Exosomes derived from umbilical cord-derived mesenchymal stem cells exposed to diabetic microenvironment enhance M2 macrophage polarization and protect against diabetic nephropathy.

The role of mesenchymal-stem-cell-derived exosomes (MSCs-Exo) in the regulation of macrophage polarization has been recognized in several diseases. There is emerging evidence that MSCs-Exo partially prevent the progression of diabetic nephropathy (DN). This study aimed to investigate whether exosomes secreted by MSCs pre-treated with a diabetic environment (Exo-pre) have a more pronounced protective effect against DN by regulating the balance of macrophages. Exo-pre and Exo-Con were isolated from the culture medium of UC-MSCs pre-treated with a diabetic mimic environment and natural UC-MSCs, respectively. Exo-pre and Exo-Con were injected into the tail veins of db/db mice three times a week for 6 weeks. Serum creatinine and serum urea nitrogen levels, the urinary protein/creatinine ratio, and histological staining were used to determine renal function and morphology. Macrophage phenotypes were analyzed by immunofluorescence, western blotting, and quantitative reverse transcription polymerase chain reaction. In vitro, lipopolysaccharide-induced M1 macrophages were incubated separately with Exo-Con and Exo-pre. We performed microRNA (miRNA) sequencing to identify candidate miRNAs and predict their target genes. An miRNA inhibitor was used to confirm the role of miRNAs in macrophage modulation. Exo-pre were more potent than Exo-Con at alleviating DN. Exo-pre administration significantly reduced the number of M1 macrophages and increased the number of M2 macrophages in the kidney compared to Exo-Con administration. Parallel outcomes were observed in the co-culture experiments. Moreover, miR-486-5p was distinctly expressed in Exo-Con and Exo-pre groups, and it played an important role in macrophage polarization by targeting PIK3R1 through the PI3K/Akt pathway. Reducing miR-486-5p levels in Exo-pre abolished macrophage polarization modulation. Exo-pre administration exhibited a superior effect on DN by remodeling the macrophage balance by shuttling miR-486-5p, which targets PIK3R1.

Predictive factors that influence the clinical efficacy of umbilical cord-derived mesenchymal stromal cells in the treatment of type 2 diabetes mellitus.

BACKGROUND: Our previous single-center, randomized, double-blinded, placebo-controlled phase 2 study evaluated the safety and effectiveness of human umbilical cord mesenchymal stromal cell (UC-MSC) transfusion for treating patients with type 2 diabetes mellitus (T2DM). Indeed, this potential treatment strategy was able to reduce insulin use by half in a considerable number of patients. However, many other patients' responses to UC-MSC transfusion were insignificant. The selection of patients who might benefit from UC-MSC treatment is crucial from a clinical standpoint. METHODS: In this post hoc analysis, 37 patients who received UC-MSC transfusions were divided into two groups based on whether their glycated hemoglobin (hemoglobin A1c, or HbA1c) level was less than 7% after receiving UC-MSC treatment. The baseline differences between the two groups were summarized, and potential factors influencing efficacy of UC-MSCs for T2DM were analyzed by univariate and multivariate logistic regression. The correlations between the relevant hormone levels and the treatment effect were further analyzed. RESULTS: At the 9-week follow-up, 59.5% of patients achieved their targeted HbA1c level. Male patients with lower baseline HbA1c and greater C-peptide area under the curve (AUCC-pep) values responded favorably to UC-MSC transfusion, according to multivariate analysis. The effectiveness of UC-MSCs transfusion was predicted by AUCC-pep (cutoff value: 14.22 ng/h/mL). Further investigation revealed that AUCC-pep was increased in male patients with greater baseline testosterone levels. CONCLUSIONS: Male patients with T2DM with greater AUCC-pep may be more likely to respond clinically to UC-MSC therapy, and further large-scale multi-ethnic clinical studies should be performed to confirm the conclusion.

[Comparison of Different Doses of ACTH Used in ACTH Stimulation Test to Determine the Subtypes of Primary Aldosteronism]. / ä¸åŒå‰‚é‡ä¿ƒè‚¾ä¸Šè ºçš®è´¨æ¿€ç´ å ´å¥‹è¯•éªŒåœ¨åŽŸå‘æ€§é†›å›ºé ®å¢žå¤šç—‡åˆ†åž‹è¯Šæ–­ä¸­çš„æ¯”è¾ƒ.

