Publications by authors named "Yan Bi"

228 Publications

Comparison of Beinaglutide Versus Metformin for Weight Loss in Overweight and Obese Non-diabetic Patients.

Exp Clin Endocrinol Diabetes 2021 Dec 2. Epub 2021 Dec 2.

Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China.

Purpose: We compared the efficacy and safety of beinaglutide, a glucagon-like peptide-1 (GLP-1) analogue with metformin in lowering the bodyweight of patients who were overweight/obese and non-diabetic.

Patients And Methods: Seventy-eight non-diabetic patients were randomly selected and beinaglutide or metformin was administered for 12 weeks. The primary endpoints were changes in body weight and the proportions of patients who lost≥5 and≥10% of their baseline body weights.

Results: A total of 64 patients completed the study; patients in the beinaglutide group exhibited more bodyweight loss than those in the metformin group [(9.5±0.8%; 9.1±0.9 kg) and (5.1±0.9%; 4.5±0.8 kg), respectively, corresponding to a difference of approximately 4.5 kg (95% confidence interval, 2.2-6.9 kg; <0.01)]. In the beinaglutide group, 90.6 and 40.6% of the patients lost≥5 and≥10% of their body weight, respectively, whereas, in the metformin group, these rates were 46.9 and 12.5%, respectively (<0.01 and 0.05). Weight loss following beinaglutide treatment mainly resulted from the loss of fat mass. Compared to metformin, beinaglutide induced a greater decrease in the body mass index, weight circumference, percent body fat, and body fat mass (total, trunk, limb, android, and gynoid). Additionally, beinaglutide decreased serum insulin levels and ameliorated insulin resistance.

Conclusions: Beinaglutide is more efficient than metformin at reducing weight and fat mass in patients who are overweight/obese and non-diabetic. Beinaglutide may be a useful therapeutic option for overweight/obesity control in the Chinese population.
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http://dx.doi.org/10.1055/a-1608-0345DOI Listing
December 2021

Umbralisib-Induced Immune-Mediated Colitis: A Concerning Adverse Effect of the Novel PI3Kδ/CK1ε Inhibitor.

ACG Case Rep J 2021 Nov 24;8(11):e00701. Epub 2021 Nov 24.

Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL.

Novel chemotherapeutic agents are developed to treat recurrent/relapsed lymphoid malignancies. Umbralisib, a novel phosphatidylinositol 3-kinase inhibitor with a selective isoform binding, has shown an improved efficacy and safety profile in clinical trials. Immune-mediated colitis, a frequently observed dose-limiting adverse event of phosphatidylinositol 3-kinase inhibitors, has been mostly observed at supratherapeutic doses in the trials, with grade 1 or 2 diarrhea being the most common adverse event at the therapeutic dose (800 mg PO QD). We present a grade-3 colitis that can be attributed to umbralisib-mediated immune toxicity in a patient with chronic lymphocytic leukemia at the therapeutic dose.
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http://dx.doi.org/10.14309/crj.0000000000000701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8613332PMC
November 2021

Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation.

Cell Biosci 2021 Nov 4;11(1):189. Epub 2021 Nov 4.

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.

Background: Nonalcoholic fatty liver disease (NAFLD) is a disorder that extends from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is effectively alleviated by lifestyle intervention. Nevertheless, DNA methylation mechanism underling the effect of environmental factors on NAFLD and NASH is still obscure. The aim of this study was to investigate the effect of exercise and diet intervention in NAFLD and NASH via DNA methylation of GAB2.

Methods: Methylation of genomic DNA in human NAFLD was quantified using Infinium Methylation EPIC BeadChip assay after exercise (Ex), low carbohydrate diet (LCD) and exercise plus low carbohydrate diet (ELCD) intervention. The output Idat files were processed using ChAMP package. False discovery rate on genome-wide analysis of DNA methylation (q < 0.05), and cytosine-guanine dinucleotides (CpGs) which are located in promoters were used for subsequent analysis (|Δβ|≥ 0.1). K-means clustering was used to cluster differentially methylated genes according to 3D genome information from Human embryonic stem cell. To quantify DNA methylation and mRNA expression of GRB2 associated binding protein 2 (GAB2) in NASH mice after Ex, low fat diet (LFD) and exercise plus low fat diet (ELFD), MassARRAY EpiTYPER and quantitative reverse transcription polymerase chain reaction were used.

Results: Both LCD and ELCD intervention on human NAFLD can induce same DNA methylation alterations at critical genes in blood, e.g., GAB2, which was also validated in liver and adipose of NASH mice after LFD and ELFD intervention. Moreover, methylation of CpG units (i.e., CpG_10.11.12) inversely correlated with mRNA expression GAB2 in adipose tissue of NASH mice after ELFD intervention.

Conclusions: We highlighted the susceptibility of DNA methylation in GAB2 to ELFD intervention, through which exercise and diet can protect against the progression of NAFLD and NASH on the genome level, and demonstrated that the DNA methylation variation in blood could mirror epigenetic signatures in target tissues of important biological function, i.e., liver and adipose tissue. Trial registration International Standard Randomized Controlled Trial Number Register (ISRCTN 42622771).
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http://dx.doi.org/10.1186/s13578-021-00701-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569968PMC
November 2021

New way, new recommendation: Individualized treatment of novel antidiabetic drugs for people living with type 2 diabetes based on the cardiorenal risks.

Authors:
Xiang Xu Yan Bi

J Evid Based Med 2021 Nov 1. Epub 2021 Nov 1.

Department of Endocrinology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

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http://dx.doi.org/10.1111/jebm.12452DOI Listing
November 2021

Exome Sequencing of Pancreatic Acinar Carcinoma Identified Distinctive Mutation Patterns.

Pancreas 2021 Aug;50(7):1007-1013

Division of Gastroenterology and Hepatology.

Objectives: Pancreatic acinar cell carcinoma (ACC) is a rare pancreatic cancer. The advancement of treatment is hampered because of the limited knowledge of its molecular mechanism.

Methods: Whole-exome sequencing was performed on DNA extracted from 11 pure ACC surgical samples. Potential germline variants were removed on the basis of polymorphic databases, alternative allele frequency, coverage depth, and Catalogue of Somatic Mutations in Cancer (COSMIC) annotations after variant calling procedure. Mutation profiles and signatures were assessed through the Mutational Patterns package.

