DNA hypomethylation of Syk induces oxidative stress and apoptosis via the PKCß/P66shc signaling pathway in diabetic kidney disease.

Epigenetic alterations, especially DNA methylation, have been shown to play a role in the pathogenesis of diabetes mellitus (DM) and its complications, including diabetic kidney disease (DKD). Spleen tyrosine kinase (Syk) is known to be involved in immune and inflammatory disorders. We, therefore, investigated the possible involvement of Syk promoter methylation in DKD, and the mechanisms underlying this process. Kidney tissues were obtained from renal biopsies of patients with early and advanced DKD. A diabetic mouse model (ApoE-/- DM) was generated from ApoE knockout (ApoE-/-) mice using a high-fat and high-glucose diet combined with low-dose streptozocin intraperitoneal injection. We also established an in vitro model using HK2 cells. A marked elevation in the expression levels of Syk, PKCß, and P66shc in renal tubules was observed in patients with DKD. In ApoE-/- DM mice, Syk expression and the binding of Sp1 to the Syk gene promoter were both increased in the kidney. In addition, the promoter region of the Syk gene exhibited hypomethylation. Syk inhibitor (R788) intervention improved renal function and alleviated pathologic changes in ApoE-/- DM mice. Moreover, R788 intervention alleviated oxidative stress and apoptosis and downregulated the expression of PKCß/P66shc signaling pathway proteins. In HK2 cells, oxLDL combined with high-glucose stimulation upregulated Sp1 expression in the nucleus (compared with control and oxLDL groups), and this was accompanied by an increase in the binding of Sp1 to the Syk gene promoter. SP1 silencing downregulated the expression of Syk and inhibited the production of reactive oxygen species and cell apoptosis. Finally, PKC agonist intervention reversed the oxidative stress and apoptosis induced by Syk inhibitor (R406). In DKD, hypomethylation at the Syk gene promoter was accompanied by an increase in Sp1 binding at the promoter. As a consequence of this enhanced Sp1 binding, Syk gene expression was upregulated. Syk inhibitors could attenuate DKD-associated oxidative stress and apoptosis via downregulation of PKCß/P66shc signaling pathway proteins. Together, our results identify Syk as a promising target for intervention in DKD.

Estimated small dense low-density lipoprotein-cholesterol and the risk of kidney and cardiovascular outcomes in diabetic kidney disease.

AIMS: This study aimed to investigate the correlations between estimated small dense low-density lipoprotein-cholesterol (esd-LDL-c) and the development of end-stage kidney disease (ESKD), cardiovascular mortality, and all-cause mortality in individuals with diabetic kidney disease (DKD) or diabetes mellitus (DM) concomitant chronic kidney disease (CKD). METHODS: We analyzed the data from a biopsy-proven DKD cohort conducted at West China Hospital of Sichuan University between 2009 and 2021 (the DKD cohort) and participants with DM and CKD in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 (the NHANES DM-CKD cohort). Cox regression analysis was also used to estimate associations between esd-LDL-c and the incidence of ESKD, cardiovascular mortality, and all-cause mortality. RESULTS: There were 175 ESKD events among 338 participants in the DKD cohort. Patients were divided into three groups based on esd-LDL-c tertiles (T1 < 33.7 mg/dL, T2 ≥ 33.7 mg/dL to <45.9 mg/dL, T3 ≥ 45.9 mg/dL). The highest tertile of esd-LDL-c was associated with ESKD (adjusted HR 2.016, 95% CI 1.144-3.554, p = .015). Furthermore, there were 99 deaths (39 cardiovascular) among 293 participants in the NHANES DM-CKD cohort. Participants were classified into three groups in line with the tertile values of esd-LDL-c in the DKD cohort. The highest tertile of esd-LDL-c was associated with cardiovascular mortality (adjusted HR 3.95, 95% CI 1.3-12, p = .016) and all-cause mortality (adjusted HR 2.37, 95% CI 1.06-5.32, p = .036). CONCLUSIONS: Higher esd-LDL-c was associated with increased risk of ESKD in people with biopsy-proven DKD, and higher cardiovascular and all-cause mortality risk among those with DM-CKD.