Objective: To compare the diagnostic value of adrenocorticotropic hormone (ACTH) stimulation test (AST) with different doses of ACTH combined with midnight administration of 1 mg dexamethasone for the determination of the subtypes of primary hyperaldosteronism (PA). Methods: This is a prospective observational study. Patients diagnosed with PA in the Department of Endocrinology, the First Medical Center of of Chinese PLA General Hospital from January 1, 2020 to September 30, 2022 underwent AST with different doses of ACTH. All patients received 1 mg dexamethasone at midnight for inhibition. Then, the patients were randomly assigned to 25-unit and 50-unit ACTH treatment groups by a ratio of 1:2. Subtype classification and diagnosis of aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) was made on the basis of adrenal venous blood samples and/or postoperative pathology and clinical follow-up findings. Receiver operating characteristics (ROC) curves were plotted to examine the diagnostic efficacy and the difference of AST by varying doses of ACTH in distinguishing APA and IHA. Results: A total of 82 patients, including 49 patients with APA (59.8%) and 33 patients with IHA (40.2%), were enrolled. There were 29 patients in the 25-unit ACTH group (35.4%) and 53 patients in the 50-unit ACTH group (64.6%). There were no significant differences in age, sex, blood pressure, minimum serum potassium, and biochemical parameters between the 25-unit and 50-unit groups. After ACTH stimulation, plasma aldosterone concentration (PAC), cortisol (F), and PAC/F at different points of time showed no statistical difference between the two groups (P>0.05). The area under the curve (AUC) of PAC in the 25-unit group was higher than that of PAC/F. The AUC of PAC reached the maximum at 90 minutes (0.948, 95% confidence interval [CI]: 0870-1.000) and the optimal cutoff was 38.0 ng/dL, which had a sensitivity of 92.9% and a specificity of 86.7% for differentiating APA and IHA. Similar to the 25-unit group, the maximum AUC of PAC in the 50-unit group was greater than that of PAC/F. The AUC of PAC reached the maximum 90 minutes (0.930, 95% CI: 0.840-0.994) and the optimal cutoff was 39.6 ng/dL, which had a sensitivity of 91.2% and a specificity of 83.3%. The AUC of PAC at different points of time in the 25-unit ACTH group (0.862-0.948) was greater than that of 50-unit ACTH group (0.823-0.930), but the difference was not statistical significance. Conclusion: AST with 25-unit or 50-unit ACTH combined with small-dose dexamethasone can be used in PA subtype determination, ie, differentiation between APA and IHA. The optimal PAC cut-off values for 25-unit or 50-unit ACTH are similar, being 38.0 ng/dL and 39.6 ng/dL, respectively, and both cutoff values show higher sensitivity and specificity at 90 min. The AST with 25-unit ACTH has the smaller dose and the better safety. Therefore, it is recommended for the diagnosis of PA subtypes.

Prevalence of obesity and associated complications in China: A cross-sectional, real-world study in 15.8 million adults.

AIM: To evaluate the prevalence of overweight/obesity and associated complications from a large, cross-sectional, nationwide database in China. MATERIALS AND METHODS: Data were obtained from 519 Meinian health check-up centres across 243 cities. Eligible participants were aged ≥18 years, with a routine check-up in 2019 (N = 21 771 683) and complete height, weight, sex and region data. The unadjusted prevalence rates of overweight/obesity were calculated by age, sex and region. In addition, the nationwide prevalence rates of overweight and obesity were standardized according to the 2010 China census by age group and sex. The prevalence of obesity-related complications by body mass index (BMI) groups was calculated using logistic regression. RESULTS: There were 15 770 094 eligible participants (median age 40 years; mean BMI 24.1 kg/m2 ; 52.8% male). By Chinese BMI classification, 34.8% were overweight and 14.1% were obese. Overweight and obesity were more prevalent in male than female participants (standardized: overweight 40.2% vs. 27.4%; obesity 17.6% vs. 9.6%, respectively). The prevalence of assessed complications was higher in participants with overweight/obesity versus those with normal BMI (P < 0.001 for trends). The most prevalent complications in participants with overweight/obesity were fatty liver disease, prediabetes, dyslipidaemia and hypertension. The number of complications increased with higher BMI. CONCLUSIONS: Overweight/obesity and related complications are highly prevalent in this population. These data may better inform management and prevention public health strategies in China.

