Effect of omentin-1 on cancer stem cell surface markers and tumour-suppressive miRNA expression in a high-glucose environment associated with colorectal cancer.

Objective: To investigate how omentin-1 impacts colorectal cancer stem cell surface markers and the expression levels of tumour-suppressive micro ribonucleic acid in a colorectal cancer-associated high-glucose environment. METHODS: The study was conducted in the First Affiliated Hospital of Anhui Medical University，Anhui, China，from April 2018 to January 2019 and comprised cluster of differentiation133 and colorectal cancer stem cells from the SW480 cell line（the human colon adenocarcinoma cell line） obtained through immunomagnetic beads-based cell isolation. The colon cancer stem cells were divided into 6 groups: Z0 (control), Z1 (1ug/mL omentin-1), Z2 (2ug/mL omentin-1), G0 (5.0g/mL glucose), G1 (1ug/mL omentin-1 and 5.0g/mL glucose), and G2 (2ug/mL omentin-1 and 5.0 g/mL glucose). After 24 hours of intervention, quantitative polymerase chain reaction and western blot test were used for the detection of messenger ribonucleic acid and protein levels of stem cell surface markers. The colorectal cancer stem cells were divided into three groups: the control group, omentin group 1 (1ug/mL omentin-1) and omentin group 2 (2ug/mL omentin-1). After 24 hours of intervention, the expression of tumour suppressor micro ribonucleic acid was measured using quantitative polymerase chain reaction. Data was analysed using SPSS 23. RESULTS: Compared to the Z0 group, cluster of differentiation133 messenger ribonucleic acid expression reduced sharply in Z1 group (p<0.05), while Z2 group saw a marked increase in the expression (p<0.05). With respect to tumour-suppressive micro ribonucleic acid expression, micro ribonucleic acid 126, 145, 34a and 342-5P in omentin group 2 exhibited an expression level significantly higher than those in the control group and the omentin group 1 (p<0.05). Conclusion: High glucose levels were found to upregulate the expression of colorectal cancer stem cell surface markers cluster of differentiation133 messenger ribonucleic acid and protein. Also, omentin-1 was found to be associated with the downregulation of cluster of differentiation133 messenger ribonucleic acid and protein expression and the upregulation of cluster of differentiation 44 messenger ribonucleic acid expression in a high-glucose environment. Finally, omentin-1 was found to have the ability to promote the expression of relevant tumour-suppressive micro ribonucleic acids 126, 14, 34a and 342-5P.

Thionamide-induced Agranulocytosis: A Retrospective Analysis of 36 Patients With Hyperthyroidism.

OBJECTIVE: Agranulocytosis is a rare but serious adverse drug reaction (ADR) of thionamide antithyroid drugs (ATDs). We explored the characteristics of ADRs in patients with hyperthyroidism. METHODS: This retrospective study included 3558 inpatients with Graves disease treated in a Class A Grade 3 hospital between 2015 and 2019. The clinical presentation and laboratory workup of patients with antithyroid drug (ATD)-induced agranulocytosis was analyzed. RESULTS: Agranulocytosis was thought to be caused by ATDs in 36 patients. The hospital length of stay was 12 (10-16) days, and hospitalization costs were approximately $2810.89 ($2156.50-$4164.67). The median duration of ATD therapy prior to agranulocytosis development was 30 (20-40) days. Fever (83.33%) and sore throat (75%) were the most common symptoms as early signs of agranulocytosis. The lowest neutrophil counts were 0.01 (0.00-0.03) × 109/L and 0.14 (0.02-0.29) × 109/L in the methimazole and propylthiouracil groups, respectively (P = .037). The recovery times of agranulocytosis were 9.32 ± 2.89 days and 5.60 ± 4.10 days in the methimazole and propylthiouracil groups, respectively (P = .016). Patients with severe agranulocytosis required a longer time to recover (P < .001) and had closer to normal serum thyroxine and triiodothyronine levels. The interval between the first symptom of agranulocytosis and ATD withdrawal was 1 (0-3) day. CONCLUSIONS: Patients with agranulocytosis needed a long hospital length of stay and incurred high costs. Methimazole was prone to causing a more serious agranulocytosis than propylthiouracil. High thyroid hormone was unlikely to play a role in adverse drug reactions. Patient education is important.