Results: A median of 34 somatic mutations were detected (range, 19-60). Three novel recurrent small deletions were identified. Common pancreatic ductal adenocarcinoma mutations or neuroendocrine tumor mutants were not found. FAT atypical cadherin 4, mucin 5B, titin, and zinc finger homeobox 3 were consistently mutated across 4 independent ACC studies. A high contribution of COSMIC mutational signature 1 was seen in ACC, indicating deamination of 5-methylcytosine. The majority of the patients had COSMIC signatures 6, 15, or 20, relating to defective DNA mismatch repair. Six patients showed COSMIC mutational signature 10 because of the altered activity of DNA polymerase epsilon.

Conclusions: Distinct mutational signatures pathways were found in ACC and targeting them may improve clinical outcome.
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http://dx.doi.org/10.1097/MPA.0000000000001870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516064PMC
August 2021

Ero1-Pdi1 module-catalysed dimerization of a nucleotide sugar transporter, FonNst2, regulates virulence of Fusarium oxysporum on watermelon.

Environ Microbiol 2021 Sep 29. Epub 2021 Sep 29.

State Key Laboratory of Rice Biology and Ministry of Agriculture Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou, 310058, China.

Fusarium oxysporum f. sp. niveum (Fon) is a soil-borne fungus causing vascular Fusarium wilt on watermelon; however, the molecular network regulating Fon virulence remains to be elucidated. Here, we report the function and mechanism of nucleotide sugar transporters (Nsts) in Fon. Fon genome harbours nine FonNst genes with distinct functions in vegetative growth, asexual production, cell wall stress response and virulence. FonNst2 and FonNst3 are required for full virulence of Fon on watermelon and FonNst2 is mainly involved in fungal colonization of the plant tissues. FonNst2 and FonNst3 form homo- or hetero-dimers but function independently in Fon virulence. FonNst2, which has UDP-galactose transporter activity in yeast, interacts with FonEro1 and FonPdi1, both of which are required for full virulence of Fon. FonNst2, FonPdi1 and FonEro1 target to endoplasmic reticulum (ER) and are essential for ER homeostasis and function. FonEro1-FonPdi1 module catalyses the dimerization of FonNst2, which is critical for Fon virulence. Undimerized FonNst2 is unstable and degraded via ER-associated protein degradation in vivo. These data demonstrate that FonEro1-FonPdi1 module-catalysed dimerization of FonNst2 is critical for Fon virulence on watermelon and provide new insights into the regulation of virulence in plant fungal pathogens via disulfide bond formation of key pathogenicity factors.
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http://dx.doi.org/10.1111/1462-2920.15789DOI Listing
September 2021

MRI-Based Radiomics Nomogram for Selecting Ovarian Preservation Treatment in Patients With Early-Stage Endometrial Cancer.

Front Oncol 2021 9;11:730281. Epub 2021 Sep 9.

Department of Radiology, Jinshan Hospital, Fudan University, Shanghai, China.

Background: Ovarian preservation treatment (OPT) was recommended in young women with early-stage endometrial cancer [superficial myometrial invasion (MI) and grades (G) 1/2-endometrioid adenocarcinoma (EEC)]. A radiomics nomogram was developed to assist radiologists in assessing the depth of MI and in selecting eligible patients for OPT.

Methods: From February 2014 to May 2021, 209 G 1/2-EEC patients younger than 45 years (mean 39 ± 4.3 years) were included. Of them, 104 retrospective patients were enrolled in the primary group, and 105 prospective patients were enrolled in the validation group. The radiomics features were extracted based on multi-parametric magnetic resonance imaging, and the least absolute shrinkage and selection operator algorithm was applied to reduce the dimensionality of the data and select the radiomics features that correlated with the depth of MI in G 1/2-EEC patients. A radiomics nomogram for evaluating the depth of MI was developed by combing the selected radiomics features with the cancer antigen 125 and tumor size. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the radiomics nomogram and of radiologists without and with the aid of the radiomics nomogram. The net reclassification index (NRI) and total integrated discrimination index (IDI) based on the total included patients to assess the clinical benefit of radiologists with the radiomics nomogram were calculated.

Results: In the primary group, for evaluating the depth of MI, the AUCs were 0.96 for the radiomics nomogram; 0.80 and 0.86 for radiologists 1 and 2 without the aid of the nomogram, respectively; and 0.98 and 0.98 for radiologists 1 and 2 with the aid of the nomogram, respectively. In the validation group, the AUCs were 0.88 for the radiomics nomogram; 0.82 and 0.83 for radiologists 1 and 2 without the aid of the nomogram, respectively; and 0.94 and 0.94 for radiologists 1 and 2 with the aid of the nomogram, respectively. The yielded NRI and IDI values were 0.29 and 0.43 for radiologist 1 and 0.23 and 0.37 for radiologist 2, respectively.

Conclusions: The radiomics nomogram outperformed radiologists and could help radiologists in assessing the depth of MI and selecting eligible OPTs in G 1/2-EEC patients.
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http://dx.doi.org/10.3389/fonc.2021.730281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459685PMC
September 2021

ONAC066, A Stress-Responsive NAC Transcription Activator, Positively Contributes to Rice Immunity Against Through Modulating Expression of and Three Cytochrome P450 Genes.

Front Plant Sci 2021 9;12:749186. Epub 2021 Sep 9.

National Key Laboratory for Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

NAC transcriptional factors constitute a large family in rice and some of them have been demonstrated to play crucial roles in rice immunity. The present study investigated the function and mechanism of in rice immunity. ONAC066 shows transcription activator activity that depends on its C-terminal region in rice cells. -OE plants exhibited enhanced resistance while -Ri and plants showed attenuated resistance to . A total of 81 genes were found to be up-regulated in -OE plants, and 26 of them were predicted to be induced by . Four genes, including and , were up-regulated in -OE plants but down-regulated in -Ri plants. ONAC066 bound to NAC core-binding site in promoter and activated expression, indicating that is a ONAC066 target. A set of cytochrome P450 genes were found to be co-expressed with and 5 of them were up-regulated in -OE plants but down-regulated in -Ri plants. ONAC066 bound to promoters of cytochrome P450 genes , , and and activated their transcription, indicating that these three cytochrome P450 genes are ONAC066 targets. These results suggest that ONAC066, as a transcription activator, positively contributes to rice immunity through modulating the expression of and a set of cytochrome P450 genes to activate defense response.
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http://dx.doi.org/10.3389/fpls.2021.749186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458891PMC
September 2021

Systemic anticoagulation is associated with decreased mortality and morbidity in acute pancreatitis.

