Publications by authors named "Hao Hu"

1,046 Publications

  • Page 1 of 1

Self-Internal-Reference Probe System for Control-Free Quantification of Mutation Abundance.

Anal Chem 2021 Sep 21. Epub 2021 Sep 21.

Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.

Gene mutations are important biomarkers for the diagnosis, classification, monitoring, and prognosis evaluation of cancers and genetic diseases. Both personalized cancer treatment and noninvasive prenatal testing require methods to accurately determine the abundance of mutation. At present, the widely adopted and convenient methods for measuring mutation abundance are mainly based on relative quantification, which requires negative samples and strict control of the analyte amounts. The development of DNA-probe-based methods that can determine the mutation abundance without negative samples nor control of analyte amount is highly preferred. The key to solving this bottleneck lies in whether the probe's response to mutation abundance can be completely independent of the number of targeted DNA strands. Herein, we propose the design of a self-internal-reference probe system. We established a theoretical model of this system and used the model to guide the design of probes. In this model, we provided quantitative corrections to the test results from the internal reference, thereby eliminating the influence of substrate amount. Therefore, the purification and quantification processes toward polymerase chain reaction (PCR) amplicons can be omitted. We applied this system to analyze unquantified PCR products aimed at cancer mutation detection and noninvasive prenatal testing.
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http://dx.doi.org/10.1021/acs.analchem.1c02877DOI Listing
September 2021

Selective Heavy Atom Effect Forming Photosensitizing Hot Spots in Double-Stranded DNA Matrix.

J Phys Chem Lett 2021 Sep 16:9205-9212. Epub 2021 Sep 16.

Analytical & Testing Centre, Sichuan University, Chengdu 610064, China.

Triplet exciton formation is essential for photosensitization-based photochemistry and photobiology. The heavy atom effect (HAE), in the form of either external or internal mode, is a basic mechanism for increasing the triplet exciton yield of photosensitizers. Herein, we report a new HAE mode by noncovalent cohosting of heavy atoms and photosensitizers in a double-stranded DNA (dsDNA) matrix. With dsDNA bearing several thymine (T) or cytosine (C) mismatches, heavy atoms (e.g., Hg or Ag) and dsDNA-staining dyes (photosensitizers) were spatially adjoined in close proximity, thus resulting in enhanced phosphorescence and O generation from the photosensitizers. The dsDNA-hosted HAE provides highly selective recognition for the heavy atoms, which is not applicable in either the external or the internal mode. Considering the simpleness and efficiency of the spatially adjoined HAE, as well as the functionality of DNA, the proposed HAE mode is appealing for various singlet oxygen- and phosphorescence-related applications.
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http://dx.doi.org/10.1021/acs.jpclett.1c02809DOI Listing
September 2021

Liraglutide ameliorates diabetes-associated cognitive dysfunction via rescuing autophagic flux.

J Pharmacol Sci 2021 Nov 24;147(3):234-244. Epub 2021 Jul 24.

Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China. Electronic address:

The incidence of diabetes-associated cognitive dysfunction is increasing. However, few clinical interventions are available to prevent the disorder. Several researches have shown that liraglutide, as a glucagon-like peptide-1 analog, has protective effects on various neurodegenerative diseases, but its roles in diabetic cognitive dysfunction are rarely reported. This study aims to investigate the protective effects of liraglutide on diabetic cognitive dysfunction and its underlying mechanisms. In vivo, the effects of liraglutide treatment were investigated in a mouse model of type 2 diabetes mellitus (T2DM). In vitro, we investigated the effects of liraglutide on the high-glucose-induced rat primary neurons. The results showed that liraglutide reduced the escape latency and increased the time in effective area in the Morris water maze test, improved the damage of hippocampal and synaptic ultrastructure, and decreased the accumulation of amyloid β protein in hippocampus of T2DM mice. Furthermore, liraglutide increased the ratio of microtubule-associated protein light 1 chain Ⅱ/Ⅰ, the expression of Beclin1 protein and Lysosome-associated membrane protein 2 in vivo and vitro. Additionally, Bafilomycin A1 which can inhibit the fusion of autophagosome and lysosome partially abolished the effects of liraglutide. These findings indicate liraglutide ameliorates diabetes-associated cognitive dysfunction by rescuing autophagic flux.
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http://dx.doi.org/10.1016/j.jphs.2021.07.004DOI Listing
November 2021

Chromogranin A Deficiency Confers Protection from Autoimmune Diabetes Via Multiple Mechanisms.

Diabetes 2021 Sep 8. Epub 2021 Sep 8.

Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA

Recognition of beta-cell antigens by autoreactive T cells is a critical step in the initiation of autoimmune Type1 diabetes (T1D). A complete protection from diabetes development in non-obese diabetic (NOD) mice harboring a point mutation in the insulin B-chain 9-23 epitope points to a dominant role of insulin in diabetogenesis. Generation of NOD mice lacking the Chromogranin A protein (NOD.ChgA) completely nullified the autoreactivity of the BDC2.5 T cell and conferred protection from diabetes onset. These results raised the issue concerning the dominant antigen that drives the autoimmune process. Here we revisited the NOD.ChgA mice and found that their lack of diabetes development may not be solely explained by the absence of Chromogranin A reactivity. NOD.ChgA mice displayed reduced presentation of insulin peptides in the islets and periphery, which corresponded to impaired T cell priming. Diabetes development in these mice was restored by antibody treatment targeting regulatory T cells or inhibiting TGFβ and PD-1 pathways. Therefore, the global deficiency of chromogranin A impairs recognition of the major diabetogenic antigen insulin, leading to broadly impaired autoimmune responses controlled by multiple regulatory mechanisms.
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http://dx.doi.org/10.2337/db21-0513DOI Listing
September 2021

circPTPN22 attenuates immune microenvironment of pancreatic cancer via STAT3 acetylation.

Cancer Gene Ther 2021 Sep 1. Epub 2021 Sep 1.

Department of General Surgery, Heping Hospital, Changzhi Medical College, Changzhi City, Shanxi Province, China.