Antithyroid arthritis syndrome: A case report and review of the literature.

A 29-year-old woman was diagnosed with Graves' disease because of her symptoms of thyrotoxicosis. After a 15-day treatment with methimazole, she began to suffer from a repeated fever, rash, and polyarticular migratory arthralgias. The clinical examination on admission showed that her white blood cell count, neutrophil count, and erythrocyte sedimentation rate (ESR) were within normal limits, while the concentration of C-creative protein (CRP) was 26.14 mg/L (ref. 0 - 10) and anti-nuclear immune body (ANA) and anti-neutrophil cytoplasmic antibody (ANCA) were both negative. Upon stopping the drug treatment, the patient's symptoms promptly disappeared. Antithyroid arthritis syndrome is poorly characterized, and the findings from our literature review indicate that this syndrome exhibits serological features that are distinct from those of antithyroid agent-induced vasculitis syndrome. Furthermore, physician's awareness of this syndrome is essential for its diagnosis in clinical practice.

Acute effects of sitagliptin on progenitor cells and soluble mediators in newly diagnosed type 2 diabetes.

OBJECTIVE: Studies have confirmed that endothelial progenitor cells (EPCs) are involved in diabetic complications. The present study assessed the action of the dipeptidyl peptidase-4 inhibitor sitagliptin on EPCs in newly diagnosed type 2 diabetes patients. MATERIALS AND METHODS: 60 newly-diagnosed type 2 diabetes patients were randomly divided into three treatment groups: sitagliptin (n = 20), metformin (n = 20), and combination sitagliptin and metformin (n = 20). Patients were treated once daily for 3 days. Before and after each treatment, the number of EPCs and concentration of soluble mediators (glucagon-like peptide 1 (GLP-1), nitric oxide (NO), endothelin-1 (ET-1), and stromal cell-derived factor-1α (SDF-1α)) were determined. RESULTS: The number of CD34+KDR+ and CD34+CD133+KDR+ EPCs and concentration of GLP-1, NO, and SDF-1α in sitagliptin and combination groups were both increased (both p < 0.05) but to a greater extent in the combination group (p < 0.05). Pearson correlation analysis and multiple linear regression analyses showed that the change in EPC numbers correlated with changes in peripheral GLP-1, NO, and SDF-1α levels (p < 0.05). CONCLUSION: Sitagliptin is able to directly increase the number of peripheral blood EPCs. This direct effect is to be important for lowering vascular risk in early diabetes before macrovascular complications appear.

Circulating FABP4, nesfatin-1, and osteocalcin concentrations in women with gestational diabetes mellitus: a meta-analysis.

OBJECTIVE: Recent studies have investigated the circulating adipocyte fatty acid binding protein (FABP4), nesfatin-1, and osteocalcin (OC) concentrations in women diagnosed with gestational diabetes mellitus (GDM), but the findings prove to be conflicting. The objective of this research was to systematically assess the relationship of circulating levels of above adipokines with GDM. METHODS: Pubmed, Embase, Web of Science, Cochrane library, OVID, and Scopus were performed to locate articles published up to January 31, 2020. Pooled standard mean differences (SMDs) with 95% confidence intervals (CIs), and 95% predictive intervals (PIs) were calculated by random-effects models to compare levels of adipokines between GDM cases and control groups. Cumulative and single-arm meta-analyses were also performed. RESULTS: Thirty-one studies comprising 4590 participants were included. No significant differences were found between GDM women and healthy controls in circulating nesfatin-1 levels (4.56 vs. 5.02 ng/mL; SMD = - 0.11, 95% CI -0.61-0.38, 95% PI -1.63-1.41). Nevertheless, circulating FABP4 and OC levels observed in GDM women outnumbered normal controls (FABP4, 23.68 vs. 16.04 ng/mL; SMD = 2.99, 95% CI 2.28-3.69, 95% PI 0.28-5.71; OC, 52.34 vs. 51.04 ng/mL; SMD = 0.68, 95% CI 0.31-1.05, 95% PI -0.48-1.84). The cumulative meta-analysis showed that the SMDs of circulating FABP4 and OC levels had stabilized between the two groups. CONCLUSIONS: Elevated circulating FABP4 and OC levels were observed in GDM women, but nesfatin-1 levels did not change, the PI of OC crossed the no-effect threshold. The results suggested that FABP4 is more suitable as a biomarker of GDM compared to OC in a future study, which is useful in identifying pregnant women who are likely to develop GDM and providing prompt management strategies.