Pancreatology 2021 Dec 8;21(8):1428-1433. Epub 2021 Sep 8.

Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA. Electronic address:

Background/objectives: Acute pancreatitis (AP) is a procoagulant state, and markers of coagulopathy are associated with AP severity. We aimed to explore the association of systemic anticoagulation therapy before AP onset with the inpatient outcomes of patients with acute pancreatitis.

Methods: This case-control, retrospective study used data from the Nationwide Inpatient Sample (Jan 2014-Dec 2016). We used medical coding data to identify patients with a principal diagnosis of AP who were receiving systemic anticoagulation therapy. Patients with anticoagulation were matched to those without it on the propensity for having anticoagulation. The propensity for having anticoagulation was estimated using a logistic regression model, matching for age, gender, race, median household income for patients' zip code, Charlson comorbidity score, region of hospital, location of hospital (urban/rural), teaching status of hospital, if admission day was on a weekend, pancreatic cancer class, obesity, tobacco usage. Secondary outcomes were inpatient outcomes and hospital expenditures.

Results: A total of 190,474 patients admitted for acute pancreatitis were identified, out of which 7827 patients were on anticoagulation. After propensity matching, 5776 matched pairs were successfully identified. Patients with AP on anticoagulation tended to have lower risk for ICU admission, acute kidney injury, organ failure or inpatient mortality. However, the group with anticoagulation had longer hospital length of stay and higher hospital costs.

Conclusions: Anticoagulation therapy may have a pivotal role in the pathogenesis and progression of AP. These data suggest a potential therapeutic role for anticoagulants in AP. Further studies are needed to better understand these observations.
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http://dx.doi.org/10.1016/j.pan.2021.09.003DOI Listing
December 2021

A study of negative life events driven depressive symptoms and academic engagement in Chinese college students.

Sci Rep 2021 08 25;11(1):17160. Epub 2021 Aug 25.

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.

Negative life events (NLEs) are an important predictor of depressive symptoms (DS). College students experiencing NLEs are at risk of developing DS that could further weaken their academic engagement (AE), while social supports may assuage such negative effect. The aim of this study was to examine the relationship between negative life events, depressive symptoms, and academic engagement, and how the NLE-DS-AE relationship is affected by the level of social support among Chinese college students. To test this hypothesis, we applied data from the Decoding Happiness Gene Cohort Study (DHGCS). Baseline depressive symptoms and academic engagement were measured at the beginning of the first academic year. Approximately 12 months later, negative life events and social support over the past year were assessed retrospectively along with current depressive symptoms and academic engagement. A total of 3629 college students (Age = 18.67 ± 0.82) were included in the study. The prevalence of depressive symptoms was 26.7% and 36.7% in college students at the beginning of the first and second academic year, respectively. Depressive symptoms predicted subsequent academic engagement rather than the reverse based on cross-lagged analyses. Using structural equation modeling analyses, findings revealed a partial mediation effect of social support between negative life events and the development of depressive symptoms, and a partial mediation effect between negative life events and academic engagement. The findings presented negative life events jeopardize the academic engagement via depressive symptoms, while social supports are able to cancel such negative effect among college students under the Chinese cultural context.
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http://dx.doi.org/10.1038/s41598-021-96768-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387499PMC
August 2021

Peripheral Administration of NMU Promotes White Adipose Tissue Beiging and Improves Glucose Tolerance.

Int J Endocrinol 2021 2;2021:6142096. Epub 2021 Aug 2.

Department of Endocrinology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.

Purpose: Targeting white adipose tissue (WAT) beiging has been proposed as an effective way to increase thermogenesis and improve glucose metabolism. Neuromedin U (NMU) is a neuropeptide that could increase energy expenditure, while its effects on WAT beiging and glucose homeostasis remain to be investigated.

Methods: Male C57BL/6 mice were fed with high fat diet (HFD) to induce obesity and hyperglycemia and then treated with chronic subcutaneous injection of NMU. Body weight and food intake were recorded daily. After 14 days of injection, intraperitoneal glucose tolerance tests and 18F-fluorodeoxyglucose micro-positron emission tomography/computed tomography (18F-FDG micro-PET/CT) scans were conducted. Subcutaneous WAT (sWAT) and interscapular brown adipose tissue were collected for the evaluation of adipocyte size, expression of uncoupling protein 1 (), and other thermogenic-related genes. Stromal vascular fraction of subcutaneous WAT was extracted for the measurement of type 2 innate lymphocytes (ILC2s) proportions.

Results: Glucose tolerance was markedly improved by peripherally administered NMU. Micro-PET/CT suggested that NMU promoted WAT beiging, which was further confirmed by haematoxylin and eosin (H&E) staining and immunohistochemistry. In diet-induced-obese (DIO) mice, NMU activated thermogenic-related genes in WAT. In addition, NMU stimulated ILC2s in the stromal vascular fraction of WAT.

Conclusion: Taken together, our study indicates that peripheral administration of NMU is a potential therapeutic strategy for the promotion of WAT beiging and the improvement of impaired glucose tolerance.
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http://dx.doi.org/10.1155/2021/6142096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373479PMC
August 2021

Body Adiposity Index Is Predictive of Weight Loss after Roux-en-Y Gastric Bypass.

Ann Nutr Metab 2021 2;77(3):168-177. Epub 2021 Aug 2.

Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Background/aims: Roux-en-Y gastric bypass (RYGB) is one of the most effective therapies for morbid obesity, yet some patients who have taken the surgery still undergo insufficient weight loss. Visceral adiposity index (VAI), lipid accumulation product (LAP), body adiposity index (BAI), and cardiometabolic index (CMI) have been regarded as clinical indicators of adiposity phenotypes that associated closely with obesity-related metabolic diseases. However, no studies have evaluated the relationship between these indexes and weight loss after bariatric surgery. In this prospective study, we aimed to evaluate whether VAI, LAP, BAI, and CMI would predict postoperative weight loss outcomes after RYGB.

