Publications by authors named "Shen Qu"

240 Publications

Serum superoxide dismutase activity: a sensitive, convenient, and economical indicator associated with the prevalence of chronic type 2 diabetic complications, especially in men.

Free Radic Res 2021 Jun 14:1-7. Epub 2021 Jun 14.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

To investigate the relationship between serum superoxide dismutase (SOD) activity and the presence of chronic complications in patients with type 2 diabetes mellitus (T2DM). We conducted a retrospective cross-sectional study in patients with T2DM. They were assigned to three groups (Q1, Q2, and Q3) by SOD levels in both sexes. Clinical characteristics, cardiovascular disease, diabetic retinopathy, nephropathy, and peripheral neuropathy were compared. The relationship between the SOD and the prevalence of chronic complications was analyzed by binary logistic regression. Statistical analysis was performed in SPSS 26.0 (SPSS Inc., Chicago, IL). A total of 645 T2DM patients (401 men and 244 women) with complete data for SOD and medical records of complications were included. In men, patients in the Q1 group (lowest serum SOD activity) had the highest prevalence of diabetes with atherosclerosis (AS) (<.001), DN (=.029), and DPN (=.001). In comparison, only DN was found to have the highest prevalence in the Q1 group in women (=.010). In the multivariate analysis, patients in the Q1 group had a 3.0-, 1.6-, 1.9-, and 2.4-fold risk for the prevalence of AS, DR, DN, and DPN, respectively, compared with the Q3 group. In women, a 7.0-fold risk for the prevalence of DN in the Q1 group was found compared with the Q3 group. After adjusting for the age, duration of T2DM, body mass index, pulse pressure, alanine transaminase, clearance of creatinine, triglyceride, glycosylated hemoglobin, and fasting C-peptide in the models, the differences found in both men and women persisted. SOD activity is related to cardiovascular and microvascular diseases in men and the prevalence of diabetic nephropathy in women in T2DM.
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http://dx.doi.org/10.1080/10715762.2021.1937146DOI Listing
June 2021

Estimation of Unit Process Data for Life Cycle Assessment Using a Decision Tree-Based Approach.

Environ Sci Technol 2021 May 29. Epub 2021 May 29.

School for Environment and Sustainability, University of Michigan, Ann Arbor, Michigan 48109, United States.

Lacking unit process data is a major challenge for developing life cycle inventory (LCI) in life cycle assessment (LCA). Previously, we developed a similarity-based approach to estimate missing unit process data, which works only when less than 5% of the data are missing in a unit process. In this study, we developed a more flexible machine learning model to estimate missing unit process data as a complement to our previous method. In particular, we adopted a decision tree-based supervised learning approach to use an existing unit process dataset (ecoinvent 3.1) to characterize the relationship between the known information (predictors) and the missing one (response). The results show that our model can successfully classify the zero and nonzero flows with a very low misclassification rate (0.79% when 10% of the data are missing). For nonzero flows, the model can accurately estimate their values with an over 0.7 when less than 20% of data are missing in one unit process. Our method can provide important data to complement primary LCI data for LCA studies and demonstrates the promising applications of machine learning techniques in LCA.
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http://dx.doi.org/10.1021/acs.est.0c07484DOI Listing
May 2021

An improved lentiviral system for efficient expression and purification of β-defensins in mammalian cells.

Biotechnol J 2021 May 30:e2100023. Epub 2021 May 30.

Department of Endocrinology and Metabolism, School of Medicine, Shanghai Tenth People's Hospital of Tongji University, No. 301 Middle Yanchang Road, Shanghai, 200072, China.

β-defensins are a family of conserved small cationic antimicrobial peptides with different significant biological functions. The majority of mammalian β-defensins are expressed in epididymis, and many of them are predicted to have post-translational modifications. However, only a few of its members have been well studied due to the limitations of expressing and purifying bioactive proteins with correct post-translational modifications efficiently. Here we developed a novel Fc tagged lentiviral system and Fc tagged prokaryotic expression systems provided new options for β-defensins expression and purification. The novel lentiviral system contains a secretive signal peptide, a N-terminal IgG Fc tag, a green fluorescent protein (GFP), and a puromycin selection marker to facilitate efficient expression and fast purification of β-defensins by protein A magnetic or agarose beads. It also enables stable and large-scale expression of β-defensins with regular biological activities and post-translational modification. Purified β-defensins such as Bin1b and a novel human β-defensin hBD129 showed antimicrobial activity, immuno-regulatory activity, and expected post-translational phosphorylation, which were not found in Escherichia coli (E. coli) expressed form. Furthermore, we successfully applied the novel system to identify mBin1b interacting proteins, explaining Bin1b in a better way. These results suggest that the novel lentiviral system is a powerful approach to produce correct post-translational processed β-defensins with bioactivities and is useful to identify their interacting proteins. This study has laid the foundation for future studies to characterize function and mechanism of novel β-defensins. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/biot.202100023DOI Listing
May 2021

Musculoskeletal ultrasound features-based scoring system can evaluate the severity of gout and asymptomatic hyperuricaemia.

Ther Adv Musculoskelet Dis 2021 12;13:1759720X211006985. Epub 2021 May 12.

Department of Endocrinology and Metabolism, Shanghai 10th People's Hospital, School of Medicine, Tongji University, 301 Yanchang Road, Shanghai 200072, China.

Objectives: To develop a tool which can evaluate the severity of the joint injury in individuals with gout and asymptomatic hyperuricaemia.

Methods: This retrospective study included 616 male patients: 245 with asymptomatic hyperuricaemia and 371 with intercritical gout. All patients underwent ultrasonography of the knee, ankle and first metatarsophalangeal (MTP) joints. Ultrasound features that were significantly different between groups were entered into a binary logistic regression analysis to identify discriminative factors. The ultrasound signs were scored based on their odds ratios, which were then used to evaluate the severity of gout and asymptomatic hyperuricaemia. The performance of the ultrasound score was validated in an additional population including 163 patients with asymptomatic hyperuricaemia and 196 patients with gout.

Results: Ultrasound signs were scored as follows: knee joint: synovial effusion, 2 points, tophus, 5 points; ankle joint: synovial effusion, 2 points, synovial hypertrophy, 5 points, tophus, 3 points, bone erosion, 7 points; and first MTP joint: double contour sign, 2 points, synovial hypertrophy, 3 points, tophus, 9 points, bone erosion, 4 points. The maximum possible total score was 42. The optimal cut-off score for gout was 6.5. The sensitivity, specificity and area under the receiver operating characteristic curve (AUC) were 86.9%, 75.2% and 0.878, respectively. The patients were stratified according to their ultrasound score (range 0-42). The prevalence of intercritical gout, tophi, and bone erosion increased with the increase of the score. In the validation population, 83.20% of 193 patients with gout had ultrasound scores above 6.5; 76.10% of 163 patients with asymptomatic hyperuricaemia had ultrasound scores under 6.5.