Circulating apelin, chemerin and omentin levels in patients with gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: The available data on the significance of circulating apelin, chemerin and omentin in women with gestational diabetes mellitus (GDM) are inconsistent. This analysis includes a systematic review of the evidence associating the serum concentrations of these adipokines with GDM. METHODS: Publications through December 2019 were retrieved from PubMed, Embase, the Cochrane Library, and Web of Science. Subgroup analysis and meta-regression were conducted to evaluate sources of heterogeneity. RESULTS: Analysis of 20 studies, including 1493 GDM patients and 1488 normal pregnant women did not find significant differences in circulating apelin and chemerin levels (apelin standardized mean difference [SMD] = 0.43, 95% confidence interval (CI): - 0.40 to 1.26, P = 0.31; chemerin SMD = 0.77, 95% CI - 0.07 to 1.61, P = 0.07). Circulating omentin was significantly lower in women with GDM than in healthy controls (SMD = - 0.72, 95% CI - 1.26 to - 0.19, P = 0.007). Publication bias was not found; sensitivity analysis confirmed the robustness of the pooled results. CONCLUSIONS: Circulating omentin was decreased in GDM patients, but apelin and chemerin levels were not changed. The results suggest that omentin has potential as a novel biomarker for the prediction and early diagnosis of GDM.

Effect of hypothyroidism on the hypothalamic-pituitary-ovarian axis and reproductive function of pregnant rats.

BACKGROUND: This study aimed to detect changes in hormone levels in the hypothalamic-pituitary-ovarian axis in Sprague-Dawley (SD) rats with hypothyroidism, and identify differences in the pregnancy and abortion rates of female adult rats. The potential role of gonadotropin releasing hormone (GnRH) as the link between the hypothalamic-pituitary-ovarian axis and reproductive function regulated by thyroid hormones was also investigated. METHODS: Female SD rats (n = 136) were causally classified into two groups: the normal-drinking-water group (n = 60) and the 0.05% propylthiouracil-drinking-water group (PTU 2 mg/kg/day, n = 76) to establish an adult rat model of hypothyroidism (6 weeks). Female and male rats at a ratio of 1:2 were used to establish a hypothyroidism pregnancy model. GnRH mRNA and GnRH receptor (GnRHR) expression in rats was detected using real time quantitative PCR(qRT-PCR) and immunohistochemistry, respectively. RESULTS: The abortion rate differed significantly between the hypothyroidism pregnancy group and the normal pregnancy group (P < 0.05). No significant differences were found in the distribution of the GnRHR among the five nuclei (hypothalamic arcuate nucleus, hypothalamic ventromedial nucleus, hypothalamic anterior nucleus, paraventricular nucleus of the hypothalamus, and ventral premammillary nucleus) of the hypothalamus and ovary (P > 0.05). Hypothyroidism had no significant effect on GnRH mRNA expression in the hypothalamic-pituitary-ovarian axis in the four groups (normal control group, normal pregnancy group, hypothyroidism pregnancy group, and hypothyroidism group) (P > 0.05). CONCLUSIONS: Hypothyroidism had an adverse impact on pregnancy in rats and may affect the distribution of pituitary GnRHR, whereas it did not obviously affect the distribution of GnRHR in the nuclei of the hypothalamus and ovary. Hypothyroidism had no effect on GnRH mRNA expression.

Systemic lupus erythematosus and renal tubular acidosis associated with hyperthyroidism. Case Report.

A case of a 42-year-old female with hyperthyroidism was subsequently diagnosed to have systemic lupus erythematosus with distal RTA. The clinical examination on admission showed swelling of the knee joints and the urinalysis showed pH 6.5, pro 3+. Her blood routine results were as follows: white blood cells 1.85×109/L, platelets 100×109/L, erythrocyte 3.06×1012/L. The serum potassium was 3.11 mmol/L, 24 hour urinary electrolyte: K 68.87 mmol/24 H, antinuclear antibodies (ANA) 1:1 000, speckled pattern. The anti-double stranded DNA antibody (anti-dsDNA), anti SS-A(52) antibody and anti SS-A(60) antibody were positive. The light microscopy and immunofluorescence showed diffuse proliferative lupus nephritis. These data were compatible with the diagnosis of systemic lupus erythematosus. The diagnosis of hyperthyroidism and distal RTA is clear. This report showed that other autoimmune disease in the diagnosis of hyperthyroidism should not be ignored.

