Publications by authors named "Yi Wang"

5,975 Publications

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Neighborhood Social Cohesion and the Health of Native Hawaiian and Other Pacific Islander Older Adults.

J Gerontol Soc Work 2021 May 11:1-21. Epub 2021 May 11.

Thompson School of Social Work & Public Health, University of Hawai'i at Mānoa, Honolulu, Hawaii, USA.

Native Hawaiian and other Pacific Islander (NHPI) older adults experience various social and health challenges. There is a growing literature linking neighborhood conditions with health, yet few have focused on NHPI older adults. This study examines associations between neighborhood social cohesion and health outcomes (i.e., self-rated health, psychological distress, and memory) in this population. Data from the 2014 Native Hawaiian and Pacific Islander National Health Interview Survey (n=1,045 with respondents aged 50+) were analyzed with logistic regression models. The level of neighborhood social cohesion was determined by responses to items on perceptions of mutual help, dependability, trust, and close relationships within the neighborhood. Higher perceived neighborhood social cohesion was associated with lower odds of having serious psychological distress or memory problems. There was no statistical association of social cohesion with self-rated health. Socially cohesive neighborhoods are important to the health of NHPI. We discuss methods to improve neighborhood social cohesion as a way to promote health equity for NHPI older adults in the United States (U.S.).
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http://dx.doi.org/10.1080/01634372.2021.1917033DOI Listing
May 2021

Exosomes in bladder cancer: novel biomarkers and targets.

J Zhejiang Univ Sci B 2021 May;22(5):341-347

Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China.

Exosomes are nanometer-sized vesicles that contain various types of biologically active components, including proteins, nucleic acids, carbohydrates, and lipids, which vary with the type and physiological state of the cell. In recent years, several studies have showed that exosomes can provide new non-invasive diagnostic and prognostic biomarkers in patients affected by cancers, including bladder cancer (BC), and the lipid bilayer membrane structure makes exosomes as promising delivery vehicles for therapeutic applications. Exosomes have the characteristics of high abundance, high stability, tissue specificity, and wide distribution in body fluids, and are secreted as various types by cells in different states, thereby possessing great potential as biomarkers for BC. Herein, we briefly summarize the functions and roles of exosomes in the occurrence and development of BC and the current progress of research on exosomes in BC, while focusing on potential clinical applications of the diagnosis, treatment, and prognosis of BC.
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http://dx.doi.org/10.1631/jzus.B2000711DOI Listing
May 2021

Decrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model.

Sci Rep 2021 May 10;11(1):9915. Epub 2021 May 10.

Innate Immunity Laboratory, Graduate School of Life Science, Hokkaido University, Sapporo, Japan.

Psychological stress has been reported to relate to dysbiosis, imbalance of the intestinal microbiota composition, and contribute to the onset and exacerbation of depression, though, underlying mechanisms of psychological stress-related dysbiosis have been unknown. It has been previously established that α-defensins, which are effector peptides of innate enteric immunity produced by Paneth cells in the small intestine, play an important role in regulation of the intestinal microbiota. However, the relationship between disruption of intestinal ecosystem and α-defensin under psychological stress is yet to be determined. Here we show using chronic social defeat stress (CSDS), a mouse depression model that (1) the exposure to CSDS significantly reduces α-defensin secretion by Paneth cells and (2) induces dysbiosis and significant composition changes in the intestinal metabolites. Furthermore, (3) they are recovered by administration of α-defensin. These results indicate that α-defensin plays an important role in maintaining homeostasis of the intestinal ecosystem under psychological stress, providing novel insights into the onset mechanism of stress-induced depression, and may further contribute to discovery of treatment targets for depression.
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http://dx.doi.org/10.1038/s41598-021-89308-yDOI Listing
May 2021

Activation of the clock gene TIMELESS by H3k27 acetylation promotes colorectal cancer tumorigenesis by binding to Myosin-9.

J Exp Clin Cancer Res 2021 May 10;40(1):162. Epub 2021 May 10.

Department of Anatomy, Histology and Embryology, Nanjing Medical University, Xuehai Building, Rm D509, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.

Background: Colorectal cancer (CRC) is a common tumor characterized by its high mortality. However, the underlying molecular mechanisms that drive CRC tumorigenesis are unclear. Clock genes have important roles in tumor development. In the present study, the expression and functions of clock gene TIMELESS (encoding the Timeless protein) in CRC were investigated.

Methods: Immunohistochemistry, cell proliferation, migration, invasion, EMT and xenograft tumor experiments were used to prove the function of Timeless in the tumorigenesis of CRC. Immunoprecipitation, mass spectrometry, Immunofluorescence and Chromatin immunoprecipitation (ChIP) were utilized to clarify the mechanism of Timeless in regulating CRC tumorigenesis.

Results: We found that Timeless was upregulated in CRC tissues compared with corresponding normal tissues and its expression was closely associated with the TNM stages and overall survival of CRC patients. Functional studies demonstrated that Timeless promoted the proliferation, invasion, and EMT of CRC cells in vitro and in vivo. Mechanistic investigations showed that Timeless activated the β-catenin signal pathway by binding to Myosin-9, which binds to β-catenin to induce its nuclear translocation. The upregulation of Timeless was attributed to CREB-binding protein (CBP)/p300-mediated H3K27 acetylation of the promoter region of Timeless.

Conclusion: Timeless regulates the tumorigenesis of CRC by binding to and regulating myosin-9, suggesting Timeless might be a potential prognostic biomarker and therapeutic target for CRC.
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http://dx.doi.org/10.1186/s13046-021-01936-4DOI Listing
May 2021

[Research Progress of the Effects of Vitamin D Supplementation on Glycemic Control and Adverse Maternal-neonatal Outcomes in Gestational Diabetes Mellitus Patients].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Apr;43(2):253-258

School of Public Health,Hangzhou Normal University Division of Health Sciences,Hangzhou 311121,China.

