Publications by authors named "Yan Han"

850 Publications

Knockout of AMPKα2 Blocked the Protection of Sestrin2 Overexpression Against Cardiac Hypertrophy Induced by Pressure Overload.

Front Pharmacol 2021 17;12:716884. Epub 2021 Nov 17.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Sestrin2 (Sesn2) has been demonstrated to be a cysteine sulfinyl reductase and protects cells from multiple stress insults, including hypoxia, endoplasmic reticulum stress, and oxidative stress. However, the roles and mechanisms of Sesn2 in pressure overload-induced mouse cardiac hypertrophy have not been clearly clarified. This study intended to investigate whether sestrin2 (Sesn2) overexpression could prevent pressure overload-induced cardiac hypertrophy via an AMPKα2 dependent pathway through conditional knockout of AMPKα2. Sesn2 expression was significantly increased in mice hearts at 2 and 4 weeks after aortic banding (AB) surgery, but decreased to 60-70% of the baseline at 8 weeks. Sesn2 overexpression (at 3, 6, and 9 folds) showed little cardiac genetic toxicity in transgenic mice. Cardiac dysfunctions induced by pressure overload were attenuated by cardiomyocyte-specific Sesn2 overexpression when measured by echocardiography and hemodynamic analysis. Results of HE and PSR staining showed that Sesn2 overexpression significantly alleviated cardiac hypertrophy and fibrosis in mice hearts induced by pressure overload. Meanwhile, adenovirus-mediated-Sesn2 overexpression markedly suppressed angiotensin II-induced neonatal rat cardiomyocyte hypertrophy . Mechanistically, Sesn2 overexpression increased AMPKα2 phosphorylation but inhibited mTORC1 phosphorylation. The cardiac protections of Sesn2 overexpression were also regulating oxidative stress by enhancing Nrf2/HO-1 signaling, restoring SOD activity, and suppressing NADPH activity. Particularly, we first proved the vital role of AMPKα2 in the regulation of Sesn2 with AMPKα2 knockout (AMPKα2-/-) mice and Sesn2 transgenic mice crossed with AMPKα2-/-, since Sesn2 overexpression failed to improve cardiac function, inhibit cardiac hypertrophy and fibrosis, and attenuate oxidative stress after AMPKα2 knockout. This study uniquely revealed that Sesn2 overexpression showed little genetic toxicity in mice hearts and inhibited mTORC1 activation and oxidative stress to protect against pressure overload-induced cardiac hypertrophy in an AMPKα2 dependent pathway. Thus, interventions through promoting Sesn2 expression might be a potential strategy for treating pathological cardiac hypertrophy and heart failure.
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http://dx.doi.org/10.3389/fphar.2021.716884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635785PMC
November 2021

Split free temporal fascia flap for reconstruction of dorsal foot and toe web injury with deep tissue exposure.

Asian J Surg 2021 Nov 23. Epub 2021 Nov 23.

Department of Plastic and Reconstructive Surgery, Xijing Hospital of Forth Military Medical University, 710032, 127 West Changle Road, Xi 'an, Shanxi, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.10.003DOI Listing
November 2021

AMH was independently associated with central obesity but not with general obesity in women with PCOS.

Endocr Connect 2021 Nov 1. Epub 2021 Nov 1.

C Liu, Fujian Medical University, Fuzhou, China.

Objective: Anti-Müllerian hormone (AMH) is recognized as the most important biomarker for ovarian reserve. In this cross-sectional study, we aimed to explore the potential association of AMH with central obesity or general obesity in women with polycystic ovary syndrome (PCOS).

Methods: In this cross-sectional study, 179 patients with PCOS were enrolled and underwent anthropometric measurements (BMI and waist circumference (WC)) and serum AMH level detection. Pearson's correlation and multivariable logistic regression analyses were performed to determine associations of AMH with central obesity and general obesity.

Results: Subjects with the increasing of body mass index (BMI) showed significantly lower values of AMH (median (IQR) 8.95 (6.03-13.60) ng/mL in normal weight group, 6.57 (4.18-8.77) ng/mL in overweight group, and 6.03 (4.34-9.44) ng/mL in obesity group, respectively, p=0.001), but higher levels of systolic blood pressure, fasting insulin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and obesity indices (WC, hip circumferences, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and Chinese visceral adiposity index (CVAI)) respectively. Compared with the group of PCOS women without central obesity, the group with central obesity had significantly lower value of AMH (median (IQR) 8.56(5.29-12.96) vs. 6.22(4.33-8.82) ng/mL; p=0.003). Pearson's correlation analysis showed that AMH were significantly and negatively correlated with BMI (r=-0.280; p<0.001), WC (r=-0.263; p<0.001), WHtR (r=-0.273; p<0.001), and CVAI (r=-0.211; p=0.006) respectively. Multivariate logistic regression analysis with adjustment for potential confounding factors showed that AMH was independently and negatively associated with central obesity, but was not significantly associated with general obesity.

Conclusions: AMH was independently and negatively associated with central obesity. Closely monitoring WC and AMH should be addressed in terms of assessing ovarian reserve in women with PCOS.
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http://dx.doi.org/10.1530/EC-21-0243DOI Listing
November 2021

An active role of reconstructive surgeon in otologic tumor surgery.

Ear Nose Throat J 2021 Nov 24:1455613211060713. Epub 2021 Nov 24.

Department of Plastic and Reconstructive Surgery, Fisrt Medical Center of Chinese PLA General Hospital, Beijing, China.

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http://dx.doi.org/10.1177/01455613211060713DOI Listing
November 2021

Prenatal serum thallium exposure and cognitive development among preschool-aged children: A prospective cohort study in China.

Environ Pollut 2021 Nov 18;293:118545. Epub 2021 Nov 18.

Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China; MOE Key Laboratory of Population Health Across Life Cycle, Hefei, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei, Anhui, China. Electronic address:

Thallium, a highly toxic heavy metal and priority pollutant, has been widely reported to cause neurodevelopmental toxicity in animals. However, accessible epidemiological studies concerning the neurodevelopmental toxicity of early-life thallium exposure in humans are limited. In a prospective birth cohort including 2164 mother-child pairs, we explored the effect of prenatal serum thallium exposure on cognitive development among preschool-aged children born in Ma'anshan, Anhui, China. Serum thallium concentrations were measured in the first trimester, second trimester, third trimester, and cord blood by inductively coupled plasma mass spectrometry (ICP-MS). Child cognitive development was appraised by the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) at 4.5 years old. Multiple informants generalized estimating equations (GEEs) were fit to jointly estimate the association between the four repeated measurements of thallium concentrations and the preschool-aged children's cognitive test scores. After adjusting for potential confounders, the visual spatial index (VSI) was 1.45 points lower in the highest tertile of serum thallium during the first trimester than in the lowest tertile (p for trend = 0.04). Moreover, children in the highest tertile of serum thallium during the third trimester had a significantly lower full-scale intelligence quotient (FSIQ) (β = -1.51, 95% CI: -2.68, -0.35), VSI (β = -1.79, 95% CI: -3.16, -0.42), fluid reasoning index (FRI) (β = -1.41, 95% CI: -2.73, -0.10), and processing speed index (PSI) (β = -1.47, 95% CI: -2.71, -0.24) scores than the children in the lowest tertile. When performing stratified analysis by child sex, the associations of first- and third-trimester thallium concentrations with cognitive test scores were more prominent in boys than in girls. Our findings revealed that maternal serum thallium exposure during the first and third trimesters, but not other periods, had detrimental effects on preschoolers' cognitive development, and these effects showed sex differences.
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http://dx.doi.org/10.1016/j.envpol.2021.118545DOI Listing
November 2021

Silencing FYVE, RhoGEF and PH domain containing 1 (FGD1) suppresses melanoma progression by inhibiting PI3K/AKT signaling pathway.

Bioengineered 2021 Nov 16. Epub 2021 Nov 16.

Department of Plastic and Reconstructive Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853 China.

Cutaneous melanoma is the leading cause of death among skin cancers despite the availability of diverse treatments. FGD1 plays an important role in multiple cancers, but how it works in cutaneous melanoma has not been illustrated. Thus, this study was intended to investigate the roles of FGD1 and its underlying mechanisms in cutaneous melanoma. Bioinformatics tools and quantitative real-time polymerase chain reaction (qRT-PCR) were used to analyze the expression of FGD1 in cutaneous melanoma. After knockdown of FGD1 in melanoma cells, the proliferation, migration and invasion of cells were analyzed by cell counting kit-8 (CCK8) assay, colony formation assay and transwell assays. Western blot was used to check the expression of key factors in PI3K/AKT pathway. In addition, nude mice models were used to study the role of FGD1 in melanoma development and metastasis in vivo. The data demonstrated that FGD1 was up-regulated and predicted a poor clinical outcome for cutaneous melanoma patients. Knockdown of FGD1 inhibited melanoma cell proliferation, migration and invasion. The expressions of p-PI3K and p-AKT were significantly decreased while the expressions of PI3K and AKT showed no marked difference in the knockdown group. Meanwhile, knockdown of FGD1 suppressed the development of melanoma in vivo. This study suggested that knockdown of FGD1 could block melanoma formation and proliferation by inhibiting PI3K/AKT signaling pathway. FGD1 might be a promising threptic target for melanoma.
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http://dx.doi.org/10.1080/21655979.2021.2005877DOI Listing
November 2021

Pollution characteristics, spatial distribution, and source identification of heavy metals in road dust in a central eastern city in China: a comprehensive survey.

Environ Monit Assess 2021 Nov 12;193(12):796. Epub 2021 Nov 12.

Key Laboratory for Synergistic Prevention of Water and Soil Environmental Pollution (Henan Province), School of Geographic Sciences, Xinyang Normal University, Henan, 464000, China.

Road dust enriched with heavy metals (HMs) is detrimental to ecosystems and human health in urban environments. In this study, it is to explore the concentrations, spatial distribution, contaminated levels, and source identification of six HMs (lead (Pb), zinc (Zn), copper (Cu), cobalt (Co), chromium (Cr), and nickel (Ni)) based on 130 road dusts in Xinyang urban area. The results indicated that the contents of Pb, Zn, Cu, and Co were higher than the background values in more than 99% of the samples, and their average concentrations were 15.2, 9.2, 8.6, and 6.3 times the background value, respectively. The spatial distribution of high-value areas for Pb, Zn, Cu, Cr, and Ni was more similar, which was associated with traffic density near major roads and population and settlement patterns. Co was relatively different from the five elements, which was distributed in the areas of residence, commerce, and industry. Furthermore, the investigated HMs were clearly polluted, with Pb, Zn, Cu, and Co indicating high levels of contamination, while Cr and Ni were moderately polluted. The comprehensive pollution of the six HMs was mostly moderate to heavy in this study. Moreover, three sources of HMs designated by correlation analysis (CA) and principal component analysis (PCA) were mixed traffic emissions and industrial waste for Cu and Cr; automotive emissions for Pb, Ni, and Zn; and mixed domestic waste and industrial activities for Co, with contributions of 42.3%, 46.4%, and 11.3% via the principal component analysis-multiple linear regression (PCA-MLR) model. The multi-factor index for pollution assessment combined with source identification is extremely effective and practical for providing reliable data support and a theoretical reference for pollution monitoring and governance.
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http://dx.doi.org/10.1007/s10661-021-09584-zDOI Listing
November 2021

Quantifying the relationship between dapagliflozin and loss of weight in type 1 diabetes mellitus patients.

J Clin Pharm Ther 2021 Nov 9. Epub 2021 Nov 9.

Department of Pharmacy, Huaian Hospital of Huaian City, Huaian, Jiangsu, China.

What Is Known And Objectives: Dapagliflozin was the first oral treatment approved in type 1 diabetes mellitus (T1DM) patients, simultaneously improving body weight. However, the time course and dose effect of dapagliflozin on loss of weight in T1DM patients was still unknown. The present study aimed to investigate quantitative relationship between dapagliflozin and loss of weight in T1DM patients based on Model-based Meta-analysis.

Methods: Five dapagliflozin dosage groups, two of them were 5 mg/day and three of them were 10 mg/day, 1612 T1DM patients were analysed with maximal effect (E ) model, and evaluation index was change rate of body weight from baseline value.

Results: In these T1DM patients, dosages were not incorporated into model, indicating no significant dose-response relationship between 5 and 10 mg/day affecting loss of weight. E and the treatment duration to reach half of the maximal effects (ET ) of dapagliflozin influencing loss of weight in T1DM patients were -4.9% and 10.4 weeks, and the duration to achieve 25%, 50%, 75%, and 80% (plateau) of E were 3.5, 10.4, 31.2, and 41.6 weeks.

What Is New And Conclusions: It was the first time to explore quantitative relationship between dapagliflozin and loss of weight in T1DM patients. To achieve the plateau period in loss of weight, 5 mg/day dapagliflozin was required for at least 41.6 weeks.
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http://dx.doi.org/10.1111/jcpt.13572DOI Listing
November 2021

First Report of Sea buckthorn Stem Wilt Caused by Fusarium proliferatum in Liaoning, China.

Plant Dis 2021 Nov 9. Epub 2021 Nov 9.