Thrombotic thrombocytopenic purpura in a patient on long-term alpha-interferon therapy for essential thrombocythemia: a case report.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is rare and severe thrombotic microangiopathy characterized by thrombocytopenia, hemolytic anemia, and renal dysfunction. In contrast, essential thrombocythemia (ET) is a myeloproliferative disease associated with an abnormal increase in platelet numbers. Previous studies reported several cases of the development of ET in patients with TTP. However, the case of an ET patient complicated with TTP has not been previously reported. In this case study, we present a patient with TTP who was previously diagnosed with ET. Therefore, to the best of our knowledge, this is the first report of TTP in ET. CASE PRESENTATION: A 31-year-old Chinese female who was previously diagnosed with ET presented with anemia and renal dysfunction. The patient had been on long-term treatment with hydroxyurea, aspirin, and alpha interferon (INF-α) for ten years. The diagnosis of TTP was confirmed by clinical features, schistocytes noted on the peripheral blood smear, and lower ADAMTS13 activity (8.5%), together with the renal biopsy results. INF-α was discontinued, and the patient was then treated with plasma exchange and corticosteroids. After one year of follow-up, the patient had a normal hemoglobin level and platelet numbers, and her ADAMTS13 activity had improved. However, the patient's renal function remains impaired. CONCLUSIONS: We report a case of an ET patient complicated with TTP that was possibly due to INF-α, highlighting the potential complications associated with long-term ET therapy. The case also highlights the importance of considering TTP in patients with pre-existing ET who present with anemia and renal dysfunction, extending the spectrum of known studies.

Development and internal validation of machine learning algorithms for end-stage renal disease risk prediction model of people with type 2 diabetes mellitus and diabetic kidney disease.

AIMS: Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) and is associated with increased morbidity and mortality in patients with diabetes. Identification of risk factors involved in the progression of DKD to ESRD is expected to result in early detection and appropriate intervention and improve prognosis. Therefore, this study aimed to establish a risk prediction model for ESRD resulting from DKD in patients with type 2 diabetes mellitus (T2DM). METHODS: Between January 2008 and July 2019, a total of 390 Chinese patients with T2DM and DKD confirmed by percutaneous renal biopsy were enrolled and followed up for at least 1 year. Four machine learning algorithms (gradient boosting machine, support vector machine, logistic regression, and random forest (RF)) were used to identify the critical clinical and pathological features and to build a risk prediction model for ESRD. RESULTS: There were 158 renal outcome events (ESRD) (40.51%) during the 3-year median follow up. The RF algorithm showed the best performance at predicting progression to ESRD, showing the highest AUC (0.90) and ACC (82.65%). The RF algorithm identified five major factors: Cystatin-C, serum albumin (sAlb), hemoglobin (Hb), 24-hour urine urinary total protein, and estimated glomerular filtration rate. A nomogram according to the aforementioned five predictive factors was constructed to predict the incidence of ESRD. CONCLUSION: Machine learning algorithms can efficiently predict the incident ESRD in DKD participants. Compared with the previous models, the importance of sAlb and Hb were highlighted in the current model.HighlightsWhat is already known? Identification of risk factors for the progression of DKD to ESRD is expected to improve the prognosis by early detection and appropriate intervention.What this study has found? Machine learning algorithms were used to construct a risk prediction model of ESRD in patients with T2DM and DKD. The major predictive factors were found to be CysC, sAlb, Hb, eGFR, and UTP.What are the implications of the study? In contrast with the treatment of participants with early-phase T2DM with or without mild kidney damage, major emphasis should be placed on indicators of kidney function, nutrition, anemia, and proteinuria for participants with T2DM and advanced DKD to delay ESRD, rather than age, sex, and control of hypertension and glycemia.

Efficacy and safety of drugs for people with type 2 diabetes mellitus and chronic kidney disease on kidney and cardiovascular outcomes: A systematic review and network meta-analysis of randomized controlled trials.

