IUGR were in the ward longer than women with mild or late onset of preeclampsia or preeclamptic women without IUGR. In addition, women with severe preeclampsia or with IUGR delayed the time for blood pressure to return to normal range. Our descriptive data reported that preeclamptic women stayed in the ward for 4-6 days after delivery, dependent on the delivery modes. Preeclamptic women with severe or early onset form or complicated with IUGR delayed the improvement of clinical symptoms after delivery. We further found that women with severe preeclampsia, and preeclampsia complicated with IUGR delayed blood pressure returning to normal range. These pre-discharge checklists may help obstetricians and midwives decide when to discharge.
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http://dx.doi.org/10.1038/s41371-021-00484-wDOI Listing
April 2021

ATF3 deficiency impairs the proliferative-secretory phase transition and decidualization in RIF patients.

Cell Death Dis 2021 Apr 12;12(4):387. Epub 2021 Apr 12.

Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, People's Republic of China.

Decidualization is a complex process involving cellular proliferation and differentiation of the endometrial stroma and is required to establish and support pregnancy. Dysregulated decidualization has been reported to be a critical cause of recurrent implantation failure (RIF). In this study, we found that Activating transcription factor 3 (ATF3) expression was significantly downregulated in the endometrium of RIF patients. Knockdown of ATF3 in human endometrium stromal cells (hESCs) hampers decidualization, while overexpression could trigger the expression of decidual marker genes, and ameliorate the decidualization of hESCs from RIF patients. Mechanistically, ATF3 promotes decidualization by upregulating FOXO1 via suppressing miR-135b expression. In addition, the endometrium of RIF patients was hyperproliferative, while overexpression of ATF3 inhibited the proliferation of hESCs through CDKN1A. These data demonstrate the critical roles of endometrial ATF3 in regulating decidualization and proliferation, and dysregulation of ATF3 in the endometrium may be a novel cause of RIF and therefore represent a potential therapeutic target for RIF.
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http://dx.doi.org/10.1038/s41419-021-03679-8DOI Listing
April 2021

Effects of PatU3 peptides on cell size and heterocyst frequency of sp. PCC 7120.

J Bacteriol 2021 Apr 12. Epub 2021 Apr 12.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei 430072, China

, one of the genes specifically found in filamentous cyanobacteria, is required for the pattern formation in heterocyst-forming species. In sp. PCC 7120, is split into and , and only is involved in heterocyst patterning. Here, we report that PatU3 is also involved in control of cell size. A deletion mutant showed remarkably smaller cell size and much higher heterocyst frequency than that of the wild type. Yeast two-hybrid and pull-down assays demonstrated a direct interaction between PatU3 and the cell division protein Ftn6. Without the N-terminal 16-aa portion (MQERFQIH), PatU3 was no longer able to interact with Ftn6. This portion of PatU3 is also required for the interaction with PatN, a protein related to heterocyst differentiation/patterning. Addition of the 16-aa peptide or AVIKRRLQ-containing peptides restored the cell size and heterocyst frequency of a deletion mutant to normal or near wild-type level. PatU3(1-16aa)-GFP, the N-terminal 16-aa sequence fused with GFP, formed polar aggregates and peripheral patches in heterocysts of 7120, whereas PatU3(1-198aa)-GFP showed a homogeneous distribution in the cytoplasm of all cells. The N-terminal AVIKRRL-containing sequence may function in intact PatU3, as a separate peptide, or both.PatU (or split into PatU5 and PatU3) is distributed in almost all filamentous cyanobacteria, including those that do not form heterocysts (except ); however, its functions other than heterocyst differentiation/patterning have not been reported before. In this study, we found that PatU3 in sp. PCC 7120 is involved in cell size determination. The N-terminal 16-aa sequence of PatU3 is required for control of cell size and interaction with the cell division protein Ftn6, and an octapeptide (aa ∼ aa) within the 16-aa sequence can restore the cell size (and heterocyst frequency) of a deletion mutant to normal. Such a peptide, if generated from PatU or PatU3 in vivo, may promote intercellular coordination in filamentous cyanobacteria.
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http://dx.doi.org/10.1128/JB.00108-21DOI Listing
April 2021

Competing-Risk Nomograms for Predicting the Prognosis of Patients With Infiltrating Lobular Carcinoma of the Breast.