Accumulating research implicated that circular RNAs exhibited significant roles in cancer development. Nonetheless, the role regarding circPTPN22 in pancreatic cancer remains unclear. Expression of circPTPN22 in pancreatic cancer cell lines and normal cells was determined with quantitative real-time PCR (qRT-PCR). Cell counting kit-8 assay and colony formation assay were used to measure the proliferation of pancreatic cancer cells. RNA immunoprecipitation and Western blot were employed for investigation the binding between circPTPN22 and STAT3. circPTPN22 expression was highly upregulated in pancreatic cancer tissues and cell lines. Knockdown of circPTPN22 inhibited cell proliferation and attenuates pancreatic cancer immune microenvironment. Furthermore, STAT3 acetylation was involved in these effects. circPTPN22 promoted STAT3 acetylation via inhibiting STAT3/SIRT1 interaction. circPTPN22 attenuates pancreatic cancer immune microenvironment by promoting STAT3 acetylation via inhibiting STAT3/SIRT1 interaction.
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http://dx.doi.org/10.1038/s41417-021-00382-wDOI Listing
September 2021

Non-enzymatic Transformation of Aflatoxin B by m29.

Front Microbiol 2021 10;12:724103. Epub 2021 Aug 10.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.

Aflatoxin B (AFB) is the most harmful mycotoxin produced by filamentous fungi and presents a serious threat to human and animal health. Therefore, it is essential to protect humans and animals from AFB-induced acute and chronic toxicity. In this study, strain m29 having a high efficiency of AFB transformation was isolated from soil. The transformation ratio by m29 was more than 97% within 24 h, and the optimum temperature for transformation was 37°C. Moreover, the AFB transforming activity was mainly attributed to the cell-free supernatant of strain m29. The metabolite that plays a crucial role in AFB transformation is likely 1,2-dimethylhydrazine or 1,1-dimethylhydrazine, as identified by GC-MS and LC-MS analysis. AFB was transformed into a product with molecular formula CHO. To the best of our knowledge, this is the first study of non-enzymatic AFB transformation by bacteria. Importantly, this AFB transformation mechanism could be universal to various microorganisms.
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http://dx.doi.org/10.3389/fmicb.2021.724103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383447PMC
August 2021

NEAT1/miR-101-dependent Up-regulation of DNA-PKcs Enhances Malignant Behaviors of Pancreatic Ductal Adenocarcinoma Cells.

J Cancer 2021 25;12(18):5622-5632. Epub 2021 Jul 25.

Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Jiangnan University, 585 Xingyuan Rd, Liangxi District, Wuxi, 214041, China.

Although we previously revealed that DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and important for gemcitabine resistance, the role of DNA-PKcs in the progression and metastasis of PDAC remain unclear. To date, the upstream signaling events stimulating DNA-PKcs overexpression in PDAC are still not well characterized. Expression of DNA-PKcs was measured by western blot. The levels of miRNA-101 and lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) were detected by real-time PCR. Cell viability was determined by CCK-8. Cell migration and cell invasion were measured by transwell assay. The regulatory relationship between NEAT1 and miR-101 was determined by a luciferase assay. DNA-PKcs expression was significantly elevated in human PDAC tissues and cells. DNA-PKcs overexpression was correlated with TNM stage and lymph node metastasis. Higher expression of DNA-PKcs was closely correlated with patients of worse overall survival (OS). DNA-PKcs knockdown suppresses malignant behaviors of PDAC cells. Further study showed that miRNA-101 level was decreased in PDAC tissues and cells, which could be responsible for DNA-PKcs overexpression and DNA-PKcs mediated oncogenic actions in PDAC cells. Moreover, NEAT1 functions as an oncogene influencing cell proliferation, migration and invasion in part by serving as a competing endogenous RNA (ceRNAs) modulating miR-101 expression, leading to up-regulation of DNA-PKcs. These findings suggest that NEAT1/miR-101-dependent up-regulation of DNA-PKcs promotes the malignant behaviors of PDAC cells. The NEAT1/miR-101/DNA-PKcs axis may serve as a viable prognostic marker and therapeutic target for PDAC.
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http://dx.doi.org/10.7150/jca.58824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364653PMC
July 2021

Correction to: West meets east: open up a dialogue on phytomedicine.

Chin Med 2021 Aug 17;16(1):79. Epub 2021 Aug 17.

Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macao SAR, China.

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http://dx.doi.org/10.1186/s13020-021-00490-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369736PMC
August 2021

Identification of novel drug targets for Alzheimer's disease by integrating genetics and proteomes from brain and blood.

Mol Psychiatry 2021 Aug 11. Epub 2021 Aug 11.

Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.

Genome-wide association studies (GWASs) have discovered numerous risk genes for Alzheimer's disease (AD), but how these genes confer AD risk is challenging to decipher. To efficiently transform genetic associations into drug targets for AD, we employed an integrative analytical pipeline using proteomes in the brain and blood by systematically applying proteome-wide association study (PWAS), Mendelian randomization (MR) and Bayesian colocalization. Collectively, we identified the brain protein abundance of 7 genes (ACE, ICA1L, TOM1L2, SNX32, EPHX2, CTSH, and RTFDC1) are causal in AD (P < 0.05/proteins identified for PWAS and MR; PPH4 >80% for Bayesian colocalization). The proteins encoded by these genes were mainly expressed on the surface of glutamatergic neurons and astrocytes. Of them, ACE with its protein abundance was also identified in significant association with AD on the blood-based studies and showed significance at the transcriptomic level. SNX32 was also found to be associated with AD at the blood transcriptomic level. Collectively, our current study results on genetic, proteomic, and transcriptomic approaches has identified compelling genes, which may provide important leads to design future functional studies and potential drug targets for AD.
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http://dx.doi.org/10.1038/s41380-021-01251-6DOI Listing
August 2021

Application of evidence-based nursing in prevention of postoperative complications of breast augmentation.

J Cosmet Dermatol 2021 Aug 11. Epub 2021 Aug 11.

Department of Plastic and Reconstructive Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.

Objective: To study the application of evidence-based nursing in prosthesis postoperative complications.

Methods: A total of 78 cases of patients who underwent prosthetic breast augmentation were selected from July 2017 to July 2019. All the patients were divided into control group and study group according to the random number table method. The patients in the control group received routine nursing interventions, and the patients in the study group performed evidence-based nursing interventions based on the control group's care. The mental health, external esthetic effects, and complications of the two groups were observed and compared.