Effects of sodium-glucose cotransporter 2 inhibitors on serum uric acid in patients with type 2 diabetes mellitus: A systematic review and network meta-analysis.

AIMS: The present study aims to determine the effects of sodium-glucose cotransporter 2 (SGLT-2) inhibitors on the serum uric acid (SUA) levels of patients with type 2 diabetes mellitus (T2DM) in Asia. METHODS: PubMed, CENTRAL, Embase and Cochrane Library databases were searched for randomized controlled trials of SGLT-2 inhibitors in patients with T2DM up to 15 July 2021, without language or date restrictions. RESULTS: In total, 19 high-quality studies (4218 participants) were included in the present network meta-analysis. All of the included SGLT-2 inhibitors (empagliflozin, dapagliflozin, canagliflozin, ipragliflozin, luseogliflozin and tofogliflozin) significantly decreased SUA levels compared with those of the control [total standard mean difference -0.965, 95% CI (-1.029, -0.901), p = .000, I2  = 98.7%] in patients with T2DM. Subgroup analysis and meta-regression showed that the combined analysis of different inhibitors might lead to heterogeneity of the results. Therefore, among the SGLT-2 inhibitors, the results of the subsequent network meta-analysis revealed that luseogliflozin and dapagliflozin ranked the highest in terms of lowering SUA levels among the SGLT-2 inhibitors. Moreover, the network meta-analysis declared that luseogliflozin (1 and 10 mg) and dapagliflozin (5 mg) led to a superior reduction in SUA in patients with T2DM. CONCLUSIONS: SGLT-2 inhibitors could significantly reduce SUA levels in patients with T2DM, particularly luseogliflozin (1 and 10 mg) and dapagliflozin (5 mg) possess the best effects. Therefore, SGLT-2 inhibitors look extremely promising as an antidiabetes treatment option in patients with T2DM with high SUA.

Case report: coexistence of primary hyperparathyroidism with giant toxic nodular goiter.

BACKGROUND: The coexistence of primary hyperparathyroidism (PHPT) and giant toxic nodular goiter is very rare. Moreover, PHPT could be easily overlooked because hyperthyroidism may also lead to hypercalcemia. A 99mTc-MIBI scan of the parathyroid glands is often negative when they are concomitant. CASE PRESENTATION: Here, we report a rare case of the coexistence of giant toxic nodular goiter and PHPT that had been ignored for many years but was successfully treated with an ultrasound-guided parathyroid adenoma microwave ablation (MWA). CONCLUSION: Reoperation for PHPT carries an increased risk of cure failure and complications. Thermal ablation has been proven effective in inactivating hyperfunctioning parathyroid lesions and in normalizing both serum parathyroid hormone (PTH) and calcium.

The effect of gestational diabetes mellitus on fetal right heart growth in late-term pregnancy: A prospective study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a complication of pregnancy strongly associated with an increased risk of structural fetal abnormalities. As the fetal heart grows quickly during the late-term pregnancy period, it is important to understand fetal heart growth before birth. This study explored how GDM affects fetal heart growth by evaluating basic echocardiography indicators during late pregnancy. METHODS: This prospective, longitudinal study included 63 GDM patients (GDM group) and 67 healthy pregnant women (control group). All subjects underwent fetal echocardiography scans at gestational weeks 28-32, 32-36, and 36-40. Twelve echocardiographic indicators were assessed at each observation and analyzed by using a mixed model. RESULTS: The left atrial diameter (LA) and left ventricular end-diastolic diameter (LV) similarly increased from the first to the third observation. The right ventricular end-diastolic diameter (RV) was significantly different between the groups, and a group × time interaction was detected. The tricuspid annular peak systolic velocity (s') increased more rapidly in the GDM than the control group during the first to second observations, and the group × time interaction was significant. The increase in the tricuspid annular plane systolic excursion (TAPSE) of the GDM group was "slow-fast", while that of the control group was "fast-slow", during three observations. After adjusting covariates, the group difference and interaction effect of TAPSE and RV remained significant. CONCLUSIONS: The differences in fetal right heart indicators between the GDM and control groups suggest that GDM may affect the structure and functional growth of the fetal right heart during late-term pregnancy.