Shenyang Agricultural University, 98428, College of Plant Protection, Shenyang, China;

Sea buckthorn(Hippophae rhamnoides L.) is a flowering shrub native to cold-temperate regions of Eurasia, which is also valuable for its berries and leaves containing various vitamins and flavonoids (Pundir et al. 2021). In late June 2020, high mortality (more than 70%) was observed in sea buckthorn in a 1.6-ha seedling nursery in Chaoyang City, Liaoning province, China, where 16 Chinese and Russian cultivars (cv.) had been planted since 2014 (cv. Shenqiuhong, eshi01 through eshi15). The mortality of two introduced sea buckthorn varieties (eshi02, eshi04) was 100% (125 trees died in total). The symptoms include massive drooping leaves and dried-up stems on 6-year-old infected trees. Pieces of tree roots and stems with brown discoloration in the xylem vessels were selected. Small tissue fragments (0.2-0.5 cm) were surface disinfested (3 min in 75% ethanol, rinsed with sterile distilled water), air-dried, and placed on potato dextrose agar (PDA) medium for 5 days at 25°C in the dark. A fungus was consistently isolated from both diseased roots and stems tissues, and a representative isolate (LC-1) was harvested. Genomic DNA was extracted for amplification and sequencing of the partial translation elongation factor-1α (EF1 and EF2 primers, accession Nos. MZ669853) (O'Donnell et al. 1998) and RNA polymerase II second largest subunit (RPB2) (7cf/11aR primers, accession Nos. MZ669854) (O'Donnell et al. 2007). The sequences were further analyzed at the Fusarium MLST (https://fusarium.mycobank.org/) for identity confirmation, and showed 99.8% (over 95.2% query coverage) and 96.4% (over 88.4% query coverage) similarity to Fusarium proliferatum (NRRL 13584, 13591). Isolates on Spezieller Nahrstoffarmer agar (SNA) produced abundant aerial white mycelia and yellow pigmentation. The 30 macroconidia measured ranged from 28.5 - 62.5 × 3.2 - 5.4 μm, were thin, slender, with 3-5 septa. The aseptate microconidia ranged from 4.7 - 13.6 × 2.2 - 4.3 μm (n = 30). Pathogenicity tests were performed on healthy, potted 1-year-old sea buckthorn seedlings (cv. eshi05) using two isolates in a greenhouse at 25 °C, 80% relative humidity, and 12-hour light/dark photoperiod. Ten potted seedlings were inoculated on the stems by placing a 5-mm-diameter mycelial plug (5-day-old PDA cultures for each isolate) into the surface of a wound created with a needle, and the inoculation sites were covered with Parafilm to maintain moisture. Ten seedlings were inoculated with PDA plugs as controls. Six to ten days after inoculation, color of the leaves in the middle of the stems was variegated, and then dark necrotic lesions on leaf margins were observed. Three weeks after inoculation, 80% of inoculated stems were wilted, while control plants remained asymptomatic. The pathogen was consistently re-isolated and the recovered isolates were identified as F. proliferatum by amplifying the EF-1α gene. The typical symptoms on inoculated plants were dark to brown necrotic lesions on chlorotic leaves initially, and black withered stems in the terminal stage, similar to those observed on sea buckthorn trees infected with Fusarium sporotrichioides in Gansu and Heilongjiang provinces (Song et al. 2010; Xia et al. 2021). To our knowledge, this is the first report of sea buckthorn stem wilt caused by F. proliferatum in Liaoning province, China, which will be beneficial for expanding knowledge of Fusarium disease in sea buckthorn and provide more information for sustainable disease management in sea buckthorn.
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http://dx.doi.org/10.1094/PDIS-09-21-1905-PDNDOI Listing
November 2021

The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation.

Front Pharmacol 2021 20;12:732874. Epub 2021 Oct 20.

Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Cerebral small vessel disease (CSVD) is a group of clinical syndromes covering all pathological processes of small vessels in the brain, which can cause stroke and serious dementia. However, as the pathogenesis of CSVD is not clear, so the treatment is limited. Endothelial cell dysfunction is earlier than clinical symptoms, such as hypertension and leukosis. Therefore, the treatment of endothelial cells is expected to be a new breakthrough. Quercetin, a flavonoid present in a variety of plants, has the function of anti-inflammation and anti-oxidation. This study aimed to investigate the protective effect of quercetin on endothelial cell injury and provide a basic theory for subsequent application in the clinic. Human brain microvascular endothelial cells (HBMECs) were cultured , and the injury model of endothelial cells was established by hypoxia and reoxygenation (H/R). The protective effects of quercetin on HBMECs were studied from the perspectives of cell viability, cell migration, angiogenesis and apoptosis. In order to further study the mechanism of quercetin, oxidative stress and endoplasmic reticulum stress were analyzed. What's more, blood-brain barrier (BBB) integrity was also studied. Quercetin can promote the viability, migration and angiogenesis of HBMECs, and inhibit the apoptosis. In addition, quercetin can also activate Keap1/Nrf2 signaling pathway, reduce ATF6/GRP78 protein expression. Further study showed that quercetin could increase the expression of Claudin-5 and Zonula occludens-1. Our experiments show that quercetin can protect HBMECs from H/R, which contains promoting cell proliferation, cell migration and angiogenesis, reducing mitochondrial membrane potential damage and inhibiting cell apoptosis. This may be related to its antioxidation and inhibition of endoplasmic reticulum stress. At the same time, quercetin can increase the level of BBB connexin, suggesting that quercetin can maintain BBB integrity.
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http://dx.doi.org/10.3389/fphar.2021.732874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564287PMC
October 2021

[Optimization of Extraction Methods and Distribution Characteristics of Antibiotics and Metabolites in Sediments of a River Water-Groundwater Interaction Zone].

Huan Jing Ke Xue 2021 Nov;42(11):5294-5302

School of Environment Studies, China University of Geosciences, Wuhan 430078, China.

The river water-groundwater interaction zone is an important area for the enrichment, degradation, and transformation of pollutants and other biogeochemical processes. The distribution characteristics of antibiotics, as organic pollutants of wide concern, in the interaction zone is essential for understanding the migration and transformation process of pollutants in the environment. Due to the sensitive changes in the redox conditions and special composition of sediments in the interaction zone, this study established an effective pretreatment method for extracting 22 antibiotics and four sulfonamide metabolites in the interaction zone, and optimized the initial state of the samples, extraction temperature, pH value of the extraction solution and organic extraction solvent. The content of antibiotics in the sediments of the river water-groundwater interaction zone and lower reaches of the Hanjiang River was also analyzed. The results show that the best recovery of the target compounds is obtained by using pH 3 acetonitrile/NaEDTA-Mcllvaine buffer(1:1, volume ratio) to digest and extract the unoxidized sediment samples at 40℃ three times using a microwave. A total of 11 antibiotics are detected in the sediments of the interaction zone in the lower reaches of the Hanjiang River, among which oxytetracycline and ofloxacin are the main compounds with the highest concentrations of 6.77 ng·g and 5.81 ng·g, respectively. The vertical distribution of antibiotics in different sediment profiles is significantly different, which may be related to the lithology of sediments, physicochemical properties of antibiotics, and interaction between surface water and groundwater.
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http://dx.doi.org/10.13227/j.hjkx.202102091DOI Listing
November 2021

Nest concealment is associated with reproductive traits across sympatric bird species.