Clin Breast Cancer 2021 Mar 18. Epub 2021 Mar 18.

Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China; School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi Province, China. Electronic address:

Background: Infiltrating lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer. We assessed the rates of cause-specific death in ILC patients with the aim of establishing competing-risk nomograms for predicting their prognosis.

Patients And Methods: Data on ILC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence function was used to calculate the cumulative incidence rates of cause-specific death, and Gray's test was applied to test the differences in cumulative incidence rates among groups. We then identified independent prognostic factors by applying the Fine-Gray proportional subdistribution hazard analysis method and established nomograms based on the results. Calibration curves and the concordance index were employed to validate the nomograms.

Results: The study enrolled 11,361 patients. The 3-, 5-, and 10-year overall cumulative incidence rates for those who died of ILC were 3.1%, 6.2%, and 12.2%, respectively, whereas the rates for those who died from other causes were 3.2%, 5.8%, and 14.1%. Age, marriage, grade, size, regional node positivity, American Joint Committee on Cancer M stage, progesterone receptor, and surgery were independent prognostic factors for dying of ILC, whereas the independent prognostic factors for dying of other causes were age, race, marriage, size, radiation, and chemotherapy. The nomograms were well calibrated and had good discrimination ability.

Conclusion: We applied competing-risk analysis to ILC patients based on the SEER database and established nomograms that perform well in predicting the cause-specific death rates at 3, 5, and 10 years after the diagnosis.
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http://dx.doi.org/10.1016/j.clbc.2021.03.008DOI Listing
March 2021

Extracellular vesicles derived from umbilical cord mesenchymal stromal cells alleviate pulmonary fibrosis by means of transforming growth factor-β signaling inhibition.

Stem Cell Res Ther 2021 Apr 12;12(1):230. Epub 2021 Apr 12.

China-Japan Union Hospital of Jilin University, 126 Xiantai St., Changchun, 130033, Jilin, China.

Background: Pulmonary fibrosis (PF), the end point of interstitial lung diseases, is characterized by myofibroblast over differentiation and excessive extracellular matrix accumulation, leading to progressive organ dysfunction and usually a terminal outcome. Studies have shown that umbilical cord-derived mesenchymal stromal cells (uMSCs) could alleviate PF; however, the underlying mechanism remains to be elucidated.

Methods: The therapeutic effects of uMSC-derived extracellular vesicles (uMSC-EVs) on PF were evaluated using bleomycin (BLM)-induced mouse models. Then, the role and mechanism of uMSC-EVs in inhibiting myofibroblast differentiation were investigated in vivo and in vitro.

Results: Treatment with uMSC-EVs alleviated the PF and enhanced the proliferation of alveolar epithelial cells in BLM-induced mice, thus improved the life quality, including the survival rate, body weight, fibrosis degree, and myofibroblast over differentiation of lung tissue. Moreover, these effects of uMSC-EVs on PF are likely achieved by inhibiting the transforming growth factor-β (TGF-β) signaling pathway, evidenced by decreased expression levels of TGF-β2 and TGF-βR2. Using mimics of uMSC-EV-specific miRNAs, we found that miR-21 and miR-23, which are highly enriched in uMSC-EVs, played a critical role in inhibiting TGF-β2 and TGF-βR2, respectively.

Conclusion: The effects of uMSCs on PF alleviation are likely achieved via EVs, which reveals a new role of uMSC-EV-derived miRNAs, opening a novel strategy for PF treatment in the clinical setting.
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http://dx.doi.org/10.1186/s13287-021-02296-8DOI Listing
April 2021

Investigation of the idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. through metabolomics using GC-MS.

BMC Complement Med Ther 2021 Apr 12;21(1):120. Epub 2021 Apr 12.

College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China.

