Publications by authors named "Chengqian Li"

26 Publications

  • Page 1 of 1

Role of CD36 rs1761667 AA genotype in the expression of inflammatory cytokines and Parkinson's disease progression: A case-control study in a northern Han Chinese population.

Neurosci Lett 2022 07 13;784:136736. Epub 2022 Jun 13.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:

Objective: This study aimed to investigate the effect of CD36 rs1761667 gene polymorphisms on the expression of CD36 and inflammatory cytokines and the progression of Parkinson's disease (PD).

Methods: A total of 138 patients with PD (60 men and 78 women) and 132 healthy controls (48 men and 84 women) from a northern Han Chinese population were enrolled in this case-control study. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the CD36 rs1761667 genotype. An enzyme-linked immunosorbent assay was used to determine the expression of CD36, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in the plasma.

Results: The frequency of the rs1761667 AA genotype was significantly higher in patients with PD than that in healthy controls, suggesting AA genotype to be a risk factor for PD. When compared with those in healthy controls, CD36 levels were significantly lower in patients with PD, whereas IL-6, IL-1β, and TNF-α levels were significantly higher in patients with PD. Furthermore, GA and AA carriers with PD showed lower levels of CD36, and GG, GA, and AA carriers showed higher levels of IL-6, IL-1β, and TNF-α than those in healthy controls. In the PD patient group, AA and GA carriers had lower expression levels of CD36 than GG carriers did, and CD36 levels were lower in AA carriers than in GA carriers. Conversely, AA carriers had elevated expression levels of IL-6 compared with that of GG and GA carriers. Logistic regression analysis revealed that IL-6, IL-1β, and TNF-α levels were risk factors for PD in a northern Han Chinese population.

Conclusion: The CD36 rs1761667 AA genotype may increase susceptibility to PD and the expression of inflammatory cytokines.
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http://dx.doi.org/10.1016/j.neulet.2022.136736DOI Listing
July 2022

Association between ABCA7 gene polymorphisms and Parkinson's disease susceptibility in a northern Chinese Han population.

Neurosci Lett 2022 07 13;784:136734. Epub 2022 Jun 13.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:

Objective: As a typical member of the ABC transporter superfamily, ABCA7 has been shown to play an important role in stalling the pathogenesis of neurodegenerative disorders through maintaining the normal microglial function, regulating cellular responses to inflammation and ER stress, and modulating lipid metabolism. Variants in the ABCA7 locus have been hypothesized to be correlated with the genetic predisposition of several neurodegenerative disorders. The goal of this study was to examine whether there is a link between three specific single nucleotide polymorphisms in the ABCA7 gene, namely, rs3764650, rs4147929, and rs3752246, with the risk of developing Parkinson's disease (PD) in a northern Chinese Han community.

Methods: In this case-control study, we recruited 821 participants, including 411 patients with sporadic PD and 410 independent, healthy controls. A Polymerase Chain Reaction-Restriction Fragment Length Polymorphism genotyping assay was used to identify polymorphisms of the three selected single nucleotide polymorphisms (rs3764650, rs4147929, and rs3752246) of the ABCA7 gene. Sanger sequencing was further applied to identify the accuracy of the genotyping results. The chi-square test was used to compare the frequencies of alleles and genotypes in patients and controls. Odds ratios and 95% confidence intervals were calculated using logistic regression.

Results: We found significant between-group differences in the alleles (A vs. G, nominal P = 0.014) and dominant models (AA + GA vs. GG, nominal P = 0.015) of rs4147929. Subgroup analysis showed that the frequency of the rs4147929 A allele in male patients with PD was significantly higher than that in male controls (nominal P = 0.036). For the rs3752246 polymorphism, the frequency of the G allele was significantly higher in patients with PD than in controls, and the dominant model fit the data best when considering the nominal P-values (nominal P = 0.019, nominal P = 0.033, respectively). Differences in G allele and genotypes frequencies between patients and controls remained significant in women (nominal P = 0.032 for allele, nominal P = 0.015 for genotype), as well as in individuals aged more than 50 years (nominal P = 0.044, nominal P = 0.020, respectively). No significant differences were observed in allele or genotype frequencies between patients with PD and healthy controls for rs3764650. The frequency of the TCG (rs3764650-rs3752246-rs4147929) haplotype was significantly lower in the PD group than in the healthy control group (odds ratio = 0.772; 95% confidence interval = 0.634-0.940; P = 0.011).

Conclusion: The rs4147929 polymorphism was significantly associated with PD susceptibility in the northern Chinese Han population. The A allele of rs4147929 was a risk factor for developing PD. The TCG haplotype presented a protective role in the pathogenesis of PD. Further studies using larger sample sizes, considering different clinical and biochemical parameters such as the cognitive status of subjects at the same time, are warranted to better clarify the effects of these common variants on the pathogenesis and development of PD.
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http://dx.doi.org/10.1016/j.neulet.2022.136734DOI Listing
July 2022

Mutation of Beclin1 acetylation site at K414 alleviates high glucose-induced podocyte impairment in the early stage of diabetic nephropathy by inhibiting hyperactivated autophagy.