Results: Before the implementation of nursing intervention, there was no significant difference in mental health indicators (SAS, SDS) between the two groups (p > 0.05). After the intervention, the SAS and SDS scores of the two groups were lower than before the intervention, and the study group was lower than the control group, and the difference was statistically significant (p < 0.05); before the implementation of nursing intervention, there was no significant difference in the scores of HADS-A and HADS-D between the two groups (p > 0.05). After the intervention, the scores of HADS-A and HADS-D of the two groups were lower than those before the intervention, and the scores of the study group were lower than those of the control group, and the difference was statistically significant (p < 0.05); 94.9% (37 / 39) was better than 71. 8% (28 / 39) in the control group. The difference was statistically significant (p < 0.05), and the total incidence of postoperative complications in the study group was 5.1% (2 / 39), which was lower than 15.4% (6 / 39) in the control group (p < 0.05).

Conclusion: Evidence-based nursing intervention is effective in preventing postoperative complications of silicone breast augmentation prosthesis. It can effectively reduce postoperative complications, improve external esthetic effects, and improve the level of mental health of patients. It is worthy of clinical promotion and application.
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http://dx.doi.org/10.1111/jocd.14375DOI Listing
August 2021

Predictors of the difficulty for endoscopic resection of gastric gastrointestinal stromal tumor and follow-up data.

J Gastroenterol Hepatol 2021 Aug 8. Epub 2021 Aug 8.

Endoscopy Center of Zhongshan Hospital, Fudan University, Shanghai, China.

Background And Aim: Gastrointestinal stromal tumors (GISTs) are among the most common submucosal tumors in the stomach that require therapeutic intervention. We aim to identify the predictors of technical difficulty during endoscopic resection of gastric GIST and to investigate follow-up outcomes.

Methods: Patients with gastric GISTs were reviewed from June 2009 to June 2020 at Zhongshan Hospital. Clinical and pathological features, endoscopic procedure information, and follow-up data were collected and analyzed. A nomogram was developed and validated internally and externally.

Results: A total of 628 GISTs were finally analyzed. The difficulty was experienced in 66 cases. GISTs size (2-3 cm: OR 2.431 P = 0.018 and > 3 cm: OR 9.765 P < 0.001), invasion depth beyond submucosal (MP: OR 2.280, P = 0.038 and MP-ex: OR 4.295, P = 0.002), and lack of experience (OR 2.075, P = 0.016) were independent risk factors of difficulty. The nomogram prediction model showed a bias-corrected C-index value of 0.778 and acquired an area under curve (AUC) of 0.756 on the external validation cohort. At the cut-off of 0.15, the nomogram's negative predictive value (NPV) and accuracy (ACC) were 94.9% and 79.8% in identifying non-difficult GISTs. Follow-up results showed that only five GIST patients had local recurrence after endoscopic resection.

Conclusions: Tumor size, invasion depth, and endoscopists' experience were risk factors for the difficulty of endoscopic GIST resection. Our nomogram provided a valuable tool for screening non-difficult GIST resection.
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http://dx.doi.org/10.1111/jgh.15650DOI Listing
August 2021

Cardioprotective Role of SIRT5 in Response to Acute Ischemia Through a Novel Liver-Cardiac Crosstalk Mechanism.

Front Cell Dev Biol 2021 22;9:687559. Epub 2021 Jul 22.

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Protein posttranslational modifications play important roles in cardiovascular diseases. The authors' previous report showed that the abundance of succinylated and glutarylated proteins was significantly lower in the serum of patients with acute myocardial infarction (AMI) than in that of healthy volunteers, suggesting a potential relationship between protein acylation and AMI. Sirtuin 5 (SIRT5) facilitates the removal of malonyl, succinyl, and glutaryl modification; however, its effects on AMI remain unknown. In this study, the levels of SIRT5 in AMI mouse model was compared. Results showed elevated hepatic SIRT5 after myocardial infarction. Hepatocyte-specific SIRT5 overexpressing mice (liver SIRT5 OE) were generated to address the possible involvement of hepatic SIRT5 in AMI. The areas of myocardial infarction, myocardial fibrosis, and cardiac function in a model of experimental myocardial infarction were compared between liver SIRT5 OE mice and wild-type (WT) mice. The liver SIRT5 OE mice showed a significantly smaller area of myocardial infarction and myocardial fibrosis than the WT mice. The fibroblast growth factor 21 (FGF21) in the blood and myocardium of liver SIRT5 OE mice after AMI was markedly elevated compared with that in WT mice. The results of mass spectrometry showed increased levels of proteins regulating tricarboxylic acid cycle, oxidative phosphorylation, and fatty acid β-oxidation pathways in the liver mitochondria of liver SIRT5 OE mice. These findings showed that SIRT5 may exhibit a cardioprotective effect in response to acute ischemia through a liver-cardiac crosstalk mechanism, probably by increasing the secretion of FGF21 and the improvement of energy metabolism.
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http://dx.doi.org/10.3389/fcell.2021.687559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339556PMC
July 2021

Predicting Pharmacist Intention to Contribute to COVID-19 Management at the Community Level: A Cross-Sectional Survey Study.

Front Public Health 2021 22;9:653335. Epub 2021 Jul 22.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao, China.

The role of pharmacists in public health management is expected to grow into a key player in the continuing measures of managing the COVID-19 pandemic, especially in the community setting. However, their intention to provide essential public health services for combating the pandemic and the impact of their attitude and beliefs are largely unknown. This study aimed to investigate the intention-to-practice COVID-19-related responsibilities of pharmacists based on the theory of planned behavior (TPB), identify the key factors predicting their intention, and explore the usefulness of the TPB model in predicting such an intention. A cross-sectional, self-administered questionnaire was completed by pharmacists in Macao between May and August 2020. Quantitative responses regarding intention-to-practice COVID-19-related duties, and the four TPB variables [attitude (A), subjective norms (SN), perceived behavioral control (PBC), and past behavior (PB)] were measured. Cronbach's alpha and composite reliability were used to determine the reliability and validity of the tool. In addition to descriptive statistics, Pearson's correlation was used to determine the strengths of the association, and multiple linear regression was used to predict the association between the intention and the four key variables. More than half of the pharmacists practicing in Macao completed the questionnaire (296/520) giving a response rate of 56.9%. Among them, 75% were 26-40 years old and 56% were female. The majority of the participants (91.9%) demonstrated a positive intention to contribute to the COVID-19 infection management (mean = 4.19 ± 0.51). The mean scores for A, SN, PBC, and PB were 4.06 ± 0.52, 3.71 ± 0.58, 3.76 ± 0.65, and 4.03 ± 0.54, respectively. A (β = 0.671), SN (β = 0.608), PBC (β = 0.563), and PB (β = 0.829) were all positively correlated with intention (all < ). It was found that 72.5% of the variance in the intention-to-practice COVID-19-related duties could be explained by the TPB model using the four key variables with A and PB being two possible predictors. Pharmacists showed favorable A, SN, PBC, and intention in participating in COVID-19 management in the community setting. Specific training, enhanced stakeholder communication, and improved pharmacy management are essential to increase the willingness of pharmacists to take part in the COVID-19 pandemic and other public health emergencies alike in the future.
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http://dx.doi.org/10.3389/fpubh.2021.653335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339551PMC
August 2021

Radiomics from Primary Tumor on Dual-Energy CT Derived Iodine Maps can Predict Cervical Lymph Node Metastasis in Papillary Thyroid Cancer.