Gestational diabetes mellitus(GDM)can cause blood glucose disorders in pregnant women and result in adverse maternal-neonatal outcomes.Vitamin D(VD)can improve glucose tolerance and insulin sensitivity,and thus theoretically,VD supplementation during pregnancy could improve glycemic control as well as maternal-neonatal outcomes in GDM patients.Although studies have shown that VD deficiency is associated with poor maternal-neonatal outcomes in GDM patients,no solid conclusion has been drawn with regard to the effects of VD supplementation on these patients.Therefore,here we summarized the research progress of the effects of VD supplementation on glycemic control and adverse maternal-neonatal outcomes in GDM patients,in an effort to guide the clinical VD supplementation during pregnancy.
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http://dx.doi.org/10.3881/j.issn.1000-503X.13177DOI Listing
April 2021

Long period exposure to serious cadmium pollution benefits an invasive plant (Alternanthera philoxeroides) competing with its native congener (Alternanthera sessilis).

Sci Total Environ 2021 Apr 30;786:147456. Epub 2021 Apr 30.

Yunnan Key Laboratory of Plant Reproductive Adaptation and Evolutionary Ecology, Yunnan University, Kunming 650504, Yunnan, China; Laboratory of Ecology and Evolutionary Biology, Yunnan University, Kunming 650504, Yunnan, China. Electronic address:

Many aggressive plants possess high tolerance to heavy metals, but little is known about their invasiveness at heavy metal polluted sites. We performed a greenhouse experiment to examine the impacts of Cd (0, 10, 30, 60, and 100 mg kg) and inter-specific competition on the reproductive capability of an invasive plant, Alternanthera philoxeroides, and its native congener, Alternanthera sessilis. We also examined the population dynamics of both native and invasive species in a simulated field experiment. Compared with A. philoxeroides, native A. sessilis was a stronger competitor as measured by vegetative growth, sexual reproduction, and dominance status in a mixed culture. However, A. philoxeroides showed great plasticity in root mass ratio that was positively affected by inter-specific competition and high Cd levels. Such high root allocation might allow for delayed growth of A. philoxeroides rhizomes as the relative cover of A. philoxeroides to A. sessilis in the field experiment gradually increased and > 1 after nine months culture, especially at high Cd treatment. Our results suggest that the invasiveness of A. philoxeroides is highly context- and time-dependent. In severely polluted environments, clonal propagation of A. sessilis is likely inhibited by the synergistic negative effects of inter-specific competition and heavy metal pollution, and a long time co-existence of these two competing species would facilitate the colonization of invasive plant.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147456DOI Listing
April 2021

APE1 facilitates PD-L1-mediated progression of laryngeal and hypopharyngeal squamous cell carcinoma.

Int Immunopharmacol 2021 May 6;97:107675. Epub 2021 May 6.

Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China. Electronic address:

Laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HSCC) seriously affect the life quality of patients. Nowadays, immunotherapy is widely used in the treatment of cancer. Tumor-infiltrating lymphocytes (TILs), programmed cell death 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1) play key roles in the immunotherapy of cancer. Moreover, study has reported that the upregulation of PD-L1 and apurinic/apyrimidinic endonuclase 1 (APE1) are associated with tumorigenesis and poor prognosis of gastric cancer. In the present study, the number of CD3+ T lymphocytes and the expressions of PD-1 and PD-L1 in LSCC and HSCC were detected in clinical samples. In addition, the expressions of PD-L1 and APE1 and their correlation were explored. The results showed that PD-1+ T lymphocytes were wildly infiltrated and PD-L1 was overexpressed in LSCC and HSCC tissues. PD-1 had a positive correlation with cancer progression, and glottic and subglottic LSCC tissues might have a more active immune microenvironment. Moreover, the results showed that upregulated co-expression of PD-L1 and APE1 was a biomarker of LSCC, and APE1 could regulate the expression of PD-L1 through NF-κB signaling pathway. In conclusion, the combine detection of the expressions of PD-1, PD-L1 and APE1 will provide predictive value for the treatment of LSCC and HSCC via immune checkpoint inhibitors, which will help us to identify the patient population more likely to benefit from the immune checkpoint inhibitors based on the tumor immune microenvironment.
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http://dx.doi.org/10.1016/j.intimp.2021.107675DOI Listing
May 2021

Inhibition of hyperactivity of the dorsal raphe 5-HTergic neurons ameliorates hippocampal seizure.

CNS Neurosci Ther 2021 May 6. Epub 2021 May 6.

Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China.

Aims: Epilepsy, frequently comorbid with depression, easily develops drug resistance. Here, we investigated how dorsal raphe (DR) and its 5-HTergic neurons are implicated in epilepsy.

Methods: In mouse hippocampal kindling model, using immunochemistry, calcium fiber photometry, and optogenetics, we investigated the causal role of DR 5-HTergic neurons in seizure of temporal lobe epilepsy (TLE). Further, deep brain stimulation (DBS) of the DR with different frequencies was applied to test its effect on hippocampal seizure and depressive-like behavior.

Results: Number of c-fos neurons in the DR and calcium activities of DR 5-HTergic neurons were both increased during kindling-induced hippocampal seizures. Optogenetic inhibition, but not activation, of DR 5-HTergic neurons conspicuously retarded seizure acquisition specially during the late period. For clinical translation, 1-Hz-specific, but not 20-Hz or 100-Hz, DBS of the DR retarded the acquisition of hippocampal seizure. This therapeutic effect may be mediated by the inhibition of DR 5-HTergic neurons, as optogenetic activation of DR 5-HTergic neurons reversed the anti-seizure effects of 1-Hz DR DBS. However, DBS treatment had no effect on depressive-like behavior.

Conclusion: Inhibition of hyperactivity of DR 5-HTergic neuron may present promising anti-seizure effect and the DR may be a potential DBS target for the therapy of TLE.
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http://dx.doi.org/10.1111/cns.13648DOI Listing
May 2021

Segregated oceanic crust trapped at the bottom mantle transition zone revealed from ambient noise interferometry.

Nat Commun 2021 May 5;12(1):2531. Epub 2021 May 5.