Glucose-lowering pharmacotherapies in Chinese adults with type 2 diabetes and cardiovascular disease or chronic kidney disease. An expert consensus reported by the Chinese Diabetes Society and the Chinese Society of Endocrinology.

Patients with type 2 diabetes mellitus (T2DM) are at risk of developing atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD), which are important causes of disabling and death in patients with T2DM. For the prevention and management of ASCVD or CKD, cardiovascular risk factors should be systematically evaluated, and ASCVD and CKD should be screened in patients with T2DM. In this consensus, we recommended that metformin should be used as the first-line therapy for patients with T2DM and ASCVD or very high cardiovascular risk, heart failure (HF) or CKD, and should be retained in the treatment regimen unless contraindicated or not tolerated. In patients with T2DM and established ASCVD or very high cardiovascular risk, addition of a glucagon-like peptide 1 receptor agonist (GLP-1RA) or sodium-glucose cotransporter type 2 (SGLT2) inhibitor with proven cardiovascular benefits should be considered independent of individualised glycated haemoglobin (HbA1C ) targets. In patients with T2DM and HF, an SGLT2 inhibitor should be preferably added regardless of HbA1C levels. In patients with T2DM and CKD, SGLT2 inhibitors should be preferred for the combination therapy independent of individualised HbA1C targets, and GLP-1RAs with proven renal benefits would be alternative if SGLT2 inhibitors are contraindicated. Moreover, the prevention of hypoglycaemia and management of multiple risk factors by comprehensive regimen, including lifestyle intervention, antihypertensive therapies, lipid-lowering treatment and antiplatelet therapies, should be kept in mind in treating patients with T2DM and ASCVD, HF or CKD.

Clinical and pathologic predictors of lymph node metastasis in papillary thyroid microcarcinomas.

Papillary thyroid microcarcinoma (PTMC) has the highest incidence among all thyroid carcinomas. Although surgery is the primary treatment for PTMC, it inevitably leads to trauma and some complications. To formulate an optimal treatment strategy, we aim to clarify the risk factors for lymph node metastasis (LNM) in PTMC patients. This study retrospectively analyzed patients who underwent thyroidectomy during 1995-2015, and grouped them according to lymph node metastasis. Age, gender, tumor size, thyroid functions, Hashimoto's thyroiditis, multifocal tumor, extrathyroidal extensions, capsular invasion were analyzed. Of the 2434 PTMC subjects, proportion of patients with no LNM (NLNM), LNM, central LNM (CLNM), lateral LNM (LLNM), CLNM + LLNM were 82.9%, 17.1%, 7.0%, 7.6% and 2.5%. Patients with NLNM were older and had a lower proportion of males compared to patients with CLNM, LLNM and CLNM + LLNM (p < 0.05). The NLNM group also had a smaller size of ultrasound tumor, lower proportion of multifocal tumor and extrathyroidal extension compared to CLNM, LLNM and CLNM + LLNM groups (p < 0.05). On univariate analyses, male gender, age <45 years, tumor size of pathology (˃0.75 cm), multifocality, and extrathyroidal extension were significantly associated with LNM. Multivariate analyses revealed that male gender, age <45 years, multifocality were risk factors for LNM. In conclusion, PTMC patients with male gender, age <45 years and multifocality should be evaluated carefully for possible LNM.

A High Level of Circulating Valine Is a Biomarker for Type 2 Diabetes and Associated with the Hypoglycemic Effect of Sitagliptin.

BACKGROUND: High levels of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were associated with an increased risk of hyperglycemia and the onset of diabetes. This study is aimed at assessing circulating valine concentrations in subjects with type 2 diabetes (T2D) and in T2D patients and high-fat diet- (HFD-) fed mice treated with the hypoglycemic agent sitagliptin (Sit) and analyzing the association of valine concentrations with metabolic parameters. METHODS: Metabolomics in HFD-fed mice were analyzed by gas chromatography-mass spectrometry (GC-MS) systems. Plasma valine concentrations were detected with a commercial kit in 53 subjects with normal glucose levels (n = 19), newly diagnosed T2D (n = 20), placebo-treated T2D (n = 7), or Sit-treated T2D (n = 7). Biochemical parameters were also assessed in all participants. RESULTS: Sit treatment markedly changed the pattern of amino acid in HFD-fed mice, especially by reducing the level of the BCAA valine. Compared with the healthy controls, the plasma valine concentrations were significantly higher in the T2D patients (p < 0.05). Correlation analysis showed that the plasma valine concentration was positively correlated with the level of fasting plasma glucose (p < 0.05). Moreover, the plasma valine concentrations were notably reduced after Sit treatment in T2D patients (p < 0.05). CONCLUSIONS: Our findings demonstrate an important effect of Sit on the BCAA valine in T2D patients and HFD-fed mice, revealing a new hypoglycemic mechanism of it. Furthermore, the results suggest that the circulating valine level might be a novel biomarker for T2D and restoring the level of valine might be a potential strategy for diabetes therapy.