A case of fulminant type 1 diabetes associated with acute renal failure.

A 56-year-old man suffered from severe diabetic ketoacidosis which was complicated by acute renal failure and rhabdomyolysis. Before admission the patient had had flu-like symptoms for 5 days and had developed polyuria and polydipsia. The clinical examination on admission showed his plasma glucose level was 80.65 mmol/L while the HbA1c was 7.4%. His amylase concentration was high without any signs of pancreatitis. The islet-associated autoantibodies (GAD antibody, islet cell antibody) were absent. These data were compatible with the diagnosis of fulminant type 1 diabetes. A continuous intravenous insulin infusion therapy was given during the acute phase to control hyperglycemia and ketoacidosis. This patient remained dependent on continuous veno-venous hemofiltration (CVVHF) for 5 days, followed by regular kidney dialysis for three times, before his renal function was finally recovered. To conclude, this is a rare case of abrupt onset fulminant type 1 diabetes with the onset of acute renal failure. Hence, early detection, quick diagnosis and immediate treatment are very important. In particular, prompt CVVHF and kidney dialysis are required and useful for rescuing the renal function.

Acromegaly and diabetes mellitus associated with hyperthyroidism.

A 66-year-old woman with acromegaly and diabetes mellitus as well as primary hyperthyroidism is described. Serum GH Levels were inappprpriately high.MRI revealed an enlarged sella turcica with intrasellar mass. Her HbAlc was 12.2% and fasting blood glucose 8.89 mmol/l. Thyroid hormone levels in serum and thyroidal radioiodine uptake values were elevated, while TSH measurements in serum were low. Anti TPO antibodies were negative, TSH receptor antibodies were normal. Thyrotoxicosis as the first presenting illness in acromegaly was particulary uncommon. An ultrasound thyroid scan showed a multinodular goiter. Histology of the pituitary lesion showed a typical eosinophilic adenoma which only secreted GH when tested with specific immunostain. Post-operatively, the patient's clinical conditions improved, however, secondary hypoadrenalism appeared.

The Description and Prediction of Incidence, Prevalence, Mortality, Disability-Adjusted Life Years Cases, and Corresponding Age-Standardized Rates for Global Diabetes.

OBJECTIVE: Diabetes is a life-long disease that poses a serious threat to safety and health. We aimed to assess the disease burden attributable to diabetes globally and by different subgroups, and to predict future disease burden using statistical models. METHODS: This study was divided into three stages. Firstly, we evaluated the disease burden attributable to diabetes globally and by different subgroups in 2019. Second, we assessed the trends from 1990 to 2019. We estimated the annual percentage change of disease burden by applying a linear regression model. Finally, the age-period-cohort model was used to predict the disease burden from 2020 to 2044. Sensitivity analysis was performed with time-series models. RESULTS: In 2019, the number of incidence cases of diabetes globally was 22239396 (95% uncertainty interval (UI): 20599519-24058945). The number of prevalence cases was 459875371 (95% UI 423474244-497980624) the number of deaths cases was 1551170 (95% UI 1445555-1650675) and the number of disability-adjusted life years cases was 70880155 (95% UI 59707574-84174005). The disease burden was lower in females than males and increased with age. The disease burden associated with type 2 diabetes mellitus was greater than that with type 1; the burden also varied across different socio-demographic index regions and different countries. The global disease burden of diabetes increased significantly over the past 30 years and will continue to increase in the future. CONCLUSION: The disease burden of diabetes contributed significantly to the global disease burden. It is important to improve treatment and diagnosis to halt the growth in disease burden.

Level of 25-hydroxyvitamin D and vitamin D receptor in diabetic foot ulcer and factor associated with diabetic foot ulcers.