Laboratory of Seismology and Physics of Earth's Interior, School of Earth and Space Sciences, University of Science and Technology of China, Hefei, China.

The recycling of oceanic crust, with distinct isotopic and chemical signature from the pyrolite mantle, plays a critical role in the chemical evolution of the Earth with insights into mantle circulation. However, the role of the mantle transition zone during this recycling remains ambiguous. We here combine the unique resolution reflected body waves (P410P and P660P) retrieved from ambient noise interferometry with mineral physics modeling, to shed new light on transition zone physics. Our joint analysis reveals a generally sharp 660-km discontinuity and the existence of a localized accumulation of oceanic crust at the bottom mantle transition zone just ahead of the stagnant Pacific slab. The basalt accumulation is plausibly derived from the segregation of oceanic crust and depleted mantle of the adjacent stagnant slab. Our findings provide direct evidence of segregated oceanic crust trapped within the mantle transition zone and new insights into imperfect whole mantle circulation.
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http://dx.doi.org/10.1038/s41467-021-22853-2DOI Listing
May 2021

Distinct clinical manifestations of obsessive-compulsive disorder are associated with cortical thickness alteration.

Aust N Z J Psychiatry 2021 May 5:48674211009623. Epub 2021 May 5.

Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Although brain structural changes have been reported in patients with obsessive-compulsive disorder (OCD), results from previous studies have been inconsistent. A growing number of studies have focused on obsessive beliefs and impulsivity which could be involved in the occurrence and maintenance of OCD symptoms. The present study aimed to examine whether there are distinct brain structural changes in patients with different OCD subgroups.

Methods: Eighty-nine patients with OCD and 42 healthy controls were recruited to undergo structural magnetic resonance imaging brain scan. OCD patients were classified into subgroups according to scores of the Obsessive Belief Questionnaire (OBQ-44) and the Barratt Impulsiveness Scale (BIS-11) using cluster analysis. Group comparisons in cortical thickness and subcortical volumes between all OCD patients and healthy controls, as well as between subgroups of OCD patients and healthy controls, were carried out.

Results: OCD patients with more obsessive beliefs and attentional impulsivity (OCD_OB_AT) had reduced cortical thickness at the inferior parietal gyrus, the superior and middle temporal gyrus and the insula compared with OCD patients with higher score on the non-planning impulsivity (OCD_NP, corrected  < 0.05). The whole group of OCD patients and both subgroups showed reduced cortical thickness at the superior parietal gyrus compared with controls (uncorrected  < 0.01, number of vertices > 100).

Conclusion: Our results suggest that apart from distinct phenomenology, there are distinct neural correlates of different OCD subgroups based on obsessive beliefs and impulsivity. These neural correlates may have clinical significance and should be considered in future research.
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http://dx.doi.org/10.1177/00048674211009623DOI Listing
May 2021

Clinical value for the detection of fetal chromosomal deletions/duplications by noninvasive prenatal testing in clinical practice.

Mol Genet Genomic Med 2021 May 5:e1687. Epub 2021 May 5.

Center for Genetic Medicine, Xuzhou Maternity and Child Health Care Hospital Affiliated to Xuzhou Medical University, Xuzhou, China.

Objective: This study was to report the experiences on the clinical value of noninvasive prenatal testing (NIPT) for the screening of fetal chromosomal deletions/duplications.

Methods: We performed a retrospective analysis of a cohort of 20,439 pregnancies undergoing NIPT from March 2017 to September 2020 at a single center. Patients with positive NIPT results for fetal chromosomal deletions or duplications had options of invasive diagnostic testing or no further testing. The data were complied from all cases with positive NIPT results for chromosomal deletions/duplications. The positive predictive value (PPV) was calculated from tabulated data.

Results: In this cohort, positive NIPT results for fetal chromosomal deletions/duplications were found in 60 pregnant women. Of the positive samples, further invasive testing was performed in 39 cases, in which 9 cases were found to be true positive. The overall PPV for chromosomal deletions/duplications was 23.1%. In addition, fetal structural anomaly was found by ultrasound examination in three cases, in which the chromosomal deletions/duplications of three cases were not verified. Moreover, an unexpected pathogenic 8p23.3 deletion was identified by invasive testing in 1 fetus with a false positive NIPT screen for 3q27.3q29 duplication.

Conclusions: In summary, positive NIPT results of chromosomal deletions/duplications were not uncommon in clinical practice, whereas the PPV for the testing was low. Hence, potential risks and high percentage of false positives for these abnormal NIPT results might be informed to pregnant women before the choice made of invasive testing.
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http://dx.doi.org/10.1002/mgg3.1687DOI Listing
May 2021

Association between interleukin-1 alpha rs1800587 polymorphism and rheumatoid arthritis: A meta-analysis.

Authors:
Huaguo Wang Yi Wang

Sci Prog 2021 Apr-Jun;104(2):368504211013647

Department of Clinical Laboratory, Wenzhou integrated traditional Chinese and Western Medicine Hospital, Wenzhou, China.

No consistent results have been reached on the relationship of interleukin-1 (IL-1) rs1800587 polymorphism with the susceptibility to rheumatoid arthritis (RA) so far. Therefore, the current meta-analysis was designed to thoroughly review relevant studies, in order to examine the relationship of IL-1A rs1800587 polymorphism with RA risk. Electronic databases were retrieved for literature regarding the relationship between IL-1A rs1800587 polymorphism and RA vulnerability according to the inclusion and exclusion criteria. Stata 12.0 software was adopted to examine the enrolled literature. Meanwhile, odds ratio (OR) and corresponding 95% confidence intervals (95% CI) were used to evaluate the association. A total of seven case-control researches (3267 patients and 2960 healthy controls) were eventually enrolled into the current meta-analysis. Our data indicated no correlation of IL-1A rs1800587 polymorphism with RA risk (TT vs CC: OR = 0.90, 95% CI = 0.73-1.11; TC vs CC: OR = 1.02, 95% CI = 0.78-1.34; Dominant model: OR = 1.04, 95% CI = 0.80-1.35; Recessive model: OR = 1.91, 95% CI = 0.74-1.12). Similarly, no association was found in subgroup analysis stratified by ethnicity. Our findings indicated no relationship between IL-1A rs1800587 polymorphism and RA vulnerability.
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http://dx.doi.org/10.1177/00368504211013647DOI Listing
May 2021

Nintedanib attenuates peritoneal fibrosis by inhibiting mesothelial-to-mesenchymal transition, inflammation and angiogenesis.