Background: The idiosyncratic hepatotoxicity of Polygonum multiflorum (PM) has attracted considerable interest, but the idiosyncratically hepatotoxic components and endogenous metabolite changes resulting from idiosyncratic hepatotoxicity of PM are not well understood. The aim of this study was to identify the idiosyncratically hepatotoxic components and potential endogenous metabolic biomarkers for PM-induced liver injury.

Methods: Serum biochemical indicators and hematoxylin and eosin (H&E) staining were evaluated to identify pathological changes. Gas chromatography/mass spectrometry (GC-MS) was performed to identify changes in metabolic biomarkers. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was applied to determine group clustering trends and differential metabolites.

Results: The results for the liver index, the liver function index and liver pathology showed that Polygonum multiflorum ethanol extract (PME), 50% ethanol elution fractions and tetrahydroxystilbene glucoside (TSG) from PME can induce idiosyncratic hepatotoxicity. TSG was the main idiosyncratically hepatotoxic component. Forty endogenous metabolites were identified in the rat liver. Six biomarkers, including lower levels of L-valine and higher levels of 3-hydroxybutyric acid, hexadecanoic acid, ribose, phosphoric acid and oxalic acid, were related to PM-induced liver injury. These differential biomarkers led to disruptions in amino acid, fatty acid, oxalate, energy and glucose metabolism. A total of 32 types of endogenous metabolites were identified in rat serum. Ten biomarkers were related to the liver injury induced by TSG, including lower levels of L-valine and L-proline and higher levels of urea, caproic acid, DL-malic acid, D-mannose, 3-hydroxybutyric acid, D-galactose, octadecane and hexadecanoic acid. These differential biomarkers led to disruptions in amino acid, glucose and fat metabolism. The mechanism of idiosyncratic hepatotoxicity in PM involves TSG-induced disruptions in amino acid metabolism, lipid metabolism, energy metabolism and glucose metabolism.

Conclusions: These findings reflect the material basis and metabolic mechanism of idiosyncratic PM hepatotoxicity.
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http://dx.doi.org/10.1186/s12906-021-03276-4DOI Listing
April 2021

Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis.

Autism 2021 Apr 12:13623613211004054. Epub 2021 Apr 12.

Children's Hospital of Fudan University, China.

Lay Abstract: The Autism Spectrum Rating Scale is a behavioural rating scale completed by parents and teachers that is useful for identifying children with an autism spectrum disorder. The development of a modified Autism Spectrum Rating Scale suitable for use in China is important for the identification of children in China with an autism spectrum disorder. In this study, we examined the Modified Chinese Autism Spectrum Rating Scale using a statistical technique known as Rasch analysis. Rasch analysis tests whether the questionnaire meets the standards for modern scientific measurement. We used Rasch analysis to examine data from 2013 children in China including 420 diagnosed with an autism spectrum disorder who had been rated by a parent or grandparent. After removing a small number of items (questions), the Modified Chinese Autism Spectrum Rating Scale met the stringent criteria for Rasch measurement. The availability of a reliable and precise tool for assessing behaviours characteristic of an autism spectrum disorder in Chinese children will improve the identification and diagnosis of autism spectrum disorder in China, thus enabling better provision of support services.
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http://dx.doi.org/10.1177/13623613211004054DOI Listing
April 2021

Predictive factors for success of awake proning in hypoxemic respiratory failure secondary to COVID-19: A retrospective cohort study.

Respir Med 2021 Apr 2;181:106379. Epub 2021 Apr 2.

Department of Internal Medicine, Divisions of Critical Care, Pulmonary and Sleep Medicine, University of Texas Health Science Center at Houston, McGovern Medical School, TX, 77030, USA. Electronic address:

Background: Awake prone positioning has been recommended as an adjunctive measure in spontaneously breathing patients with hypoxemic respiratory failure during the COVID-19 pandemic. It remains uncertain as to how long this should be implemented, what variables to follow and who would be the ideal candidates for this adjunctive therapy.

Methods: A retrospective chart review of patients admitted from April to August 2020 within our institution with multifocal pneumonia and hypoxemic respiratory failure secondary to COVID-19 who underwent awake-proning for at least 3 hours was conducted.