Conclusion: The scoring system based on the differential ultrasound signs can effectively evaluate the severity of joint injury in individuals with gout and asymptomatic hyperuricaemia.
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http://dx.doi.org/10.1177/1759720X211006985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120533PMC
May 2021

Immune Phenotyping of Patients With Acute Vogt-Koyanagi-Harada Syndrome Before and After Glucocorticoids Therapy.

Front Immunol 2021 28;12:659150. Epub 2021 Apr 28.

Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Previous studies have established that disturbed lymphocytes are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) syndrome. Accordingly, glucocorticoids (GCs), with their well-recognized immune-suppressive function, have been widely used for treatment of VKH patients with acute relapses. However, the systemic response of diverse immune cells to GC therapy in VKH is poorly characterized. To address this issue, we analyzed immune cell subpopulations and their phenotype, as well as cytokine profiles in peripheral blood from VKH patients (n=25) and health controls (HCs, n=21) by flow cytometry and luminex technique, respectively. For 16 patients underwent GC therapy (methylprednisolone, MP), the aforementioned measurements as well as the transcriptome data from patients before and after one-week's GC therapy were also compared to interrogate the systemic immune response to GC therapy. Lymphocyte composition in the blood was different in VKH patients and HCs. VKH patients had significantly higher numbers of T cells with more activated, polarized and differentiated phenotype, more unswitched memory B cells and monocytes, as compared to HCs. MP treatment resulted in decreased frequencies of T cells and NK cells, inhibited NK cell activation and T cell differentiation, and more profoundly, a marked shift in the distribution of monocyte subsets. Collectively, our findings suggest that advanced activation and differentiation, as well as dysregulated numbers of peripheral lymphocytes are the major immunological features of VKH, and GC therapy with MP not only inhibits T cell activation directly, but also affects monocyte subsets, which might combinatorically result in the inhibition of the pathogenic immune response.
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http://dx.doi.org/10.3389/fimmu.2021.659150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113950PMC
April 2021

Glucagon-like Peptide-1 Improves Fatty Liver and Enhances Thermogenesis in Brown Adipose Tissue via Inhibiting BMP4-Related Signaling Pathway in High-Fat-Diet-Induced Obese Mice.

Int J Endocrinol 2021 26;2021:6620289. Epub 2021 Apr 26.

Thyriod Research Center of Shanghai, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Tongji University, Shanghai 200072, China.

Objective: Glucagon-like peptide-1 (GLP-1) receptor agonist is effective in decreasing blood glucose and body weight. It could improve fatty liver with unclear mechanisms. Hence, we aimed to explore whether GLP-1 could improve fatty liver by regulating the BMP4-related signaling pathway.

Methods: Fifteen C57BL/6 mice were randomly assigned to 3 groups. Group A and Group B were fed with a high-fat diet (HFD) to induce fatty liver while Group C was fed with a regular diet (RD) for 24 weeks. Group A and Group B received a subcutaneous injection of exenatide and vehicle (0.9% NaCl), respectively, once daily at doses of 10 nmol/kg during the last 8 weeks. Bodyweight, liver weight, and lipid levels were measured. Histological analyses of liver tissue were performed. The expression of protein and gene measured by western blotting and real-time polymerase chain reaction (RT-PCR) was compared.

Results: Eight-week exenatide treatment significantly decreased body weight in Group A (from 44.08 ± 2.89 g to 39.22 ± 1.88 g,  = 0.045). Group A had lower body weight and liver weight than Group B at 24 weeks (39.22 ± 1.88 g vs. 47.34 ± 2.43 g,  = 0.001 and 1.70 ± 0.20 g vs. 2.48 ± 0.19 g,  = 0.001, respectively). Moreover, Group A showed significantly less liver steatosis than Group B. Additionally, Group A led to slightly decreased serum triglyceride (TG) and cholesterol (TC) levels compared to Group B. Western blotting showed that exenatide could prevent HFD-induced upregulation of BMP4 levels and downstream activation of Smad1/5/8 and the P38 MAPK signaling pathway in the liver. Furthermore, exenatide treatment could reduce BMP4 and enhance UCP-1 (an important thermogenin) in brown adipose tissue (BAT).

Conclusion: Exenatide could improve HFD-induced hepatic steatosis and enhance thermogenesis in BAT, which may be partly attributed to the inhibition of the BMP4-related signaling pathway.
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http://dx.doi.org/10.1155/2021/6620289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093078PMC
April 2021

Effects of Internet-Based Support Program on Parenting Outcomes for Primiparous Women: A Pilot Study.

Int J Environ Res Public Health 2021 04 21;18(9). Epub 2021 Apr 21.

Health Science Centre, Shenzhen University, Shenzhen 518060, China.

(1) Some primiparous women are usually confronted with many parenting problems after childbirth, which can negatively influence the wellbeing of some mothers and infants. Evidence identified that internet interventions can include more tailored information, reach a larger research group, and supply more anonymity than face-to-face traditional interventions. Therefore, the internet-based support program (ISP) was designed to improve the parenting outcomes for Chinese first-time mothers. (2) : A multicenter, single-blinded, pilot randomized controlled trial was conducted. From May to October 2020, a total of 44 participants were recruited in the obstetrical wards of two tertiary hospitals in China. Eighteen women in the control group received routine postnatal care; while eighteen women in the intervention group accessed to the ISP and routine postnatal care. The duration of intervention was not less than three months. Intervention outcomes were assessed through questionnaires before randomization (T0), immediately after intervention (T1), and three months after intervention (T2). The Self-efficacy in Infant Care Scale (SICS), Edinburgh Postnatal Depression Scale (EPDS), and Postpartum Social Support Scale (PSSS) were included to measure MSE, postpartum depression (PPD), and social support, respectively. (3) No significant difference between the two groups were found in terms of the baseline social-demographic characteristics; and the scores of SICS, EPDS and PSSS at T0 ( > 0.05). Repeated measures multivariate analysis of covariance found that women in the intervention group had a higher MSE score at T1 (6.63, = 0.007), and T2 (5.75, = 0.020); a lower EPDS score at T1 (3.11, = 0.003), and T2 (2.50, = 0.005); and a higher PSSS score at T1 (4.30, = 0.001); and no significant difference at T2 (0.35, = 0.743), compared with women in the control group. (4) : The effect of ISP was evaluated to significantly increase primiparous women's MSE, social support, and to alleviate their PPD symptoms. However, the small sample in pilot study restricted the research results. Therefore, the ISP should be further investigated with a larger, diverse sample to confirm whether it should be adopted as routine postnatal care to support primiparous women on parenting outcomes and mental wellbeing in the early stage of motherhood.
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http://dx.doi.org/10.3390/ijerph18094402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122326PMC
April 2021

Horeau amplification in the sequential acylative kinetic resolution of (±)-1,2-diols and (±)-1,3-diols in flow.