Methods: This study included 38 men and 67 women who have undergone RYGB between January 2017 and May 2018 and recorded their %TWL (percent of total weight loss), %EBMIL (percent of excess body mass index loss), %EWL (percent of excess weight loss), anthropometric indices, and biochemical parameters before and 12 months after the surgery. In addition, VAI, LAP, BAI, and CMI were measured with anthropometric measures or lipid profiles using related equations and analyzed with metabolic characteristics.

Results: Subjects with lower BAI (<32.54 in men and 37.39 in women) displayed higher %EBMIL and %EWL 12 months after surgery. BAI was independently associated with %EWL 12 months after surgery in both men and women (both p < 0.05). The area under the receiver operating characteristic curve for BAI was significantly higher (0.773 in men and 0.818 in women) than VAI, LAP, and CMI.

Conclusions: BAI serves as a reliable surrogate marker of the weight loss outcome after RYGB. The predictivity of adiposity indexes in beneficial outcomes after weight loss therapies is of important referential value for the implementation and optimization of individualized and refined weight loss treatments for obese patients.
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http://dx.doi.org/10.1159/000516522DOI Listing
August 2021

Better Islet Function and Cardiovascular Autonomic Function in Chinese Type 2 Diabetic Patients with Pure Small Fiber Neuropathy than with Mixed Neuropathy.

Diabetes Ther 2021 Sep 2;12(9):2423-2436. Epub 2021 Aug 2.

Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.

Introduction: The clinical characteristics and outcomes of small fiber neuropathy (SFN) in Chinese patients with type 2 diabetes mellitus (T2DM) have not been thoroughly described. In this study, we investigated the metabolic and neurological indexes and the prognosis of patients with T2DM based on skin biopsy.

Methods: A total of 34 healthy Chinese volunteers were recruited for skin biopsy to establish the reference range of intra-epidermal nerve fiber density (IENFD), and 89 patients with T2DM attending the Nanjing Drum Tower Hospital were evaluated at baseline. Of these 89 patients, 17 with pure SFN and nine with mixed diabetic polyneuropathy (DPN) were reassessed at the end of the follow-up.

Results: Glycated hemoglobin and postprandial blood glucose levels were lower (P = 0.005 and P = 0.041, respectively) and postprandial C-peptide and insulin levels were higher (P = 0.001 and P = 0.019, respectively) in the pure SFN group than in the mixed DPN group. A partial correlation study showed that there was a negative correlation between IENFD of the distal leg and cardiovascular autonomic reflex test (CART) scores (r = - 0.513, P = 0.001) after adjusting for age and duration of diabetes. Only vitamin B12 level (P = 0.028) and motor nerve conduction velocity (MCV) of the common peroneal nerve (P = 0.045) were increased in the patients with pure SFN at the final visit while MCVs of the common peroneal nerve (P = 0.025) and tibial nerve (P = 0.047) were decreased in the mixed DPN group at the final visit.

Conclusion: Better islet function and cardiovascular autonomic function were observed in patients with pure SFN compared with mixed DPN. The metabolic and neurological indexes remained relatively stable in the patients with pure SFN during the follow-up.
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http://dx.doi.org/10.1007/s13300-021-01111-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385000PMC
September 2021

RGCC balances self-renewal and neuronal differentiation of neural stem cells in the developing mammalian neocortex.

EMBO Rep 2021 09 29;22(9):e51781. Epub 2021 Jul 29.

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai, China.

During neocortical development, neural stem cells (NSCs) divide symmetrically to self-renew at the early stage and then divide asymmetrically to generate post-mitotic neurons. The molecular mechanisms regulating the balance between NSC self-renewal and neurogenesis are not fully understood. Using mouse in utero electroporation (IUE) technique and in vitro human NSC differentiation models including cerebral organoids (hCOs), we show here that regulator of cell cycle (RGCC) modulates NSC self-renewal and neuronal differentiation by affecting cell cycle regulation and spindle orientation. RGCC deficiency hampers normal cell cycle process and dysregulates the mitotic spindle, thus driving more cells to divide asymmetrically. These modulations diminish the NSC population and cause NSC pre-differentiation that eventually leads to brain developmental malformation in hCOs. We further show that RGCC might regulate NSC spindle orientation by affecting the organization of centrosome and microtubules. Our results demonstrate that RGCC is essential to maintain the NSC pool during cortical development and suggest that RGCC defects could have etiological roles in human brain malformations.
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http://dx.doi.org/10.15252/embr.202051781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419700PMC
September 2021

Pancreas-specific CHRM3 activation causes pancreatitis in mice.

JCI Insight 2021 Sep 8;6(17). Epub 2021 Sep 8.

Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, USA.

Hyperstimulation of the cholecystokinin 1 receptor (CCK1R), a G protein-coupled receptor (GPCR), in pancreatic acinar cells is commonly used to induce pancreatitis in rodents. Human pancreatic acinar cells lack CCK1R but express cholinergic receptor muscarinic 3 (M3R), another GPCR. To test whether M3R activation is involved in pancreatitis, a mutant M3R was conditionally expressed in pancreatic acinar cells in mice. This mutant receptor loses responsiveness to its native ligand, acetylcholine, but can be activated by an inert small molecule, clozapine-N-oxide (CNO). Intracellular calcium and amylase were elicited by CNO in pancreatic acinar cells isolated from mutant M3R mice but not WT mice. Similarly, acute pancreatitis (AP) could be induced by a single injection of CNO in the transgenic mice but not WT mice. Compared with the cerulein-induced AP, CNO caused more widespread acinar cell death and inflammation. Furthermore, chronic pancreatitis developed at 4 weeks after 3 episodes of CNO-induced AP. In contrast, in mice with 3 recurrent episodes of cerulein-included AP, pancreas histology was restored in 4 weeks. Furthermore, the M3R antagonist ameliorated the severity of cerulein-induced AP in WT mice. We conclude that M3R activation can cause the pathogenesis of pancreatitis. This model may provide an alternative approach for pancreatitis research.
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http://dx.doi.org/10.1172/jci.insight.132585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492327PMC
September 2021

Connecting Peripheral to Central Neuropathy: Examination of Nerve Conduction Combined with Olfactory Tests in Patients with Type 2 Diabetes.

Diabetes Metab Syndr Obes 2021 6;14:3097-3107. Epub 2021 Jul 6.

Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People's Republic of China.