Results: Improvement in respiratory parameters including ROX (SpO2/Fio2/ Respiratory Rate) indices and inflammatory markers within 4 days of institution of awake proning predicted a higher chance for success of this strategy in preventing need for mechanical ventilation. Moreover, benefits of awake proning were limited to patients with mild to moderate ARDS.

Conclusions: Awake prone positioning can be safely performed with improvement in oxygenation. However, its institution may be beneficial only in patients with mild to moderate ARDS and requires careful evaluation of respiratory parameters and serum inflammatory markers to avoid a delay in endotracheal intubation and consequent increase in mortality rates.
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http://dx.doi.org/10.1016/j.rmed.2021.106379DOI Listing
April 2021

Influence of ambient temperature and diurnal temperature variation on the premature rupture of membranes in East China: A distributed lag nonlinear time series analysis.

Environ Res 2021 Apr 9:111145. Epub 2021 Apr 9.

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China. Electronic address:

Background: . Extreme ambient temperature has an adverse effect on pregnancy outcomes, but the conclusions have been inconsistent. The influence of ambient temperature and diurnal temperature variation on the premature rupture of membranes (PROM) needs further study.

Methods And Findings: . The daily data of PROMs, daily meteorological and air pollutant were obtained. After controlling for potential confounding factors, the quasi-Poisson generalized additive model (GAM) combined with the distributed lag nonlinear model (DLNM) was used to analyze the association between temperature or diurnal temperature variation and PROM, including preterm premature rupture of membranes (PPROM) and term premature rupture of membranes (term PROM). Compared with the median temperature(18.7°C), the mean temperature of 5-7 days lagging beyond 31.5°C and below -1.5°C was positively correlated with PROM; the mean temperature had more sensitive effect on the term PROM. Exposure to extremely high temperatures (97.5 percentile, 32°C) had a 6-day lagging relative risk (RR) (95% CI: 1.005-1.160) of 1.08 for PROM and a 6-day lagging RR of 1.079 (95% CI: 1.005-1.159) for term PROM; Exposure to a high diurnal temperature variation (diurnal temperature variation greater than 16°C) was positively correlated with the term PROM. Compared with the 2.5 percentile diurnal temperature variation (2°C), exposure to the 95 percentile diurnal temperature variation (17°C) significantly increased the risk of term PROM (RR: 1.229, 95% CI: 1.029 -1.467).

Conclusions: . Exposure to a high-temperature and a high diurnal temperature variation environment will increase the relative risks of PROM. For pregnant women in the 3 trimester, it is important to reduce exposure to extremely high-temperatures and greater diurnal temperature changes.
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http://dx.doi.org/10.1016/j.envres.2021.111145DOI Listing
April 2021

Geochemical and Mineralogical Characteristics of the Li-Sr-Enriched Coal in the Wenjiaba Mine, Guizhou, SW China.

ACS Omega 2021 Apr 22;6(13):8816-8828. Epub 2021 Mar 22.

Aerophotogrammetry and Remote Sensing Bureau, China National Administration of Coal Geology, Xi'an 710199, China.

This paper reports the mineralogical and geochemical compositions of C6 coal in the Late Permian Longtan Formation of the Wenjiaba Mine, Northern Guizhou in southwest (SW) China. The geochemical and mineralogical studies are the basis for the potential recovery of critical metals. The Longtan Formation, which is one of the major coal-bearing strata in SW China, contains dozens of coal seams. C6 coal is the main mineable coal seam in the Wenjiaba Mine and the whole coalfield. Proximate and ultimate analyses, inductively coupled plasma mass spectrometry (ICP-MS) and X-ray fluorescence (XRF) spectrometry on trace and major element concentrations, and X-ray diffraction and SEM-EDS analyses were carried out. Results suggest that this anthracite coal is characterized by low ash yield and medium sulfur content. The minerals are mainly composed of clay minerals (kaolinite, chlorite, illite, and mixed-layer illite/smectite), pyrite, and carbonates. Lithium is significantly enriched in C6 coal, with an average of 124 μg/g, and it has a higher concentration in the lower portion of the coal seam than that in the upper one. Strontium is significantly enriched in samples WJB-05 and WJB-06, with concentrations of 3030 and 4580 μg/g, respectively, but it is normal or just slightly enriched in other benches of C6 coal. Additionally, Cu, Nb, and Ta are slightly enriched in the coal. Lithium, dominantly hosted by kaolinite in C6 coals, has a recovery potential. Celestine is one of the major Sr-bearing minerals in C6 coal.
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http://dx.doi.org/10.1021/acsomega.0c05663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027998PMC
April 2021