Org Biomol Chem 2021 Apr;19(16):3620-3627

EaStCHEM, School of Chemistry, University of St Andrews, St Andrews, Fife KY16 9ST, UK.

The sequential acylative kinetic resolution (KR) of C2-symmetric (±)-1,2-syn and (±)-1,3-anti-diols using a packed bed microreactor loaded with the polystyrene-supported isothiourea, HyperBTM, is demonstrated in flow. The sequential KRs of C2-symmetric (±)-1,2-syn and (±)-1,3-anti-diols exploits Horeau amplification, with each composed of two successive KR processes, with each substrate class significantly differing in the relative rate constants for each KR process. Optimisation of the continuous flow set-up for both C2-symmetric (±)-1,2-syn and (±)-1,3-anti-diol substrate classes allowed isolation of reaction products in both high enantiopurity and yield. In addition to the successful KR of C2-symmetric (±)-1,2-syn and (±)-1,3-anti-diols, the application of this process to the more conceptually-complex scenario involving the sequential KR of C1-symmetric (±)-1,3-anti-diols was demonstrated, which involves eight independent rate constants.
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http://dx.doi.org/10.1039/d1ob00304fDOI Listing
April 2021

COVID-19 may increase the risk of insulin resistance in adult patients without diabetes: A 6-month prospective study.

Endocr Pract 2021 Apr 19. Epub 2021 Apr 19.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address:

Objective: During the coronavirus disease 2019 (COVID-19) pandemic, exploring insulin resistance and β-cell activity is important for understanding COVID-19-associated new-onset diabetes. This study aimed to assess insulin sensitivity and fasting insulin secretion in COVID-19 patients without diabetes on admission and at 3 and 6 months after discharge.

Methods: This 6-month prospective study assessed data from the records of 64 patients without diabetes diagnosed with COVID-19 at Wenzhou Central Hospital, China. Each patient was followed up for 3 and 6 months after discharge. Repeated measures analysis of variance was used to investigate differences in multiple measurements of the same variable at different times. Linear regression analysis was performed to analyze the contributor for changes in triglyceride-glucose (TyG) index.

Results: Fasting C-peptide levels in patients at baseline were lower than the normal range (1.1-4.4 μg/L). Compared with baseline, patients had significantly elevated fasting C-peptide levels (0.35±0.24 vs. 2.36±0.98 vs. 2.52±1.11 μg/L, P˂0.001), HOMA-CP (0.42, IQR 0.36-0.62 vs. 2.54, IQR 1.95-3.42 vs. 2.90, IQR 2.02-4.23, P˂0.001) and TyG indexes (8.57±0.47 vs. 8.73±0.60 vs. 8.82±0.62, P=0.006), and decreased fasting glucose levels (5.84±1.21 vs. 4.95±0.76 vs. 5.40±0.68 mmol/L, P=0.003) during the 3 and 6-month follow-up. Male gender [β (95%CI): -0.312 (-0.590, -0.034)], age [0.012 (0.001, 0.023)], interferon-alfa treatment during hospitalization [0.540 (0.029, 1.051)], and changes in TC [0.217 (0.069, 0.366)] and HDL [-0.477 (-0.881, -0.074)] levels were significantly associated with changes in the TyG index.

Conclusions: Our study provided the first evidence that COVID-19 may increase the risk of insulin resistance in patients without diabetes.
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http://dx.doi.org/10.1016/j.eprac.2021.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054613PMC
April 2021

Thyroid Hormone-Regulated Expression of Period2 Promotes Liver Urate Production.

Front Cell Dev Biol 2021 1;9:636802. Epub 2021 Apr 1.

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

The relationship between thyroid hormones and serum urate is unclear. Our aim is to analyze the correlation between uric acid and thyroid hormones in gout patients and to explore the effect and mechanism of triiodothyronine on liver uric acid production. Eighty men patients with gout were selected to analyze the correlation between blood urate and thyroid function-related hormone levels. Stepwise multiple linear regression was used to analyze factors affecting blood urate in patients with gout. Levels of urate in serum, liver, and cell culture supernatant were measured after triiodothyronine treatment. Purine levels (adenine, guanine, and hypoxanthine) were also measured. Expression levels of Period2 and nucleotide metabolism enzymes were analyzed after triiodothyronine treatment and Period2-shRNA lentivirus transduction. Chromatin immunoprecipitation was used to analyze the effects of triiodothyronine and thyroid hormone receptor-β on Period2 expression. The results showed that in patients FT3 influenced the serum urate level. Furthermore, urate level increased in mouse liver and cell culture supernatant following treatment with triiodothyronine. Purine levels in mouse liver increased, accompanied by upregulation of enzymes involved in nucleotide metabolism. These phenomena were reversed in Period2 knockout mice. Triiodothyronine promoted the binding of thyroid hormone receptor-β to the Period2 promoter and subsequent transcription of Period2. Triiodothyronine also enhanced nuclear expression of Sirt1, which synergistically enhanced Period2 expression. The study demonstrated that triiodothyronine is independently positively correlated with serum urate and liver uric acid production through Period2, providing novel insights into the purine metabolism underlying hyperuricemia/gout pathophysiology.
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http://dx.doi.org/10.3389/fcell.2021.636802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047155PMC
April 2021

Low 25-hydroxyvitamin D is associated with arterial stiffness in Chinese with Type 2 diabetes mellitus.

Eur J Clin Nutr 2021 Mar 31. Epub 2021 Mar 31.

Department of Endocrinology and Metabolism, Tongji University School of Medicine, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.

Objectives: Arterial stiffness (AS), one of the complications of diabetes, associated with many metabolic factors. This study aimed to investigate the association between 25-hydroxyvitamin D(25(OH)D) and AS in type 2 diabetes mellitus (T2DM).

Methods: We identified 1335 diabetic patients from the Department of Endocrinology, Shanghai Tenth People's Hospital. Finally, 603 T2DM patients were included in the study. They were divided into two groups: AS group (baPWV ≥ 15,500 cm/s) and the control group (baPWV < 1550 cm/s).

Results: (1) Heart rate (HR) and systolic pressure (SBP) were higher while body weight and body mass index (BMI) were smaller in AS group than the control group (all P < 0.05). (2) Compared to patients without AS, patients with AS showed lower 25(OH)D and higher rate of 25(OH)D deficiency (42 ± 16 vs. 45 ± 17 mol/l, 68% vs. 64%, all P < 0.05). (3) BaPWV was negatively associated with 25(OH)D (r = -0.12, P = 0.004), while positively associated with age, duration of diabetes, HR, SBP, and low-density lipoprotein cholesterol and negatively associated with body weight and BMI (all P < 0.05). (4) Multiple linear regression showed that 25(OH)D was the negatively influencing factor of baPWV (β = -2.2, P = 0.01). Logistic regression showed that age and SBP were risk factor of AS (OR:1.07, 95% CI: 1.05-1.10, P < 0.001; OR:1.03, 95% CI: 1.02-1.04, P < 0.001) while 25(OH)D was protective factor of AS (OR:0.987, 95% CI: 0.976-0.998, P = 0.024).