Acad Radiol 2021 Aug 5. Epub 2021 Aug 5.

Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing. Electronic address:

Rationale And Objectives: To develop and validate 2 iodine maps based radiomics nomograms for preoperatively predicting cervical lymph node metastasis (LNM) and central lymph node metastasis (CLNM) in papillary thyroid cancer (PTC).

Materials And Methods: A total of 346 patients with PTC were enrolled and allocated to training (242) and validation (104) sets. Radiomics features were extracted from arterial and venous phase iodine maps, respectively. Aggregated machine-learning strategy was applied for features selection and construction of 2 radiomics scores (LN rad-score; CLN rad-score). Logistic regression model was employed to establish two radiomics nomograms (nomogram 1: predicting LNM; nomogram 2: predicting CLNM) after incorporating LN or CLN rad-score with clinical predictors. Nomograms performance was determined by discrimination, calibration and clinical usefulness.

Results: Nomogram 1 incorporated LN rad-score, age (categorized by 55) and CT reported LN status; Nomogram 2 incorporated CLN rad-score, capsule contact >25% and CT reported CLN status. 2 nomograms both showed good discrimination and calibration in the training (AUC = 0.847; AUC = 0.837) and validation cohorts (AUC = 0.807; AUC = 0.795). Significant improved AUC, net reclassification index (NRI) and integrated discriminatory improvement (IDI) confirmed additional great predictive value of 2 rad-scores, compared with clinical models without radiomics. Decision curve analysis indicated clinical utility of nomograms. 2 nomograms both demonstrated favorable predictive efficacy in CT reported LN or CLN negative subgroup (AUC = 0.766; AUC = 0.744).

Conclusion: The presented 2 radiomics nomograms are useful tools for preoperative prediction of LNM and CLNM in PTC.
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http://dx.doi.org/10.1016/j.acra.2021.06.014DOI Listing
August 2021

Molecular Dynamic Investigation of the Anisotropic Response of Aluminum Surface by Ions Beam Sputtering.

Micromachines (Basel) 2021 Jul 20;12(7). Epub 2021 Jul 20.

College of Intelligence Science, National University of Defense Technology, Changsha 410073, China.

Aluminum optics are widely used in modern optical systems because of their high specific stiffness and high reflectance. With the applied optical frequency band moving to visible, traditional processing technology cannot meet the processing precision. Ion beam sputtering (IBS) provides a highly deterministic technology for high-precision aluminum optics fabrication. However, the surface quality is deteriorated after IBS. The interaction between the bombard atoms and the surface morphology evolution mechanism are not clear, and systematic research is needed. Thus, in this paper, the IBS process for single crystal aluminum with different crystallographic orientations are studied by the molecular dynamics method. The ion beam sputter process is firstly demonstrated. Then, the variation of sputter yield of the three crystal faces is analyzed. The sputter yield difference of different crystal surfaces causes the appearance of the relief structure. Then, the gravel structure generates on the single crystal surfaces and dominates the morphology evolution. The state of the atom diffusion of the specific crystal surfaces will determine the form of the gravel structure. Furthermore, the form and distribution of subsurface damage and stress distribution of three different crystal surfaces are analyzed. Although there are great differences in defect distribution, no stress concentration was found in three workpieces, which verifies that the ion beam sputter is a stress-free machining method. The process of IBS and the mechanism of morphology evolution of aluminum are revealed. The regularity and mechanism will provide a guidance for the application of IBS in aluminum optics manufacture fields.
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http://dx.doi.org/10.3390/mi12070848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305627PMC
July 2021

Comparative efficacy of single-inhaler triple therapies for COPD: A protocol for systematic review and network meta-analysis.

PLoS One 2021 5;16(8):e0255545. Epub 2021 Aug 5.

Shenzhen Institute of Artificial Intelligence and Robotics for Society, Shenzhen, China.

Introduction: 2021 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Reports recommends that patients with clinically significant symptoms and exacerbations of chronic obstructive pulmonary disease (COPD) should escalate to triple therapy, a combined use of inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA) and long-acting b2-agonists (LABA)(ICS/LAMA/LABA). Triple therapy in fixed-dose combinations (FDCs), i.e., combining ICS, LABA with LAMA and administrating by a single inhalation device, has appeared in recent years. This study aims to compare the efficacy of triple therapy in FDCs in treating patients with moderate to severe COPD.

Methods And Analyses: Literature search will be conducted on PubMed, Embase and Web of science, according to pre-specified and corresponding search strategies, for relevant reports published since the inception dates of the databases. Randomised controlled trials (RCT) which compared the triple therapy in FDCs with other pharmacological therapies will be included. The Cochrane risk of bias assessment tool (RoB 2) will be used to assess the RCT quality. The outcomes will be analyzed as rate ratios and mean differences under a random-effects model in a frequentist network meta-analysis (NMA). Additional statistical analyses including subgroup analysis, sensitivity analysis, and publication bias analysis will be performed to assess the evidential heterogeneity and robustness. The strength of evidence from the NMA will be evaluated with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) methods.

Ethics And Dissemination: No ethics approval is required as this systematic review and network meta-analysis do not collect confidential personal data and do not carry out interventions in treating patients.

Protocol Registration Number: CRD42021240823.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255545PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341520PMC
August 2021

Influence of post-label delay time on the performance of 3D pseudo-continuous arterial spin labeling magnetic resonance imaging in the characterization of parotid gland tumors.

Eur Radiol 2021 Aug 4. Epub 2021 Aug 4.

Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Rd, Gulou District, Nanjing, People's Republic of China.