Aim: Few studies have investigated the associations between diabetic peripheral neuropathy (DPN) and cognitive decline. Olfactory impairment is related to neurodegenerative diseases and type 2 diabetes mellitus (T2DM); however, the cognitive alterations of patients with DPN and the role of olfactory function in DPN are not known. We explored alterations in cognition with DPN and the associations of neuropathy parameters with cognition and olfaction.

Methods: Healthy controls (HCs) and patients with T2DM underwent nerve-conduction tests, detailed cognitive assessment, olfactory-behavior tests, and odor-induced functional magnetic resonance imaging (fMRI). T2DM patients were divided into two groups (non-DPN [NDPN] and DPN). Olfactory brain regions showing different activation between the two groups were selected for functional connectivity (FC) analyses. A structural equation model (SEM) was also generated to demonstrate the association among cognition, olfactory, and neuropathy parameters.

Results: One hundred individuals (36 HCs, 36 NDPN, and 28 DPN) were matched for age, sex, and educational level. Compared with the NDPN group, the DPN group had significantly lower scores for memory and processing speed, as well as lower olfactory identification and memory scores, decreased activation of the left frontal lobe, and reduced seed-based functional connectivity in the right insula. The nerve conduction velocity in patients with T2DM was associated with cognitive functions. The association between nerve conduction and executive function was mediated by olfactory behavior.

Conclusion: Patients with DPN had worse cognition than the NDPN patients in the domains of memory and processing speed. Cognitive dysfunction could be predicted by olfactory-behavior tests and electrophysiological examination.
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http://dx.doi.org/10.2147/DMSO.S312021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276992PMC
July 2021

Associations Between Obesity and Kidney Disease in Chinese Men and Women With Type 2 Diabetes: A Retrospective Cohort Study.

Can J Diabetes 2021 May 19. Epub 2021 May 19.

Department of Endocrinology, Drum Tower Clinical College of Nanjing Medical University, Nanjing, China; Department of Endocrinology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China. Electronic address:

Background: Our aim in this study was to explore the risk factors for kidney disease in Chinese men and women with type 2 diabetes (T2D) and to clarify the relationship between obesity and the risk of chronic kidney disease (CKD).

Methods: This retrospective study included 3,194 patients with T2D. Among 2,574 T2D patients without CKD at baseline, 753 with follow-up records of at least 12 months were included in the retrospective cohort. Logistic regression and Cox regression were used to evaluate the risk for CKD in men and women. A restricted cubic spline model was used to analyze the association of body mass index (BMI) and waist circumference (WC) with CKD risk.

Results: Multivariate logistic regression analysis suggested that obesity was a risk factor for T2D with CKD in men but not in women. After a median follow-up period of 2.8 years, the incidence of CKD in men with obesity was significantly higher than that in men with obesity with T2D (p=0.039), but there was no statistically significant difference between women with obesity and women without obesity with T2D (p=0.825). In the restricted cubic spline model analysis, BMI and WC were associated with CKD risk in a nonlinear fashion in males and females. The risk of CKD was higher in males with a BMI of ≥29.5 kg/m or a WC of ≥100 cm, whereas there was no difference observed in females.

Conclusions: Obesity was strongly related to T2D with CKD in men. Male diabetes patients with obesity, especially abdominal obesity, are more likely to develop CKD.
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http://dx.doi.org/10.1016/j.jcjd.2021.05.005DOI Listing
May 2021

Quantitative sensory testing can effectively predict cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus.

Acta Diabetol 2021 Nov 17;58(11):1541-1549. Epub 2021 Jun 17.

Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No 321 Zhongshan Road, Nanjing, 210008, China.

Aims: Cardiovascular autonomic neuropathy (CAN) is one of the most serious types of diabetic autonomic neuropathy and is a class of small fibre neuropathy. Among many inspection methods, quantitative sensory testing is an effective and convenient method for diagnosing diabetic small fibre neuropathy. This cross-sectional study aimed to identify the correlation between the development of cardiovascular autonomic neuropathy and quantitative sensory testing parameters in patients with type 2 diabetes mellitus.

Methods: A total of 266 participants with type 2 diabetes mellitus from Nanjing Drum Tower Hospital were enrolled in this study, and each of them received cardiovascular reflex tests (CARTs) and quantitative sensory testing, including testing of cold, warm, cold pain, and heat pain detection thresholds (CDT, WDT, CPT, and HPT, respectively). The results of CARTs were compared with the thermal detection thresholds in quantitative sensory testing by using SPSS 26.0.

Results: A total of 266 participants were divided into the CAN group, early CAN (ECAN) group, and without CAN (NCAN) group. There were significant differences in quantitative sensory testing parameters among three groups, and CARTs presented a positive correlation with the WDT and HPT and a negative correlation with the CDT. Moreover, after adjusting for age, sex, diabetes duration, and other influencing factors, WDT, HPT, and CDT were independent risk factors for cardiovascular autonomic neuropathy.

Conclusions: The thermal detection thresholds, including cold, warm, and heat pain detection thresholds, in quantitative sensory testing were found to be significantly related to the results of CARTs. Some thermal detection thresholds were independent risk factors for cardiovascular autonomic neuropathy. Therefore, this study showed that quantitative sensory testing has a reliable predictive ability for the occurrence and development of cardiovascular autonomic neuropathy.
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http://dx.doi.org/10.1007/s00592-021-01744-4DOI Listing
November 2021

Corneal confocal microscopy: A useful tool for diagnosis of small fiber neuropathy in type 2 diabetes.

J Diabetes Investig 2021 Jun 16. Epub 2021 Jun 16.

Department of Endocrinology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.

Aim: To investigate the diagnostic utility of corneal confocal microscopy (CCM) for small fiber neuropathy in type 2 diabetes.

Materials And Methods: There were 186 participants with type 2 diabetes enrolled in this cross-sectional research. Pure small fiber neuropathy and mixed fiber neuropathy were defined using clinical examination, electromyography, and quantitative sensory testing. Demographics and clinical data, corneal confocal microscopy parameters, and other neuropathy measures were compared among the groups. The diagnostic utility of corneal confocal microscopy for small fiber neuropathy was assessed by the receiver operating curve.

Results: Of the 186 patients, 24.7% had a pure small fiber neuropathy and 17.2% of patients were diagnosed with mixed fiber neuropathy. The corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), and corneal nerve fiber length (CNFL) were significantly lower in subjects with pure small fiber neuropathy compared with those without diabetic peripheral neuropathy (all P < 0.05). The receiver operating curve analysis for corneal confocal microscopy diagnosing small fiber neuropathy demonstrated the area under the curve for CNFD of 0.791, CNFL of 0.778, CNBD of 0.710.