AIM: To evaluate the comparative efficacy and safety of promising kidney protection drugs, including sodium-glucose cotransporter-2 inhibitors (SGLT-2Is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl-peptidase IV Inhibitors (DPP-4Is), aldosterone receptor agonists (MRAs), endothelin receptor antagonist (ERAs), pentoxifylline (PTF), and pirfenidone (PFD), on cardiovascular and kidney outcomes in type 2 diabetes (T2DM) and chronic kidney disease (CKD) population. METHODS: PubMed, Embase, and Cochrane Library were searched from inception to August 12, 2022. We used the Bayesian model for network meta-analyses, registered in the PROSPERO (CRD42022343601). RESULTS: This network meta-analysis identified 2589 citations, and included 27 eligible trials, enrolling 50,237 patients. All results presented below were moderate to high quality. For kidney outcomes, SGLT-2Is were optimal in terms of reducing composite kidney events (RR 0.69, 95%CI 0.61-0.79), and slowing eGFR slope (MD1.34, 95%CI 1.06-1.62). Then MRAs (RR 0.77, 95%CI 0.68-0.88; MD 1.31, 95%CI 0.89-1.74), GLP-1RAs (RR 0.78, 95%CI 0.62-0.97; MD 0.75, 95%CI 0.46-1.05), and ERAs (RR 0.75, 95%CI 0.57-0.99; MD 0.7, 95%CI 0.3-1.1) were followed in parallel. For cardiovascular outcomes, SGLT-2 inhibitors were also among the best for lowing the risk of heart failure hospitalization (RR 0.67, 95%CI 0.57-0.78), followed by GLP-1RAs (RR 0.73, 95%CI 0.55-0.97) and MRAs (RR 0.79, 95%CI 0.67-0.92). SGLT-2Is (RR 0.8, 95%CI 0.71-0.89) and GLP-1RAs (RR 0.72, 95%CI 0.6-0.86) had comparable effects to reduce the risk of major adverse cardiovascular events. MRAs were possibly associated with increased drug discontinuation due to adverse events (RR 1.21, 95%CI 1.05-1.38). For the hyperkalemia outcome, MRAs (RR 2.08, 95%CI 1.86-2.33) were linked to the risk of hyperkalemia, whereas SGLT-2Is (RR 0.78, 95%CI 0.65-0.93) were in contrast. CONCLUSIONS: SGLT-2Is significantly reduced kidney and cardiovascular risk in T2DM and CKD, subsequently GLP-1RAs and MRAs. SGLT-2Is-MRAs combination might be a recommended treatment regimen for maximizing kidney and cardiovascular protection but with a low risk of hyperkalemia in T2DM and CKD.

Lower bile acids as an independent risk factor for renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease.

Aims: Abnormalities of glucolipid metabolism are critical mechanisms involved in the progression of diabetic kidney disease (DKD). Bile acids have an essential role in regulating glucolipid metabolism. This study investigated the clinicopathological characteristics of DKD patients with different bile acid levels and explored the relationship between bile acids and renal outcomes of DKD patients. Methods: We retrospectively reviewed and evaluated the histopathological features and clinical features of our cohort of 184 patients with type 2 diabetes mellitus and biopsy-proven DKD. Patients were divided into the lower bile acids group (≤2.8 mmol/L) and higher bile acids group (>2.8 mmol/L) based on the cutoff value of bile acids obtained using the time-dependent receiver-operating characteristic curve. Renal outcomes were defined as end-stage renal disease (ESRD). The influence of bile acids on renal outcomes and correlations between bile acids and clinicopathological indicators were evaluated. Results: Bile acids were positively correlated with age (r = 0.152; P = 0.040) and serum albumin (r = 0.148; P = 0.045) and negatively correlated with total cholesterol (r = -0.151; P = 0.041) and glomerular class (r = -0.164; P =0.027). During follow-up, 64 of 184 patients (34.78%) experienced progression to ESRD. Lower levels of proteinuria, serum albumin, and bile acids were independently associated with an increased risk of ESRD (hazard ratio, R=5.319; 95% confidence interval, 1.208-23.425). Conclusions: Bile acids are an independent risk factor for adverse renal outcomes of DKD patients. The serum level of bile acids should be maintained at more than 2.8 mmol/L in DKD patients. Bile acid analogs or their downstream signaling pathway agonists may offer a promising strategy for treating DKD.

Intravitreal vascular endothelial growth factor inhibitors did not increase the risk of end-stage renal disease in patients with biopsy-proven diabetic kidney disease based on matched study.