Mol Biol Rep 2022 May 17;49(5):3919-3926. Epub 2022 Feb 17.

Department of Endocrinology and Metabolism, First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China.

Background: Our group recently reported that a mutation of the novel Beclin1 K414R acetylation site impacts the stability of Beclin1 protein, which decreases autophagy in adipocytes and further impedes adipocyte differentiation and lipolysis. This study was to explore whether Beclin1 acetylation plays a role in the early renal injury induced by high glucose and to further investigate the K414R mutation site in podocytes.

Methods: Male Sprague-Dawley rats were randomized to con (control) and diabetic nephropathy (DN) groups. The DN group was induced by a single 55 mg/kg intraperitoneal injection of streptozotocin and fed a high-fat and high-sugar diet (the con group received an equal volume of the vehicle and fed a plain diet), after 3 days of induction, blood glucose levels were measured to confirm the onset of diabetes. Then, at weeks 0 and 4, the biochemical index was assayed and renal cortex tissues were harvested. MPC5 podocytes were cultured in vitro. Beclin1 (K414R)-pLVX-ZsGreen1-N1(wild-type or mutant) lentiviral plasmids were transfected into podocytes. Western blot or immunoprecipitation was used to test proteins or the acetylation levels respectively, and immunohistochemistry was used to analyze morphological changes of podocytes. Immunofluorescence was used to detect the aggregation of LC3 puncta.

Results: The acetylation level of Beclin1 was upregulated with podocyte injury exacerbated in high glucose at 24 h and that a mutation at K414R could inhibit hyperactivated autophagy, which ameliorated podocyte impairment.

Conclusion: These findings suggest that the acetylation site at K414 is a critical molecule and drug target and that further research into this area is warranted.
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http://dx.doi.org/10.1007/s11033-022-07242-2DOI Listing
May 2022

PCSK9 inhibitor recaticimab for hypercholesterolemia on stable statin dose: a randomized, double-blind, placebo-controlled phase 1b/2 study.

BMC Med 2022 01 18;20(1):13. Epub 2022 Jan 18.

Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, China.

Background: Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in patients with hypercholesterolemia.

Methods: In this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule).

Results: A total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from -48.37 to -59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase.

Conclusion: Recaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo.

Trial Registration: ClinicalTrials.gov , number NCT03944109.
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http://dx.doi.org/10.1186/s12916-021-02208-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763618PMC
January 2022

Ghrelin Alleviates Endoplasmic Reticulum Stress in MC3T3E1 Cells by Inhibiting AMPK Phosphorylation.

Oxid Med Cell Longev 2021 11;2021:9940355. Epub 2021 Oct 11.

Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266555, China.

Ghrelin is a gastric endocrine peptide that has been found to be involved in the process of energy homeostasis and bone physiology in recent years. To explore the effects of ghrelin on endoplasmic reticulum stress (ERS) in MC3T3E1 cells and its possible mechanism, an ERS model was induced by tunicamycin (TM) in the osteoblast line MC3T3E1. TM at 1.5 g/mL was selected as the experimental concentration found by CCK8 assay. Through the determination of apoptosis, reactive oxygen species production, and endoplasmic reticulum stress-related gene expression, we found that ERS induced by TM can be relieved by ghrelin in a concentration-dependent manner ( < 0.001). Compared with the TM group, ghrelin reduced the expression of ERS-related marker genes induced by TM. Compared with the GSK621 + TM group without ghrelin pretreatment, the mRNA expression of genes in the ghrelin pretreatment group decreased significantly ( < 0.001). The results of protein analysis showed that the levels of BIP, p-AMPK, and cleaved-caspase3 in the TM group increased significantly, while the levels decreased after ghrelin pretreatment. In group GSK621 + TM compared with group GSK621 + ghrelin+TM, ghrelin pretreatment significantly reduced the level of p-AMPK, which is consistent with the trend of the ERS-related proteins BIP and cleaved-caspase3. In conclusion, ghrelin alleviates the ERS induced by TM in a concentration-dependent manner and may or at least partly alleviate the apoptosis induced by ERS in MC3T3E1 cells by inhibiting the phosphorylation of AMPK.
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http://dx.doi.org/10.1155/2021/9940355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523291PMC
February 2022

Influencing Factors and Cumulative Risk Analysis of Cervical Lymph Node Metastasis of Papillary Thyroid Microcarcinoma.

Front Oncol 2021 30;11:644645. Epub 2021 Sep 30.

Department of Endocrine and Metabolic Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China.

Objective: To explore the influencing factors and cumulative risk of lymph node metastasis (LNM) in papillary thyroid microcarcinoma (PTMC) patients.

Methods: 607 patients confirmed PTMC pathologically after thyroidectomy were enrolled in this retrospective study. The rate of LNM was calculated. Different clinicopathological characteristics were compared in PTMC patients with and without LNM and in different subgroups of LNM, respectively. Correlation between clinicopathological characteristics and LNM was analyzed and the cumulative risk of LNM according to different clinicopathological characteristics was calculated.