Conclusions: Patients with type 2 diabetes with pure small fiber neuropathy showed more corneal nerve loss compared with those without diabetic peripheral neuropathy. It was revealed that corneal confocal microscopy can be a reasonable marker in the diagnosis of small fiber neuropathy in type 2 diabetes.
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http://dx.doi.org/10.1111/jdi.13616DOI Listing
June 2021

One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study.

Stem Cell Res Ther 2021 06 10;12(1):340. Epub 2021 Jun 10.

Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, No 321, Zhongshan Road, Nanjing, 210008, Jiangsu, China.

Background: The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D.

Methods: This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses.

Results: After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed.

Conclusion: One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone.

Trial Registration: ChiCTR2100045434 . Registered on April 15, 2021-retrospectively registered, http://www.chictr.org.cn/.
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http://dx.doi.org/10.1186/s13287-021-02417-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194026PMC
June 2021

Colchicine as an Alternative First-Line Treatment of Sclerosing Mesenteritis: A Retrospective Study.

Dig Dis Sci 2021 Jun 4. Epub 2021 Jun 4.

Division of Gastroenterology and Hepatology, Mayo Clinic Florida, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA.

Background: Sclerosing mesenteritis is a rare condition characterized by chronic inflammation and fibrotic changes of the mesentery.

Aims: To determine the long-term management and outcomes of patients with sclerosing mesenteritis.

Methods: Patients with biopsy-proven sclerosing mesenteritis at the Mayo Clinic between January 2006 and December 2016 were identified. Clinical data were collected retrospectively.

Results: One hundred and three patients were identified, median age 68.0 years (range 35.0-85.3). Most patients were symptomatic (87.4%) at presentation. Patients received no treatment (52.4%), medical therapy (42.7%) or surgery (4.9%) on initial diagnosis. The most common initial regimens were prednisone plus tamoxifen (41.9%), prednisone alone (23.3%), and prednisone plus colchicine (11.6%) with 55.6%, 57.2%, and 60% of patients improving, respectively, p = 0.85 for a difference in response rates. At least half of the patients responded to prednisone plus tamoxifen, prednisone plus colchicine, or prednisone alone at 6.0, 7.2, and 8.4 months, respectively. At a median follow-up of 45.6 months (95% CI 24.1-69.7), 65.4% of patients were receiving medical therapy. Of those receiving tamoxifen-based, steroid-based, or steroid-sparing regimens, 100%, 87.5%, and 77.8% had improved by their last follow-up appointment respectively, p = 0.15.

Conclusion: Prednisone plus colchicine has a similar efficacy to prednisone plus tamoxifen for the initial and long-term treatment of sclerosing mesenteritis. The majority of patients were initiated on medical therapy over the long term with most reporting symptomatic improvement within a year. Death from SM was rare.
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http://dx.doi.org/10.1007/s10620-021-07081-4DOI Listing
June 2021

Risk Prediction Model of Gestational Diabetes Mellitus in a Chinese Population Based on a Risk Scoring System.

Diabetes Ther 2021 Jun 15;12(6):1721-1734. Epub 2021 May 15.

Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321, Zhongshan Road, Nanjing, 210008, China.

Introduction: Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes. Accurate models for early prediction of GDM are lacking. This study aimed to explore an early risk prediction model to identify women at high risk of GDM through a risk scoring system.

Methods: This was a retrospective cohort study of 785 control pregnancies and 855 women with GDM. Maternal clinical characteristics and biochemical measures were extracted from the medical records. Logistic regression analysis was used to obtain coefficients of selected predictors for GDM in the training cohort. The discrimination and calibration of the risk scores were evaluated by the receiver-operating characteristic (ROC) curve and a Hosmer-Lemeshow test in the internal and external validation cohort, respectively.

Results: In the training cohort (total = 1640), two risk scores were developed, one including predictors collected at the first antenatal care visit for early prediction of GDM, such as age, height, pre-pregnancy body mass index, educational background, family history of diabetes, menstrual history, history of cesarean delivery, GDM, polycystic ovary syndrome, hypertension, and fasting blood glucose (FBG), and the total risk score also including FBG and triglyceride values during 14-20 gestational weeks. Our total risk score yielded an area under the curve (AUC) of 0.845 (95% CI = 0.805-0.884). This performed better in an external validation cohort, with an AUC of 0.886 (95% CI = 0.856-0.916).

Conclusion: The GDM risk score, which incorporates several potential clinical features with routine biochemical measures of GDM, appears to be a sensitive and reliable screening tool for earlier detection of GDM risk.
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http://dx.doi.org/10.1007/s13300-021-01066-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179863PMC
June 2021

Effect of Integrative Neuromuscular Training for Injury Prevention and Sports Performance of Female Badminton Players.

Biomed Res Int 2021 23;2021:5555853. Epub 2021 Apr 23.

Institute of Sports Medicine, Beijing Tsinghua Changgung Hospital, Beijing, China.

Objectives: Investigate the effects of integrated neuromuscular training (INT) on injury prevention and the performance of professional female badminton athletes by comparing their preintervention and postintervention tests. The study hypothesized that integrated neuromuscular training can improve the asymmetry and improve the sport performance of female badminton players.

Methods: According to pretest value based on functional movement screening, 38 participants were divided into a high-risk group (HG) and a low-risk group (LG) with 22 and 16 people in each group. Two groups of athletes took part in an 8-week INT program consisting of four 90-min sessions each week. The asymmetries in movement, physical fitness, and special abilities were tested before and after the intervention. Independent sample -test was used for the statistical analysis.

Results: This research found indicated that 8 weeks of INT influenced FMS scores in both groups (HG and LG). The change of inline lunge (ES = 0.42, ES = 0.21) and trunk stability push-up (ES = -0.58, ES = -0.20) showed significant differences ( < 0.05), and the change of the FMS scores (ES = 0.81, ES = 0.65), deep squat (ES = 0.6, ES = 0.3), and rotation stability (ES = -0.65, ES = -0.72) showed very significant differences ( < 0.01). Compared to the pretest, most of the physical fitness parameters improved significantly in the HG and LG groups except strength index, and special abilities of the HG and LG group women badminton athletes showed a substantial increase.