Ecol Evol 2021 Oct 17;11(20):14079-14087. Epub 2021 Sep 17.

Engineering Research Center of Ecology and Agricultural Use of Wetland, Ministry of Education College of Life Sciences, Yangtze University Jingzhou China.

Nest-site characteristics are thought to play an important role in reproductive performance in birds (e.g., influencing reproductive success and predation risk). Nest-site characteristics such as concealment may be particularly critical at high elevation where nests are exposed to challenging environmental conditions. In this study, we conducted both conventional and phylogenetically controlled analyses to investigate whether nest concealment affected several reproductive traits across 21 sympatric bird species living on Tibet Plateau (3,400 m altitude). Qualitatively equivalent results were reached in analyses, regardless of phylogenetic controls. We found that clutch size, incubation period, nestling period, and nest success were strongly and positively associated with nest concealment across species. Our study addressed such a high-elevation bird community that is lacking in the previous studies. This study adds to theory that while there are a few exceptions, overall evidence supports a positive effect of nest concealment on reproductive performance across coexisting alpine species.
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http://dx.doi.org/10.1002/ece3.8117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525109PMC
October 2021

Antiferromagnetism in Ni-Based Superconductors.

Adv Mater 2021 Oct 27:e2106117. Epub 2021 Oct 27.

School of Materials Science and Engineering, Beihang University, Beijing, 100191, China.

Due to the lack of any magnetic order down to 1.7 K in the parent bulk compound NdNiO , the recently discovered 9-15 K superconductivity in the infinite-layer Nd Sr NiO thin films has provided an exciting playground for unearthing new superconductivity mechanisms. Herein, the successful synthesis of a series of superconducting Nd Sr NiO thin films ranging from 8 to 40 nm is reported. The large exchange bias effect is observed between the superconducting Nd Sr NiO films and a thin ferromagnetic layer, which suggests the existence of the antiferromagnetic order. Furthermore, the existence of the antiferromagnetic order is evidenced by X-ray magnetic linear dichroism measurements. These experimental results are fundamentally critical for the current field.
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http://dx.doi.org/10.1002/adma.202106117DOI Listing
October 2021

Structural mechanisms of assembly, permeation, gating, and pharmacology of native human rod CNG channel.

Neuron 2021 Oct 13. Epub 2021 Oct 13.

Howard Hughes Medical Institute and Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address:

Mammalian cyclic nucleotide-gated (CNG) channels are nonselective cation channels activated by cGMP or cAMP and play essential roles in the signal transduction of the visual and olfactory sensory systems. CNGA1, the principal component of the CNG channel from rod photoreceptors, can by itself form a functional homotetrameric channel and has been used as the model system in the majority of rod CNG studies. However, the native rod CNG functions as a heterotetramer consisting of three A1 and one B1 subunits and exhibits different functional properties than the CNGA1 homomer. Here we present the functional analysis of human rod CNGA1/B1 heterotetramer and its cryo-EM structures in apo, cGMP-bound, cAMP-bound, and L-cis-Diltiazem-blocked states. These structures, with resolution ranging from 2.6 to 3.3 Å, elucidate the structural mechanisms underlying the 3:1 subunit stoichiometry, the asymmetrical gating upon cGMP activation, and the unique pharmacological property of the native rod CNG channel.
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http://dx.doi.org/10.1016/j.neuron.2021.10.006DOI Listing
October 2021

Comparing containment measures among nations by epidemiological effects of COVID-19.

Natl Sci Rev 2020 Dec 19;7(12):1847-1851. Epub 2020 Sep 19.

Center for Statistical Science, Peking University, China.

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http://dx.doi.org/10.1093/nsr/nwaa243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543445PMC
December 2020

Antimicrobial Susceptibility of Ertapenem in Isolates Collected Within the China Gonococcal Resistance Surveillance Programme (China-GRSP) 2018.

Infect Drug Resist 2021 12;14:4183-4189. Epub 2021 Oct 12.

STD Reference Laboratory, Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People's Republic of China.

Purpose: This study aimed to determine the minimum inhibitory concentrations (MICs) of ertapenem on collected from eight Chinese provinces in 2018.

Methods: The MICs of ertapenem on 503 isolates (415 isolates selected randomly and 88 isolates selected with preference) were measured using the agar dilution method. For comparison, the MICs of ceftriaxone and azithromycin were detected.

Results: Among 415 randomly selected isolates, the MIC range for ertapenem was from ≤0.008 mg/L to 0.5 mg/L. The corresponding MIC and MIC were 0.06 and 0.125 mg/L, respectively. Twelve of 415 isolates (2.9%) exhibited MIC values ≥0.25 mg/L, and only one isolate (0.2%) had a MIC of 0.5 mg/L. By comparing all 503 tested isolates, a correlation of = 0.487 ( <0.001) between ertapenem and ceftriaxone MIC was observed, and the correlation between MICs of ertapenem and azithromycin was low ( = -0.12, = 0.007). In 24 ceftriaxone-decreased susceptibility isolates, four isolates (16.7%) showed a MIC ≥0.25 mg/L for ertapenem. In 85 azithromycin resistant isolates, three isolates (3.5%) showed a MIC ≥0.25 mg/L for ertapenem.

Conclusion: The in vitro results suggest that ertapenem has satisfactory susceptibility in isolates collected from eight provinces in China; hence, it might be a promising treatment option for resistant gonococcal infections.
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http://dx.doi.org/10.2147/IDR.S335252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520434PMC
October 2021

ALKBH5 Facilitates Hypoxia-Induced Paraspeckle Assembly and IL8 Secretion to Generate an Immunosuppressive Tumor Microenvironment.

Cancer Res 2021 Dec 20;81(23):5876-5888. Epub 2021 Oct 20.

Department of Neurosurgery, Tianjin Medical University General Hospital and Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, China.