MACROD1/LRP16 Enhances LPS-Stimulated Inflammatory Responses by Up-Regulating a Rac1-Dependent Pathway in Adipocytes.

BACKGROUND/AIMS: Chronic inflammation contributes to the development of type 2 diabetes mellitus by targeting the insulin receptor substrate protein-1 (IRS-1) signaling pathway. Previous studies showed that Leukemia related protein 16 (LRP16) reduced insulin stimulated glucose uptake in adipocytes by impairing the IRS-1 signaling pathway. We explored the mechanism by which LRP16 promotes the inflammatory response. METHODS: We screened LRP16 induced proteins in the lipopolysaccharide (LPS)-stimulated inflammatory response using liquid chromatography-mass spectrometry (LC-MS) and analyzed the potential biological functions of these proteins using online bioinformatics tools. mRNA expression and protein expression of target genes were measured by real time PCR and Western blot, respectively. RESULTS: A total of 390 differentially expressed proteins were identified. The mitogen-activated protein kinase (MAPK) signaling pathway was the primary activated pathway in LRP16-expressing cells. Overexpression of LRP16 activated ERK1/2 and Rac1, which are two key players related to the MAPK signaling pathway. Furthermore, knock down of endogenous LRP16 by RNA interference (RNAi) reduced Rac1 expression, ERK activation, and inflammatory cytokine expression in human adipocytes stimulated by LPS. The stimulatory effect of LRP16 was diminished by suppressing Rac1 expression and treating the cells with the ERK specific inhibitor, PD98059. CONCLUSION: These findings revealed the functions of LRP16 in promoting the inflammatory response through activating the Rac1-MAPK1/ERK pathway in human adipocytes.

[Type B insulin resistance syndrome: 3 cases report and literature review].

OBJECTIVE: To understand type B insulin resistance syndrome (B-IRS) by reviewing 3 cases from our center and cases from literatures. METHODS: The clinical characteristics, diagnosis, treatment and follow-up data of the 3 patients with B-IRS were evaluated. RESULTS: All the 3 patients were middle-aged women with severe hyperglycemia or paradoxical hypoglycemia. The clinical findings were as follows. (1)B-IRS was associated with several autoimmune diseases such as systemic lupus erythematosus (SLE) and sclerosis. (2) The metabolic abnormalities of B-IRS include weight loss, severe hyperinsulinemia, high level of adiponectin, and low level of insulin-like growth factor type 1(IGF-1) and TG. (3)B-IRS was characterized with nonspecific serological disorders (such as leukopenia, thrombocytopenia and hypoalbuminemia) and changes (decreased complements and elevated IgG and/or IgA), and with specific immunological abnormalities[such as high titer of antinuclear antibody(ANA), positive in anti-SSA, anti-SSB and anti-dsDNA antibodies). Positive in anti-insulin receptor antibody was of diagnostic value but not necessary. (4) Treatments include insulin in combination with immunosuppressive therapy. Patients with H. pylori (Hp) infection may be benefit with eradication therapy. CONCLUSIONS: B-IRS is rare but not difficult to identify. Treatments include therapy of the underlying diseases and high dose of insulin.

[A retrospective study of the impact of diabetes mellitus on survival in patients with lung cancer].