J Cell Mol Med 2021 May 5. Epub 2021 May 5.

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Nintedanib, an Food and Drug Administration (FDA) approved multiple tyrosine kinase inhibitor, exhibits an anti-fibrotic effect in lung and kidneys. Its effect on peritoneal fibrosis remains unexplored. In this study, we found that nintedanib administration lessened chlorhexidine gluconate (CG)-induced peritoneal fibrosis and reduced collagen I and fibronectin expression. This coincided with suppressed phosphorylation of platelet-derived growth factor receptor, fibroblast growth factor receptors, vascular endothelial growth factor receptor and Src family kinase. Mechanistically, nintedanib inhibited injury-induced mesothelial-to-mesenchymal transition (MMT), as demonstrated by decreased expression of α-smooth muscle antigen and vimentin and preserved expression of E-cadherin in the CG-injured peritoneum and cultured human peritoneal mesothelial cells exposed to transforming growth factor-β1. Nintedanib also suppressed expression of Snail and Twist, two transcription factors associated with MMT in vivo and in vitro. Moreover, nintedanib treatment inhibited expression of several cytokines/chemokines, including tumour necrosis factor-α, interleukin-1β and interleukin-6, monocyte chemoattractant protein-1 and prevented infiltration of macrophages to the injured peritoneum. Finally, nintedanib reduced CG-induced peritoneal vascularization. These data suggest that nintedanib may attenuate peritoneal fibrosis by inhibiting MMT, inflammation, and angiogenesis and have therapeutic potential for the prevention and treatment of peritoneal fibrosis in patients on peritoneal dialysis.
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http://dx.doi.org/10.1111/jcmm.16518DOI Listing
May 2021

Aminoglycosides in the Intensive Care Unit: What Is New in Population PK Modeling?

Antibiotics (Basel) 2021 Apr 29;10(5). Epub 2021 Apr 29.

Faculté de Pharmacie, Université de Montréal, Montréal, QC H3T 1J4, Canada.

Background: Although aminoglycosides are often used as treatment for Gram-negative infections, optimal dosing regimens remain unclear, especially in ICU patients. This is due to a large between- and within-subject variability in the aminoglycoside pharmacokinetics in this population.

Objective: This review provides comprehensive data on the pharmacokinetics of aminoglycosides in patients hospitalized in the ICU by summarizing all published PopPK models in ICU patients for amikacin, gentamicin, and tobramycin. The objective was to determine the presence of a consensus on the structural model used, significant covariates included, and therapeutic targets considered during dosing regimen simulations.

Method: A literature search was conducted in the Medline/PubMed database, using the terms: 'amikacin', 'gentamicin', 'tobramycin', 'pharmacokinetic(s)', 'nonlinear mixed effect', 'population', 'intensive care', and 'critically ill'.

Results: Nineteen articles were retained where amikacin, gentamicin, and tobramycin pharmacokinetics were described in six, 11, and five models, respectively. A two-compartment model was used to describe amikacin and tobramycin pharmacokinetics, whereas a one-compartment model majorly described gentamicin pharmacokinetics. The most recurrent significant covariates were renal clearance and bodyweight. Across all aminoglycosides, mean interindividual variability in clearance and volume of distribution were 41.6% and 22.0%, respectively. A common consensus for an optimal dosing regimen for each aminoglycoside was not reached.

Conclusions: This review showed models developed for amikacin, from 2015 until now, and for gentamicin and tobramycin from the past decades. Despite the growing challenges of external evaluation, the latter should be more considered during model development. Further research including new covariates, additional simulated dosing regimens, and external validation should be considered to better understand aminoglycoside pharmacokinetics in ICU patients.
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http://dx.doi.org/10.3390/antibiotics10050507DOI Listing
April 2021

Hydrogen sulfide alleviates the anxiety-like and depressive-like behaviors of type 1 diabetic mice via inhibiting inflammation and ferroptosis.

Life Sci 2021 May 1:119551. Epub 2021 May 1.

School of Medicine and State Key Laboratory of Medicinal Chemical Biology, Nankai University, 94 Weijin Road, Tianjin 300071, China. Electronic address:

Studies reported that sodium hydrosulfide (NaHS) can remit the depressive-like and anxiety-like behaviors induced by type 1 diabetes mellitus (T1DM). However, the mechanism is still unclear. In this study, we aimed to investigate the mechanism of NaHS on T1DM. Mice were randomly divided into four groups, including the control group (CON group), DM group, DM + 5.6 mg/kg NaHS group, and CON + 5.6 mg/kg NaHS group. Data showed that NaHS did attenuate the depressive-like and anxiety-like behaviors by OFT, EPM test, FST, and TST. Results suggest that NaHS markedly alleviated the ferroptosis in the prefrontal cortex (PFC) of diabetic mice by reducing iron deposition and oxidative stress, increasing the expression of GPX4 and SLC7A11. Moreover, NaHS could dampen the activation of microglias and the release of pro-inflammatory cytokines, enhance the protein expression of sirtuin 6 (Sirt6) and the interaction between Sirt6 and the acetylation of histoneH3 lysine9 (H3K9ac), and decrease the protein expressions of the Notch1 receptor and H3K9ac. In vitro experiment, NaHS ameliorated the ferroptosis via increasing the protein expressions of SLC7A11, glutathione peroxidase 4 (GPX4), and cystathionine β-synthase (CBS), reducing the pro-inflammatory cytokines, decreasing the levels of Fe, MDA, ROS, and lipid ROS. In conclusion, our results suggested that NaHS did alleviate anxiety-like and depressive-like behaviors. It can inhibit inflammation via modulating Sirt6 and was able to decrease the ferroptosis in the PFC of type 1 diabetic mice and the BV2 cells.
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http://dx.doi.org/10.1016/j.lfs.2021.119551DOI Listing
May 2021

Adhesion behaviors on four special wettable surfaces: natural sources, mechanisms, fabrications and applications.