Objective: To evaluate the influence of post-label delay times (PLDs) on the performance of 3D pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging for characterizing parotid gland tumors and to explore the optimal PLDs for the differential diagnosis.

Materials And Method: Fifty-eight consecutive patients with parotid gland tumors were enrolled, including 33 patients with pleomorphic adenomas (PAs), 16 patients with Warthin's tumors (WTs), and 9 patients with malignant tumors (MTs). 3D pCASL was scanned for each patient five times, with PLDs of 1025 ms, 1525 ms, 2025 ms, 2525 ms, and 3025 ms. Tumor blood flow (TBF) was calculated, and compared among different PLDs and tumor groups. Performance of TBF at different PLDs was evaluated using receiver operating characteristic analysis.

Results: With an increasing PLD, TBF tended to gradually increase in PAs (p < 0.001), while TBF tended to slightly increase and then gradually decrease in WTs (p = 0.001), and PAs showed significantly lower TBF than WTs at all 5 PLDs (p < 0.05). PAs showed significantly lower TBF than MTs at 4 PLDs (p < 0.05), except at 3025 ms (p = 0.062). WTs showed higher TBF than MTs at all 5 PLDs; however, differences did not reach significance (p > 0.05). Setting a TBF of 64.350 mL/100g/min at a PLD of 1525 ms, or a TBF of 23.700 mL/100g/min at a PLD of 1025 ms as the cutoff values, optimal performance could be obtained for differentiating PAs from WTs (AUC = 0.905) or from MTs (AUC = 0.872).

Conclusions: Short PLDs (1025 ms or 1525 ms) are suggested to be used in 3D pCASL for characterizing parotid gland tumors in clinical practice.

Key Points: • With 5 different PLDs, 3D pCASL can reflect the variation of blood flow in parotid gland tumors. • 3D pCASL is useful for characterizing PAs from WTs or MTs. • Short PLDs (1025 ms or 1525 ms) are suggested to be used in 3D pCASL for characterizing parotid gland tumors in clinical practice.
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http://dx.doi.org/10.1007/s00330-021-08220-1DOI Listing
August 2021

Molecular basis for lipid recognition by the prostaglandin D receptor CRTH2.

Proc Natl Acad Sci U S A 2021 Aug;118(32)

Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;

Prostaglandin D (PGD) signals through the G protein-coupled receptor (GPCR) CRTH2 to mediate various inflammatory responses. CRTH2 is the only member of the prostanoid receptor family that is phylogenetically distant from others, implying a nonconserved mechanism of lipid action on CRTH2. Here, we report a crystal structure of human CRTH2 bound to a PGD derivative, 15R-methyl-PGD (15mPGD), by serial femtosecond crystallography. The structure revealed a "polar group in"-binding mode of 15mPGD contrasting the "polar group out"-binding mode of PGE in its receptor EP3. Structural comparison analysis suggested that these two lipid-binding modes, associated with distinct charge distributions of ligand-binding pockets, may apply to other lipid GPCRs. Molecular dynamics simulations together with mutagenesis studies also identified charged residues at the ligand entry port that function to capture lipid ligands of CRTH2 from the lipid bilayer. Together, our studies suggest critical roles of charge environment in lipid recognition by GPCRs.
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http://dx.doi.org/10.1073/pnas.2102813118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364189PMC
August 2021

Fermitin family homolog 2 (Kindlin-2) affects vascularization during the wound healing process by regulating the Wnt/β-catenin signaling pathway in vascular endothelial cells.

Bioengineered 2021 Dec;12(1):4654-4665

Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Kindlin-2 is a member of the FERM-containing cytoskeletal protein family that regulates cell-matrix interactions. Previous studies have shown that Kindlin-2 recruits focal adhesion proteins and regulates integration by binding to the focal adhesion region of the integrin β-segment. Although Kindlin-2 has been reported to be involved in various skin diseases and many kinds of tumors, its role in the skin wound healing process remains unclear. The aim of the present study was to investigate the role of Kindlin-2 in the regulation of wound healing. The effects of Kindlin-2 on wound healing were studied by a wound healing model, kindlin-2 (±) mice. The effects of Kindlin-2 on cell migration, cellular tube formation, and cell adhesion and spreading were evaluated in human umbilical vein endothelial cells (HUVECs) with downregulated Kindlin-2 expression. We found that the expression of kindlin-2 was elevated in wound healing tissues and that interfering with the expression of Kindlin-2 delayed the wound healing process and reduced neovascularization. We found that the wound healing of kindlin-2 (±) mice was delayed, with a decreased number of new blood vessels. Furthermore, depletion of Kindlin-2 impaired HUVEC spreading, migration and tube formation. Intriguingly, we found that kindlin-2 binds to β-catenin in the Wnt/β-catenin signaling pathway and cooperates with β-catenin to enter the nucleus from the cytoplasm, activating the downstream Wnt/β-catenin signaling pathway. Taken together, these results help to elucidate the mechanism of Kindlin-2 in the regulation of the wound healing process and provide a theoretical basis for further study of wound healing and abnormal healing.
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http://dx.doi.org/10.1080/21655979.2021.1957526DOI Listing
December 2021

Overexpression of Karrikins Receptor Gene Promotes the Cold Stress Tolerance via Regulating the Redox Homeostasis in .

Front Plant Sci 2021 15;12:657960. Epub 2021 Jul 15.

Key Laboratory of the High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.

() is the receptor gene for karrikins, recently found to be involved in seed germination, hypocotyl development, and the alleviation of salinity and osmotic stresses. Nevertheless, whether could regulate cold tolerance remains elusive. In the present study, we identified that mutants of had a high mortality rate, while overexpression of, a bioenergy plant, () significantly recovered the plants after cold stress. The results showed that the overexpression lines (OEs) had significantly increased levels of proline, total soluble sugars, and total soluble protein. Meanwhile, OEs had a much higher expression of cold-stress-acclimation-relate genes, such as and under cold stress. Moreover, the results showed that OEs were hypersensitive to abscisic acid (ABA), and ABA signaling genes were w significantly affected in OEs under cold stress, suggesting a potential interaction between and ABA downstream signaling. In OEs, the electrolyte leakage, hydrogen peroxide, and malondialdehyde contents were reduced under cold stress in . OEs enhanced the anti-oxidants like ascorbate peroxidase, catalase, peroxidase, superoxide dismutase, and total glutathione level under cold stress. Conclusively, these results provide novel insights into the understanding of karrikins role in the regulation of cold stress adaptation.
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http://dx.doi.org/10.3389/fpls.2021.657960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320022PMC
July 2021

Brain Metastases Status and Immunotherapy Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis.