BACKGROUND: At present, there is no clinical study to elucidate the correlation between vitamin D deficiency and the incidence of diabetic foot osteomyelitis (DFO).This study aims to clarify levels of 25-hydroxyvitamin D [25(OH)VD] in peripheral blood and vitamin D receptor (VDR) expression in wound margin tissues (T-VDR) of patients with type 2 diabetes mellitus (T2DM) with diabetic foot ulcer (DFU) and DFO, and to determine its correlation with treatment outcomes of DFU and DFO, and and its value as a potential biomarker for the diagnosis of DFU and DFO. METHODS: 156 T2DM patients with DFU (DFU group), 100 T2DM patients without DFU (T2DM group), and 100 healthy controls (NC group). The DFU group patients were subdivided into DFO (n = 80) and NDFO groups (n = 76). The level of serum 25(OH)VD was measured via chemiluminescence immunoassay, and T-VDR expression level was determined by quantitative real-time PCR. RESULTS: The levels of serum 25(OH)VD in the DFU group were significantly lower than the T2DM group [(10.3 (5.8, 18.7) vs 15.7 (8.6, 24.6) ng/mL, P = 0.002)]. Similarly, the levels of serum 25(OH)VD and T-VDR expression in the DFO group were statistically lower than the NDFO group [9.2 (5.2, 20.5) vs 12.8 (6.9, 22.1) ng/mL, P = 0.006)], [1.96 (0.61, 3.97) vs 3.11 (1.36, 5.11), P = 0.004)], respectively. Furthermore, the levels of serum 25(OH)VD and T-VDR expression in DFU patients were positively correlated with the ulcer healing rate of foot ulcer after 8 weeks of treatment ( P = 0.031, P = 0.016, respectively). Multivariate logistic regression analysis showed that low level of serum 25(OH)VD was an independent risk factor for DFU and DFO (ORDFU = 2.42, ORDFO = 3.05, P = 0.008, 0.001, respectively), and decreased T-VDR expression level was an independent risk factor for DFO (OR = 2.83, P = 0.004). Meanwhile, the ROC curve analysis indicated that the AUC of serum 25(OH)VD level for the diagnosis of DFU and DFO was 0.821 (95% CI, 0.754-0.886, P < 0.001) and 0.786 (95%CI, 0.643-0.867, P < 0.001), respectively. When establishing a diagnosis of DFO, the AUC of T-VDR expression level was 0.703 (95%CI: 0.618-0.853, P < 0.001). CONCLUSIONS: The levels of serum 25(OH)VD and T-VDR expression in DFU and DFO decreased. Serum 25(OH)VD and T-VDR are potentially valuable biomarkers for diagnosis and prognosis of DFU and DFO. .

Effect of Hypoglycemic Drugs on Kisspeptin Expression in the Hypothalamic Arcuate Nucleus of PCOS Rats.

Background: To investigate the change in hypothalamic kisspeptin-1 (Kiss1) expression during the development of polycystic ovary syndrome (PCOS) and hypoglycemic drug intervention. Methods: Letrozole lavage was used to construct a polycystic ovary rat model. After successful modeling, we treated PCOS rats with metformin, pioglitazone, and acarbose, and we then observed changes in weight, estrus, glucose tolerance, insulin resistance, sex hormones, and hypothalamic kiss1 expression. Results: PCOS rats exhibited increased body weight, abnormal estrous cycle, impaired glucose tolerance, insulin resistance, increased testosterone level, increased luteinizing hormone level, and increased Kiss1 expression in the hypothalamus. However, intervention with metformin, pioglitazone, and acarbose improved the reproductive and metabolic disorders as well as reduced hypothalamic Kiss1 expression. Conclusion: The expression of hypothalamic Kiss1 may play an important role in the pathogenesis of PCOS. Metformin, pioglitazone, and acarbose may reduce the expression of hypothalamic Kiss1 by improving insulin resistance, thereby improving reproductive and metabolic disorders in PCOS rats.

SLC26A4 mutation in Pendred syndrome with hypokalemia: A case report.