Results: (1) There were 228 cases (37.56%) of PTMC combined with LNM. Compared with the non-lymph node metastasis group, the proportion of age <55 years, male, multiple foci, bilateral foci, diameter>0.5cm, extracapsular invasion, HT and intermediate-to-high risk stratification for recurrence of the LNM group was significantly increased (all <0.05);(2) Multivariate logistic regression analysis showed that age <55years, male, multiple foci, diameter>0.5cm,HT were independently positively correlated with LNM (all 0.05); (3) Subgroup analysis showed that women aged <55 years combined with HT and aged≥55 years combined with BMI≥25 kg/m were independently positively associated with LNM; (4) With the increase of the tumor diameter, the cumulative risk of LNM in group of age <55 years, males, and multiple foci increased gradually, and was higher than those of age≥55 years, females and single foci, respectively. (5) Among the 228 cases of LNM, the proportion of lymph nodes (LN) >5 and the positive rate of LN were both higher in male group than that in the female group. The proportion of multiple foci and HT in LLNM group was higher than that in CLNM group (all P<0.05).

Conclusion: Age <55 years, males, multiple foci, diameter >0.5cm and HT were independent risk factors of LNM; HT was an independent risk factor for LNM in female <55 years old, and BMI≥25 kg/m was an independent risk factor for LNM in female ≥55 years old; The increase of tumor diameter in age <55 years, males, multiple foci, and bilateral foci increased the cumulative risk of LNM, respectively; The number of LNM and the positive rate of LNM were both higher in male, and patients with multiple foci or HT were more likely to develop into LLNM.
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http://dx.doi.org/10.3389/fonc.2021.644645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514816PMC
September 2021

Measurement of talc in flour by the prompt-gamma ray neutron activation analysis method.

Appl Radiat Isot 2021 Dec 10;178:109932. Epub 2021 Sep 10.

College of Physics, Jilin University, Changchun, 130012, China.

Prompt gamma-ray neutron activation analysis method (PGNAA) was used to measure the talc content in flour. Neutron activation prompt gamma spectrum measured by NaI(Tl) detector has complex components, poor energy resolution, and high Compton plateau, how to obtain accurate element content from the prompt γ spectrum is one of the core problems of PGNAA. To reduce the systematic uncertainty caused by the variation of the neutron energy spectrum and γ self-absorption in different samples, the spectral decomposition method based on library least-squares was improved. As a result, the average relative deviation between the calculated values from measured spectra and the theoretical values based on the known composition was reduced from 6.1% to 0.3%. The relative uncertainty of 30 measurements on the same sample was reduced from 4.8% to 3.0%. The detection time can be reduced to 1 min, which meets the requirement of on-line measurement for talc in flour.
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http://dx.doi.org/10.1016/j.apradiso.2021.109932DOI Listing
December 2021

Reduced Serum Magnesium Levels Are Associated with the Occurrence of Retinopathy in Patients with Type 2 Diabetes Mellitus: a Retrospective Study.

Biol Trace Elem Res 2022 May 18;200(5):2025-2032. Epub 2021 Jul 18.

Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266000, Shandong, China.

The aim of this study is to explore the relationship between serum magnesium (Mg) level and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). The clinical data of 2222 patients with T2DM, including 713 patients with DR and 1509 patients without DR, between September 2016 and August 2020 in our hospital, were analyzed retrospectively. Further, the role and predictive value of serum Mg on the prevalence of DR were determined through logistic regression and the receiver operating characteristic (ROC) curve respectively. The level of serum Mg was lower in DR group than that in non-DR group (0.92 vs 0.88 mmol/L, P < 0.001). Stratified serum Mg levels into quartiles (Q1-Q4), the first (Q1, Mg ≤ 0.85 mmol/L) and fourth quartile (Q4, ≥ 0.96 mmol/L) represented the lowest and highest quartile, respectively. And the incidence of DR was obviously higher in Q1 and Q2 than that in Q3 and Q4 (50.9% and 30.2% vs 23.5% and 21%, respectively). Logistic regression demonstrated that there remained an independent association between lower serum Mg levels and the occurrence of DR (OR were 3.907 and 1.709 in Q1 and Q2, respectively) no matter whether the interference of confounding variables. ROC curve showed the best cut-off value of serum Mg level in predicting the occurrence of DR was 0.875 mmol/L. Lower Mg levels are related with an increased risk of developing DR. Serum Mg level can be a potential clinical indicator to help identify DR in patients with T2DM.
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http://dx.doi.org/10.1007/s12011-021-02824-wDOI Listing
May 2022

Mutation of the novel acetylation site at K414R of BECN1 is involved in adipocyte differentiation and lipolysis.

J Cell Mol Med 2021 07 4;25(14):6855-6863. Epub 2021 Jun 4.

Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, China.