Soft Matter 2021 May 4. Epub 2021 May 4.

State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, People's Republic of China.

The study of adhesion behaviors on solid-liquid surfaces plays an important role in scientific research and development in various fields, such as medicine, biology and agriculture. The contact angle and sliding angle of the liquid on the solid surface are commonly used to characterize and measure the wettability of a particular surface. They have a wide range of values, which results in different wettability. It boils down to the adhesion of solid surfaces to liquids. This feature article is aimed at revealing the essence of the adhesion behavior from the aspects of controlling the chemical composition or changing the geometrical microstructure of the surface, and reviewing the natural sources, wetting models, preparation methods and applications of four kinds of typical solid-liquid surfaces (low-adhesion superhydrophobic surfaces, high-adhesion superhydrophobic surfaces, slippery liquid-infused porous surfaces (SLIPS) and hydrophilic/superhydrophilic surfaces). Last, a summary and outlook on this field are given to point out the current challenges and the potential research directions of surface adhesion in the coming future.
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http://dx.doi.org/10.1039/d1sm00248aDOI Listing
May 2021

COVID-19 and Alzheimer's disease: how one crisis worsens the other.

Transl Neurodegener 2021 04 30;10(1):15. Epub 2021 Apr 30.

Center for Translational Neurodegeneration and Regenerative Therapy, Tenth People's Hospital of Tongji University, Shanghai, 200072, China.

Alzheimer's disease (AD) has emerged as a key comorbidity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The morbidity and mortality of COVID-19 are elevated in AD due to multiple pathological changes in AD patients such as the excessive expression of viral receptor angiotensin converting enzyme 2 and pro-inflammatory molecules, various AD complications including diabetes, lifestyle alterations in AD, and drug-drug interactions. Meanwhile, COVID-19 has also been reported to cause various neurologic symptoms including cognitive impairment that may ultimately result in AD, probably through the invasion of SARS-CoV-2 into the central nervous system, COVID-19-induced inflammation, long-term hospitalization and delirium, and post-COVID-19 syndrome. In addition, the COVID-19 crisis also worsens behavioral symptoms in uninfected AD patients and poses new challenges for AD prevention. In this review, we first introduce the symptoms and pathogenesis of COVID-19 and AD. Next, we provide a comprehensive discussion on the aggravating effects of AD on COVID-19 and the underlying mechanisms from molecular to social levels. We also highlight the influence of COVID-19 on cognitive function, and propose possible routes of viral invasion into the brain and potential mechanisms underlying the COVID-19-induced cognitive impairment. Last, we summarize the negative impacts of COVID-19 pandemic on uninfected AD patients and dementia prevention.
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http://dx.doi.org/10.1186/s40035-021-00237-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090526PMC
April 2021

Melanocortin 4 receptor signals at the neuronal primary cilium to control food intake and body weight.

J Clin Invest 2021 May;131(9)

Department of Medicine and The Diabetes Center and.

The melanocortin 4 receptor (MC4R) plays a critical role in the long-term regulation of energy homeostasis, and mutations in the MC4R are the most common cause of monogenic obesity. However, the precise molecular and cellular mechanisms underlying the maintenance of energy balance within MC4R-expressing neurons are unknown. We recently reported that the MC4R localizes to the primary cilium, a cellular organelle that allows for partitioning of incoming cellular signals, raising the question of whether the MC4R functions in this organelle. Here, using mouse genetic approaches, we found that cilia were required specifically on MC4R-expressing neurons for the control of energy homeostasis. Moreover, these cilia were critical for pharmacological activators of the MC4R to exert an anorexigenic effect. The MC4R is expressed in multiple brain regions. Using targeted deletion of primary cilia, we found that cilia in the paraventricular nucleus of the hypothalamus (PVN) were essential to restrict food intake. MC4R activation increased adenylyl cyclase (AC) activity. As with the removal of cilia, inhibition of AC activity in the cilia of MC4R-expressing neurons of the PVN caused hyperphagia and obesity. Thus, the MC4R signaled via PVN neuron cilia to control food intake and body weight. We propose that defects in ciliary localization of the MC4R cause obesity in human inherited obesity syndromes and ciliopathies.
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http://dx.doi.org/10.1172/JCI142064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087202PMC
May 2021

Heterozygous Recurrent Mutations Inducing Dysfunction of Gene in Patients With Short Stature.

Front Cell Dev Biol 2021 14;9:661747. Epub 2021 Apr 14.

Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Purpose: ROR2, a member of the ROR family, is essential for skeletal development as a receptor of Wnt5a. The present study aims to investigate the mutational spectrum of in children with short stature and to identify the underlying molecular mechanisms.

Methods: We retrospectively analyzed clinical phenotype and whole-exome sequencing (WES) data of 426 patients with short stature through mutation screening of . We subsequently examined the changes in protein expression and subcellular location in caused by the mutations. The mRNA expression of downstream signaling molecules of the Wnt5a-ROR2 pathway was also examined.

Results: We identified 12 mutations in in 21 patients, including 10 missense, one nonsense, and one frameshift. Among all missense variants, four recurrent missense variants [c.1675G > A(p.Gly559Ser), c.2212C > T(p.Arg738Cys), c.1930G > A(p.Asp644Asn), c.2117G > A(p.Arg706Gln)] were analyzed by experiments . The c.1675G > A mutation significantly altered the expression and the cellular localization of the ROR2 protein. The c.1675G > A mutation also caused a significantly decreased expression of c-Jun. In contrast, other missense variants did not confer any disruptive effect on the biological functions of ROR2.