Purpose: This study aimed to investigate the effects of intravitreal (IVT) VEGFi on long-term renal outcomes in patients with biopsy-proven diabetic kidney disease (DKD). Patients and methods: Patients prescribed IVT VEGFi (VEGFi group) were enrolled from a retrospective cohort with biopsy-proven DKD, and those not prescribed VEGFi (non-VEGFi group) were enrolled by 1:3 propensity score matching, adjusted for clinical and pathological baseline indicators. The primary endpoint is defined as end-stage renal disease (ESRD) and the secondary endpoint is defined as all-cause mortality. Results: Compared with patients in non-VEGFi group, patients with VEGFi had a higher proportion of diabetic retinopathy (DR) (50.9% vs 100%, p < 0.001) before matching. Standardized mean difference (SMD) of age, DR, duration of diabetes, the proportion of hypertension, eGFR, initial proteinuria, serum albumin, hemoglobin, the proportion of RAAS inhibitor and interstitial fibrosis and tubular atrophy (IFTA) were >10%. After matching, there was no significant difference in clinical pathology between the two groups. Except for the proportion of hypertension, the SMD of other indicators was <10%. Endpoints such as ESRD (Log-Rank p = 0.772) and all-cause mortality (Log-Rank p = 0.834) were not significantly different between the two groups. Conclusion: Our data suggested that IVT VEGFi did not increase the incidence of ESRD and all-cause mortality in patients with DKD.

Clinical and Pathological Features of Chinese Patients with Type 2 Diabetes, Biopsy-Proven Diabetic Kidney Disease, and Rapid eGFR Decline.

Objective: The rate of kidney function decline in patients with diabetic kidney disease (DKD) is known to differ. This study analyzed the clinicopathologic features and related risk factors affecting long-term renal survival in Chinese type 2 diabetic patients with rapid estimated glomerular filtration rate (eGFR) decline. Methods: In this retrospective descriptive study, 191 DKD patients were first classified as rapid eGFR decliners and slow eGFR decliners on the basis of the median eGFR slope value (-8.0 mL/min/1.73 m2/year). In total, 96 patients with rapid eGFR decline were included in the analyses and subsequently allocated to end-stage renal disease (ESRD) and non-ESRD groups. Baseline clinicopathological data of rapid eGFR decliners were collected. Cox proportional hazard analysis was performed to calculate the hazard ratios (HRs) for progression to ESRD. Results: During a median follow-up of 25 months, 52 (54.2%) rapid eGFR decliners progressed to ESRD. These 52 rapid eGFR decliners had poorer renal function, lower hemoglobin and albumin concentrations, higher total cholesterol and baseline proteinuria levels, and more severe interstitial inflammation than those who did not progress to ESRD. After adjustment for age, gender, baseline eGFR, proteinuria, hemoglobin level, serum albumin concentration, and histopathologic parameters, multivariate Cox proportional hazard analysis revealed that eGFR (HR 0.973, 95% CI 0.956-0.989) and proteinuria (HR 1.125, 95% CI 1.030-1.228) were associated with the increased risk of progression to ESRD. Conclusion: Higher proteinuria and lower eGFR were independent risk factors for renal progression in Chinese patients with type 2 diabetes and rapid eGFR decline.

Early-onset of type 2 diabetes mellitus is a risk factor for diabetic nephropathy progression: a biopsy-based study.

Several studies show that patients with early-onset diabetes have higher risk of diabetic complications than those diagnosed in middle age. However, whether early-onset of type 2 diabetes mellitus (T2DM) is a risk factor for diabetic nephropathy (DN) progression remains unclear, especially a lack of data in biopsy-confirmed cohort. In This study, we enrolled 257 patients with T2DM and biopsy-confirmed DN to investigate the role of early-onset T2DM in DN progression. Participants were divided into two groups according to the age of T2DM diagnosis: early-onset group (less than 40 years) and later-onset group (40 years or older). We found that patients with early-onset T2DM had higher glomerular grades and arteriolar hyalinosis scores than those in later-onset group. After adjusted for confounding factors, early-onset of T2DM remained an independent predictor of end-stage renal disease (ESRD) for patients with DN. In conclusion, although with the comparable renal function and proteinuria, patients with early-onset T2DM and DN had worse renal pathological changes than those with later-onset. Early-onset of T2DM might be an important predictor of ESRD for patients with DN, which called more attention to early supervision and prevention for patients with early-onset T2DM and DN.