Non-small cell lung cancer with MET exon 14 skipping alteration responding to immunotherapy: a case report.

Ann Transl Med 2021 Mar;9(5):424

Department of Thoracic Surgery/Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory and National Clinical Research Center for Respiratory Disease, Guangzhou, China.

Immunotherapy has been proved to be a promising candidate for advanced non-small cell lung cancer (NSCLC). Despite MET mutations are regarded as an independent factor of programmed death ligand 1 (PD-L1) high expression, the efficacy of immune checkpoint inhibitors (ICIs) across NSCLC harboring Mesenchymal-epithelial transition factor exon 14 skipping alteration (METex14) is still uncleared. Moreover, when the resistance of PD-1 antibody occurs, the questions of how to interpret the resistance and how to overcome the resistance are worth exploring. We report a case of NSCLC with METex14 developed a right femoral metastasis after responding well to neoadjuvant immunotherapy, a successful lobectomy, and adjuvant immunotherapy. The subsequent attempts of MET targeted inhibitor, concurrent chemoradiotherapy, and notably programmed cell death protein 1 (PD-1) antibody plus vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) failed to prevent disease progression. However, a regimen of anti-PD-1 plus anti-cytotoxic t-lymphocyte associated protein 4 (CTLA-4) reversed the progression to a complete response. This case shows that METex14 had a significant response to immunotherapy, which would be especially beneficial for those who developed targeted therapy resistance. Importantly, this is the first case reporting that salvage CTLA-4 antibody and PD-1 antibody could reverse the progression in NSCLC harboring METex14 when the anti-PD-1 resistance occurred.
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http://dx.doi.org/10.21037/atm-20-6829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033371PMC
March 2021

Genetically predicted bipolar disorder is causally associated with an increased risk of breast cancer: a two-sample Mendelian randomization analysis.

Ann Transl Med 2021 Mar;9(5):401

Department of Thoracic Oncology and Surgery, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Epidemiologic findings suggested that bipolar disorder (BD) may be associated with an increased risk of breast cancer. However, there are few studies that comprehensively evaluating their correlation and the causal effect remains unknown. With a two-sample Mendelian randomization (MR) approach, we were able to investigate the causal relationship between genetically predicted BD and breast cancer risk.

Methods: Utilizing 14 BD-related single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) identified by the latest genome-wide association studies (GWASs), we investigated the correlation between genetically predicted BD and breast cancer risk using summary statistics from the Breast Cancer Association Consortium, with a total of 122,977 cases and 105,974 controls. Study-specific estimates were summarized using inverse variance weighted (IVW) method. To further evaluate the pleiotropy, the weighted median and the MR-Egger regression method were implemented. Subgroup analyses according to different immunohistochemical types of breast cancer were also conducted.

Results: MR analyses demonstrated that genetically predicted BD was causally associated with an increased risk of breast cancer (OR =1.059; 95% CI: 1.008-1.112, P=0.0229). When results were examined by immunohistochemical type, no causal effects between genetically predicted BD and estrogen receptor (ER)-positive breast cancer (OR =1.049, 95% CI: 0.999-1.102 P=0.0556) and ER-negative breast cancer (OR =1.032, 95% CI: 0.953-1.116 P=0.4407) were observed. Additionally, the results demonstrated the absence of the horizontal pleiotropy.