Conclusion: We expanded the mutational spectrum of in patients with short stature. Functional experiments potentially revealed a novel molecular mechanism that the c.1675G > A mutation in might affect the expression of downstream Wnt5a-ROR2 pathway gene by disturbing the subcellular localization and expression of the protein.
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http://dx.doi.org/10.3389/fcell.2021.661747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080376PMC
April 2021

ΜicroRNA-122 protects against ischemic stroke by targeting Maf1.

Exp Ther Med 2021 Jun 14;21(6):616. Epub 2021 Apr 14.

Medical College, Institute of Microanalysis, Dalian University, Dalian, Liaoning 116622, P.R. China.

The protection of brain tissue against damage and the reduction of infarct size is crucial for improving patient prognosis following ischemic stroke. Therefore, the present study aimed to investigate the regulatory effect of microRNA (miR)-122 and its target gene repressor of RNA polymerase III transcription MAF1 homolog (Maf1) on the infarct area in ischemic stroke. Reverse transcription-quantitative PCR (RT-qPCR) was performed to determine miR-122 expression levels in an ischemic stroke [middle cerebral artery occlusion (MCAO)] mouse model. Nissl staining was conducted to measure the infarct area of the MCAO mouse model. Moreover, RT-qPCR was performed to investigate the relationship between the expression of Maf1 and miR-122 in the MCAO mouse model. Dual-luciferase reporter assay and miR-122 mimic or inhibitor treatment were conducted to verify that miR-122 targeted and inhibited Maf1 expression. The results suggested that miR-122 was upregulated in the brain tissue of MCAO model mice. miR-122 overexpression effectively reduced the size of the infarct area in comparison with a control and miR-122 knockdown in brain tissue resulted in the opposite effect. Moreover, Maf1 was confirmed to be a direct target of miR-122. The results of a dual-luciferase reporter assay indicated that miR-122 bound to the 3'-untranslated region of Maf1. Maf1 expression decreased after stroke model induction in comparison with that in sham animals, and Maf1 expression was negatively associated with the expression of miR-122. In addition, miR-122 knockdown increased Maf1 expression levels, whereas miR-122 overexpression decreased Maf1 expression levels in comparison with a control. In conclusion, the results suggested that miR-122 improved the outcome of acute ischemic stroke by reducing the expression of Maf1.
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http://dx.doi.org/10.3892/etm.2021.10048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082594PMC
June 2021

HIV Pre-Exposure Prophylaxis, Condoms, or Both? Insights on Risk Compensation Through a Discrete Choice Experiment and Latent Class Analysis Among Men Who Have Sex With Men.

Value Health 2021 May 22;24(5):714-723. Epub 2021 Mar 22.

National Centre for Infectious Diseases, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Objectives: We considered how decision making around human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) among gay, bisexual, and other men who have sex with men (GBMSM) is made in the context of one's perceived risk of HIV acquisition and the availability of condoms.

Methods: We recruited 648 GBMSM aged 18 years old and residing in Singapore through Grindr. Participants were given information on PrEP and participated in a discrete choice experiment requiring them to choose between 2 baskets of PrEP attributes and compare the chosen "PrEP only" option to default options of "condoms only" or "PrEP with condoms." Generalized multinomial logit model was used to examine the scaling effect and preference heterogeneity. Latent class analysis was conducted to examine preference heterogeneity in the sample.

Results: Latent class analysis revealed 3 classes of GBMSM: PrEP conservatives (53.9%), moderates (31.1%), and liberals (14.9%). PrEP conservatives were more likely to report greater utility when using condoms only compared with PrEP only, as well as PrEP with condoms, compared with PrEP only, and more likely to report the lowest utility for PrEP as perceived HIV risk increased. PrEP liberals were more likely to report greatest utilities for PrEP only compared with condoms only, as well as PrEP only compared with PrEP with condoms. The utility for PrEP was not affected by perceived risk of HIV or sexually transmitted infections when risks were low.

Conclusion: This study provides some evidence for risk compensation among a class of GBMSM who already perceived themselves to be good candidates for PrEP before the discrete choice experiment.
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http://dx.doi.org/10.1016/j.jval.2020.11.023DOI Listing
May 2021

Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient.

Breast Cancer Res 2021 May 1;23(1):53. Epub 2021 May 1.

State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.

We identified a rare missense germline mutation in BARD1 (c.403G>A or p.Asp135Asn) as pathogenic using integrated genomics and transcriptomics profiling of germline and tumor samples from an early-onset triple-negative breast cancer patient who later was administrated with a PARP inhibitor for 2 months. We demonstrated in cell and mouse models that, compared to the wild-type, (1) c.403G>A mutant cell lines were more sensitive to irradiation, a DNA damage agent, and a PARP inhibitor; (2) c.403G>A mutation inhibited interaction between BARD1 and RAD51 (but not BRCA1); and (3) c.403G>A mutant mice were hypersensitive to ionizing radiation. Our study shed lights on the clinical interpretation of rare germline mutations of BARD1.
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http://dx.doi.org/10.1186/s13058-021-01428-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088670PMC
May 2021

Basic leucine zipper (bZIP) transcription factor genes and their responses to drought stress in ginseng, Panax ginseng C.A. Meyer.

BMC Genomics 2021 May 1;22(1):316. Epub 2021 May 1.

College of Life Science, Jilin Agricultural University, 2888 Xincheng Street, 130118, Changchun, Jilin, China.

Background: Ginseng is an important medicinal herb in Asia and Northern America. The basic leucine zipper (bZIP) transcription factor genes play important roles in many biological processes and plant responses to abiotic and biotic stresses, such as drought stress. Nevertheless, the genes remain unknown in ginseng.