BECN1, a protein essential for autophagy, is involved in adipocyte differentiation, lipolysis and insulin resistance. The discovery of new mechanisms for modifying BECN1 in adipocytes may provide novel therapeutic targets for obesity. This study aimed to investigate the impact of mutations at the acetylation sites of BECN1 on adipocyte differentiation and lipolysis. We found that Ace-BECN1 levels were increased in 3T3-L1 adipocyte differentiation and isoproterenol-/TNF-α-stimulated lipolysis and in subcutaneous and visceral adipose tissues of high-fat diet mice. K414 was identified as an acetylation site of BECN1, which affects the stability of the BECN1 protein. Mutation at K414 of BECN1 affected autophagy, differentiation and lipolysis in 3T3-L1 adipocytes. These data indicated the potential of BECN1 K414 as a key molecule and a drug target for regulating autophagy and lipid metabolism in adipocytes.
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http://dx.doi.org/10.1111/jcmm.16692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278081PMC
July 2021

Molecular Mechanisms Underlying Reciprocal Interactions Between Sleep Disorders and Parkinson's Disease.

Front Neurosci 2020 10;14:592989. Epub 2021 Feb 10.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Sleep-wake disruptions are among the most prevalent and burdensome non-motor symptoms of Parkinson's disease (PD). Clinical studies have demonstrated that these disturbances can precede the onset of typical motor symptoms by years, indicating that they may play a primary function in the pathogenesis of PD. Animal studies suggest that sleep facilitates the removal of metabolic wastes through the glymphatic system convective flow from the periarterial space to the perivenous space, upregulates antioxidative defenses, and promotes the maintenance of neuronal protein homeostasis. Therefore, disruptions to the sleep-wake cycle have been associated with inefficient metabolic clearance and increased oxidative stress in the central nervous system (CNS). This leads to excessive accumulation of alpha-synuclein and the induction of neuronal loss, both of which have been proposed to be contributing factors to the pathogenesis and progression of PD. Additionally, recent studies have suggested that PD-related pathophysiological alterations during the prodromal phase disrupt sleep and circadian rhythms. Taken together, these findings indicate potential mechanistic interactions between sleep-wake disorders and PD progression as proposed in this review. Further research into the hypothetical mechanisms underlying these interactions would be valuable, as positive findings may provide promising insights into novel therapeutic interventions for PD.
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http://dx.doi.org/10.3389/fnins.2020.592989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902929PMC
February 2021

Zonisamide for the Treatment of Parkinson Disease: A Current Update.

Front Neurosci 2020 21;14:574652. Epub 2020 Dec 21.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.

Zonisamide has been used as an add-on treatment in order to overcome the deficiencies of the general therapies currently used to resolve the motor complications and non-motor symptoms of Parkinson disease. Various trials have been designed to investigate the mechanism of action and treatment effects of zonisamide in this condition. Most clinical trials of zonisamide in Parkinson disease were from Japan. The vast majority of studies used changes in the Unified Parkinson's Disease Rating Scale (UPDRS) scores and daily "OFF" time as primary endpoints. Based on adequate randomized controlled trials, zonisamide is considered a safe and efficacious add-on treatment in Parkinson disease. The most convincing proof is available for a dosage of 25-50 mg, which was shown to lead to a significant reduction in the UPDRS III score and daily "OFF" time, without increasing disabling dyskinesia. Furthermore, zonisamide may play a beneficial role in improving non-motor symptoms in PD, including impulsive-compulsive disorder, rapid eye movement sleep behavior disorder, and dementia. Among the various mechanisms reported, inhibition of monoamine oxidase-B, blocking of T-type calcium channels, modulation of the levodopa-dopamine metabolism, modulation of receptor expression, and neuroprotection are the most often cited. The mechanisms underlying neuroprotection, including modulation of dopamine turnover, induction of neurotrophic factor expression, inhibition of oxidative stress and apoptosis, inhibition of neuroinflammation, modulation of synaptic transmission, and modulation of gene expression, have been most extensively studied. This review focuses on structure, pharmacokinetics, mechanisms, therapeutic effectiveness, and safety and tolerability of zonisamide in patients with Parkinson disease.
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http://dx.doi.org/10.3389/fnins.2020.574652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779619PMC
December 2020

Association of non-alcoholic fatty liver disease with diabetic retinopathy in type 2 diabetic patients: A meta-analysis of observational studies.

J Diabetes Investig 2021 Aug 1;12(8):1471-1479. Epub 2021 Feb 1.

Department of Endocrine and Metabolic Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China.

Aims/introduction: Non-alcoholic fatty liver disease (NAFLD) is becoming more and more prevalent in type 2 diabetes mellitus. Evidence connecting NAFLD to diabetic retinopathy (DR) is increasing, but the results vary. Thus, we undertook a meta-analysis to explore the effect of NAFLD on diabetic retinopathy in patients with type 2 diabetes mellitus.

Materials And Methods: PubMed, Embase, Cochrane and Scopus database were searched for until September 30, 2019. Original studies analyzing the association between NAFLD and diabetic retinopathy in the type 2 diabetic population were included. This meta-analysis was processed by RevMan 5.3 software. Subgroup analyses based on countries were carried out. The pooled odds ratios and 95% confidence intervals were used to evaluate the association between NAFLD and diabetic retinopathy incidence. The I test was used to assess heterogeneity of studies.