Conclusions: Our findings provided evidence for a causal relationship between genetically predicted BD and an increased risk of breast cancer overall. Further studies are warranted to investigate the underlying mechanism.
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http://dx.doi.org/10.21037/atm-20-5372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033315PMC
March 2021

Developing and validating a novel nomogram used a competing-risks model for predicting the prognosis of primary fallopian tube carcinoma: a retrospective study based on the SEER database.

Ann Transl Med 2021 Mar;9(5):378

Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Background: The current prognostic methods for primary fallopian tube carcinoma (PFTC) are inadequate. This study is the first to use a competing-risks model to perform an accurate analysis of the prognostic factors for PFTC cause-specific death (CSD). We used the model to established a nomogram for the 3-, 5-, and 8-year CSD rates based on the identified prognostic factors.

Methods: This study selected 1,924 patients from the SEER (Surveillance, Epidemiology, and End Results) database. The cumulative incidence function (CIF) was used in univariate analyses, and Gray's test was used to determine the intergroup difference in the CIF. We then used the subdistribution proportional hazards model in a multivariate analysis. We finally used the prognostic factors identified in the analysis of the competing-risks model to construct a 3-, 5-, and 8-year CSD nomogram for PFTC patients. The concordance index (C-index) and calibration plots were used to evaluate the discrimination ability and consistency of the model.

Results: The subdistribution proportional hazards model showed that age, histological type, FIGO stage, and the log of the ratio between the numbers of positive and negative lymph nodes (LODDS) were independent prognostic factors for CSD. The 3-, 5-, and 8-year C-indexes were 0.744, 0.744, and 0.733 in the training cohort, and 0.737, 0.748, and 0.721 in the validation cohort. In the calibration plots, the forecast lines were very close to the reference lines.

Conclusions: This study is the first to analyze the prognostic factors for PFTC based on a competing-risks model. This model indicates that age, histological type, FIGO stage, and LODDS are significant prognostic factors affecting CSD in PFTC patients. We have also constructed the first 3-, 5-, and 8-year CSD nomogram for PFTC patients. This nomogram exhibits good discrimination ability and accuracy and can help clinicians to provide individualized prognostic analysis for PFTC patients.
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http://dx.doi.org/10.21037/atm-20-5398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033332PMC
March 2021

Lung cancers and pulmonary nodules detected by computed tomography scan: a population-level analysis of screening cohorts.

Ann Transl Med 2021 Mar;9(5):372

Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Heath & China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China.

Background: An increasing number and proportion of younger lung cancer patients have been observed worldwide, raising concerns on the optimal age to begin screening. This study aimed to investigate the association between age and findings in initial CT scans.

Methods: We searched for low-dose CT screening cohorts from electronic databases. Single-arm syntheses weighted by sample size were performed to calculate the detection rates of pulmonary nodules, lung cancers (all stages and stage I), and the proportion of stage I diseases in lung cancers. In addition, we included patients who underwent chest CT in our center as a supplementary cohort. The correlation between the detection rates and age was evaluated by the Pearson Correlation Coefficient.

Results: A total of 37 studies involving 163,442 participants were included. We found the detection rates of pulmonary nodules and lung cancers increased with age. However, the proportion of stage I diseases in lung cancers declined with increased starting age and was significantly higher in the 40-year group than in other groups (40 45, 50, 55, P<0.001). In addition, the ratio of early-stage lung cancer to the number of nodules declined with age. Similarly, in our center, the detection rates of nodules (R=0.86, P≤0.001), all lung cancer (R=0.99, P≤0.001) and stage I diseases (R=0.87, P=0.001) increased with age, while the proportion of stage I diseases consistently declined with age (R=0.97, P≤0.001).

Conclusions: Starting lung cancer screening at an earlier age is associated with a higher probability of identifying a curable disease, urging future research to determine the optimal starting age.
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http://dx.doi.org/10.21037/atm-20-5210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033365PMC
March 2021

Audiometric Phenotypes of Noise-Induced Hearing Loss by Data-Driven Cluster Analysis and Their Relevant Characteristics.

Front Med (Lausanne) 2021 25;8:662045. Epub 2021 Mar 25.