RATIONALE: Pendred syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss, inner ear malformations, goiter, and abnormal organification of iodide. It is caused by mutations in SLC26A4 gene, which encodes pendrin (a transporter of chloride, bicarbonate, and iodide). Pendred syndrome is a common cause of syndromic deafness, but the metabolic abnormalities it causes are often overlooked. Here, we report the case of a patient diagnosed with Pendred syndrome with hypokalemia. PATIENT CONCERNS: A 53-year-old deaf-mute woman was hospitalized due to severe limb asthenia. The emergency examination showed that her blood potassium level was 1.8 mmol/L. DIAGNOSES: Through the genetic test, we found a mutation of SLC26A4 gene in NM_000441: c.2027T>A, p.L676Q, as well as the SLC26A4 exon 5-6 deletion. These genetic variations pointed to Pendred syndrome (an autosomal recessive disorder that mainly affects the inner ear, thyroid, and kidney) which is a common cause of syndromic deafness. INTERVENTIONS: The patient was treated with potassium supplements and screened for the cause of hypokalemia. OUTCOMES: The patient was discharged after her potassium levels rose to the normal range. LESSONS: Patients with Pendred syndrome may also have certain metabolic abnormalities; thus, more attention should be paid to them during clinical diagnosis.

Alterations of Cerebral Blood Flow and Its Connectivity in Olfactory-Related Brain Regions of Type 2 Diabetes Mellitus Patients.

To investigate the alteration of cerebral blood flow (CBF) and its connectivity patterns in olfactory-related regions of type 2 diabetes mellitus (T2DM) patients using arterial spin labeling (ASL). Sixty-nine patients with T2DM and 63 healthy controls (HCs) underwent ASL scanning using 3.0T magnetic resonance imaging. We compared the CBF values of the olfactory-related brain regions between the two groups and analyzed the correlation between their changes and clinical variables. We also used these regions as seeds to explore the differences in CBF connectivity patterns in olfactory-related brain regions between the T2DM patients and HCs. Compared with the HC group, the CBF of the right orbital part of the inferior frontal gyrus (OIFG), right insula, and bilateral olfactory cortex was decreased in the T2DM patients. Moreover, the duration of the patients was negatively correlated with the CBF changes in the right OIFG, right insula, and right olfactory cortex. The CBF changes in the right OIFG were positively correlated with the Self-Rating Depression Scale scores, those in the right insula were negatively correlated with the max blood glucose of continuous glucose, and those in the right olfactory cortex were negatively correlated with the mean blood glucose of continuous glucose. In addition, the T2DM patients also showed decreased CBF connectivity between the right OIFG and the left temporal pole of the middle temporal gyrus and increased CBF connectivity between the right medial orbital part of the superior frontal gyrus and the right orbital part of the superior frontal gyrus and between the right olfactory cortex and the bilateral caudate and the left putamen. Patients with T2DM have decreased CBF and altered CBF connectivity in multiple olfactory-related brain regions. These changes may help explain why olfactory dysfunction occurs in patients with T2DM, thus providing insights into the neuropathological mechanism of olfactory dysfunction and cognitive decline in T2DM patients.

Compensatory thalamocortical functional hyperconnectivity in type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is associated with brain damage and cognitive decline. Despite the fact that the thalamus involves aspects of cognition and is typically affected in T2DM, existing knowledge of subregion-level thalamic damage and its associations with cognitive performance in T2DM patients is limited. The thalamus was subdivided into 8 subregions in each hemisphere. Resting-state functional and structural MRI data were collected to calculate resting-state functional connectivity (rsFC) and gray matter volume (GMV) of each thalamic subregion in 62 T2DM patients and 50 healthy controls. Compared with controls, T2DM patients showed increased rsFC of the medial pre-frontal thalamus, posterior parietal thalamus, and occipital thalamus with multiple cortical regions. Moreover, these thalamic functional hyperconnectivity were associated with better cognitive performance and lower glucose variability in T2DM patients. However, there were no group differences in GMV for any thalamic subregions. These findings suggest a possible neural compensation mechanism whereby selective thalamocortical functional hyperconnectivity facilitated by better glycemic control help to preserve cognitive ability in T2DM patients, which may ultimately inform intervention and prevention of T2DM-related cognitive decline in real-world clinical settings.

Brain Structure as a Correlate of Odor Identification and Cognition in Type 2 Diabetes.