Association between serum uric acid and renal outcome in patients with biopsy-confirmed diabetic nephropathy.

OBJECTIVE: To investigate the relationship between serum uric acid (SUA) level and renal outcome in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). METHODS: A total of 393 Chinese patients with T2DM and biopsy-proven DN and followed at least 1 year were enrolled in this study. Patients were stratified by the quartiles of baseline level of SUA: Q1 group: 286.02 ± 46.66 µmol/L (n = 98); Q2 group: 358.23 ± 14.03 µmol/L (n = 99); Q3 group: 405.50 ± 14.59 µmol/L (n = 98) and Q4 group: 499.14 ± 56.97µmol/L (n = 98). Renal outcome was defined by progression to end-stage renal disease (ESRD). Kaplan-Meier survival analysis and Cox proportional hazards model were used to analyze the association between SUA quartiles and the renal outcomes. RESULTS: During the median 3-year follow-up period, there were 173 ESRD outcome events (44.02%). No significant difference between SUA level and the risk of progression of DN (P = 0.747) was shown in the Kaplan-Meier survival analysis. In multivariable-adjusted model, hazard ratios for developing ESRD were 1.364 (0.621-2.992; P = 0.439), 1.518 (0.768-3.002; P = 0.230) and 1.411 (0.706-2.821; P = 0.330) for the Q2, Q3 and Q4, respectively, in comparison with the Q1 (P = 0.652). CONCLUSIONS: No significant association between SUA level and renal outcome of ESRD in Chinese patients with T2DM and DN was found in our study. Besides, the role of uric acid-lowering therapy in delaying DN progression and improving ESRD outcome had not yet been proven. Further study was needed to clarify the renal benefit of the uric acid-lowering therapy in the treatment of DN.

Mammary myoid hamartomas: reports of two cases and a review of the literature.

The purpose of this report is to determine the clinicopathological and immuno-phenotypical characteristics of myoid hamartoma of the breast (MHB). The clinical data, histological morphology, and immunohistochemical results of 2 patients diagnosed with MHB were analyzed, and 15 cases of MHB reported in China were reviewed. Both patients were female, aged 28 and 35 years old, and their lesions were located in the upper outer quadrant of the left breast and the right breast respectively. The lesions measured 3 cm × 3 cm × 2.5 cm and 6.5 cm × 6 cm × 4.5 cm. A gross examination indicated a grayish solid block with clear boundaries. A microscopic examination showed different proportions of ducts and acini, beam myoid cells, adipose tissue, and fibrous stroma. The myoid cell bundles of both specimens were positive for vimentin, SMA, h-caldesmon and desmin, but negative for ER, PR, PCK, s-100, Calponin, and P63. Both cases were confirmed as MHB based on their clinical, histological and immuno-phenotypical characteristics. Our findings provide further insights into the pathological basis of MHB, which can help avoid both misdiagnosis and missed diagnosis.

Hawthorne leaf flavonoids prevent oxidative stress injury of renal tissues in rats with diabetic kidney disease by regulating the p38 MAPK signaling pathway.

Objectives: Diabetic kidney disease (DKD) is the primary microvascular complication of diabetes. The incidence rate of DKD has increased worldwide, and DKD has become one of the most important causes of end-stage renal disease. In this study, we aimed to investigate the effects of hawthorn leaf flavonoids (HLF) on oxidative stress injury of renal tissue in DKD rats, and elucidate their mechanism(s) of action. Methods: A total of 35 male Sprague Dawley rats were randomly divided into the control group (CON group) and model group. Rats in the model group were fed a diet containing high sugar and fat and were injected with streptozotocin (STZ) into the abdominal cavity to induce diabetes. Diabetic rats that showed >50% increase in 24 h urine volume and >30 mg of 24 h urine protein excretion were selected as DKD model rats. After DKD models were successfully established, model rats were randomly divided into the diabetic kidney disease group (DKD group), irbesartan group (IRB group), and hawthorn leaf flavonoids group (HLF group). All rats were sacrificed at 12 weeks (w) after DKD models were established. Body weight and 24 h urinary protein levels were measured at 4 w, 8 w, and 12 w, respectively. Blood was collected to measure the levels of urea nitrogen, creatinine, triglyceride, nitric oxide, malondialdehyde, and superoxide dismutase. Pathologic changes in renal tissue were examined by hematoxylin and eosin (H&E) and Masson staining. Protein expression of p38MAPK and p-p38MAPK was determined by immunohistochemistry. Results: Our data showed that HLFs improved the general condition and body weight, and reduced the levels of urinary protein in model rats. Rats in the DKD group had more serious pathological damage in the kidney when compared to rats in the HLFs group. In addition, rats in the HLF group had significantly lower levels of urea nitrogen, creatinine, triglyceride, and malondialdehyde, and significantly higher levels of nitric oxide and superoxide dismutase than rats in the DKD group. Furthermore, p38MAPK and p-p38MAPK protein levels were significantly higher in rats in the DKD group compared to rats in the HLF group. Conclusions: HLFs have a protective effect against DKD in rats. The underlying mechanism may involve the reduction of oxidative stress by inactivation of the p38MAPK signaling pathway in renal tissues.