Department of Otolaryngology-Head and Neck Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The definition of notched audiogram for noise-induced hearing loss (NIHL) is presently based on clinical experience, but audiometric phenotypes of NIHL are highly heterogeneous. The data-driven clustering of subtypes could provide refined characteristics of NIHL, and help identify individuals with typical NIHL at diagnosis. This cross-sectional study initially recruited 12,218 occupational noise-exposed employees aged 18-60 years from two factories of a shipyard in Eastern China. Of these, 10,307 subjects with no history of otological injurie or disease, family history of hearing loss, or history of ototoxic drug use were eventually enrolled. All these subjects completed health behavior questionnaires, cumulative noise exposure (CNE) measurement, and pure-tone audiometry. We did data-driven cluster analysis (k-means clustering) in subjects with hearing loss audiograms ( = 6,599) consist of two independent datasets ( = 4,461 and = 2,138). Multinomial logistic regression was performed to analyze the relevant characteristics of subjects with different audiometric phenotypes compared to those subjects with normal hearing audiograms ( = 3,708). A total of 10,307 subjects (9,165 males [88.9%], mean age 34.5 [8.8] years, mean CNE 91.2 [22.7] dB[A]) were included, 3,708 (36.0%) of them had completely normal hearing, the other 6,599 (64.0%) with hearing loss audiograms were clustered into four audiometric phenotypes, which were replicable in two distinct datasets. We named the four clusters as the 4-6 kHz sharp-notched, 4-6 kHz flat-notched, 3-8 kHz notched, and 1-8 kHz notched audiogram. Among them, except for the 4-6 kHz flat-notched audiogram which was not significantly related to NIHL, the other three phenotypes with different relevant characteristics were strongly associated with noise exposure. In particular, the 4-6 kHz sharp-notched audiogram might be a typical subtype of NIHL. By data-driven cluster analysis of the large-scale noise-exposed population, we identified three audiometric phenotypes associated with distinct NIHL subtypes. Data-driven sub-stratification of audiograms might eventually contribute to the precise diagnosis and treatment of NIHL.
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http://dx.doi.org/10.3389/fmed.2021.662045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027076PMC
March 2021

Adipose-Derived Stromal Cell-Sheets Sandwiched, Book-Shaped Acellular Dermal Matrix Capable of Sustained Release of Basic Fibroblast Growth Factor Promote Diabetic Wound Healing.

Front Cell Dev Biol 2021 25;9:646967. Epub 2021 Mar 25.

The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.

The management of diabetic wounds is a therapeutic challenge in clinical settings. Current tissue engineering strategies for diabetic wound healing are insufficient, owing to the lack of an appropriate scaffold that can load a large number of stem cells and induce the interaction of stem cells to form granulation tissue. Herein we fabricated a book-shaped decellularized dermal matrix (BDDM), which shows a high resemblance to native dermal tissue in terms of its histology, microstructure, and ingredients, is non-cytotoxic and low-immunogenic, and allows adipose-derived stromal cell (ASC) attachment and proliferation. Then, a collagen-binding domain (CBD) capable of binding collagen was fused into basic fibroblast growth factor (bFGF) to synthetize a recombinant growth factor (termed as CBD-bFGF). After that, CBD-bFGF was tethered onto the collagen fibers of BDDM to improve its endothelial inducibility. Finally, a functional scaffold (CBD-bFGF/BDDM) was fabricated. and experiments demonstrated that CBD-bFGF/BDDM can release tethered bFGF with a sustained release profile, steadily inducing the interaction of stem cells down to endothelial differentiation. ASCs were cultured to form a cell sheet and then sandwiched by CBD-bFGF/BDDM, thus enlarging the number of stem cells loaded into the scaffold. Using a rat model, the ASC sheets sandwiched with CBD-bFGF/BDDM (ASCs/CBD-bFGF/BDDM) were capable of enhancing the formation of granulation tissue, promoting angiogenesis, and facilitating collagen deposition and remodeling. Therefore, the findings of this study demonstrate that ASCs/CBD-bFGF/BDDM could be applicable for diabetic wound healing.
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http://dx.doi.org/10.3389/fcell.2021.646967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027315PMC
March 2021