The dynamic changes of RNA N6-methyl-adenosine (mA) during cancer progression contribute to quick adaption to microenvironmental changes. Here, we profiled the cancer cell mA dynamics in the hypoxic tumor niche and its pathological consequences in glioblastoma multiforme (GBM). The mA demethylase ALKBH5 was induced in GBM models under hypoxic conditions and was associated with a hypoxic gene signature in GBM patient samples. Depletion or inactivation of ALKBH5 in GBM cells significantly suppressed hypoxia-induced tumor-associated macrophage (TAM) recruitment and immunosuppression in allograft tumors. Expression and secretion of CXCL8/IL8 were significantly suppressed in ALKBH5-deficient tumors. However, ALKBH5 did not regulate CXCL8 mA directly. Instead, hypoxia-induced ALKBH5 erased mA deposition from the lncRNA NEAT1, stabilizing the transcript and facilitating NEAT1-mediated paraspeckle assembly, which led to relocation of the transcriptional repressor SFPQ from the CXCL8 promoter to paraspeckles and, ultimately, upregulation of CXCL8/IL8 expression. Accordingly, ectopic expression of CXCL8 in ALKBH5-deficient GBM cells partially restored TAM recruitment and tumor progression. Together, this study links hypoxia-induced epitranscriptomic changes to the emergence of an immunosuppressive microenvironment facilitating tumor evasion. SIGNIFICANCE: Hypoxia induces tumor immune microenvironment remodeling through an ALKBH5-mediated epigenetic and epitranscriptomic mechanism, providing potential immunotherapeutic strategies for treating glioblastoma.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-1456DOI Listing
December 2021

Loss of the wild-type KRAS allele promotes pancreatic cancer progression through functional activation of YAP1.

Oncogene 2021 Oct 18. Epub 2021 Oct 18.

The Department of Pathology & Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.

Human pancreatic ductal adenocarcinoma (PDAC) harboring one KRAS mutant allele often displays increasing genomic loss of the remaining wild-type (WT) allele (known as LOH at KRAS) as tumors progress to metastasis, yet the molecular ramification of this WT allelic loss is unknown. In this study, we showed that the restoration of WT KRAS expression in human PDAC cell lines with LOH at KRAS significantly attenuated the malignancy of PDAC cells both in vitro and in vivo, demonstrating a tumor-suppressive role of the WT KRAS allele. Through RNA-Seq, we identified the HIPPO signaling pathway to be positively regulated by WT KRAS in PDAC cells. In accordance with this observation, PDAC cells with LOH at KRAS exhibited increased nuclear localization and activation of transcriptional co-activator YAP1. Mechanistically, we discovered that WT KRAS expression sequestered YAP1 from the nucleus, through enhanced 14-3-3zeta interaction with phosphorylated YAP1 at S127. Consistently, expression of a constitutively-active YAP1 mutant in PDAC cells bypassed the growth inhibitory effects of WT KRAS. In patient samples, we found that the YAP1-activation genes were significantly upregulated in tumors with LOH at KRAS, and YAP1 nuclear localization predicted poor survival for PDAC patients. Collectively, our results reveal that the WT allelic loss leads to functional activation of YAP1 and enhanced tumor malignancy, which explains the selection advantage of the tumor cells with LOH at KRAS during pancreatic cancer clonal evolution and progression to metastasis, and should be taken into consideration in future therapeutic strategies targeting KRAS.
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http://dx.doi.org/10.1038/s41388-021-02040-9DOI Listing
October 2021

3D-printed models improve surgical planning for correction of severe postburn ankle contracture with an external fixator.

J Zhejiang Univ Sci B 2021 Oct;22(10):866-875

Department of Plastic and Reconstructive Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.

Gradual distraction with an external fixator is a widely used treatment for severe postburn ankle contracture (SPAC). However, application of external fixators is complex, and conventional two-dimensional (2D) imaging-based surgical planning is not particularly helpful due to a lack of spatial geometry. The purpose of this study was to evaluate the surgical planning process for this procedure with patient-specific three-dimension-printed models (3DPMs). In this study, patients coming from two centers were divided into two cohorts (3DPM group vs. control group) depending on whether a 3DPM was used for preoperative surgical planning. Operation duration, improvement in metatarsal-tibial angle (MTA), range of motion (ROM), the American Orthopedic Foot and Ankle Society (AOFAS) scores, complications, and patient-reported satisfaction were compared between two groups. The 3DPM group had significantly shorter operation duration than the control group ((2.0±0.3) h vs. (3.2±0.3) h, <0.01). MTA, ROM, and AOFAS scores between the two groups showed no significant differences pre-operation, after the removal of the external fixator, or at follow-up. Plantigrade feet were achieved and gait was substantially improved in all patients at the final follow-up. Pin-tract infections occurred in two patients (one in each group) during distraction and were treated with wound care and oral antibiotics. Patients in the 3DPM group reported higher satisfaction than those in the control group, owing to better patient-surgeon communication. Surgical planning using patient-specific 3DPMs significantly reduced operation duration and increased patient satisfaction, while providing similar improvements in ankle movement and function compared to traditional surgical planning for the correction of SPAC with external fixators.
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http://dx.doi.org/10.1631/jzus.B2000576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505459PMC
October 2021

Human antigen R promotes angiogenesis of endothelial cells cultured with adipose stem cells derived exosomes via overexpression of vascular endothelial growth factor in vitro.

Adipocyte 2021 12;10(1):475-482

Department of Plastic and Reconstructive Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China.

Recent studies showed that exosomes obtained from adipose-derived stem cells (ADSCs) could improve the angiogenesis of fat grafts via overexpression of vascular endothelial growth factor (VEGF). Human antigen R (HuR) promotes the expression of VEGF in many cancers, but the effect of HuR in normal endothelial cells in the presence of ADSC-derived exosomes remains unclear. We aimed to investigate the effect of HuR on the expression of VEGF and angiogenesis of human umbilical vein endothelial cells (HUVECs) cultured with ADSCs-derived exosomes. The HuR-overexpressed HUVECs (HuR-HUVECs) were cocultured with ADSCs-derived exosomes. qRT-PCR and Western blotting were performed to examine the stability and expression of VEGF-A mRNA and protein. The proliferation, migration, and proangiogenic capacity of HuR-HUVECs were evaluated using cell counting kit-8 (CCK-8), scratch wound healing, and Matrigel tube formation assay. qRT-PCR showed that HuR-HUVECs had higher expression and slower attenuation of VEGF-A mRNA. Western blotting confirmed higher expression of VEGF-A in HuR-HUVECs. CCK-8, scratch wound healing, and Matrigel tube formation assay demonstrated an increased proangiogenic effect in HuR-HUVECs. HuR promotes angiogenesis of HUVECs cocultured with ADSCs-derived exosomes via stabilization and overexpression of VEGF in vitro. The HuR/VEGF pathway is an important regulatory mechanism of angiogenesis in endothelial cells.
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http://dx.doi.org/10.1080/21623945.2021.1982577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510607PMC
December 2021

A Bayesian network meta-analysis regarding the comparative efficacy of therapeutics for ALK-positive, brain metastatic non-small cell lung cancer.