OBJECTIVE: To investigate the impact of diabetes mellitus (DM) on survival in patients with lung cancer. METHODS: This is a retrospective study of 1 096 patients died from lung cancer collected from clinical records in Chinese PLA General Hospital. Survival time of lung cancer with and without DM was compared using Log-rank analysis and Cox regression model. RESULTS: One hundred and eighty-one patients (16.5%) had DM. The median survival time of the lung cancer patients with DM was 9 months, whereas, the median survival time of the patients without DM was 8 months. Log-rank analysis showed that this difference was significant (P<0.05). Moreover, the 1-, 2-, and 3-year survival rate in lung cancer patients with and without DM were 43% vs 35%, 27% vs 17%, and 16% vs 10%, respectively. After adjusting for age, gender, histology, stage of lung cancer and treatment, Cox regression analysis showed that the hazard ratio for survival in lung cancer patients with DM was 0.74 (95%CI 0.61-0.89, P<0.05) compared with those without DM. In non-small-cell lung cancer(NSCLC)patients, the hazard ratio for survival in lung cancer patients with DM was 0.69 (95%CI 0.56-0.85, P<0.05). However, this association disappeared in small-cell lung cancer (SCLC) patients. In advanced lung cancer patients (stage III-IV), diabetes was also a significant factor for survival (HR=0.74, 95%CI 0.61-0.91, P<0.05). CONCLUSION: Patients with advanced NSCLC with DM have longer survival time compared with those without DM.

[The changes in renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome].

OBJECTIVE: Cushing's syndrome is a clinical condition resulting from chronic exposure to excess glucocorticoid. As a consequence, long-term hypercortisolism contributes significantly to the development of systemic disorders by direct and/or indirect effects. The present study was to analyze the changes of renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome on the standard posture test. METHODS: We retrospectively reviewed 150 patients with histologically confirmed Cushing's syndrome treated at the PLA General Hospital between 2002 and 2014. Among them, 128 patients were diagnosed as adreno-cortico-tropic-hormone (ACTH)-independent Cushing's syndrome, and 22 were ACTH-dependent Cushing's syndrome. All patients were undertaken the posture test. Plasma renin activity (PRA), angiotensin II, plasma aldosterone concertration (PAC) levels were measured before and after the test. RESULTS: Basal plasma PRA [0.5 (0.2,1.3)µg·L(-1)·h(-1), angiotensin II [(48.9±20.1) ng/L] and PAC [(285.0±128.1) pmol/L] levels were within the normal range in supine position. Compared with the subjects with ACTH-independent Cushing's syndrome, the basal PAC levels were higher in subjects with ACTH-dependent Cushing's syndrome [(348.0±130.4) pmol/L vs (274.2±125.0) pmol/L, P<0.05]. However, the PAC response in subjects with ACTH-dependent Cushing's syndrome [(49.7±26.4)%] was significantly lower than that in those with ACTH-independent Cushing's syndrome [(81.2±69.3)%] upon upright posture stimulation (P<0.05). There were no statistical significances in PRA and angiotensin II levels between the two groups. The basal PAC and PRA levels were positively correlated with ACTH, whereas PAC response was negatively correlated with ACTH. CONCLUSIONS: The renin-angiotensin-aldosterone-system activity in subjects with Cushing's syndrome was similar to that in normal control. The basal PAC level and its response to upright posture are differently associated with ACTH level in Cushing's syndrome.

[The diagnosis, treatment and following up of 7 patients with 45, X/46, XY mixed gonadal dysgenesis].

OBJECTIVE: To investigate the clinical features, therapeutic regimens and follow-up information of patients with 45, X/46, XY mixed gonadal dysgenesis in order to improve the diagnosis and treatment of the disease. METHODS: We performed a retrospective review of patients with 45, X/46, XY mosaicism hospitalized in Chinese PLA General Hospital between 2000 and 2014. The clinical features,sex hormones,treatment and follow-up information were summarized. RESULTS: (1) Seven patients ranging 12-17 years old were diagnosed as having 45, X/46, XY mixed gonadal dysgenesis. Six of them had female sex of rearing and one had male. (2) All of them presented with short stature and growth retardation, and had similar specific somatic signs to Turner syndrome. (3) The external genitalia presented with a wide variety of phenotypes. One patient presented with male phenotype with hypospadia, one presented with clitoridauxe, and five presented with female phenotype. The masculinization scores for the external genitalia showed that five patients presented with female phenotype, one patient with mild undervirilization and one patient with ambiguous genitalia. (4) By surgical exploration and ultrasound, two patients were found with testes and one was with ovary-like gonads. No gonad could be detected in the other four patients. (5) Five patients were treated with recombinant human growth hormone (rhGH). Two patients received sex hormone replacement therapy with one patient taking testosterone, whose penis became enlarged and erect after treatment, and one taking artificial cycle. CONCLUSIONS: The patients with 45, X/46, XY mosaicism share similar specific somatic signs to Turner syndrome. The 45, X/46, XY mosaicism presents with a wide spectrum of phenotypes with the highest proportion of being genital ambiguity. RhGH, testosterone and artificial cycle can be used accordingly.