Conclusion: Integrated neuromuscular training can effectively improve the asymmetry of female badminton athletes' limbs, prevent sports injury, and improve the athlete's performance ability. However, athletes in different risk groups have certain differences in the degree of improvement in their motor skills.
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http://dx.doi.org/10.1155/2021/5555853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093055PMC
June 2021

Comparison of idiopathic recurrent acute pancreatitis [IRAP] and recurrent acute pancreatitis with genetic mutations.

Dig Liver Dis 2021 Oct 7;53(10):1294-1300. Epub 2021 May 7.

Division of Gastroenterology and Hepatology, Presbyterian Healthcare Services, Albuquerque, New Mexico, USA. Electronic address:

Background: Idiopathic recurrent acute pancreatitis (IRAP) describes frequent episodes of pancreatitis without an etiology found using current testing. We compared the natural history of IRAP with recurrent acute pancreatitis with genetic mutations.

Methods: Retrospective cohort of patients with recurrent acute pancreatitis (≥2 episodes) and negative conventional testing. All patients had ≥1 episode after cholecystectomy and completed genetic testing. Primary outcomes were chronic pancreatitis incidence, pancreatic cancer, and mortality. Secondary outcomes included opioid and ERCP utilization.

Results: 128 patients met criteria for presumed IRAP. 35 patients met criteria for true IRAP. 12 patients had recurrent acute pancreatitis with gene mutations. Chronic pancreatitis developed in 27 (77.1%) IRAP patients over a median of 6 years. Chronic pancreatitis incidence was similar in IRAP and CFTR mutation carriers; but developed later in SPINK1 carriers. No patients developed pancreatic cancer or died from pancreatic-related causes. Patients were frequently treated with oral opioids and ERCP, without significant differences within or between groups.

Conclusion: IRAP and pancreatitis in mutation carriers is associated with chronic pancreatitis. Important differences in natural history were observed, but no association was found with cancer or pancreas-related mortality. Efforts to understand the genetic contributions to IRAP, minimize opioids and unnecessary ERCPs are encouraged.
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http://dx.doi.org/10.1016/j.dld.2021.04.013DOI Listing
October 2021

Treatment Approach of Refractory : A Comprehensive Review.

J Prim Care Community Health 2021 Jan-Dec;12:21501327211014087

Mayo Clinic, Jacksonville, FL, USA.

is the most common infection in the world and is associated with gastrointestinal and extra-gastrointestinal manifestations, including peptic ulcer disease, gastrointestinal bleeding, and lymphoproliferative disorders. Despite being discovered less than half a century ago, antibiotic resistance, exacerbated by medication non-adherence and inefficacy of proton pump inhibitors, has grown substantially, explaining the rising incidence of refractory infection. In this review, we discuss risk factors, treatment options, surveillance and follow-up, as well as emerging therapies for refractory .
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http://dx.doi.org/10.1177/21501327211014087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114244PMC
June 2021

Comparison of insulin glargine 300 U/mL versus glargine 100 U/mL on glycemic control and hypoglycemic events in East Asian patients with type 2 diabetes: A Patient-level meta-analysis of phase 3 studies.

Diabetes Res Clin Pract 2021 Jun 1;176:108848. Epub 2021 May 1.

Sanofi, Shanghai, China.

Aims: To evaluate efficacy and safety of Gla-300 with Gla-100 in a patient-level meta-analysis among large East Asian patients with type 2 diabetes mellitus (T2DM).

Methods: A patient level meta-analysis of three EDITION studies with similar design and endpoints were conducted over 6-months treatment period. The analysis included 547 patients treated with Gla-300 and 348 patients treated with Gla-100.

Results: Over 6-month treatment period, mean change in HbA1c was similar for Gla-300 [Least square (LS) mean, (SE): -1.13 (0.05) % and Gla-100: -1.14 (0.05) %], showing non-inferiority of Gla-300 to Gla-100 (LS mean difference: 0.02%, 95% CI: -0.08 to 0.11). Gla-300 was associated with reduced risk of hypoglycemic event (confirmed ≤ 3.9 mmol/L or severe) vs Gla-100 at any time of day or at night (00:00-05:59 h). The event rates of hypoglycemia were consistently lower with Gla-300 than Gla-100. Severe hypoglycemia was rare in both treatment groups. Weight gain was minimal in both treatment groups.

Conclusion: Gla-300 provides comparable glycemic control to Gla-100 in East Asian patients with broad clinical spectrum of T2DM, with consistently less hypoglycemia at any time of the day and night.
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http://dx.doi.org/10.1016/j.diabres.2021.108848DOI Listing
June 2021

Association of Omental Adipocyte Hypertrophy and Fibrosis with Human Obesity and Type 2 Diabetes.

Obesity (Silver Spring) 2021 06 4;29(6):976-984. Epub 2021 May 4.

Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu, China.

Objective: Morphological alterations including adipocyte hypertrophy and fibrosis deposition are important surrogate markers of visceral adipose tissue function, but the relationships between these morphological changes and type 2 diabetes mellitus (T2DM) and impaired insulin sensitivity are poorly defined.

Methods: Omental adipose tissue was obtained from 66 individuals with obesity but without T2DM (OB group), 93 individuals with both obesity and T2DM (T2DM group), and 15 individuals with normal BMI and normal glucose tolerance (NGT group). Adipocyte diameter and volume were measured through pathological section analysis. Pericellular and perilobular fibrosis was determined through picrosirius red staining and immunochemistry, while fibrosis-related genes were tested through gene expression and hydroxyproline content.

Results: Compared with the NGT and OB groups, individuals from the T2DM group displayed increased adipocyte diameter and volume levels. Increased adipocyte size (diameter and volume) was positively associated with hyperglycemia and insulin resistance and inversely correlated with insulin sensitivity (using the Matsuda whole-body insulin sensitivity index assessment of insulin sensitivity) and β-cell function (disposition index 30 and disposition index 120). The fibrosis levels of the OB group were the highest out of the three groups, whereas the fibrosis levels of T2DM individuals were lower than the OB group but higher than the NGT group. Although fibrosis was negatively correlated with T2DM, fibrosis deposition was not remarkably associated with impaired systemic insulin sensitivity and glucose metabolism.