Background: It has been reported that type 2 diabetes (T2DM) is associated with olfactory identification (OI) impairments and cognitive decline. However, the relationship between OI impairments and cognitive decline is largely unknown in T2DM patients. Methods: Sixty-eight T2DM patients and 68 healthy controls underwent 3D-T1 MRI scans, olfactory and cognitive assessments. The cortical thickness of olfaction-related brain regions, olfactory and cognitive scores were compared between groups. Correlation analyses were carried out among cognition, olfaction, and cortical thickness of olfaction-related brain regions. Results: First, the cognitive and olfactory test scores of T2DM patients were lower than healthy subjects. Second, higher olfactory scores were associated with increased cortical thickness in the left parahippocampal gyrus and bilateral insula in T2DM. Third, higher olfactory scores were associated with higher cognitive performance in T2DM. Fourth, some cognitive performances were related to cortical thickness in the left parahippocampal gyrus and left insula in T2DM. Conclusion: These findings indicated that olfactory dysfunction may be useful for future applications that attempt to predict cognitive decline or develop tailored therapies in T2DM patients.

Comprehensive Analyses of Type 1 Diabetes Ketosis- or Ketoacidosis-Related Genes in Activated CD56+CD16+ NK Cells.

Objectives: Alterations in natural killer (NK) cells activity cause damage to pancreatic islets in type 1 diabetes mellitus (T1DM). The aim of this study is to identify T1DM ketosis- or ketoacidosis-related genes in activated CD56+CD16+ NK cells. Methods: Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using the GEO2R tool. Enrichment analyses were performed using Metascape online database and GSEA software. Cell-specific gene co-expression network was built using NetworkAnalyst tools. Cytoscape software was used to identify hub genes and construct co-expressed networks. Target miRNAs were predicted based on the DIANA-micro T, miRDB, and miRWalk online databases. Results: A total of 70 DEGs were identified between T1DM patients recovered from ketosis or ketoacidosis and healthy control blood samples in GSE44314. Among the DEGs, 10 hub genes were screened out. The mature NK cell-specific gene co-expression network for DEGs in T1DM was built using NetworkAnalyst tools. DEGs between activated CD56+CD16+ NK cells and CD56brightCD16- NK cells were identified from GSE1511. After intersection, 13 overlapping genes between GSE44314 and GSE1511 microarray datasets were screened out, in which 7 hub genes were identified. Additionally, 59 target miRNAs were predicted according to the 7 hub genes. After validating with the exosome miRNA expression profile dataset of GSE97123, seven differentially expressed miRNAs (DEmiRNAs) in plasma-derived exosome were selected. Finally, a mRNA-miRNA network was constructed, which was involved in the T1DM ketosis or ketoacidosis process. Conclusion: This work identified seven hub genes in activated CD56+CD16+ NK cells and seven miRNAs in plasma-derived exosome as potential predictors of T1DM ketoacidosis, which provided a novel insight for the pathogenesis at the transcriptome level.

Long-term follow-up of a case of MEN1 and literature review.

OBJECTIVE: To investigate the diagnosis and treatment of Multiple Endocrine Neoplasia Type 1 (MEN1), improve our understanding of the disease and highlight the importance of life-long follow-up of affected individuals. METHODS: A retrospective analysis was performed on 1 MEN1 patient with long-term follow-up at the First Affiliated Hospital of Anhui Medical University. RESULTS: A 51-year-old woman was diagnosed with MEN1 14 years ago, but exhibited a suspected disease course of at least 20 years. Prior to admission, the patient reported a cough lasting for two months. The patient's thyroid hormone, sex hormone, insulin, cortisol, parathyroid hormone, and ACTH circadian rhythm findings were within normal ranges. The patient exhibited elevated blood calcium levels. Examination led to the detection of thymoma and pancreatic neoplasms, whereas no obvious abnormalities were detected in her parathyroid gland or adrenal gland as determined via computed tomography (CT). Genetic analyses revealed a mutation in the MEN1 gene in this patient. As the patient had no relevant clinical symptoms, she refused surgical treatment, and follow-up was continued. It was learned through follow-up that the patient underwent anterior mediastinal lesion resection and partial rib resection in June 2020 because she re-examined the chest CT showed that the anterior mediastinal mass was significantly larger than that in 2019. Pathology suggested neuroendocrine tumors. The patient is currently recovering well. CONCLUSION: MEN1 is an uncommon condition in clinical settings, and it is important that clinicians be made aware of this disorder so that they can provide patients with appropriate and timely treatments.