[The relationship between calcaneus bone mineral density and metabolic syndrome].

OBJECTIVE: To evaluate the association between calcaneus bone mineral density (BMD) and metabolic syndrome (MS). METHODS: A cross-sectional study was carried out in 5 552 subjects with 1 987 men and 3 565 women (age:40-87 years old). MS was defined according to Chinese Diabetes Society criteria. BMD was assessed by quantitative ultrasound. RESULTS: The proportion of MS was 29.0% in male and 24.4% in female. There were no differences in BMD between MS and non-MS subjects in both genders. Linear trend analysis displayed that BMD was positively associated with the increase of MS components in post-menopausal women after adjustment of age, ALT, creatinine and exercises (P < 0.05). Moreover, multiple regression analysis showed that BMD was inversely correlated with age (ß = -0.034, P < 0.001) and positively correlated with BMI (ß = 0.046, P = 0.001) , TG (ß = 0.066, P = 0.034) and systolic blood pressure (SBP) (ß = 0.007, P = 0.039) in post-menopausal women with MS. CONCLUSIONS: BMD tended to increase with the numbers of MS components in post-menopausal women. It was positively correlated with BMI, TG and SBP in postmenopausal women with MS.

[Gender-related clinical characteristics in patients with differentiated thyroid cancers].

OBJECTIVE: To investigate the clinical characteristics of patients with different gender who diagnosed as differentiated thyroid cancers (DTC). METHODS: A cohort of patients with DTC underwent surgery in Chinese PLA General Hospital from October 2001 to may 2011 was retrospectively studied. RESULTS: (1) A total of 1 756 patients with DTC were enrolled in the study and a marked female preponderance was found with the female/male ratio of 2.32: 1. The peak incidence was 35-45 years old in both genders.Higher prevalence of DTC was observed in the male patients with a single nodule than in the males with multinodulars (36.42% vs 28.90%, P < 0.01), while no statistical difference was found in the female patients (33.60% vs 31.77%, P > 0.05). (2) Ultrasound examination revealed that, the female DTC patients with microcalcification thyroid nodules were more than the male patients (69.26% vs 62.62%, P < 0.05), while less in female patients with undefined boundary thyroid nodules (57.79% vs 72.01%, P < 0.01). The tumor size was shown to be smaller in the women than in the men [(1.6 ± 1.3) cm vs (1.8 ± 1.5) cm, P < 0.01]. (3) Higher rates of III/IV TNM Stage, lymph node metastasis and extrathyroidal invasion were found in the men than in the women (21.74% vs 14.51%, P < 0.01, 33.27% vs 23.80%, P < 0.01 and 10.59% vs 7.17%, P < 0.01). CONCLUSION: There is significant gender-related difference of clinical characteristics in the patients with DTC.

[A correlation study between serum direct bilirubin and lipid in type 2 diabetic patients].