Conclusions: Compared with fibrosis deposition, adipocyte hypertrophy is more closely associated with T2DM and impaired systemic insulin sensitivity.
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http://dx.doi.org/10.1002/oby.23155DOI Listing
June 2021

Advanced glycation end product levels were correlated with inflammation and carotid atherosclerosis in type 2 diabetes patients.

Open Life Sci 2020 11;15(1):364-372. Epub 2020 Jun 11.

Department of Endocrinology, Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China.

Diabetes mellitus with atherosclerosis (AS) adds to the social burden. This study aimed to investigate whether advanced glycation end product (AGE) levels were correlated with inflammation and carotid AS (CAS) in type 2 diabetes mellitus (T2DM) patients. A total of 50 elderly T2DM patients and 50 age-matched senior healthy subjects were recruited in this study. T2DM patients were classified into two groups based on the intima-media thickness (IMT) of the carotid artery from color Doppler ultrasonography. Patients with IMT > 1 mm were classified into the T2DM + CAS group ( = 28), and patients with IMT < 1 mm were assigned as the T2DM + non-atherosclerosis (NAS) group ( = 22). The plasma levels of AGEs, receptor for AGE (RAGE), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) of all subjects were measured by enzyme-linked immunosorbent assay. The T-lymphocyte subsets were analyzed by a flow detector. T2DM + CAS patients showed significantly higher concentrations of AGEs, RAGE, TNF-α, and IFN-γ in the peripheral blood. The highest levels of CD4+ T cells were observed in the T2DM + CAS group. The AGE level was positively correlated with the concentrations of RAGE, TNF-α, IFN-γ, and CD4+. In summary, the results showed that the levels of AGEs may be correlated with the inflammatory status in T2DM patients with CAS.
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http://dx.doi.org/10.1515/biol-2020-0042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874589PMC
June 2020

Hippocampal subfields atrophy contribute more to cognitive impairment in middle-aged patients with type 2 diabetes rather than microvascular lesions.

Acta Diabetol 2021 Aug 22;58(8):1023-1033. Epub 2021 Mar 22.

Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Rd, Nanjing, 210008, China.

Aims: Neurodegeneration and microvascular lesions are related to cognitive impairment in type 2 diabetes mellitus (T2DM). We aimed to use the volume of hippocampal subfields and the burden of white matter hyperintensities (WMH) as neurodegeneration and microangiopathy markers, respectively, to investigate their potential associations with cognitive impairment in T2DM patients.

Methods: A total of 76 T2DM patients and 45 neurologically unimpaired normal controls were enrolled between February 2016 to August 2018. All participants underwent structural magnetic resonance imaging (MRI) and Montreal Cognitive Assessment (MoCA). The T2DM patients were divided into the T2DM without mild cognitive impairment (T2noMCI) group (n = 44) and the T2DM with mild cognitive impairment (T2MCI) group (n = 32) according to MoCA scores. We used automatic brain segmentation and quantitative technique to assess the volume of twelve hippocampal subfields and WMH on MRI. We used age, sex, education, and total intracranial volume as our covariates and the Bonferroni method for multiple comparison correction.

Results: Both the T2MCI group and T2noMCI group showed significant hippocampal subfields atrophy compared to the controls, which were mainly in the left hippocampal tail, left CA1, bilateral molecular layer, bilateral dentate gyrus, and bilateral CA4 (all p < 0.0042). No significant differences in the volume of total WMH, deep-WMH, and periventricular-WMH were found among the three groups. The HbA1c levels were significantly negatively correlated with hippocampal atrophy, and the MoCA scores were positively correlated with bilateral hippocampal volume in T2DM patients and all samples. Mediation analyses demonstrated that the association of HbA1c levels with cognitive function was mediated by hippocampal subfields volume.

Conclusion: Widespread hippocampal atrophies across the subfields have been found in middle-aged T2DM patients, which was positively correlated with the MoCA scores and negatively correlated with the HbA1c levels. The association of HbA1c levels with cognitive function was mediated by some crucial hippocampal subfields volume. In middle-aged patients with T2DM, the neurodegeneration is more strongly associated with cognitive impairment than microvascular lesions. Trail Registeration This study was registered on Clinical-Trails.gov (NCT02738671).
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http://dx.doi.org/10.1007/s00592-020-01670-xDOI Listing
August 2021

Are Chinese Patients with Type 2 Diabetes and a Body Mass Index of 27.5-32.5 kg/m Suitable for Metabolic Surgery? A One-Year Post-Surgery Study.

Diabetes Ther 2021 May 19;12(5):1429-1444. Epub 2021 Mar 19.

Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Introduction: The aim of this study was to clarify the efficacy and safety of metabolic surgery in Chinese patients with type 2 diabetes mellitus (T2DM) and a body mass index (BMI) of 27.5-32.5 kg/m.

Methods: A total of 99 patients with T2DM were enrolled in this retrospective cohort study. Of these patients, 53 had a BMI of 27.5-32.5 kg/m and had undergone metabolic surgery (n = 21) or were on conventional antidiabetic therapy (n = 32)]; 46 had a BMI ≥ 32.5 kg/m and all had undergone metabolic surgery. Primary endpoints included the triple endpoint [hemoglobin A1c < 6.5%, low-density lipoprotein cholesterol (LDL-C) < 2.6 mmol/L, and systolic blood pressure (SBP) < 130 mmHg] and successful weight loss 1 year later. Remission of diabetes, glucose and lipid metabolism, medication usage, and adverse events were evaluated.

Results: Of patients with BMI 27.5-32.5 kg/m undergoing metabolic surgery, 33.33% achieved the composite endpoints, and 100% achieved successful weight loss. This result was similar to that in patients with BMI ≥ 32.5 and better than those with BMI 27.5-32.5 kg/m receiving conventional antidiabetic therapy. A significant and similar reduction in BMI, waist circumference, SBP, serum LDL-C, hemoglobin A1c, and uric acid, as well as similar frequency postoperative adverse events, were confirmed in both metabolic surgery groups. Patients with BMI 27.5-32.5 kg/m who had undergonemetabolic surgery showed more metabolic improvement than those only receiving medications but they experienced more adverse events.

Conclusion: A BMI cutoff of 27.5 kg/m for metabolic surgery may be suitable for Chinese patients with T2DM.
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http://dx.doi.org/10.1007/s13300-021-01027-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099981PMC
May 2021
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