Results: We retrieved 414 articles, and nine studies involving 7,170 patients were included in the final analysis. The pooled effects estimate suggested that NAFLD was not associated with the risk of diabetic retinopathy in patients with type 2 diabetes mellitus. Subgroup analysis suggested that in China, Korea and Iran, patients with type 2 diabetes mellitus with NAFLD had a decreased risk for diabetic retinopathy compared with the non-NAFLD individuals. However, in Italy and India, patients with type 2 diabetes mellitus with NAFLD had an increased risk for diabetic retinopathy compared with the non-NAFLD individuals. In addition, no relevance between NAFLD and diabetic retinopathy was found in America.

Conclusions: On the whole, there was no association between NAFLD and diabetic retinopathy in individuals with type 2 diabetes mellitus. However, subgroup analysis showed that a difference of country may have an influence on the result.
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http://dx.doi.org/10.1111/jdi.13489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354494PMC
August 2021

Ultra-rapid delivery of specialty field hospitals to combat COVID-19: Lessons learned from the Hospital project in Wuhan.

Autom Constr 2020 Nov 4;119:103345. Epub 2020 Jul 4.

Central-South Architectural Design Institute, Wuhan, Hubei, China.

With the outbreak of the 2019 novel coronavirus (COVID-19) epidemic in Wuhan, China, in January 2020, the escalating number of confirmed and suspected cases overwhelmed the admission capacity of the designated hospitals. Two specialty field hospitals- and -were designed, built and commissioned in record time (9-12 days) to address the outbreak. This study documents the design and construction of Hospital. Based on data collected from various sources such as the semi-structured interviews of key stakeholders from Hospital, this study found that adhering to a product, organization, and process (POP) modeling approach combined with building information modeling (BIM) allowed for the ultra-rapid creation, management, and communication of project-related information, resulting in the successful development of this fully functional, state-of-the-art infectious disease specialty hospital. With the unfortunate ongoing international COVID-19 outbreak, many countries and regions face similar hospital capacity problems. It is thus expected that the lessons learned from the design, construction and commissioning of Hospital can provide a valuable reference to the development of specialty field hospitals in other countries and regions.
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http://dx.doi.org/10.1016/j.autcon.2020.103345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334964PMC
November 2020

The effects and safety of activators of glucokinase versus placebo in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

Endocr J 2021 Feb 1;68(2):189-194. Epub 2020 Oct 1.

Department of Endocrinology and Metabolism, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

We undertook a systematic review and meta-analysis to assess the effects and safety of activators of glucokinase (GKAs) in patients with type 2 diabetes mellitus (T2DM). 11 RCTs, including 2,429 participants, are enrolled in our study. According to different doses, we divided the studies into 3 groups: low-dose group, medium-dose group and high-dose group for subgroup analysis. There were decreases of HbA1c in all dose group (WMD = -0.27, 95%CI (-0.51~ -0.03), Z = 2.17, p = 0.03; WMD = -0.37, 95%CI (-0.58~ -0.16), Z = 3.41, p = 0.0006; WMD = -0.60, 95%CI (-0.86~ -0.33), Z = 4.43, p < 0.00001). Though the total risk of hypoglycemia is absolutely low, in the high-dose group higher hypoglycemia than the placebo can be observed (RR = 0.03, 95%CI (0.00~0.06), Z = 2.27, p = 0.02). In addition, the study found that the drug was less likely to have adverse reactions such as diarrhea, headache and dizziness, nasopharyngitis and upper respiratory tract infection (RR = 0.76, 95%CI (0.36~1.60), Z = 0.73, p = 0.47; RR = 1.26, 95%CI (0.73~2.17), Z = 0.83, p = 0.41; RR = 0.71, 95%CI (0.41~1.22), Z = 1.25, p = 0.21; RR = 1.61, 95%CI (0.77~3.36), Z = 1.26, p = 0.21). It concludes that GKAs are relatively effective and safe in the treatment of patients with T2DM, but in consideration of the potential risk of hypoglycemia in the high-dose group, the low-dose and medium-dose group, in the clinical practice, can be an excellent choice.
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http://dx.doi.org/10.1507/endocrj.EJ20-0286DOI Listing
February 2021

Effects of irisin on osteoblast apoptosis and osteoporosis in postmenopausal osteoporosis rats through upregulating Nrf2 and inhibiting NLRP3 inflammasome.

Exp Ther Med 2020 Feb 10;19(2):1084-1090. Epub 2019 Dec 10.

Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.