Pharmacol Res 2021 Dec 6;174:105931. Epub 2021 Oct 6.

Departments of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, PR China; China Pituitary Disease Registry Center, Chinese Pituitary Adenoma Cooperative Group, Beijing, PR China; China Alliance of Rare Diseases, Beijing, PR China. Electronic address:

More clinical evidence is needed regarding the ranking priority of interventions for ALK-positive, brain metastatic (BM) non-small cell lung cancer (NSCLC). Eligible randomized controlled trials (RCTs) were identified. Progression-free survival (PFS), objective response rate (ORR) and overall survival (OS) for the intended populations were analyzed with random effects, Bayesian network meta-analysis with the estimated hazard ratio (HR) and odds ratio (OR) with 95% credible interval (95% CrIs). We included 11 RCTs (2687 NSCLC and 991 BM patients) investigating 7 treatments and 5 medication classes. For PFS for BM patients, lorlatinib (hazard ratio (HR): 0.01, 95% CrI: 0.001-0.12), alectinib (HR: 0.05, 95% CrI: 0.01-0.21) and brigatinib (HR: 0.07, 95% CrI: 0.007-0.76) were top-ranking individual treatments; for ORR for BM patients, brigatinib, lorlatinib and alectinib were top-ranking treatments. For PFS for all NSCLC patients, the top-ranking individual treatments were lorlatinib (HR: 0.05, 95% CrI: 0.02-0.13), alectinib (HR: 0.09, 95% CrI: 0.05-0.18) and brigatinib (HR: 0.11, 95% CrI: 0.05-0.28). For OS for all NSCLC patients, we found that no individual treatments were superior to chemotherapy, whereas the following top-ranking interventions were alectinib (HR: 0.29, 95% CrI: 0.03-1.68), lorlatinib (HR: 0.41, 95% CrI: 0.04-4.13), and ceritinib (HR: 0.63, 95% CrI: 0.10-4.25). The results of individual treatments and medication classes were similar. Data were limited in regard to subgroup analyses and adverse events of BM patients. Lorlatinib has the most statistical superiority for BM patients, but ORR differences between third- and second-generation inhibitors are not obvious. All things considered, alectinib is recommended as first-line treatment, followed by lorlatinib, especially after developing drug resistance to alectinib.
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http://dx.doi.org/10.1016/j.phrs.2021.105931DOI Listing
December 2021

Ajuba functions as a co-activator of C/EBPβ to induce expression of PPARγ and C/EBPα during adipogenesis.

Mol Cell Endocrinol 2022 Jan 5;539:111485. Epub 2021 Oct 5.

Hongqiao International Institute of Medicine, Tongren Hospital/Faculty of Basic Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry & Molecular Cellular Biology, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China. Electronic address:

Adipogenesis is regulated by a complicated network of transcription factors among which PPARγ and C/EBP family members are the major regulators. During adipogenesis, C/EBPβ is induced early and then transactivates PPARγ and C/EBPα, which cooperatively induce genes whose expressions give rise to the mature adipocyte phenotype. Identifying the factors that influence the expression and activity of C/EBPβ should provide additional insight into the mechanisms regulating adipogenesis. Here, we demonstrate that depletion of Ajuba in 3T3-L1 cells significantly decreases mRNA and protein levels of PPARγ and C/EBPα and impairs adipocyte differentiation, while overexpression increases expression of these genes and promotes adipocyte differentiation. Moreover, restoration of C/EBPα or PPARγ expression in Ajuba-deficient 3T3-L1 cells improves the impaired lipid accumulation. Mechanistically, Ajuba interacts with C/EBPβ and recruits CBP to facilitate the binding of C/EBPβ to the promoter of PPARγ and C/EBPα, resulting in increased H3 histone acetylation and target gene expression. Collectively, these data indicate that Ajuba functions as a co-activator of C/EBPβ, and may be an important therapeutic target for combating obesity-related diseases.
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http://dx.doi.org/10.1016/j.mce.2021.111485DOI Listing
January 2022

KLF9 (Kruppel Like Factor 9) induced PFKFB3 (6-Phosphofructo-2-Kinase/Fructose-2, 6-Biphosphatase 3) downregulation inhibits the proliferation, metastasis and aerobic glycolysis of cutaneous squamous cell carcinoma cells.

Bioengineered 2021 12;12(1):7563-7576

Department of Plastic and Reconstructive Surgery, The First Medical Center, Chinese Pla General Hospital, Beijing, China.

Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer in humans with increasing incidence. In this paper, we focused on the effects of krueppel-like factor 9 (KLF9) on the progression of CSCC cells by binding to PFKFB3. mRNA and protein expressions of KLF9 and PFKFB3 in human HaCaT and CSCC cells were, respectively, examined by RT-qPCR analysis and Western blot. The viability, proliferation, invasion and migration of A431 cells after transfection were analyzed with MTT, clone formation, transwell and wound healing assays. The levels of glucose, lactic acid and ATP in transfected A431 cells were detected by their commercial kits. Ki-67 expression in transfected A431 cells was determined using immunofluorescence analysis and in tumor tissues was analyzed by immunohistochemistry. The levels of migration, EMT and aerobic glycolysis-related proteins were tested with Western blot. The combination of KLF9 and PFKFB3 was confirmed by dual-luciferase reporter assay and ChIP. As a result, PFKFB3 expression was elevated in CSCC cells compared with HaCaT. Knockdown of PFKFB3 restrained the proliferation, metastasis, and aerobic glycolysis of CSCC cells. In addition, KLF9 could bind to PFKFB3. Downregulation of KLF9 crippled the inhibitory effect of knockdown of PFKFB3 on the proliferation, metastasis, and aerobic glycolysis of CSCC cells. In conclusion, PFKFB3 was transcriptionally regulated by KLF9, and PFKFB3 silencing inhibits the proliferation, metastasis, and aerobic glycolysis of cutaneous squamous cell carcinoma cells.
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http://dx.doi.org/10.1080/21655979.2021.1980644DOI Listing
December 2021

A label-free electrochemical immunosensing platform based on PEI-rGO/[email protected] NRs for rapid and sensitive detection of zearalenone.

Bioelectrochemistry 2022 Feb 24;143:107955. Epub 2021 Sep 24.

Sinograin Zhengzhou Depot Ltd. Company, Zhengzhou, Henan 450066, PR China.