Front Immunol 2021 14;12:669398. Epub 2021 Jul 14.

Department of Radiation Therapy, General Hospital of Southern Theater Command, Guangzhou, China.

Background: Brain metastases (BMs) indicate poor outcomes and are commonly excluded in immunotherapy clinical trials in advanced lung cancer; moreover, the effect of BM status on immunotherapy efficacy is inconsistent and inconclusive. Therefore, we conducted a meta-analysis to assess the influence of BM status on immunotherapy efficacy in advanced lung cancer.

Methods: Electronic databases and all major conference proceedings were searched without language restrictions according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We extracted randomized clinical trials on lung cancer immunotherapy that had available overall survival (OS) and/or progression-free survival (PFS) data based on the BM status. All analyses were performed using random effects models.

Results: Fourteen randomized clinical trials with 9,089 patients were identified. Immunotherapy conferred a survival advantage to BM patients [OS-hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58-0.90; P = 0.004; and PFS-HR, 0.68; 95% CI, 0.52-0.87, P = 0.003]. Non-BM patients could also derive a survival benefit from immunotherapy (OS-HR, 0.76; 95% CI, 0.71-0.80; P <0.001; and PFS-HR, 0.68; 95% CI, 0.56-0.82, P <0.001). The pooled ratios of OS-HRs and PFS-HRs reported in BM patients non-BM patients were 0.96 (95% CI, 0.78-1.18; P = 0.72) and 0.97 (95% CI, 0.79-1.20; P = 0.78), respectively, indicating no statistically significant difference between them. Subsequent sensitivity analyses did not alter the results. Subgroup analyses according to tumor type, line of therapy, immunotherapy type, study design, and representation of BM patients reconfirmed these findings.

Conclusion: We demonstrated that BM status did not significantly influence the immunotherapy efficacy in lung cancer, suggesting that both BM and non-BM patients could obtain comparable benefits.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier (CRD42020207446).
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http://dx.doi.org/10.3389/fimmu.2021.669398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316922PMC
July 2021

Long Sleep Duration Associated With Cognitive Impairment in Chinese Community-Dwelling Older Adults.

J Nerv Ment Dis 2021 Jul 30. Epub 2021 Jul 30.

Shanghai University of Medicine and Health Science Affiliated First Rehabilitation Hospital Shanghai University of Traditional Chinese Medicine College of Rehabilitation Sciences, Shanghai University of Medicine and Health Sciences, Shanghai, China.

Abstract: We aimed to examine the association between sleep duration and impaired cognitive function in different cognitive domains in Chinese community-dwelling older adults. A total of 1591 participants (≥60 years) were divided into five groups: ≤6 hours (very short sleep duration), >6 to 7 hours (short sleep duration), ≥7 to 8 hours (moderate sleep duration), >8 to 9 hours (moderately long sleep duration), and >9 hours (long sleep duration), according to sleep duration. Cognitive function was assessed using the Mini-Mental State Examination. Long sleep duration significantly increased the likelihood of cognitive impairment. In addition to attention, long sleep duration was negatively related to poorer global cognition and other cognitive domain functions. With the stratification of age groups, long sleep duration was negatively associated with other cognitive domain functions except delayed recall in older elderly (≥75 years) people, but not in younger elderly (60-74 years) people. Long sleep duration was associated with higher rates of cognitive impairment, poorer global cognition, and declined orientation, memory, language ability, and executive function in Chinese community-dwelling older adults, which was more significant in older elderly people.
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http://dx.doi.org/10.1097/NMD.0000000000001401DOI Listing
July 2021

Antipsychotics Effects on Network-Level Reconfiguration of Cortical Morphometry in First-Episode Schizophrenia.

Schizophr Bull 2021 Jul 27. Epub 2021 Jul 27.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu, PR China.

Cortical thickness reductions are evident in schizophrenia (SZ). Associations between antipsychotic medications (APMs) and cortical morphometry have been explored in SZ patients. This raises the question of whether the reconfiguration of morphological architecture by APM plays potential compensatory roles for abnormalities in the cerebral cortex. Structural magnetic resonance imaging was obtained from 127 medication-naive first-episode SZ patients and 133 matched healthy controls. Patients received 12 weeks of APM and were categorized as responders (n = 75) or nonresponders (NRs, n = 52) at follow-up. Using surface-based morphometry and structural covariance (SC) analysis, this study investigated the short-term effects of antipsychotics on cortical thickness and cortico-cortical covariance. Global efficiency was computed to characterize network integration of the large-scale structural connectome. The relationship between covariance and cortical thinning was examined by SC analysis among the top-n regions with thickness reduction. Widespread cortical thickness reductions were observed in pre-APM patients. Post-APM patients showed more reductions in cortical thickness, even in the frontotemporal regions without baseline reductions. Covariance analysis revealed strong cortico-cortical covariance and higher network integration in responders than in NRs. For the NRs, some of the prefrontal and temporal nodes were not covariant between the top-n regions with cortical thickness reduction. Antipsychotic effects are not restricted to a single brain region but rather exhibit a network-level covariance pattern. Neuroimaging connectomics highlights the positive effects of antipsychotics on the reconfiguration of brain architecture, suggesting that abnormalities in regional morphology may be compensated by increasing interregional covariance when symptoms are controlled by antipsychotics.
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http://dx.doi.org/10.1093/schbul/sbab082DOI Listing
July 2021

Quality Evaluation of Randomized Controlled Trials of Species: A Systematic Review.

Evid Based Complement Alternat Med 2021 1;2021:9989546. Epub 2021 Jul 1.

Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao, China.

Background: is a worldwide used medicinal plant for its various medicinal functions, and the number of randomized controlled trials (RCTs) of is increasing in recent years. This study aims to evaluate the reporting quality and risk of bias of the current RCT reports of different species.

Methods: Six databases including Embase, PubMed, Web of Science, the Cochrane Library, ClinicalTrial.gov, and China National Knowledge Infrastructure were searched to identify RCTs that used as a single intervention and were published in English or Chinese from inception to December 2020. The Consolidated Standards of Reporting Trials (CONSORT) 2010 statement was used as the checklist for assessment, and a scoring system was applied to the evaluation of RCTs. Score 0 represents no reporting or inadequate reporting, and score 1 represents adequate reporting. The risk of bias of the included studies was also assessed using the Cochrane Risk of Bias tool.