The nuclear factor E2-related factor 2 (Nrf2)/NLR family, pyrin domain containing protein 3 (NLRP3) plays an important role in osteoporosis (OP), so the effects of irisin on postmenopausal OP rats and osteoblast apoptosis through Nrf2/NLRP3 were explored in the present study. A total of 45 specific pathogen-free Sprague-Dawley rats were selected and divided into OP model group (OP group, n=15), 1 mmol/l irisin treatment group (irisin group, n=15) and normal control group (control group, n=15). After the trial period, the content of serum ALP was detected, the levels of tumor necrosis factor-α (TNF-α) in the serum and bone tissues were observed via ELISA, and the bone microstructure was observed via CT. Osteoblast apoptosis was determined through TUNEL assay, the content of apoptosis genes caspase-3 and Bcl-2, and key genes in Runt-related transcription factor 2 (Runx2), osteocalcin (OC), Nrf2 and NLRP3 was detected via RT-PCR. The protein expression of Bcl-2, Nrf2 and NLRP3 was determined via western blotting. The serum ALP level was increased in OP group compared with that in control group (P<0.05), while it declined in the irisin group. The content of TNF-α and interleukin-6 (IL-6) was significantly higher in OP group, while the content in the irisin group was close to that in the control group. The trabecular thickness, number and bone mineral density in the irisin group were all obviously larger and higher, respectively, than those in the OP group. The mRNA expression of Runx2, OC, Bcl-2 and Nrf2 in the irisin group were obviously higher (P<0.05), while that of caspase-3 and NLRP3 showed the opposite trends. The protein expression of Bcl-2 and Nrf2 in the irisin group was remarkably higher than those in the OP group, while that of NLRP3 was the opposite. irisin can upregulate Nrf2, inhibit NLRP3 inflammasome and lower the content of inflammatory factors, thereby suppressing osteoblast apoptosis in postmenopausal OP rats and reducing the incidence of postmenopausal OP.
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http://dx.doi.org/10.3892/etm.2019.8313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966163PMC
February 2020

Risk analysis and management for highway operations safety using a covariate-balanced determinant detector.

Accid Anal Prev 2019 Dec 1;133:105290. Epub 2019 Oct 1.

Department of Construction Management, School of Civil Engineering & Mechanics, Huazhong University of Science & Technology, Wuhan, Hubei, China.

Highway operations are marred with inherent risks of injury or death, making risk management critical for ensuring the adequate safety of the people involved. This paper investigates the interaction between various highway safety risk factors and effective risk mitigation strategies related to such interaction. The Covariate-Balanced Determinant Detector (CBDD) technique is used to estimate the quantity of both individual and combined risks, and their effect on highway operations safety. Through this technique, the most dangerous risk combinations have been identified and corresponding risk mitigation scenarios have been developed. The results illustrate that the most dangerous scenarios probably result from the interactive effect of risk factors rather than individual factors, and the effect of mitigation strategies should be evaluated in response to a risk scenario before it is implemented.
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http://dx.doi.org/10.1016/j.aap.2019.105290DOI Listing
December 2019

Detection and Structural Characterization of Nucleophiles Trapped Reactive Metabolites of Limonin Using Liquid Chromatography-Mass Spectrometry.

J Anal Methods Chem 2018 17;2018:3797389. Epub 2018 Apr 17.

Department of Endocrinology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266071, China.

Limonin (LIM), a furan-containing limonoid, is one of the most abundant components of Turcz. Recent studies demonstrated that LIM has great potential for inhibiting the activity of drug-metabolizing enzymes. However, the mechanisms of LIM-induced enzyme inactivation processes remain unexplored. The main objective of this study was to identify the reactive metabolites of LIM using liquid chromatography-mass spectrometry. Three nucleophiles, glutathione (GSH), -acetyl cysteine (NAC), and -acetyl lysine (NAL), were used to trap the reactive metabolites of LIM in and models. Two different types of mass spectrometry, a hybrid quadrupole time-of-flight (Q-TOF) mass spectrometry and a LTQ velos Pro ion trap mass spectrometry, were employed to acquire structural information of nucleophile adducts of LIM. In total, six nucleophile adducts of LIM (M1-M6) with their isomers were identified; among them, M1 was a GSH and NAL conjugate of LIM, M2-M4 were glutathione adducts of LIM, M5 was a NAC and NAL conjugate of LIM, and M6 was a NAC adduct of LIM. Additionally, CYP3A4 was found to be the key enzyme responsible for the bioactivation of limonin. This metabolism study largely facilitates the understanding of mechanisms of limonin-induced enzyme inactivation processes.
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http://dx.doi.org/10.1155/2018/3797389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932435PMC
April 2018

Hashimoto's Thyroiditis is an Important Risk Factor of Papillary Thyroid Microcarcinoma in Younger Adults.

Horm Metab Res 2017 Oct 31;49(10):732-738. Epub 2017 Aug 31.

Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, China.

The association between autoimmune thyroid disease and thyroid cancer remains unclear. We performed a matched case-control study to assess the association between Hashimoto's thyroiditis and papillary thyroid microcarcinoma (PTMC). A total of 927 PTMC cases and 927 age- and gender- matched controls selected from the same population were recruited. Odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the strength of the association between Hashimoto's thyroiditis and PTMC. Conditional logistic regression analysis was carried out, and stratified analyses by age, gender and types of thyroid antibodies were also performed. Hashimoto's thyroiditis was significantly associated with increased risk of PTMC (OR=1.87, 95% CI 1.49-2.34, p<0.001). Stratified analysis by thyroid antibodies also found obvious associations of PTMC risk with TPOAb positivity (OR=1.58, p=0.001) and TGAb positivity (OR=2.35, p<0.001). Stratified analyses by age showed that the association between Hashimoto's thyroiditis and PTMC risk was more significant in younger adults aged between 18 and 30 years (OR=11.48, p<0.001). Further stratified analyses by thyroid antibodies also found that the associations of PTMC risk with TPOAb positivity or TGAb positivity were more significant in younger adults aged between 18 and 30, and the ORs were 8.27 (p<0.001) and 12.71 (p<0.001), respectively. This study suggests an obvious relationship between Hashimoto's thyroiditis and PTMC risk, and Hashimoto's thyroiditis is an important risk of PTMC in younger adults.
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http://dx.doi.org/10.1055/s-0043-117892DOI Listing
October 2017

Expressions of miRNAs in papillary thyroid carcinoma and their associations with the clinical characteristics of PTC.