Conclusions: T2DM patients with AS had lower 25(OH)D and higher rate of 25(OH)D deficiency. There was a negative relationship between 25(OH)D and AS assessed by baPWV.
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http://dx.doi.org/10.1038/s41430-021-00870-0DOI Listing
March 2021

Henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.

Diabetes Obes Metab 2021 Mar 26. Epub 2021 Mar 26.

Jiangsu Hengrui Medicine Co., Ltd, Shanghai, China.

Aim: To evaluate the efficacy and safety of henagliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin.

Material And Methods: This multicentre phase 3 trial included a 24-week randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Patients with a glycated haemoglobin (HbA1c) level of 7.0% (53 mmol/mol) to 10.5% (91 mmol/mol) were randomized and treated with once-daily placebo (n = 161), henagliflozin 5 mg (n = 162), or henagliflozin 10 mg (n = 160). After 24 weeks, patients on placebo were switched to 5 mg or 10 mg henagliflozin for the additional 28-week treatment, and patients on henagliflozin during 24-week treatment period maintained this initial therapy. The primary endpoint was change in HbA1c from baseline to Week 24.

Results: At Week 24, the least squares mean HbA1c changes versus placebo from baseline were - 0.76% (-8.3 mmol/mol) and - 0.80% (-8.7 mmol/mol) for henagliflozin 5 and 10 mg, respectively (all P < 0.0001). Compared with the placebo group, both doses of henagliflozin lowered fasting plasma glucose, 2-hour postprandial plasma glucose, body weight and blood pressure, and increased the proportions of patients achieving HbA1c <7.0% (53 mmol/mol) at Week 24. The trends in these improvements were sustained over an additional 28 weeks. Slightly higher proportions of ketosis and presence of urine ketone bodies were observed in patients treated with henagliflozin compared to placebo at Week 24. No diabetic ketoacidosis or episodes of severe hypoglycaemia were reported.

Conclusions: Henagliflozin 5 mg or 10 mg as add-on therapy to metformin provided a new therapeutic option for the treatment of T2DM patients who have inadequate glycaemic control with metformin alone, and was generally well tolerated.
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http://dx.doi.org/10.1111/dom.14389DOI Listing
March 2021

Urban Air Pollution Mapping Using Fleet Vehicles as Mobile Monitors and Machine Learning.

Environ Sci Technol 2021 04 24;55(8):5579-5588. Epub 2021 Mar 24.

School for Environment and Sustainability, University of Michigan, Ann Arbor, Michigan 48109-1382, United States.

Spatially explicit urban air quality information is important for developing effective air quality control measures. Traditionally, urban air quality is measured by networks of stationary monitors that are not universally available and sparsely sited. Mobile air quality monitoring using equipped vehicles is a promising alternative but has focused on vehicle-level experiments and lacks fleet-level demonstration. Here, we equipped 260 electric vehicles in a ride-hailing fleet in Beijing, China with low-cost sensors to collect real-time, spatial-resolved data on fine particulate matter (PM) concentrations. Using this data, we developed a decision tree model to infer the distribution of PM concentrations in Beijing at 1 km by 1 km and 1 h resolution. Our results are able to show both short- and long-term variations of urban PM concentrations and identify local air pollution hotspots. Compared with a benchmark model that only uses data from stationary monitoring sits, our model has shown significant improvement with the coefficient of determination increased from 0.56 to 0.80 and root mean square error decreased from 12.6 to 8.1 μg/m. To the best of our knowledge, this study collects the largest mobile sensor data for urban air quality monitoring, which are augmented by state-of-the-art machine learning techniques to derive high-quality urban air pollution mapping. Our results demonstrate the potential and necessity of using fleet vehicles as routine mobile sensors combined with advanced data science methods to provide high-resolution urban air quality monitoring.
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http://dx.doi.org/10.1021/acs.est.0c08034DOI Listing
April 2021

Visceral and subcutaneous adipose tissue, which one induced thyroid dysfunction in patients with morbid obesity.

Surg Obes Relat Dis 2021 Jun 17;17(6):1175-1181. Epub 2021 Feb 17.

Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital affiliated to Tongji University, Tongji Medical School, Shanghai, P.R. China.

Background: Thyroid dysfunction in patients with morbid obesity usually resolves after bariatric surgery. However, the role of diverse types of adipose tissue in the process remains unknown.

Objectives: We aim to investigate the effects of visceral and subcutaneous fat on thyroid function in a Chinese population with morbid obesity who underwent sleeve gastrectomy (SG).

Setting: University hospital, Shanghai, China METHODS: Repeated measurement data of thyroid hormone and body fat were collected at 0, 3, 6, 12, 24, and 36 months after sleeve gastrectomy. Dual-energy X-ray absorptiometer and quantitative computerized tomography (CT) were used to compute visceral fat and subcutaneous fat. Repeated measures correlation (rmmcorr) package was employed for correlation analysis with generalized additive mixed model (GAMM) determining the independent factors.

Results: Thyroid stimulating-hormone (TSH) showed notable decrease at 36 months after surgery, coupled with reduction of BMI (38.08 kg/cm versus 24.28 kg/cm), C-reactive protein (CRP), visceral adipose tissue (786.74 cm versus 367.44 cm), body fat rate, and waistline (118.13 cm versus 100.87 cm). Only visceral fat, diabetes, and CRP proved to be independent variables for TSH decline, without correlation with subcutaneous fat.

Conclusion: The present study is first to report the effects of different types of body fat on thyroid function in a Chinese population with morbid obesity, revealing that loss of visceral fat is the key to improving endocrine and metabolic activity after bariatric surgery.
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http://dx.doi.org/10.1016/j.soard.2021.02.012DOI Listing
June 2021

Allosteric communication in class A β-lactamases occurs via cooperative coupling of loop dynamics.

Elife 2021 Mar 23;10. Epub 2021 Mar 23.

University College London School of Pharmacy, Pharmaceutical and Biological Chemistry, London, United Kingdom.