Results: A total of 39 RCTs were included in this study, including 23 RCTs of (. ), 8 RCTs of (. ), and 8 RCTs of (. ). None of the included studies met all the CONSORT statement criteria, and the reporting quality of RCTs of the three species was all generally poor. Based on the risk of bias assessment, the majority of included studies were judged to have an unclear risk of bias in most domains due to inadequate reporting.

Conclusions: There is inadequate reporting among the included RCTs of different species, and RCTs of with higher reporting quality and better methodological quality are needed.
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http://dx.doi.org/10.1155/2021/9989546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266448PMC
July 2021

An efficient cell culture system for the studies of heterogeneous astrocytes: Time gradient digestion.

J Neurosci Methods 2021 Oct 22;362:109292. Epub 2021 Jul 22.

Laboratory of Medical Systems Biology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623 Guangzhou, China; Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623 Guangzhou, China; Third Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, China; School of Medicine, South China University of Technology, 510006 Guangzhou, China. Electronic address:

Background: Astrocytes are the most abundant glial cell type in mammal brain, but there exists a lot of unknown in cell development and cell function. We aim to establish an astrocytes culture system for obtaining highly enriched primary astrocytes from the neonatal mouse brain and separating Aldh1l1Gfap and Aldh1l1Gfap cells.

New Method: C57BL/J6 mouse pups at postnatal 1-4 days were used for cell preparation. Brain cortex was collected and digested with 0.25% trypsin followed by 0.5 mg/ml DNase. Cells were plated on PDL-coated flasks. After 8-10 days culture, cells were shaken at 260 rpm for 4 h at 37 ℃ to remove oligodendrocytes and microglia cells. Time gradient digestion was performed to obtain astrocyte subtypes. The digestion time was 0-2 min and 2-4 min, and 4-6 min. Flow cytometry, Immunostaining, CCK-8 assay and EdU staining was carried out to investigate the purity of the astrocytes, the ability of cell proliferation and to identify different subtypes.

Results: After shaking, percentage of oligodendrocytes significantly decreased from 22.6 ± 3.6% to 7.4 ± 1.4% (CNPase cells) and from 4.36 ± 0.6% to 0.75 ± 0.2% (Pdgfrα cells) while percentage of microglia cells reduced from 4.4 ± 0.2% to 0.6 ± 0.2%. Aldh1l1Gfap astrocytes were the dominant cell types in 0-2 min group while Aldh1l1Gfap astrocytes were the dominant cell types in 2-4 min group. Moreover, compared with Aldh1l1Gfap astrocytes, Aldh1l1Gfap astrocytes had a higher proliferative ability.

Comparison With Existing Methods: Aldh1l1Gfap and Aldh1l1Gfap cells were separated. The percentage of residual Tmem119 and Gfap cells showed no significant difference. However, the percentage of Pdgfrα cells were significant decreased, and the time consuming of the new system was lower. The astrocytes acquired possess higher viability.

Conclusions: A new astrocytes culture system with time gradient digestion was established. Highly enriched primary astrocytes from the neonatal mouse brain were obtained with short shaking time. Aldh1l1Gfap and Aldh1l1Gfap cells were separated by different digestion condition. This system has advantages of high efficiency and low cost, which deserves promising application in management of astrocytes research in central nerve system.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109292DOI Listing
October 2021

Adventitious root primordia formation and development in the stem of var. slip.

Plant Signal Behav 2021 Jul 21:1949147. Epub 2021 Jul 21.

College of Landscape Architecture-Sichuan Agricultural University, Chengdu- Sichuan, China.

There are about 4-6 slips on a fruit, and they are good materials for effective regeneration of var. . Adventitious root (AR) induction is essential for the propagation of slips. Growth regulator treatment, and culture medium are imperative factors that affect slip growth and rooting. In order to screen the optimal methods for slips rooting and reveal the anatomic procedure of slip rooting, this study induced slip rooting by different treatment of growth regulator, culture medium, observed the slip stem structure, AR origination and formation procedure through paraffin sections. The results showed that, slip cuttings treated with 100 mg/L of Aminobenzotriazole (ABT) for 6 hrs, cultured in river sand: coconut chaff: garden soil 2:2:1 medium is the optimal method for rooting. The proper supplementary of ABT can enhance the soluble sugar content, soluble protein content, polyphenol oxidase (PPO) activity and peroxidase (POD) enzyme activity, which resulted in the improvement of rooting. The slip stem structure is quite different from other monocots, which consists of epidermis, cortex, and stele with vascular tissues distributed in the cortex and stele. The AR primordia originates from the parenchyma cells located on the borderline between the cortex and stele. The vascular tissues in the AR develop and are connected with vascular tissue of the stem before the AR grew out the stem. The number of primary xylem poles in AR is about 30.
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http://dx.doi.org/10.1080/15592324.2021.1949147DOI Listing
July 2021

Association Between Physical Performance and Cognitive Function in Chinese Community-Dwelling Older Adults: Serial Mediation of Malnutrition and Depression.

Clin Interv Aging 2021 12;16:1327-1335. Epub 2021 Jul 12.

Department of Rehabilitation Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, People's Republic of China.

Purpose: We aimed to propose a serial mediational model to further analyze the relationship between poor physical performance, malnutrition, depression and cognitive impairment in Chinese community-dwelling older adults.

Patients And Methods: This study consisted of 1386 community-dwelling Chinese older adults aged 65 years and older in Shanghai, China. Mild cognitive impairment (MCI) was assessed by the Mini-Mental State Examination (MMSE) and Instrumental Activities Of Daily Living (IADL). Physical performance was assessed by short physical performance battery (SPPB). Malnutrition was defined with the Mini Nutritional Assessment (MNA). Depressive symptoms were evaluated by the 30-item Geriatric Depression Scale (GDS). Serial multiple mediator models were used.

Results: The mean age of the final analysis sample was 73.62±6.14, and 57.6% (n=809) were females. The prevalence of MCI was 14.35% (n=199). Physical performance (p<0.001), nutritional status (p=0.025), and depressive symptoms (p=0.002) were correlated with MCI. The serial mediational model revealed that MNA and GDS scores significantly mediated association of SPPB and MMSE scores (c'=0.4728, p<0.001). Furthermore, depressive symptoms significantly mediated the association of physical performance and cognition (p=0.0311), while malnutrition had no independent mediating effect between these two factors (p=0.794).