In this work, we design an immunosensor for zearalenone (ZEN) detection with PEI-rGO/[email protected] NRs nanocomposite as the modification material. PEI-rGO/[email protected] NRs nanocomposite have good stability, conductivity and a large specific surface area, so they are chosen as the substrate material for the modified electrode, which is beneficial in improving the detection performance of the sensor. When antibody binds to ZEN, the current signal decreases, and the response signal changes after ZEN incubation, recorded by differential pulse voltammetry (DPV) methods. Under the optimised conditions, the electrochemical response of the constructed immunosensor shows a linear relation to a wide concentration range from 1 pg/mL to 1 × 10 pg/mL with a detection limit of 0.02 pg/mL. Additionally, the proposed electrochemical immunosensor has high selectivity, good stability and great potential for the trace detection of ZEN in real samples.
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http://dx.doi.org/10.1016/j.bioelechem.2021.107955DOI Listing
February 2022

Cytokine release syndrome after haploidentical hematopoietic stem cell transplantation with antithymocyte globulin: risk factors analysis and poor impact on outcomes for non-remisssion patients.

Hematology 2021 Dec;26(1):809-817

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Introduction: Cytokine release syndrome (CRS) is a common complication after T-replete HLA haploidentical hematopoietic cell transplantation (haplo-HCT) with PTCy. We aim to assess the incidence, severity, and impact of CRS on clinical outcomes of patients who received haplo-HCT using Beijing Protocol.

Methods: This was a single-enter retrospective analysis of 286 subjects who received haplo-HCT with Antithymocyte Globulin (ATG).

Results: We identified 147/268 (54.9%) patients who developed CRS, grade 1 CRS (32.5%) and grade ≥2 CRS (22.4%). Eight patients developed severe CRS. The incidence and severity of CRS did not show significant discrimination among patients who received different doses of ATG. By multivariable analysis, age and the disease status at transplantation were significantly associated with the occurrence of CRS ( =.000 and = .021). In the univariate analysis for the severity of CRS, compared with CRS grade ≥2, patients with CRS grade 0-1 had higher 1-year overall survival (OS) ( = .009). The cumulative incidence of 100-day grades II-IV acute GVHD was 12.4%. The incidence did not show significant differences between patients with CRS or not. The devolvement of CRS is associated with worse OS, inferior disease-free survival, and higher nonrelapse mortality significantly. But the result appeared to be limited to patients in uncomplete remission status before transplantation.

Discussion And Conclusions: CRS is less frequent and milder with a protocol based on ATG. CRS can potentially affect the outcomes after haplo-HCT especially for patients in an uncomplete remission. Prospective clinical trials are needed to provide an appropriate scheme for CRS prophylaxis.
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http://dx.doi.org/10.1080/16078454.2021.1978752DOI Listing
December 2021

Established pulmonary hypertension in rats was reversed by a combination of a HIF-2α antagonist and a p53 agonist.

Br J Pharmacol 2021 Oct 2. Epub 2021 Oct 2.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background And Purpose: Recent studies reported therapeutic effects of monotherapy with either tumour suppressor p53 (p53) agonist or hypoxia-inducible factor 2α (HIF-2α) antagonist for pulmonary hypertension (PH). This study investigated whether a combined treatment of p53 agonist, Nutlin3a, and HIF-2α antagonist, PT2385, would be more effective than monotherapy, based on the cell type-divergent regulation of p53 in pulmonary arterial smooth muscle cells (PASMC) and endothelial cells (PAEC) in patients and animals with PH.

Experimental Approach: The SU5416/hypoxia-induced PH (SuHx-PH) rat model was used, along with cultured human PASMC and PAEC. Western blot, RT-PCR, siRNA and immunohistochemical methods were used along with echocardiography and studies with isolated pulmonary arteries.

Key Results: Hypoxia-induced proliferation of PASMC is associated with decreased p53, whereas hypoxia-induced PAEC apoptosis is associated with increased p53, via a HIF-2α-dependent mechanism. Combined treatment with Nutlin3a and PT2385 is more effective by simultaneously inhibiting the hypoxia-induced PASMC proliferation and PAEC apoptosis, overcoming the side-effects of monotherapy. These are (i) Nutlin3a exacerbates hypoxia-induced PAEC apoptosis by inducing p53 in PAEC and (ii) PT2385 inhibits PAEC apoptosis because HIF-2α is predominantly expressed in PAEC but lacks direct effects on the hypoxia-induced PASMC proliferation. In rats, combination treatment is more effective than monotherapy in reversing established SuHx-PH, especially in protecting pulmonary arterial vasculature, by normalizing smooth muscle thickening, protecting against endothelial damage and improving function.

Conclusion And Implications: Combination treatment confers greater therapeutic efficacy against PH through a selective modulation of p53 and HIF-2α in PASMC and PAEC.
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http://dx.doi.org/10.1111/bph.15696DOI Listing
October 2021

High On-Treatment Platelet Reactivity as Predictor of Long-term Clinical Outcomes in Stroke Patients with Antiplatelet Agents.

Transl Stroke Res 2021 Oct 1. Epub 2021 Oct 1.

Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Shanghai, China.

The purpose was to explore the value of high on-treatment platelet reactivity (HTPR) in predicting long-term clinical outcomes for stroke patients. The platelet reactivity was assayed after being treated with either 75 mg clopidogrel or 100 mg aspirin daily with VerifyNow System in stroke patients. HTPR for clopidogrel was defined as PRU ≥ 208, and that for aspirin was defined as ARU ≥ 550. CYP2C19 genotyping was performed using the Sequenom MassARRAY iPLEX platform. The primary endpoint was a composite of recurrent ischemic stroke, transient ischemic attack, myocardial infarction, or ischemic vascular death. The safety endpoint was bleeding. In the clopidogrel group, among 345 patients recruited, 174 of them were categorized as HTPR. A total of 270 patients were followed up for 54 months. There was a significant association between HTPR and the primary endpoint (HR 2.13 [95% CI, 1.43-3.15], p < 0.001). Among the 314 participants genotyped for CYP2C19, 187 (59.6%) were classified as CYP2C19 loss-of-function allele carriers. Patients with at least 1 loss-of-function allele were more likely to present with HTPR (OR 2.61 [95%CI, 1.43-4.77], p = 0.008), and had a higher risk of the primary endpoint (HR 2.05 [95% CI, 1.30, 3.25], p = 0.002). In the aspirin group, among 140 patients recruited, 28 of them were categorized as HTPR. A total of 121 patients were followed up for 30 months. Similarly, there was a significant association between HTPR and the primary endpoint (HR 3.28 [95% CI, 1.52-7.71], p = 0.002). HTPR is an independent risk factor for ischemic events during long-term follow-up in stroke patients. Platelet function testing is helpful to evaluate the effect of antiplatelet therapy for stroke patients.
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http://dx.doi.org/10.1007/s12975-021-00949-7DOI Listing
October 2021

Intracellular ATP Signaling Contributes to FAM3A-Induced PDX1 Upregulation in Pancreatic Beta Cells.