Understanding allostery in enzymes and tools to identify it offer promising alternative strategies to inhibitor development. Through a combination of equilibrium and nonequilibrium molecular dynamics simulations, we identify allosteric effects and communication pathways in two prototypical class A β-lactamases, TEM-1 and KPC-2, which are important determinants of antibiotic resistance. The nonequilibrium simulations reveal pathways of communication operating over distances of 30 Å or more. Propagation of the signal occurs through cooperative coupling of loop dynamics. Notably, 50% or more of clinically relevant amino acid substitutions map onto the identified signal transduction pathways. This suggests that clinically important variation may affect, or be driven by, differences in allosteric behavior, providing a mechanism by which amino acid substitutions may affect the relationship between spectrum of activity, catalytic turnover, and potential allosteric behavior in this clinically important enzyme family. Simulations of the type presented here will help in identifying and analyzing such differences.
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http://dx.doi.org/10.7554/eLife.66567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060031PMC
March 2021

Lower Baseline Serum Triglyceride Levels Are Associated With Higher Decrease in Body Mass Index After Laparoscopy Sleeve Gastrectomy Among Obese Patients.

Front Endocrinol (Lausanne) 2021 22;12:633856. Epub 2021 Feb 22.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine Tongji University, Shanghai, China.

Aims: To investigate the predictive value of baseline serum triglyceride (TG) levels for improvements of metabolism after laparoscopic sleeve gastrectomy (LSG).

Methods: 112 obese patients [body mass index (BMI) ≥ 35 kg/m] underwent LSG and with complete information of anthropometric and metabolic parameters were divided into normal TG group (group A) and high TG group (group B), while group A had TG levels ≤ 1.7 mmol/L, and group B had TG levels > 1.7 mmol/L. The post-operative changes (Δ) in metabolic parameters between the two groups were compared.

Results: In the whole cohort, the metabolic parameters were significantly improved at 6 months after LSG. BMI and waist circumference (WC) decreased significantly in the two groups. The ΔBMI among group A and group B were 11.42±3.23 vs 9.13±2.77 kg/m (p<0.001), respectively. ΔBMI was positively correlated with ΔWC (r=0.696, p<0.001), Δfasting insulin level (r=0.440, p=0.002), Δfasting serum C peptide level (r=0.453, p=0.002), and Δhomeostasis model assessment insulin resistance index (r=0.418, p=0.004) in group A. Compared with group B, group A had a significantly higher odds ratio (OR) of 2.83 (95% confidence interval [CI]1.25-6.38, p=0.012)and 2.73 (95% CI 1.11-6.72, p=0.029) for ΔBMI and ΔWC after adjustment for age and gender, respectively.

Conclusions: Obese patients with baseline TG levels under 1.7 mmol/L had greater loss of weight at six months follow-up later LSG. This finding suggests that baseline TG level may have a predictive value for weight loss, at least in the short-term follow-up.
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http://dx.doi.org/10.3389/fendo.2021.633856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937917PMC
February 2021

Hyperuricemia causes kidney damage by promoting autophagy and NLRP3-mediated inflammation in rats with urate oxidase deficiency.

Dis Model Mech 2021 Mar 24;14(3). Epub 2021 Mar 24.

Department of Endocrinology and Metabolism, Shanghai 10th People's Hospital, Tongji University, Shanghai 200072, China

Epidemiological research has shown that elevated serum urate concentration is a risk factor for the development of kidney disease; however, the mechanisms underlying this process have not yet been elucidated. To examine the role of urate in the kidney, we used Wistar rats to functionally disrupt expression of urate oxidase (UOX) by using the CRISPR/Cas9 system. In comparison to wild-type (WT) rats, serum urate levels spontaneously and persistently increased in -KO rats, without showing a significant decrease in survival rate. Architecture and function of the kidneys in -KO rats were impaired. Injury to the kidney resulted in increased interstitial fibrosis, macrophage infiltration, increased expression of NLRP3 and IL-1β, and activation of multiple cell-signaling pathways associated with autophagy, such as AMPK, p38 MAPK, ERK and JNK pathways. Inhibition of autophagy with the PI3K inhibitor 3-MA abrogated the development of kidney damage and attenuated renal fibrosis, macrophage infiltration, and expression of NLRP3 and IL-1β in injured kidneys. In conclusion, the -KO rat is a great model to study hyperuricemia-related diseases. Hyperuricemia-induced autophagy and NLRP3-dependent inflammation are critically involved in the development of renal damage and, therefore, highlight the inhibition of autophagy and inflammation in search of therapeutic strategies to treat uric acid nephropathy.
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http://dx.doi.org/10.1242/dmm.048041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015218PMC
March 2021

Obesity-associated up-regulation of lipocalin 2 protects gastric mucosa cells from apoptotic cell death by reducing endoplasmic reticulum stress.

Cell Death Dis 2021 02 26;12(2):221. Epub 2021 Feb 26.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.

Gastric mucosal injury is a less well known complication of obesity. Its mechanism remains to be further elucidated. Here, we explored the protective role of lipocalin 2 (LCN2) against endoplasmic reticulum stress and cell apoptosis in gastric mucosa in patients and mice with obesity. Through molecular and genetic analyses in clinical species, LCN2 secreted by parietal cells expression is elevated in obese. Immunofluorescence, TUNEL, and colorimetry results show that a more significant upregulation of pro-inflammatory factors and increased amount of apoptotic cells in gastric tissue sections in obese groups. Loss- and gain-of-function experiments in gastric epithelial cells demonstrate that increased LCN2 protected against obesity associated gastric injury by inhibiting apoptosis and improving inflammatory state. In addition, this protective effect was mediated by repressing ER stress. Our findings identify LCN2 as a gastric hormone could be a compensatory protective factor against gastric injury in obese.
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http://dx.doi.org/10.1038/s41419-021-03512-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910621PMC
February 2021

Identification of Potential BRAF Inhibitor Joint Therapy Targets in PTC based on WGCAN and DCGA.

J Cancer 2021 21;12(6):1779-1791. Epub 2021 Jan 21.

Shanghai Center for Thyroid Disease, Shanghai Tenth People's Hospital, Shanghai, China.

As the most common mutation in papillary thyroid cancer (PTC), B-type Raf kinase V600E mutation ( ) has become an important target for the clinical treatment of PTC. However, the clinical application still faces the problem of resistance to BRAF inhibitors (BRAFi). Therefore, exploring BRAF-associated prognostic factors to providing potential joint targets is important for combined targeted therapy with BRAFi. In this study, we combined transcript data and clinical information from 199 wild-type ( ) patients and 283 mutant patients collected from The Cancer Genome Atlas (TCGA), and screened 455 BRAF- associated genes through differential analysis and weighted gene co-expression network analysis. Based on these -associated genes, we performed functional enrichment analysis and co-expression differential analysis and constructed a core co-expression network. Next, genes in the differential co-expression network were used to predict drugs for therapy in the crowd extracted expression of differential signatures (CREEDS) database, and the key genes were selected based on the hub co-expression network through survival analyses and receiver operating characteristic (ROC) curve analyses. Finally, we obtained eight BRAF -associated biomarkers with both prognostic and diagnostic values as potential BRAFi joint targets, including , , , , , , , and . Among these genes, FN1, MET, PROS1, and were validated through GEO database. Two novel biomarkers, PROS1 and , were further validated by qRT-PCR experiment. Besides, we obtained four potential targeted drugs that could be used in combination with BRAFi to treat PTC, including MET inhibitor, ERBB3 inhibitor, anti-NaPi2b antibody-drug conjugate, and carboplatin through literature review. The study provided potential drug targets for combination therapy with BRAFi for PTC to overcome the drug resistance for BRAFi.
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http://dx.doi.org/10.7150/jca.51551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890315PMC
January 2021

Mitochondrial haplogroup G is associated with nonalcoholic fatty liver disease, while haplogroup A mitigates the effects of PNPLA3.

