Empagliflozin's role in early tubular protection for type 2 diabetes patients.

BACKGROUND: Patients with type 2 diabetes often face early tubular injury, necessitating effective treatment strategies. This study aimed to evaluate the impact of the SGLT2 inhibitor empagliflozin on early tubular injury biomarkers in type 2 diabetes patients with normoalbuminuria. METHODS: A randomized controlled clinical study comprising 54 patients selected based on specific criteria was conducted. Patients were divided into an intervention group (empagliflozin, n = 27) and a control group (n = 27) and treated for 6 weeks. Tubular injury biomarkers KIM-1 and NGAL were assessed pre- and post-treatment. RESULTS: Both groups demonstrated comparable baseline characteristics. Post-treatment, fasting and postprandial blood glucose levels decreased similarly in both groups. The intervention group exhibited better improvements in total cholesterol, low-density lipoprotein, and blood uric acid levels. Renal function indicators, including UACR and eGFR, showed greater enhancements in the intervention group. Significant reductions in KIM-1 and NGAL were observed in the intervention group. CONCLUSION: Treatment with empagliflozin in type 2 diabetes patients with normoalbuminuria led to a notable decrease in tubular injury biomarkers KIM-1 and NGAL. These findings highlight the potential of SGLT2 inhibitors in early tubular protection, offering a new therapeutic approach.

Assessing early tubular protective effects of SGLT2 inhibitor empagliflozin against type 2 diabetes mellitus using functional magnetic resonance imaging.

AIMS: To observe the alterations in functional magnetic resonance imaging parameters in normoalbuminuric type 2 diabetic patients undergoing SGLT2 inhibitor empagliflozin treatment and investigate the early tubular protective effects of the inhibitor. METHODS: This study was performed in normoalbuminuric type 2 diabetes mellitus patients (UACR < 30 mg/g, eGFR ≥ 60 ml/min/1.73 m2). The patients were divided into the intervention group (empagliflozin) and the control group (27 cases each). The intervention group was treated with 10 mg/day empagliflozin tablets orally, while the control group had adjustments to their basic treatment stage. The patients were treated for 6 weeks. RESULTS: The baseline clinical data of the two groups were comparable (P˃0.05). The intervention group exhibited better improvements in blood lipid profiles and more significant reductions in blood uric acid levels compared to the control group (P < 0.05). The two groups had No significant difference in blood pressure changes (P˃0.05). Notably, the intervention group demonstrated a greater reduction in UACR and a more substantial decline in eGFR than the control group (P < 0.05). Regarding functional magnetic resonance imaging parameters, the MD value of the renal medulla region in the intervention group increased after treatment, while the MR2* value of the renal medulla region decreased (P < 0.05). CONCLUSIONS: SGLT2 inhibitor empagliflozin can reduce UACR and eGFR levels in early type 2 diabetic patients with normal proteinuria. Moreover, empagliflozin therapy led to an increase in the MD value and a decrease in the MR2* value of the renal medulla, evidencing the early tubular protective effects of this therapy.

Correlation Between Functional Magnetic Resonance Imaging and Renal Tubular Injury Markers in Early Assessment Of Renal Tubular Injury in Type 2 Diabetes Mellitus.

Objective: Both functional magnetic resonance imaging and renal tubular injury markers have been proved to be able to detect early renal damage in normoalbuminuric diabetic patients. This study mainly explored the functional magnetic resonance imaging parameters and renal tubular injury markers in the early evaluation of type 2 diabetes. Methods: A case observation study was established, and 62 patients with early-stage low-risk type 2 diabetes mellitus with normoalbuminuric (UACR<30 mg/g, eGFR≥60 ml/min/1.73 m2) were included for analysis. Urine kidney damage was determined by ELISA. Kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) assessment of renal tubular injury, and use of intravoxel incoherent motion magnetic resonance Imaging (intravoxel incoherent motion, IVIM) and blood oxygen level dependent magnetic resonance imaging (blood oxygen level dependent, BOLD) to evaluate renal cortex, medulla blood perfusion, water molecule diffusion, oxygenation level and other functional information, using linear correlation to analyze the correlation between functional magnetic resonance imaging parameters and markers of renal tubular injury. Results: The correlation analysis between IVIM parameters and renal tubular injury markers showed that KIM-1 was inversely correlated with the MD value of the renal medulla region parameter (r = -0.24, P = .03), and was closely related to the other IVIM cortex and medulla. There was no correlation between qualitative parameters (P > .05), and no correlation between NGAL and all parameters of IVIM (P > .05). The correlation analysis between BOLD parameters and renal tubular injury markers showed that KIM-1 was positively correlated with renal medulla region parameter MR2* value (r = 0.26, P = .04) and MCR value (r = 0.28, P = .03), respectively. There was also a positive correlation between NGAL and renal medulla region parameter MR2* value (r = 0.24, P = .04). Conclusion: In the early low-risk type 2 diabetic patients with normoalbuminuria, the more obvious the renal medullary water molecule diffusion disorder, the higher the renal tubular injury marker KIM-1, and the more severe renal medullary hypoxia, the renal tubular injury. The higher the markers KIM-1 and NGAL are, it is proved that the hypoxia and water diffusion disorder in the early renal medulla are related to renal tubular damage.

Relationship of liver fat content with systemic metabolism and chronic complications in patients with type 2 diabetes mellitus.