Cancer Biomark 2017 ;18(1):87-94

Endocrinology Department, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Background: The sensitivity and specificity of biomarkers which have been used in clinical practice for diagnosis of papillary thyroid carcinoma (PTC) are low, it is essential to develop novel diagnostic and prognostic biomarkers for PTC.

Objective: To explore the expressions of miR-940, miR-15a, miR-16 and IL-23 in PTC tissues and plasma and their associations with the clinical characteristics of PTC.

Methods: We investigated the expressions of miR-940, miR-15a, miR-16 and IL-23 in plasma and thyroid tissues of PTC, nodular goiter and healthy people with qRT-PCR, and further analyzed the associations between their levels and the clinical characteristics of PTC.

Results: Level of IL-23 expression was higher while levels of miR-940, miR-15a and miR-16 expression in the PTC tissues were lower compared with the nodular goiter tissues and perineoplastic thyroid tissues. And the levels of miR-940, miR-15a, miR-16 and IL-23 expression in the PTC tissues were associated with some clinical characteristics of PTC, including bilateral tumor, multicentricity, extrallyroidal invasion, cervical lymph node metastasis, distant metastasis and clinical advanced stages (III/IV).

Conclusions: Expressions of miR-940, miR-15a, miR-16 and IL-23 in PTC tissues might be useful biomarkers and promising targets in the diagnosis of papillary thyroid carcinoma.
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http://dx.doi.org/10.3233/CBM-161723DOI Listing
March 2017

HDL cholesterol and risk of diabetic nephropathy in patient with type 1 diabetes: A meta-analysis of cohort studies.

Diabetes Res Clin Pract 2016 Dec 20;122:84-91. Epub 2016 Oct 20.

Laboratory of Thyroid Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China. Electronic address:

A meta-analysis was conducted to assess the impact of HDL on risk of diabetic nephropathy in T1DM patients. Ten papers containing (7698) participants were included in this meta-analysis. Our meta-analysis suggest that the risk of diabetic nephropathy was decreased with HDL in type 1 diabetes.
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http://dx.doi.org/10.1016/j.diabres.2016.10.013DOI Listing
December 2016

Study on biomass based nanofibers preparation by electrospinning.

J Nanosci Nanotechnol 2014 Sep;14(9):7204-10

The electrospinnability of lignin was improved by blending in a solution of polyacrylonitrile (PAN) resulting in the reduction of the nanofiber cost. The compositions containing low concentration of the lignin shows good spinnability. The influences of main process parameters, such as flow rate, voltage and concentration on the nanofibers morphology were studied by scanning electron microscope (SEM). The results indicated that by changing parameters, nanofibers with good morphology were obtained. According to the study, when other parameters were kept unchanged, the parameters to prepare ideal nanofibers are as follows: flow rate is 0.04 mm/h; the voltage is 25 kV and the lignin amount is 2 wt.%. The results of this work showed that this novel method is a quite promising technique for preparation of biomass based carbon nanofiber precursors.
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http://dx.doi.org/10.1166/jnn.2014.8976DOI Listing
September 2014

Associations of miR-146a and miR-146b expression and clinical characteristics in papillary thyroid carcinoma.

Cancer Biomark 2015 ;15(1):33-40

Endocrinology Department, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Background: Human miRNAs have emerged as potentially useful diagnostic and prognostic markers in cancer within the past decade. Abnormal expression of microRNA-146 (miR-146) has been found in several classes of cancers.

Objective: To explore expression and clinical associations of miR-146a and miR-146b in papillary thyroid carcinoma.

Methods: We investigated expressions of miR-146a and miR-146b in tissues and peripheral blood among 128 patients with primary PTC, 120 patients with nodular goiter and 120 healthy controls by RT-PCR. Furthermore, the associations between the miR-146a and miR-146b expression and clinical parameters of PTC were analyzed.

Results: Levels of miR-146a and miR-146b expression in PTC tissues were higher compared to the nodular goiter tissues (P=0.014 and 0.001) and perineoplastic thyroid tissues (P=0.023 and 0.002). Positive associations were found between levels of miR-146a expression in PTC tissues and gender (female), cervical lymph node metastasis, multifocality, extra tyroidal invasion and advanced clinical TNM stages (III and IV). For miR-146b, there were positive association between levels of miR-146b expression and female, extra tyroidal invasion and advanced clinical TNM stages.

Conclusions: Up-regulation of miR-146a and miR-146b expression in tissues was related to carcinogenesis and deterioration of PTC. MicroRNA-146a and miR-146b expressed in thyroid tissue may act as potential biomarkers for PTC patients.
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http://dx.doi.org/10.3233/CBM-140431DOI Listing
August 2015

Main air pollutants and diabetes-associated mortality: a systematic review and meta-analysis.