Endocrinol Diabetes Metab 2021 01 6;4(1):e00187. Epub 2020 Oct 6.

Department of Endocrinology Shanghai Tenth People's Hospital Tongji University Shanghai China.

Objectives: Mitochondrial dysfunction plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We hypothesized that mitochondrial DNA (mtDNA) haplogroups affect the risk of NAFLD in Han Chinese patients and interact with PNPLA3 genotypes.

Design: NAFLD and control patients were recruited from a tertiary care centre. The mitochondrial genome was amplified in overlapping segments and sequenced. Mitochondrial haplogroups were determined using Mitomaster. rs738409 genotyping was performed using restriction fragment length polymorphism analysis.

Patients: We enrolled 655 NAFLD patients and 504 controls.

Results: More NAFLD patients encoded haplogroup G; odds ratio (OR) 1.85 (95% confidence interval [CI] 1.16, 2.80). Subhaplogroup G3 was present more frequently in NAFLD patients (25.8% vs 6.5%). The CG genotype resulted in an OR of 1.66 (95% CI 1.25, 2.21), and the GG genotype resulted in an OR of 2.33 (95% CI 1.72, 3.17) for NAFLD. Patients with mitochondrial haplogroup A had a significantly higher frequency of genotype GG. Among patients with haplogroup A, no  genotype was associated with increased NAFLD risk (CG: OR 1.17, 95% CI 0.55, 2.34; GG: OR 1.04 95% CI 0.66, 2.65). Excluding haplogroup A, the OR for CG was 1.58 (95% CI 1.18, 2.12), and the OR for GG was 1.81 (95% CI 1.30, 2.51).

Conclusion: Haplogroup G was associated with an increased risk of NAFLD GG genotype was overrepresented among patients encoding haplogroup A and was not associated with NAFLD risk among haplogroup A patients. Mitochondrial genetics influence NAFLD risk and interact with  genotypes.
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http://dx.doi.org/10.1002/edm2.187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831202PMC
January 2021

Nomograms for Predicting Non-remission in Patients Who Underwent Bariatric Surgery: A Multicenter Retrospective Study in China.

Obes Surg 2021 05 8;31(5):1967-1978. Epub 2021 Jan 8.

Affiliated Hospital of Southwest Jiaotong University, Chengdu, 610036, China.

Background: As a reflection of the increasing global incidence of obesity, there is a corresponding increase in the proportion of obese patients undergoing bariatric surgery. This study reviewed the factors and outcomes of patients who underwent bariatric surgical procedures and determined the relationships and developed a nomogram to calculate individualized patient risk.

Methods: The nomogram was based on a retrospective study on 259 patients who underwent bariatric surgery at the Chengdu Third People's Hospital from June 2017 to June 2019. The predictive accuracy and discriminative ability of the nomogram were determined by the ROC curve and C-index, respectively. The results were validated using bootstrap resampling and a retrospective study on 121 patients operated on from May 2015 to May 2019 at the Tenth People's Hospital of Shanghai.

Results: The predictors contained in the prediction nomogram included age, sex, surgical approach, hyperlipidemia, blood pressure (BP), hyperuricemia, body mass index (BMI), and waist circumference (WC). The 6-month model displayed good discrimination with a C-index of 0.765 (95% CI: 0.756 to 0.774) and good calibration. The 1-year model reached a C-index of 0.768 (95% CI, 0.759 to 0.777) in the training cohort.

Conclusions: The proposed nomogram resulted in more accurate non-remission prediction for patients with obesity after bariatric surgery and may provide a reference for the preoperative choice of surgical methods.
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http://dx.doi.org/10.1007/s11695-020-05206-8DOI Listing
May 2021

Calcification of lower extremity arteries is related to the presence of osteoporosis in postmenopausal women with type 2 diabetes mellitus: a cross-sectional observational study.

Osteoporos Int 2021 Jun 7;32(6):1185-1193. Epub 2021 Jan 7.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

It is unknown whether there is any relationship between extremity arterial macroangiopathy and osteoporosis in type 2 diabetic mellitus (T2DM) patients. We provide evidence to show the association between lower extremity arterial calcification and the presence of osteoporosis in postmenopausal T2DM women, but not in T2DM men of similar age.

Purpose: To investigate the relationship between lower extremity arterial calcification and the presence of osteoporosis in type 2 diabetic mellitus (T2DM) patients.

Methods: We performed a retrospective cross-sectional study in patients with T2DM. They were assigned into two groups (patients with or without vascular calcification) in both sexes. Clinical characteristics, presence of osteoporosis, and bone metabolic markers were compared. Arterial calcification was determined by ultrasonography examination. Osteoporosis was defined based on the measurements from dual-energy X-ray absorptiometry. The relationship between the lower extremity arterial calcification and the presence of osteoporosis was analyzed. Statistical analysis was performed in SPSS 26.0.

Results: A total of 933 T2DM patients (535 men ≥ 50 years old, and 398 postmenopausal women) were identified and analyzed. A significant association between arterial calcification and osteoporosis was only observed in women, with a higher prevalence of osteoporosis observed in women with calcification (40.8%) than in women without calcification (26.9%) (P = 0.004). Compared to women without calcification, women with calcification had lower bone mineral densities in the hip (P < 0.001) and femoral neck (P < 0.001). Ordinal logistic regression analysis showed that women with calcification had a nearly 2-fold increased risk for osteoporosis, even after adjusting for age, duration of T2DM, body mass index, pulse pressure, clearance of creatinine, glycosylated hemoglobin, and fasting C-peptide. Similar differences were not identified between men with and without calcification.

Conclusion: Calcification of lower extremity arteries is related with the presence of osteoporosis in postmenopausal T2DM women.
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http://dx.doi.org/10.1007/s00198-020-05775-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128735PMC
June 2021

Hepatic Steatosis Is Associated with Elevated Serum Iron in Patients with Obesity and Improves after Laparoscopic Sleeve Gastrectomy.

Obes Facts 2021 22;14(1):64-71. Epub 2020 Dec 22.

Department of Endocrinology and Metabolism, Tongji University School of Medicine, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China,

Background: Iron is closely related to metabolism. However, the relationship between iron and hepatic steatosis has not been fully elucidated.

Objective: We aimed to investigate the triangular relationship between iron and hepatic steatosis and laparoscopic sleeve gastrectomy (LSG) in patients with obesity.