[The best waist circumference cut-point for identifying cardiovascular risk factors among adolescents: a preliminary study].

OBJECTIVE: To explore the best waist circumference (WC) cut-point for identifying cardiovascular risk factors among adolescents. METHODS: Human basic parameters were measured among 3986 adolescents aged 14 - 18 in Qinhuangdao. Receiver operator characteristic curve (ROC) analysis was employed to determine the optimal WC cut-point for detecting cardiovascular risk factors. RESULTS: The prevalence of the clustering of cardiovascular risk factors significantly increased after the WC was >or= 80th percentiles (77.0 - 79.0 cm for the boys and 70.0 - 72.5 cm for the girls). The age standardization detection rate was 24.9% in boys and 9.9% in girls. ROC analysis showed that the optimal WC cut-point was 80th percentiles, with the sensitivity of 84.3% and specificity of 85.9% in boys, and with sensitivity of 90.7% and specificity of 83.2% in girls. CONCLUSION: There is a significant correlation between WC and cardiovascular risk factors. The optimal WC cut-point for predicting the clustering of cardiovascular risk factors is the 80th percentile.

[Study of HPLC-DAD fingerprint on complex traditional Chinese medicine proprietary preparation-Baoji pills].

OBJECTIVE: Based on 'Back-tracking' method, identification and quality evaluation of complex traditional Chinese medicine (TCM) preparation of Baoji pills (BJP) were carried out by HPLC fingerprint analysis. METHOD: HPLC-DAD fingerprint of BJP was conducted with Zorbax SB-C18 column and non-linear elution with the mobile phase consisted of acetonitrile-0.5% glacial acetic acid at column temperature 30 degrees C and detective wavelengths of 250 nm and 283 nm. From the established chromatographic pattern of BJP, track backward to the corresponding crude herbal drugs in the formula, attribution ofmost peaks in the BJP fingerprint can be disclosed. RESULT: The BJP HPLC fingerprint consisted of 44 peaks among which 35 peaks were assigned by parallel comparison with the fingerprint of the 10 corresponding crude drugs in the formula such as pueraria, pummelo peel, and magnolia bark, etc. and 22 peaks we reidentified by comparison with the chemical reference substances. CONCLUSION: The established HPLC fingerprint represents the whole character of BJP, which enhanced the specialty for control and assessment of the product quality. It exemplified much more effective for quality control than selecting any marker for qualitative or quantitative testing target. And the Back-tracking' experimental method extended the study mentality for complex formula TCM products chromatographic fingerprinting analysis.

The Involvement of Notch1-RBP-Jk/Msx2 Signaling Pathway in Aortic Calcification of Diabetic Nephropathy Rats.

BACKGROUND: This study explored the changes in expression of vascular smooth muscle cell (VSMC) markers and osteogenic markers, as well as the involvement of Notch1-RBP-Jk/Msx2 pathway in a rat model of diabetic nephropathy (DN) with vascular calcification. METHODS: A rat model of DN with concomitant vascular calcification was created by intraperitoneal injection of streptozotocin followed by administration of vitamin D3 and nicotine. Biochemical analysis and histological examination of aortic tissue were performed. VSMC markers and osteogenic markers as well as target molecules in Notch1-RBP-Jk/Msx2 were determined by quantitative real-time polymerase chain reaction and immunohistochemical analysis. RESULTS: Serum calcium and phosphorus levels were significantly increased in model rats as compared to that in normal controls. Diabetic rats with vascular calcification exhibited mineral deposits in aortic intima-media accompanied by decreased expression of VSMC markers and increased expression of osteogenic markers. Notch1, RBP-Jk, Msx2, Jagged1, and N1-ICD were barely expressed in the aortic wall of normal rats. In contrast, these were significantly increased in the model group at all time points (8, 12, and 16 weeks), as compared to that in the normal rats. CONCLUSION: Activation of the Notch1-RBP-Jk/Msx2 signaling pathway may be involved in the development and progression of vascular calcification in DN.