Eur J Endocrinol 2014 Nov;171(5):R183-90

Department of EndocrinologyThe Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, ChinaDepartment of RheumatologyFirst Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaEssencemed ClinicWeifang 261000, China

Objective: Exposure to high levels of air pollutants may be linked to diabetes-associated mortality, but the associations remain unclear. To assess the associations between main air pollutants and diabetes-associated mortality, a systematic review and meta-analysis was performed.

Methods: PubMed, Embase and Web of Science were searched for studies investigating the associations between increments in gaseous (nitrogen dioxide (NO2), sulphur dioxide, ozone (O3) and carbon monoxide) and particulate matter (PM; diameter<2.5 μm (PM2.5) or <10 μm (PM10)) air pollutants and diabetes-associated mortality. Using a random-effects model, relative risks (RRs) and 95% CIs were calculated per interquartile range (IQR) increment or per 10 μg/m3 increment in pollutant concentrations.

Results: Out of 925 identified articles, 36 were reviewed in depth and 12 studies from 13 articles satisfying the inclusion criteria (five time-series, five case-crossovers and two cohorts) were finally included. Increased risk of diabetes-associated mortality was associated with higher levels of PM2.5 (per 10 μg/m3: RR=1.123, 95% CI 1.036-1.217, P=0.005, I2=96.1%), PM10 (per 10 μg/m3: RR=1.008, 95% CI 1.004-1.013, P<0.001, I2=0%), NO2 (per 10 μg/m3: RR=1.024, 95% CI 1.007-1.041, P=0.006, I2=49.7%) and O3 (per IQR increment: RR=1.065, 95% CI 1.017-1.115, P=0.007, I2=0.0%). No obvious risk of publication bias was observed.

Conclusions: Exposure to high levels of air pollutants is significantly associated with an increased risk of diabetes-associated mortality.
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http://dx.doi.org/10.1530/EJE-14-0287DOI Listing
November 2014

Blood 25-hydroxyvitamin D levels and overall mortality in patients with colorectal cancer: a dose-response meta-analysis.

Eur J Cancer 2014 Aug 27;50(12):2173-5. Epub 2014 May 27.

Department of Endocrinology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, China. Electronic address:

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http://dx.doi.org/10.1016/j.ejca.2014.05.004DOI Listing
August 2014

Ghrelin but not nesfatin-1 affects certain forms of learning and memory in both rats and mice.

Brain Res 2013 Dec 19;1541:42-51. Epub 2013 Oct 19.

Department of Physiology, Medical College of Qingdao University, Qingdao, Shandong 266071, China.

Ghrelin and nesfatin-1 are two recently discovered peptide hormones that play opposite roles in the food intake, body-weight control and energy homeostasis in both human and rodents. Beyond its appetite-control function, increasing evidence has shown that ghrelin affects multiple advanced activities in the central nervous system, including memory and emotion. Nesfatin-1 was also widely expressed in extra-hypothalamic brain regions including hippocampus and amygdala. However, the possible actions of nesfatin-1 in those important brain regions are largely unknown. In this study, we micro-infused ghrelin or nesfatin-1 into the lateral amygdala (LA) or area CA1 of the dorsal hippocampus (CA1) and investigated the immediate effects of those two peptide hormones on cognitive and affective behaviors. We found that the micro infusion of ghrelin into the LA or the CA1 interfered with certain types of learning and memory in both rats and mice, while nesfatin-1 had no effect. Our data thus suggested that although nesfatin-1 works as a functional antagonist of ghrelin in the feeding control, only ghrelin affects learning and memory.
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http://dx.doi.org/10.1016/j.brainres.2013.10.022DOI Listing
December 2013

Long term effects of the implantation of autologous bone marrow mononuclear cells for type 2 diabetes mellitus.

Endocr J 2012 13;59(11):1031-9. Epub 2012 Jul 13.

Stem Cell Research Center, the Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, China.

Previous studies have shown that several types of stem cells can differentiate into insulin-secreting islet beta-cells and that these cells can reduce blood glucose in some trials, but there has been no report of a long-term follow-up. We assessed the long-term effects of the use of autologous bone marrow mononuclear cells in the treatment of type 2 diabetes mellitus (T2DM). Based on the willingness to receive implantation of bone marrow mononuclear cells, One hundred and eighteen patients with T2DM were divided into two groups; the patients in group I were treated with autologous bone marrow mononuclear cells and patients in group II were treated with insulin intensification therapy. Mononuclear cells from bone marrow were injected back into the patient's pancreas via a catheter. Patients were followed-up after the operation at monthly intervals for the first 3 months and thereafter every 3 months for the next 33 months, the occurrence of any side effects and the results of laboratory examinations were evaluated. There were no reported acute or chronic side effects in group I and both the HbA1c and C-peptide in group I patients were significantly better than either pretherapy values or group II patients during the follow-up period. These data suggested that the implantation of autologous bone marrow mononuclear cells for the treatment of T2DM is safe and effective. This therapy can partially restore the function of islet beta-cells and maintain blood glucose homeostasis in a longer time.
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http://dx.doi.org/10.1507/endocrj.ej12-0092DOI Listing
May 2013
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