Methods: A total of 297 patients with obesity and 43 healthy individuals with a normal BMI were enrolled. Eighty-two patients underwent LSG. Anthropometrics, glucose-lipid metabolic markers, and hepatic steatosis assessed by FibroScan (CAP value and E value) were measured at baseline, and again at follow-up time intervals of 6 months and 1 year after surgery.

Results: (1) Iron was significantly higher in patients with obesity or overweight than in the individuals with normal BMI (8.18 ± 1.47 vs. 7.46 ± 0.99 mmol/L, p = 0.002). Iron was also higher in subjects with high blood pressure, dyslipidemia, and hyperuricemia than non-corresponding disorders (all p < 0.05). Moreover, iron was significantly higher in the severe than mild or moderate non-alcoholic fatty liver disease (NAFLD) group (p = 0.046 and 0.018). (2) Iron was positively associated with body weight, BMI, waist-to-hip ratio, uric acid, liver enzymes, postprandial blood glucose, fasting insulin, HOMA-IR, triglycerides, free fatty acid, and hepatic steatosis (CAP value), and negatively associated with high-density lipoprotein cholesterol (all p < 0.05). Iron was also positively associated with the visceral adipose area in patients with obesity and negatively associated with the subcutaneous adipose area in patients with overweight (all p < 0.05). (3) Iron levels and CAP values were decreased gradually 6 months and 1 year after surgery (all p < 0.05).

Conclusions: Overall, our results indicated that iron is associated with hepatic steatosis in obesity. The iron level was significantly higher in patients with severe NAFLD than with mild or moderate NAFLD. LSG may reduce iron levels while improving fat deposition in the liver.
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http://dx.doi.org/10.1159/000511736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983566PMC
December 2020

The Increased Risk of Thyroid Cancer-Specific Mortality With Tumor Size in Stage IVB Patients.

Front Oncol 2020 5;10:560203. Epub 2020 Nov 5.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

To investigate the risk-stratifying utility of tumor size and a threshold for further stratification on cancer-specific mortality of thyroid cancer (TC) patients in stage IVB. One thousand three hundred and forty-five patients (620 males and 725 females) with initial distant metastasis over 55 years between 2004 and 2016 from Surveillance, Epidemiology, and End Results databases were investigated, with a median follow-up time of 23 months [interquartile range (IQR), 5-56 months] and a median age of 70 years (IQR, 63-77 years). TC-specific mortality rates were calculated under different classifications. Cox regressions were used to calculate hazard ratios (HRs) and Kaplan-Meier Analyses were conducted to investigate TC-specific survivals. In the whole cohort, patients with tumors >4 cm had the highest TC-specific mortality (67.9%, 330/486), followed by tumor size >1 cm but ≤ 4 cm (43.08%, 190/441), and tumor size ≤ 1 cm (32.69%, 34/104). Kaplan-Meier curves showed the increased tumor size was associated with a statistically significant decrease in TC-specific survival ( < 0.001). Papillary thyroid cancer (PTC) patients with tumors >4 cm had significantly higher hazard ratios (HRs) of 2.84 (1.72-4.70) and 3.11 (1.84-5.26) after adjusting age, gender, race, and radiation treatment, compared with patients with tumors ≤ 1 cm ( < 0.001). The TC-specific mortalities and survivals were further investigated among more detailed subgroups divided by different tumor size, and a threshold of 3 cm could be observed ( < 0.005) for risk stratification. Mortality risk increased with tumor size in PTC patients in stage IVB. Our findings demonstrated the possibility of further stratification in IVB stage in current TNM staging system. Patients with tumor size over 3 cm had an excessively high risk of PTC-specific mortality, which may justify the necessity of more aggressive treatment for them.
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http://dx.doi.org/10.3389/fonc.2020.560203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678015PMC
November 2020

Harnessing hyperuricemia to atherosclerosis and understanding its mechanistic dependence.

Med Res Rev 2021 01 20;41(1):616-629. Epub 2020 Oct 20.

Department of Endocrinology and Metabolism, School of Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.

Atherosclerosis is regarded as the disease of the arterial vasculature. The main characteristics of atherosclerosis are the abnormal accumulation of lipids, increased inflammatory cells, matrix deposits, and proliferation of smooth muscle cells. Diabetes mellitus, obesity, and hyperlipidemia are the most studied risk factors of atherosclerosis. One least studied risk factor is the uric acid (UA), a high UA in circulation is interlinked with many pathological processes. Several epidemiological studies suggest elevated UA levels as an essential biomarker in the forecast of several cardiovascular diseases. Available evidence claims that UA upholds the atherosclerosis process via disturbing lipid metabolism, reducing the nitric oxide synthesis in endothelial cells, promoting the proliferation of vascular smooth muscle cells, and overwhelms inflammation. In endothelial dysfunction and coronary artery lesions, UA is considered as an independent predictor. The updated studies on the involvement of hyperuricemia in atherosclerosis prove that treatment with xanthine oxidase (XO) inhibitors not just benefits the treatment of hyperuricemia but also reduces the burden of atherosclerosis to a greater extent. In this review, we highlight how the hyperuricemia affects vascular integrity, causes atherosclerosis, and the mechanism of action of XO inhibitors on atherosclerosis.
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http://dx.doi.org/10.1002/med.21742DOI Listing
January 2021

Redirection of lower eyelid eyelashes by eyelid margin splitting and anterior lamellar repositioning for patients with non-entropion trichiasis.

J Plast Reconstr Aesthet Surg 2021 02 20;74(2):382-386. Epub 2020 Sep 20.

Department of Ophthalmology, Tongji Hospital, Tongji University School of Medicine, 389 Xin Cun Road, Shanghai 200065, China. Electronic address:

Objective: To report outcomes of a surgical technique of eyelid margin splitting and anterior lamellar repositioning with lower eyelid non-entropion trichiasis.

Method: A total of 13 patients (5 males and 8 females) with lower eyelid non-entropion trichiasis who had undergone eyelid margin splitting and anterior lamellar repositioning at Tongji Hospital from January 2018 to June 2018 were retrospectively reviewed.

Result: All patients underwent surgery successfully, and 13 patients (23 eyes) were followed up for 9-18 months (mean 12.23±3.14 months). Symptoms were entirely relieved in all patients without the need for further surgery, and all patients were satisfied with the appearance after surgery. The lower lid margin was a flat platform with normal anatomical landmarks, and the lower eyelid eyelashes were no longer in contact with the globe. However, one patient relapsed 7 months after surgery.

Conclusion: Patients with lower eyelid non-entropion trichiasis can be treated effectively through eyelid margin splitting and anterior lamellar repositioning with inapparent skin scarring.
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http://dx.doi.org/10.1016/j.bjps.2020.08.113DOI Listing
February 2021

Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study).