OBJECTIVE: To investigate the association between DBil with normal range and serum lipid in type 2 diabetic patients. METHODS: A total of 979 subjects with type 2 diabetes admitted to the Department of Endocrinology of Chinese PLA General Hospital from June 2012 to June 2013 were included for the study. Serum DBil, TC, TG, HDL-C and LDL-C levels were collected for the analyses. Subjects were divided into four groups based on the DBil levels: Q1 group (<2.2 µmol/L), Q2 group (2.2-< 2.9 µmol/L), Q3 group (2.9-< 3.9 µmol/L) and Q4 group ( ≥ 3.9 µmol/L) . RESULTS: (1) TC, TG, LDL-C levels were significantly lower in Q4 group than those in the other three Q groups after adjustment of age, gender, duration of diabetes, BMI, smoking, drinking, glycosylated hemoglobin A1c (HbA1c) , fasting plasma glucose (FPG), medication, ALT, AST and fatty liver. No difference could be viewed in HDL-C level between each group (P = 0.65). (2) Pearson correlation analyses showed that DBil was inversely correlated with TC (r = -0.33, P < 0.01), TG (r = -0.23, P < 0.01), LDL-C (r = -0.18, P < 0.01), and positively correlated with HDL-C level in men (r = 0.14, P < 0.01), respectively. Multiple linear regression analyses showed DBil was an independent impact factor for TC, TG and LDL-C. (3) Compared with Q1 group, the odds ratio (OR) for dyslipidemia was 0.54 (95%CI 0.35-0.82, P < 0.01), 0.56 (95%CI 0.37-0.85, P < 0.01) and 0.44 (95%CI 0.29-0.69, P < 0.01) in Q2, Q3 and Q4 group, respectively, after age, gender, duration of diabetes, BMI, smoking, drinking, HbA1c, FPG, medication, ALT, AST and fatty liver were adjusted. Moreover, the OR for dyslipidemia was much lower in Q4 man subjects with age<55 years , HbA1c ≥ 6.5%, BMI<25 kg/m(2), and with no fatty liver. CONCLUSION: DBil in normal range was closely associated with lipid profile in type 2 diabetes. It might play a protective effect in dyslipidemia.

Comparing the accuracy of four machine learning models in predicting type 2 diabetes onset within the Chinese population: a retrospective study.

OBJECTIVE: To evaluate the effectiveness of machine learning (ML) models in predicting 5-year type 2 diabetes mellitus (T2DM) risk within the Chinese population by retrospectively analyzing annual health checkup records. METHODS: We included 46,247 patients (32,372 and 13,875 in training and validation sets, respectively) from a national health checkup center database. Univariate and multivariate Cox analyses were performed to identify factors influencing T2DM risk. Extreme Gradient Boosting (XGBoost), support vector machine (SVM), logistic regression (LR), and random forest (RF) models were trained to predict 5-year T2DM risk. Model performances were analyzed using receiver operating characteristic (ROC) curves for discrimination and calibration plots for prediction accuracy. RESULTS: Key variables included fasting plasma glucose, age, and sedentary time. The LR model showed good accuracy with respective areas under the ROC (AUCs) of 0.914 and 0.913 in training and validation sets; the RF model exhibited favorable AUCs of 0.998 and 0.838. In calibration analysis, the LR model displayed good fit for low-risk patients; the RF model exhibited satisfactory fit for low- and high-risk patients. CONCLUSIONS: LR and RF models can effectively predict T2DM risk in the Chinese population. These models may help identify high-risk patients and guide interventions to prevent complications and disabilities.

The phenotype and related gene expressions of macrophages in adipose tissue of T2D mice following MSCs infusion.

BACKGROUND: Infusion of mesenchymal stem cells (MSCs) induces polarization of M2 macrophages in adipose tissue of type 2 diabetes (T2D) mice. Studies have shown that M2 macrophages were divided into four sub-phenotypes (M2a, M2b, M2c and M2d) with different functions, and manuscripts have also confirmed that macrophages co-cultured with MSCs were not matched with known four phenotype macrophages. Therefore, our study explored the phenotype and related gene expressions of macrophages in the adipose tissue of T2D mice with/without MSCs infusion. METHODS: We induced a T2D mouse model by using high-fat diets and streptozotocin (STZ) injection. The mice were divided into three groups: the control group, the T2D group, and the MSCs group. MSCs were systemically injected once a week for 6 weeks. The phenotype of macrophages in adipose tissue was detected via flow cytometric analysis. We also investigated the gene expression of macrophages in different groups via SMART-RNA-sequencing and quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS: The present study found that the macrophages of adipose tissue in the MSCs group were polarized to the M2 phenotype mixed with four sub-phenotypes. Besides, M2a and M2c held a dominant position, while M2b and M2d (tumor-associated macrophages, TAMs) exhibited a decreasing trend after infusion of MSCs. Moreover, the MSCs group did not appear to express higher levels of tumor-associated, inflammation-associated, or fibrosis-associated genes in comparison to the T2D group. CONCLUSION: The present results unveiled that the macrophage phenotype was inclined to be present in a hybridity state of four M2 sub-phenotypes and the genes related to tumor-promoting, pro-inflammation and pro-fibrosis were not increased after MSCs injection.