Exp Clin Endocrinol Diabetes 2021 Sep 30. Epub 2021 Sep 30.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science of the Ministry of Education, Center for Non-coding RNA Medicine, Peking University Health Science Center, Beijing 100191, China.

FAM3A is a recently identified mitochondrial protein that stimulates pancreatic-duodenal homeobox 1 (PDX1) and insulin expressions by promoting ATP release in islet β cells. In this study, the role of intracellular ATP in FAM3A-induced PDX1 expression in pancreatic β cells was further examined. Acute FAM3A inhibition using siRNA transfection in mouse pancreatic islets significantly reduced PDX1 expression, impaired insulin secretion, and caused glucose intolerance in normal mice. , FAM3A overexpression elevated both intracellular and extracellular ATP contents and promoted PDX1 expression and insulin secretion. FAM3A-induced increase in cellular calcium (Ca) levels, PDX1 expression, and insulin secretion, while these were significantly repressed by inhibitors of P2 receptors or the L-type Ca channels. FAM3A-induced PDX1 expression was abolished by a calmodulin inhibitor. Likewise, FAM3A-induced β-cell proliferation was also inhibited by a P2 receptor inhibitor and an L-type Ca channels inhibitor. Both intracellular and extracellular ATP contributed to FAM3A-induced PDX1 expression, insulin secretion, and proliferation of pancreatic β cells.
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http://dx.doi.org/10.1055/a-1608-0607DOI Listing
September 2021

The Accuracy of Molecular Detection Targeting the Mutation C2611T for Detecting Moderate-Level Azithromycin Resistance in : A Systematic Review and Meta-Analysis.

Antibiotics (Basel) 2021 Aug 24;10(9). Epub 2021 Aug 24.

National Center for STD Control, Chinese Center for Disease Control and Prevention, Department of Reference STD Lab, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China.

Background: is now recognized as a commonly reported sexually transmitted pathogen, and the increasing drug resistance of has become a serious public health problem. The accuracy of molecular detection for detecting moderate-level azithromycin resistance is not well-established. We summarized the data from studies of the 23S rRNA mutation at position 2611 with azithromycin resistance to determine the relationship between the mutation and resistance.

Methods And Findings: In this systematic review and meta-analysis, two researchers independently searched six databases for studies with data for the azithromycin minimum inhibitory concentrations (MICs) and the 23S rRNA mutation C2611T of each isolate. Since the breakpoint of moderate-level resistance to azithromycin (ML-AzmR) was not determined, we divided the moderate level into two groups according to the range of MICs (moderate resistance limited to 2-128 mg/L or 4-128 mg/L) for data extraction. A random-effects model was used to calculate the pooled sensitivity rate, the specificity rate, the pooled positive likelihood ratio (PLR), the negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR). Meta-regression analyses by detection method, isolates sampling (a random sample or not), location, and sample size were performed to explore the possible causes of heterogeneity. The potential publication bias of the included studies was conducted by the Deeks' test. We included 20 studies in our study: 20 studies have data of with MICs between 2 and 128 mg/L with mutation or without mutation at position 2611(4759 samples), and 14 studies have data of with MICs between 4 and 128 mg/L (3367 samples). In the group with the moderate level of 2-128 mg/L, the pooled sensitivity rate of the molecular assays was determined to be 71.9% (95% CI, 67.6-74%), the pooled specificity rate was 98.7% (95% CI, 98.2-99.0%), and the DOR ranged from 55.0 to 351.3 (mean, 139.1). In the 4-128 mg/L group, the pooled sensitivity rate was 91.9% (95% CI, 88.9-94.2%), the pooled specificity rate was 95.9% (95% CI, 95.1-96.6%), and the DOR ranged from 41.9 to 364.1 (mean, 123.6).

Conclusion: Through this meta-analysis, we found that the C2611T mutation of 23S rRNA is valuable for the molecular diagnostic of moderate-level azithromycin resistance (ML-AzmR) in , especially when the moderate level is set at 4-128 mg/L. This rapid molecular detection method can be used for the rapid identification of ML-AzmR isolates in the clinic.
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http://dx.doi.org/10.3390/antibiotics10091027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471969PMC
August 2021

Not FIT for Use: Fecal Immunochemical Testing in the Inpatient and Emergency Settings.

Am J Med 2021 Sep 9. Epub 2021 Sep 9.

Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis; Division of Gastroenterology and Hepatology, Department of Medicine, Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Ind. Electronic address:

Background: Fecal immunochemical testing (FIT) is widely used for colorectal cancer screening, its only indication. Its effect on clinical decision-making beyond screening is unknown. We studied the use of FIT in emergency and inpatient settings and its impact on patient care.

Methods: Using electronic medical records, we reviewed all non-ambulatory FITs performed from November 2017 to October 2019 at a tertiary care community hospital. We collected data on demographics, indications, gastroenterology consultations, and endoscopic procedures. Multivariate logistic regression was performed to determine the effect of FIT on gastroenterology consultation and endoscopy.

Results: We identified 550 patients with at least 1 FIT test. Only 3 FITs (0.5%) were performed for colorectal cancer screening. FITs were primarily ordered from the emergency department (45.3%) or inpatient hospital floor (42.2%). Anemia (44.0%), followed by gastrointestinal bleeding (40.9%), were the most common indications. FIT was positive in 253 patients (46.0%), and gastroenterology consultation was obtained for 47.4% (n = 120), compared with 14.5% (n = 43) of the 297 FIT-negative patients (odds ratio 3.28; 95% confidence interval, 2.23-4.82, P < .0001). A potential bleeding source was identified in 80% of patients with reported or witnessed overt gastrointestinal bleeding, a similar proportion (80.7%; P = .92) to patients who were FIT positive with overt gastrointestinal bleeding. Multivariate analysis showed that melena, hematemesis, and a positive FIT were associated with gastroenterology consultation (all P < .05), while only melena (odds ratio 3.34; 95% confidence interval, 1.48-7.54) was associated with endoscopy.

Conclusions: Nearly all emergency department and inpatient FIT use was inappropriate. FIT resulted in more gastroenterology consultation but was not independently associated with inpatient endoscopy.
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http://dx.doi.org/10.1016/j.amjmed.2021.08.004DOI Listing
September 2021
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