Results: Here, we report 91 bZIP genes identified from ginseng, designated PgbZIP genes. These PgbZIP genes were alternatively spliced into 273 transcripts. Phylogenetic analysis grouped the PgbZIP genes into ten groups, including A, B, C, D, E, F, G, H, I and S. Gene Ontology (GO) categorized the PgbZIP genes into five functional subcategories, suggesting that they have diversified in functionality, even though their putative proteins share a number of conserved motifs. These 273 PgbZIP transcripts expressed differentially across 14 tissues, the roots of different ages and the roots of different genotypes. However, the transcripts of the genes expressed coordinately and were more likely to form a co-expression network. Furthermore, we studied the responses of the PgbZIP genes to drought stress in ginseng using a random selection of five PgbZIP genes, including PgbZIP25, PgbZIP38, PgbZIP39, PgbZIP53 and PgbZIP54. The results showed that all five PgbZIP genes responded to drought stress in ginseng, indicating that the PgbZIP genes play important roles in ginseng responses to drought stress.

Conclusions: These results provide knowledge and gene resources for deeper functional analysis of the PgbZIP genes and molecular tools for enhanced drought tolerance breeding in ginseng.
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http://dx.doi.org/10.1186/s12864-021-07624-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088647PMC
May 2021

Membrane separation processes for enrichment of bovine and caprine milk oligosaccharides from dairy byproducts.

Authors:
Yi Wang Jinghua Yu

Compr Rev Food Sci Food Saf 2021 May 1. Epub 2021 May 1.

State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology, Tianjin, China.

Breast milk is an ideal source of human milk oligosaccharides (HMOs) for isolation and purification. However, breast milk is not for sale and at most is distributed to neonatal intensive care units as donor milk. To overcome this limitation, isolating HMOs analogs including bovine milk oligosaccharides (BMOs) and caprine milk oligosaccharides (CMOs) from other sources is timely and significant. Advances in the development of equipment and analytical methods have revealed that dairy processing byproducts are good sources of BMOs and CMOs. Enrichment of these oligosaccharides from dairy byproducts, such as whey, permeate, and mother liquor, is of increasing academic and economic value. The commonly employed approach for oligosaccharides purification is chromatographic technique, but it is only used at lab scale. In the dairy industry, chromatographic methods (large-scale ion exchange, 10,000 L size) are currently routinely used for the isolation/purification of milk proteins (e.g., lactoferrin). In contrast, membrane technology has been proven to be a suitable approach for the isolation and purification of BMOs and CMOs from dairy byproducts. Therefore, this review simply introduces BMOs and CMOs in dairy processing byproducts. This review also summarizes membrane separation processes for isolating and purifying BMOs and CMOs from different dairy byproducts. Finally, the technological challenges and solutions of each processing strategy are discussed in detail.
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http://dx.doi.org/10.1111/1541-4337.12758DOI Listing
May 2021

Cholinergic Signaling, Neural Excitability, and Epilepsy.

Molecules 2021 Apr 13;26(8). Epub 2021 Apr 13.

Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.

Epilepsy is a common brain disorder characterized by recurrent epileptic seizures with neuronal hyperexcitability. Apart from the classical imbalance between excitatory glutamatergic transmission and inhibitory γ-aminobutyric acidergic transmission, cumulative evidence suggest that cholinergic signaling is crucially involved in the modulation of neural excitability and epilepsy. In this review, we briefly describe the distribution of cholinergic neurons, muscarinic, and nicotinic receptors in the central nervous system and their relationship with neural excitability. Then, we summarize the findings from experimental and clinical research on the role of cholinergic signaling in epilepsy. Furthermore, we provide some perspectives on future investigation to reveal the precise role of the cholinergic system in epilepsy.
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http://dx.doi.org/10.3390/molecules26082258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070422PMC
April 2021

Transcriptome-Wide Analysis for Ginsenoside Rb3 Synthesis-Related Genes and Study on the Expression of Methyl Jasmonate Treatment in .

Life (Basel) 2021 Apr 25;11(5). Epub 2021 Apr 25.

College of Life Science, Jilin Agricultural University, Changchun 130118, China.

C. A. Meyer is a kind of renascent herb that belongs to the genus in the family . It is a traditional Chinese precious herbal medicine with a long history of medicinal use. Ginsenoside Rb3 is one of the important active ingredients in ginseng and has important physiological activity in the treatment of many diseases. In this study, we screened and systematically analyzed the candidate genes related to ginsenoside Rb3 synthesis through bioinformatics methods; discussed the functions, expression patterns, and interactions of the genes related to ginsenoside Rb3 synthesis; and finally, selected seven genes, mainly that directly contribute to the synthesis of ginsenoside Rb3. This study provides a reference for revealing the expression rules of ginsenoside Rb3 synthesis-related genes and elucidating the regulatory mechanism of methyl jasmonate, lays a theoretical foundation for the research of ginsenoside Rb3 synthesis, and provides theoretical and technical support for the factory production of ginsenoside monomer saponins.
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http://dx.doi.org/10.3390/life11050387DOI Listing
April 2021

Exosomal microRNAs: Pleiotropic Impacts on Breast Cancer Metastasis and Their Clinical Perspectives.

Biology (Basel) 2021 Apr 7;10(4). Epub 2021 Apr 7.

Department of Pathophysiology, Basic Medical College, Nanchang University, Nanchang 330006, China.

As a major threat factor for female health, breast cancer (BC) has garnered a lot of attention for its malignancy and diverse molecules participating in its carcinogenesis process. Among these complex carcinogenesis processes, cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis are the major causes for the occurrence of metastasis and chemoresistance which account for cancer malignancy. MicroRNAs packaged and secreted in exosomes are termed "exosomal microRNAs (miRNAs)". Nowadays, more researches have uncovered the roles of exosomal miRNAs played in BC metastasis. In this review, we recapitulated the dual actions of exosomal miRNAs exerted in the aggressiveness of BC by influencing migration, invasion, and distant metastasis. Next, we presented how exosomal miRNAs modify angiogenesis and stemness maintenance. Clinically, several exosomal miRNAs can govern the transformation between drug sensitivity and chemoresistance. Since the balance of the number and type of exosomal miRNAs is disturbed in pathological conditions, they are able to serve as instructive biomarkers for BC diagnosis and prognosis. More efforts are needed to connect the theoretical studies and clinical traits together. This review provides an outline of the pleiotropic impacts of exosomal miRNAs on BC metastasis and their clinical implications, paving the way for future personalized drugs.
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http://dx.doi.org/10.3390/biology10040307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067993PMC
April 2021

Circulating fatty acids and risk of gestational diabetes mellitus: prospective analyses in China.