[Studies on quality control standard of zhishidaozhi tabloid pills].

OBJECTIVE: To develop the quality control standard of Zhishidaozhi Tabloid Pills. METHOD: Applying TLC to identify Radix et Rhizoma Rhei, Fructus Aurantii Immaturus, Rhizoma Coptidis, Radix Scutellariae, and HPLC to determine the content of emodin of Radix et Rhizoma Rhei. RESULT: Radix et Rhizoma Rhei, Fructus Aurantii Immaturus, Rhizoma Coptidis and Radix Scutellariae could be indentified by TLC. Emodin showed a good linear relationship at a rang of 0.0612-0.612 microgram, r = 0.9999. The average recovery was 97.9%, and RSD was 2.1%. CONCLUSION: The methods are accurate and quick, and can be used for the quality control of Zhishidaozhi Tabloid Pills.

The change in one-hour postload plasma glucose levels, and an analysis of its related factors in abdominally obese Han Chinese men with normal glucose tolerance.

OBJECTIVE: This study was to observe the difference in one-hour postload plasma glucose levels and analyze its related factors in abdominally obese men with normal glucose tolerance (NGT). DESIGN: This case-control study included 36 abdominally obese men (waist circumference ≥90 cm) and 31 non-abdominally obese men (waist circumference <90 cm) aged 20-50 years with NGT. Cases and controls were matched in age. All subjects underwent oral glucose tolerance test with 75 g of oral anhydrous glucose. RESULTS: 0.5 and 1-h postload plasma glucose levels were higher in abdominally obese group than in non-abdominally obese group (P<.05). Fasting plasma glucose (FPG), 2 and 3-h postload plasma glucose were similar in the two groups (P>.05). 1-h postload plasma glucose was positively correlated with body mass index (r=0.454), waist circumference (WC) (r=0.519), systolic blood pressure (r=0.456), diastolic blood pressure (r=0.338), triglycerides (r=0.439), and negatively correlated with high density lipoprotein cholesterol (r=-0.391), 1/fasting insulin (r=-0.459), insulinogenic index (r=-0.357) and disposition index (r=-0.602) (P<.01). In multiple regression analysis, 1-h postload plasma glucose maintained an independent association with disposition index (ß=-1.367, P=.000), WC (ß=0.103, P=.000) and triglycerides (ß=0.185, P=.017). CONCLUSIONS: The present study demonstrated that the level of one-hour postload plasma glucose was elevated in abdominally obese men with NGT. Besides FPG and 2-h postload plasma glucose, we must also pay attention to the measurement of one-hour postload plasma glucose. Disposition index, WC and triglycerides were independently related factors for elevated one-hour postload plasma glucose.

Value of dual-energy X-ray absorptiometry derived parameters vs anthropometric obesity indices in the assessment of early atherosclerosis in abdominally obese men.

OBJECTIVE: The purpose of this study was to evaluate the value of dual-energy X-ray absorptiometry (DEXA) derived parameters vs anthropometric obesity indices in the assessment of early atherosclerosis in abdominally obese men. METHODS: This case-control study included 44 abdominally obese men (waist circumference ≥ 90 cm) and 30 non-abdominally obese men (waist circumference < 90 cm) who were between 20 and 50 years of age. All subjects were of the Han ethnicity. The carotid intima-media thickness (CIMT) was used as a surrogate marker of early atherosclerosis. In the first multiple linear regression model, body fat distribution was assessed by anthropometric obesity indices, while in the second one it was quantified by DEXA-derived parameters. RESULTS: CIMT (0.74 ± 0.11 vs 0.67 ± 0.04 mm) were significantly higher in the abdominally obese men than in the non-abdominally obese men (P < 0.01). CIMT was positively correlated with anthropometric obesity indices (r: 0.352-0.488, P < 0.01) and the indices from DEXA(r: 0.244-0.482, P < 0.05). The correlation coefficients of anthropometric obesity indices and the indices from DEXA were highest for waist to height ratio and trunk fat mass, respectively. In model 1, 23.8% of the total variance of CIMT was due to waist to height ratio. In model 2, trunk fat mass explained 23.2% of the total variance of CIMT. CONCLUSIONS: The present study demonstrates the importance of characterizing body fat distribution in identifying early atherosclerosis. Body fat distribution evaluated by dualenergy X-ray absorptiometry was associated with CIMT, but was not superior to anthropometric measurements.