Conclusion: Our study examined the serial multiple mediation roles of nutritional status and depressive symptoms on the relationship between physical performance and cognitive function in community-dwelling Chinese older adults. Older adults who were in poor physical condition tend to have worse nutritional status, more severe depression, and poorer cognitive function.
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http://dx.doi.org/10.2147/CIA.S315892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285124PMC
July 2021

Usefulness of readout-segmented EPI-based diffusion tensor imaging of lacrimal gland for detection and disease staging in thyroid-associated ophthalmopathy.

BMC Ophthalmol 2021 Jul 20;21(1):281. Epub 2021 Jul 20.

Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Address: No. 300, Guangzhou Rd, Gulou district, Nanjing, P.R. China.

Background: Dysfunction of lacrimal gland (LG) gains increasing attention in patients with thyroid-associated ophthalmopathy (TAO), while the underlying pathological change is still not fully established. This study aimed to evaluate the utility of readout-segmented echo-planar imaging (rs-EPI)-based diffusion tensor imaging (DTI) in non-invasively detecting microstructural alterations of LG in patients with TAO, as well as in discriminating disease activity.

Methods: Thirty TAO patients and 15 age- and sex- matched healthy controls, who underwent rs-EPI-based DTI, were retrospectively enrolled. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of LG, and clinical-endocrinological variables were collected and compared. The correlations between FA and ADC values of LG and serum thyroid biochemical markers were also assessed.

Results: TAO group showed significantly lower FA (P < 0.001) and higher ADC (P = 0.014) of LG than healthy group. Active subgroup had significantly lower FA (P < 0.001) and higher ADC (P < 0.001) than inactive subgroup. In TAO group, FA of LG was significantly and negatively correlated with TRAb (r=-0.475, P = 0.008), while ADC of LG showed no significant correlation (P > 0.05). The area under receiver operating characteristic curve of FA was significantly greater than that under curve of ADC for discriminating disease activity (0.832 vs. 0.570, P = 0.009).

Conclusions: rs-EPI-based DTI is a useful tool to characterize the microstructural change of LG in patients with TAO. The derived metrics, particularly FA, can help to reveal disease activity.
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http://dx.doi.org/10.1186/s12886-021-02044-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290601PMC
July 2021

Policy Interventions, Development Trends, and Service Innovations of Internet Hospitals in China: Documentary Analysis and Qualitative Interview Study.

J Med Internet Res 2021 Jul 20;23(7):e22330. Epub 2021 Jul 20.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.

Background: Internet hospitals have been encouraged by the Chinese government to develop an innovative medical service model that mainly uses new internet-based technologies to increase access to health care and improve the quality and efficiency of health care delivery. However, the academic exploration of the institutional and sectoral development of internet hospitals in China is scarce in the existing literature.

Objective: This study aimed to investigate the policy interventions, development trends, and service innovations of internet hospitals in China. It is expected that the findings from this study will contribute to the further innovation of internet hospitals in China and provide references for the international development of internet hospitals for personalized digital health and patient-centric services.

Methods: This study analyzed official policies related to internet hospitals that were implemented by the government in China since 2005. The data of formally approved internet hospitals were collected from official websites to analyze development trends. In-depth semistructured interviews were conducted with 58 key stakeholders who represented comprehensive viewpoints about the service innovations of internet hospitals between March and November 2019.

Results: In total, 25 policies that promoted the development of internet hospitals in China were identified. These policies encompassed informatization infrastructure construction, medical resource integration, development model design, service model design, and payment model design. Of the 268 internet hospitals that had received an official license from the government, 153 public internet hospitals had been built mainly by medical institutions. Public tertiary hospitals were the main actors in founding internet hospitals that were created to provide services that targeted patients with common diseases or chronic diseases or patients living in remote and rural areas. Promoting convenient access to high-quality medical resources and saving patients' and their families' time were the key values of internet hospitals.

Conclusions: The policy interventions strongly promoted the development of internet hospitals in China. Public tertiary hospitals led the development of internet hospitals. However, internet hospitals in China have mainly played roles that are complementary to those of physical medical institutions. The service model of internet hospitals needs more distinguished innovations to provide personalized digital health and patient-centric services.
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http://dx.doi.org/10.2196/22330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335616PMC
July 2021

Remdesivir Versus Standard-of-Care for Severe Coronavirus Disease 2019 Infection: An Analysis of 28-Day Mortality.

Open Forum Infect Dis 2021 Jul 26;8(7):ofab278. Epub 2021 May 26.

Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom.

Background: Remdesivir is approved by the US Food and Drug Administration for the treatment of patients hospitalized with coronavirus disease 2019 (COVID-19) and has been shown to shorten time to recovery and improve clinical outcomes in randomized trials.

Methods: This was the final day 28 comparative analysis of data from a phase 3, randomized, open-label study comparing 2 remdesivir regimens (5 vs 10 days, combined for this analysis [remdesivir cohort]) and a real-world retrospective longitudinal cohort study of patients receiving standard-of-care treatment (nonremdesivir cohort). Eligible patients, aged ≥18 years, had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), oxygen saturation ≤94% on room air or required supplemental oxygen, with pulmonary infiltrates. Propensity score matching (up to 1:10 ratio) was used to ensure comparable populations. We assessed day 14 clinical recovery (determined using a 7-point ordinal scale) and day 28 all-cause mortality (coprimary endpoints).

Results: A total of 368 (remdesivir) and 1399 (nonremdesivir) patients were included in the matched analysis. The day 14 clinical recovery rate was significantly higher among the remdesivir versus the nonremdesivir cohort (65.2% vs 57.1%; odds ratio [OR], 1.49; 95% confidence interval [CI], 1.16-1.90; = 0.002). The day 28 mortality rate was significantly lower in the remdesivir cohort versus the nonremdesivir cohort (12.0% vs 16.2%; OR, 0.67; 95% CI, 0.47-.95;  = .03).

Conclusions: Remdesivir was associated with significantly higher rates of day 14 clinical recovery, and lower day 28 mortality, compared with standard-of-care treatment in hospitalized patients with COVID-19. These data, taken together, support the use of remdesivir to improve clinical recovery and decrease mortality from SARS-CoV-2 infection.
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http://dx.doi.org/10.1093/ofid/ofab278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244650PMC
July 2021
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