Eur J Endocrinol 2021 Apr 1. Epub 2021 Apr 1.

J Wu, The George Institute for Global Health, University of New South Wales, Sydney, Australia.

Objective We aimed to examine prospective associations between circulating fatty acids in early pregnancy and incident gestational diabetes mellitus (GDM) among Chinese pregnant women. Methods Analyses were based on two prospective nested case-control studies conducted in western China (336 GDM cases and 672 matched controls) and central China (305 cases and 305 matched controls). Fasting plasma fatty acids in early pregnancy (gestational age at enrollment: 10.4 weeks [standard deviation, 2.0]) and 13.2 weeks [1.0], respectively) were determined by gas chromatography-mass spectrometry, and GDM was diagnosed based on the International Association of Diabetes in Pregnancy Study Groups criteria during 24-28 weeks of gestation. Multiple metabolic biomarkers (HOMA-IR [homeostatic model assessment for insulin resistance], HbA1c, c-peptide, high-sensitivity C-reactive protein, adiponectin, leptin, and blood lipids) were additionally measured among 672 non-GDM controls at enrollment. Results Higher levels of saturated fatty acids (SFAs) 14:0 (pooled odds ratio, 1.41 for each 1-standard deviation increase; 95% confidence interval, 1.25, 1.59) and 16:0 (1.19; 1.05, 1.35) were associated with higher odds of GDM. Higher levels of n-6 polyunsaturated fatty acid (PUFA) 18:2n-6 was strongly associated with lower odds of GDM (0.69; 0.60, 0.80). In non-GDM pregnant women, higher SFAs 14:0 and 16:0 but lower n-6 PUFA 18:2n-6 were generally correlated with unfavorable metabolic profiles. Conclusions We documented adverse associations of 14:0 and 16:0 but a protective association of 18:2n-6 with GDM among Chinese pregnant women. Our findings highlight the distinct roles of specific fatty acids in the onset of GDM.
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http://dx.doi.org/10.1530/EJE-21-0118DOI Listing
April 2021

Clinical outcomes, quality of life, and costs evaluation of peritoneal dialysis management models in Shanghai Songjiang District: a multi-center and prospective cohort study.

Ren Fail 2021 Dec;43(1):754-765

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

The new Family-Community-Hospital (FCH) three-level comprehensive management aimed to improve the efficiency and scale of peritoneal dialysis (PD) to meet the increased population of end-stage renal disease (ESRD). Our study focused on the clinical outcomes, quality of life, and costs evaluation of this model in a multi-center and prospective cohort study. A total of 190 ESRD patients who commenced PD at Shanghai Songjiang District were enrolled. According to different PD management models, patients were divided into the Family-Community-Hospital three-level management model ( = 90) and the conventional all-course central hospital management model ( = 100). The primary outcome was clinical outcomes of PD. The secondary outcomes were health-related quality of life (HRQOL) and medical costs evaluation. Compared to conventional management, community-based FCH management achieved a similar dialysis therapeutic effect, including dropout rate ( = 0.366), peritonitis rate ( = 0.965), patient survival ( = 0.441), and technique survival ( = 0.589). Follow-up data showed that similar levels of the renal and peritoneal functions, serum albumin, cholesterol and triglyceride, PTH, serum calcium, and phosphorus between the two groups (all  > 0.05). HRQOL survey showed that the FCH management model helped to improve the psychological status of PD patients, including social functioning ( = 0.006), role-emotional ( = 0.032), and mental health ( = 0.036). FCH management also reduced the hospitalization ( = 0.009) and outpatient visits ( = 0.001) and saved annual hospitalization costs ( = 0.005), outpatient costs ( = 0.026), and transport costs ( = 0.006). Compared with conventional management, community-based FCH management achieved similar outcomes, improved psychological health, reduced medical budgets, and thus had a good social prospect.
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http://dx.doi.org/10.1080/0886022X.2021.1918164DOI Listing
December 2021

Associations between air pollution indicators and prevalent and incident diabetes in an African American cohort, the Jackson Heart Study.

Environ Epidemiol 2021 Jun 22;5(3):e140. Epub 2021 Apr 22.

Department of Environmental Health, Indianapolis, Fairbanks School of Public Health, Indiana University, Indiana.

Background: Diabetes is especially prevalent among African Americans. Prior studies suggest that long-term exposure to ambient air pollution may be associated with greater incidence of diabetes, but results remain heterogeneous. Few studies have included large numbers of African Americans.

Methods: We assessed diabetes status and concentrations of 1- and 3-year fine particulate matter (PM) and ozone (O) among African American participants of the Jackson Heart Study at visits 1 (2000-2004, N = 5128) and 2 (2005-2008, N = 2839). We used mixed-effect modified Poisson regression to estimate risk ratios (RRs) and 95% confidence intervals (CIs) of incidence of diabetes by visit 2 and prevalence ratios (PRs) of the association between air pollution exposure and prevalent diabetes at visits 1 and 2. We adjusted for potential confounding by patient characteristics, as well as inverse probability weights of diabetes at visit 2, accounting for clustering by census tract.

Results: We observed associations between incident diabetes and interquartile range increase in 1-year O (RR 1.34, 95% CI = 1.11, 1.61) and 3-year O (RR 0.88, 95% CI = 0.76, 1.02). We observed associations between prevalent diabetes and 1-year PM (PR 1.08, 95% CI = 1.00, 1.17), 1-year O (PR 1.18, 95% CI = 1.10, 1.27), and 3-year O (PR 0.95, 95% CI = 0.90, 1.01) at visit 2.

Conclusions: Our results provide some evidence of positive associations between indicators of long-term PM and O exposure and diabetes. This study is particularly relevant to African Americans, who have higher prevalence of diabetes but relatively few studies of environmental pollution risk factors.
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http://dx.doi.org/10.1097/EE9.0000000000000140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078431PMC
June 2021