Nat Commun 2020 10 6;11(1):5015. Epub 2020 Oct 6.

Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, Liaoning Province, China.

Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], -1.04[-1.19, -0.89]%) and BBR-alone group (-0.99[-1.16, -0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (-0.59[-0.75, -0.44]%, -0.53[-0.68, -0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).
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http://dx.doi.org/10.1038/s41467-020-18414-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538905PMC
October 2020

J-shaped association between fasting blood glucose levels and COVID-19 severity in patients without diabetes.

Diabetes Res Clin Pract 2020 Oct 25;168:108381. Epub 2020 Aug 25.

Departments of Infectious Disease, The Ding Li Clinical College of Wenzhou Medical University and Sixth People's Hospital of Wenzhou, Wenzhou, Zhejiang, China. Electronic address:

Aims: Coronavirus disease 2019 (COVID-19) has become a recognized worldwide pandemic. Researchers now know that mortality from COVID-19 can be reduced through early prevention measures. This retrospective, multi-centered study of 293 COVID-19 patients without diabetes explores the association between fasting blood glucose (FBG) levels and the risk of COVID-19 disease progression, with the goal of providing clinical evidence for glycemic targets in patients.

Methods: The multivariate stepwise binary logistic regression analysis was used to test the dose-response effects of FBG levels on the risk of severe and critical condition in COVID-19 patients.

Results: FBG levels were plotted in quintiles with set at <4.74, 4.74-5.21, 5.21-5.78, 5.78-7.05, and ≧7.05 mmol/L. The constituent ratio of severe or critical cases in each FBG quintile was 20.7%, 1.7%, 13.8%, 27.1%, and 67.2%, respectively (P < 0.0001). When the second quintile was used as the reference, the adjusted odds ratios (AORs) (95%CI) for the risk of severe/critical condition in COVID-19 was 25.33 (2.77, 231.64), 1.00 (Reference), 3.13 (0.33, 29.67), 10.59 (1.23, 91.24), 38.93 (4.36, 347.48) per FBG quintile respectively (P < 0.001).

Conclusions: We provide evidence of J-shaped associations between FBG and risk of severe and critical condition in non-diabetes patients with COVID-19, with nadir at 4.74-5.78 mmol/L.
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http://dx.doi.org/10.1016/j.diabres.2020.108381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445136PMC
October 2020

Frontline nurses' burnout, anxiety, depression, and fear statuses and their associated factors during the COVID-19 outbreak in Wuhan, China: A large-scale cross-sectional study.

EClinicalMedicine 2020 Jul 27;24:100424. Epub 2020 Jun 27.

School of Medicine, Xiamen University, Xiamen, Fujian, PR China.

Background: During the Coronavirus Disease 2019 (COVID-19) pandemic, frontline nurses face enormous mental health challenges. Epidemiological data on the mental health statuses of frontline nurses are still limited. The aim of this study was to examine mental health (burnout, anxiety, depression, and fear) and their associated factors among frontline nurses who were caring for COVID-19 patients in Wuhan, China.

Methods: A large-scale cross-sectional, descriptive, correlational study design was used. A total of 2,014 eligible frontline nurses from two hospitals in Wuhan, China, participated in the study. Besides sociodemographic and background data, a set of valid and reliable instruments were used to measure outcomes of burnout, anxiety, depression, fear, skin lesion, self-efficacy, resilience, and social support via the online survey in February 2020.

Findings: On average, the participants had a moderate level of burnout and a high level of fear. About half of the nurses reported moderate and high work burnout, as shown in emotional exhaustion ( = 1,218, 60.5%), depersonalization ( = 853, 42.3%), and personal accomplishment ( = 1,219, 60.6%). The findings showed that 288 (14.3%), 217 (10.7%), and 1,837 (91.2%) nurses reported moderate and high levels of anxiety, depression, and fear, respectively. The majority of the nurses ( = 1,910, 94.8%) had one or more skin lesions, and 1,950 (96.8%) nurses expressed their frontline work willingness. Mental health outcomes were statistically positively correlated with skin lesion and negatively correlated with self-efficacy, resilience, social support, and frontline work willingness.

Interpretation: The frontline nurses experienced a variety of mental health challenges, especially burnout and fear, which warrant attention and support from policymakers. Future interventions at the national and organisational levels are needed to improve mental health during this pandemic by preventing and managing skin lesions, building self-efficacy and resilience, providing sufficient social support, and ensuring frontline work willingness.
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http://dx.doi.org/10.1016/j.eclinm.2020.100424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320259PMC
July 2020

Glucose-Lipid Metabolism in Obesity with Elevated Prolactin Levels and Alteration of Prolactin Levels After Laparoscopic Sleeve Gastrectomy.

Obes Surg 2020 10 22;30(10):4004-4013. Epub 2020 Jul 22.

Department of Endocrinology and Metabolism, School of Medicine, Shanghai Tenth People's Hospital of Tongji University, No. 301 Middle Yanchang Road, Shanghai, 200072, China.

Purpose: We investigated the differences in metabolism between obesity with or without increased prolactin (PRL) and the change in PRL after laparoscopic sleeve gastrectomy (LSG).

Methods: Patients were divided into two groups: obesity with normal PRL (NP, n = 123) and high PRL (HP, n = 108). Glucose-lipid metabolism and inflammation were measured. A total of 115 patients with obesity (NP, n = 64; HP, n = 51) underwent LSG were recruited, and PRL was measured at 12 months after LSG.

Results: (1) Blood glucose (BG), total cholesterol (TCH), LDL, triglyceride, and TNF-α were lower in the HP than in the NP group in the cross-sectional study (all P < 0.05). (2) PRL was negatively associated with neck circumference, waist-to-hip ratio, systolic blood pressure, heart rate, basal metabolism rate (BMR), ALP, TCH, and LDL in all subjects. PRL levels were positively associated with weight, HC, and BMR in males but were negatively associated with ALT, AST, ALP, BG 30 min, BG 60 min, FFA, and TCH in females (all P < 0.05). (3) Regression analysis showed that PRL negatively correlated with ALP and LDL-C in the whole baseline (β = - 0.051, P = 0.002; β = - 1.372, P = 0.033). PRL was a negative factor for ALP in females and a positive factor for BMR2 in males (β = - 0.099, P = 0.041; β = 0.005, P = 0.006). (4) PRL decreased in the HP group and increased in the NP group at 12 months post-operation (all P < 0.05). Increased PRL was associated with a change in TCH in the NP group (P < 0.05).

Conclusion: Increased PRL resulted in improved glucose-lipid metabolism and chronic low-grade inflammation. LSG led to increased PRL in NP and decreased PRL in HP. Improved lipid was associated with increased PRL in NP after surgery.

Clinical Trial Registration Number: ChiCTR-OCS-12002381.
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http://dx.doi.org/10.1007/s11695-020-04771-2DOI Listing
October 2020