Coexistence of non-alcoholic fatty liver disease with elevated alanine aminotransferase is associated with insulin resistance in young Han males.

Elevated alanine aminotransferase (ALT) and non-alcoholic fatty liver disease (NAFLD) have been associated with insulin resistance (IR). The objective of this study was to determine whether elevated ALT and NAFLD were useful for early and definitive determination of IR and to compare their coexistence with conventional risk factors in young Han males. Anthropometric and metabolic measurements were assessed in 216 young Han males (19.3 ± 0.8 years). NAFLD was diagnosed using ultrasonography, and the homeostasis model assessment of insulin resistance (HOMA-IR) served as an index of IR. Subjects in the fourth HOMA-IR quartile had a significantly higher frequency of abdominal obesity, elevated blood pressure and ALT, and NAFLD compared to subjects in quartiles 1-3 (P < 0.05). Using multivariate logistic regression analysis, risk of IR increased by 2.33-fold (95% CI: 1.00-5.42, P = 0.050) in participants with NAFLD. In addition, the coexistence of NAFLD and elevated ALT were significantly associated with HOMA-IR and participants with both elevated ALT and NAFLD had a 4.65-fold (95% CI: 1.55-13.97, P = 0.006) increased risk of IR. Coexistence of NAFLD and elevated ALT are associated with IR in young Han males and might be useful for early detection of IR as compared to conventional risk factors.

Glycemic variability in abdominally obese men with normal glucose tolerance as assessed by continuous glucose monitoring system.

The purpose of this study was to observe both the glycemic variability in abdominally obese men with normal glucose tolerance (NGT) and the relationship between glycemic variability and early atherosclerosis. This case-control study included 23 abdominally obese men (waist circumference (WC) ≥90 cm) and 23 nonabdominally obese men (WC <90 cm) with NGT who were between 20 and 50 years of age. All subjects were of the Han ethnicity. The cases and controls were age-matched. A continuous glucose monitoring system (CGMS) was used in this study. With the CGMS, the standard deviation of blood glucose (SDBG) and the mean amplitude of glucose excursion (MAGE) were calculated to estimate glycemic variability. The carotid intima-media thickness (CIMT) was used as a surrogate marker of early atherosclerosis. Mean blood glucose (MBG) (6.13 ± 0.94 vs. 5.55 ± 0.87 mmol/l), SDBG (0.89 ± 0.34 vs. 0.64 ± 0.24 mmol/l), MAGE (2.05 ± 0.83 vs. 1.57 ± 0.52 mmol/l), and CIMT (0.73 ± 0.12 vs. 0.67 ± 0.05 mm) were significantly higher in the abdominally obese men than in the nonabdominally obese men (P < 0.05). WC positively correlated with MBG (r = 0.302, P = 0.041), SDBG (r = 0.362, P = 0.013), MAGE (r = 0.302, P = 0.041), and CIMT (r = 0.487, P = 0.001). CIMT did not correlate with MBG (r = 0.206, P = 0.169), SDBG (r = 0.114, P = 0.450), and MAGE (r = 0.085, P = 0.574). After multivariate analysis, WC was still significantly associated with MBG (ß = 0.025, P = 0.041), SDBG (ß = 0.010, P = 0.013), MAGE (ß = 0.019, P = 0.042), and CIMT (ß = 0.008, P = 0.022). This study demonstrates that glycemic variability is increased in abdominally obese men with NGT. A relationship between glycemic variability and atherosclerosis was not observed in this study and requires further investigation.