OBJECTIVE: This study investigated the correlation of liver fat content (LFC) with metabolic characteristics and its association with chronic complications in type 2 diabetes mellitus (T2DM) patients. METHODS: Eighty-one prospectively enrolled T2DM patients were divided into non-alcoholic fatty liver disease (NAFLD) group and the non-NAFLD group according to the presence of NAFL complications. LFC was determined by MRI IDEAL-IQ Sequence, and patients were divided into 4 groups according to LFC by quartile method. Basic information, metabolic indexes, and occurrence of chronic complications in different groups were analyzed and compared. RESULTS: BMI, SBP, DBP, TG, ALT, AST, GGT, UA, HbA1c, FCP, 2 h CP, HOMA-IR, and HOMA-IS in the NAFLD group were significantly higher than the non-NAFLD group (P < 0.05). The incidences of chronic complications in the NAFLD group were higher than in the non-NAFLD group but not statistically significant (P > 0.05). BMI, SBP, DBP, TC, TG, ALT, AST, FCP, 2 h CP, HOMA-IR, and HOMA-IS showed significant differences between the patients with different LFC, and these indexes were significantly higher in patients with higher LFC than those with lower LFC (P < 0.05). Moreover, diabetes duration, TC, HOMA-IR, and LFC were the risk factors for ASCVD complications, while diabetes duration, TG, and LDL-C were risk factors for DN complications. Also, diabetes duration and SBP were risk factors for both DR and DPN complications in T2DM patients (P < 0.05). CONCLUSION: LFC is positively correlated with the severity of the systemic metabolic disorder and chronic complications in T2DM patients.

Effectiveness and Practicality of eKTANG as a Digital Treatment for Diabetes and Relevant Influence Factors.

BACKGROUND: This work explored the effect of eKTANG, a new healthcare mode for diabetes patients, on diabetes management. METHODS: Allowing general utilization of medical service and health management based on Internet, eKTANG obtained the precise data like blood glucose and blood pressure examined by an intelligent glucometer, from which doctors and the nursing team will promptly analyze the data and return feedback to the patients. In our study, overall 204 patients receiving eKTANG management over 3 months in First Affiliated Hospital of Jinan University from May 2019 to Aug 2020 were enrolled as the research objects, with data collected from patient records. RESULTS: Through the biochemical test on relevant indexes of blood glucose, it was observed that FBG, PBG, HbA1c, TG, TC, LDL levels after management were lower than before whereas HDL expression after were lower than before. Contrasted with substandard group, standard group performed younger age, lower proportion of the married, decreased proportion of microvascular and macrovascular complications, longer course of disease, more frequent glucose monitoring, declined time of hyperglycemia and time of alarms, elevated time of euglycemia, increased proportion of diet control, more amount of exercise and higher compliance, as the number of patients choosing oral medicine in standard group was more than substandard group. The course of disease and time of hyperglycemia were risk factors of HbA1c standard reaching whereas frequency of glucose monitoring (≥1 time/week) and time of euglycemia were protective factors. CONCLUSION: eKTANG effectively improved diabetes management.

Rab35 regulates insulin secretion via phogrin in pancreatic ß cells.

Dysfunction of pancreatic ß cell insulin secretion is related to the pathogenesis of type 2 diabetes (T2D). Rab proteins have been shown to be key players in insulin secretion by pancreatic ß cells, and phogrin is a marker for the processes of exocytosis and insulin secretion. The purposes of this study were to clarify the regulatory role of Rab35 in insulin secretion and analyse the Rab35/phogrin interaction mechanism in ß-TC-6 cells. We studied the effects of Rab35 gene overexpression and interference on insulin secretion and phogrin expression and levels in ß-TC-6 cells. The Rab35/phogrin interaction was verified by GST pulldown, co-IP and co-localisation experiments. Here, we report that Rab35 is mainly distributed in the ß-TC-6-cell plasma membrane and cytoplasm. Rab35 overexpression promotes insulin secretion and decreases phogrin expression in ß-TC-6 cells, whereas its silencing significantly inhibits insulin secretion, promotes phogrin expression (p < 0.05) and causes phogrin redistribution. Furthermore, Rab35 silencing suppresses exocytosis of insulin. Rab35 interacts with phogrin, and both proteins co-localise in the plasma membranes and cytoplasm of ß-TC-6 cells. Our study presents novel evidence that Rab35 regulates insulin secretion by inhibiting phogrin expression and causing intracellular phogrin redistribution in pancreatic ß cells.

Effect of Huangqisan Pellets on PI3K/Akt/mTOR Signaling Pathway and Autophagy in Kidney of Diabetic Nephropathy Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Huangqisan pellets （HQS） on the phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway and autophagy in the kidney of diabetic nephropathy （DN） rats. MethodDN rat model was established through high-fat diet combined with intraperitoneal injection of streptozotocin （35 mg·kg-1）. DN rats were randomly assigned into model group， irbesartan （0.027 g·kg-1） group， low-dose HQS （0.54 g·kg-1） group and high-dose HQS （1.08 g·kg-1） group. The levels of 24 h urinary total protein （UTP）， serum albumin （Alb）， serum creatinine （SCr）， urea nitrogen （BUN）， triglyceride （TG） and total cholesterol （TC） were measured after 12 weeks of continuous administration. The pathological changes of renal tissue were observed via hematoxylin-eosin （HE） staining. The expression of podocyte split diaphragm proteins nephrin and podocin in the renal tissue were detected by immunohistochemistry. The protein levels and phosphorylation of key proteins in PI3K/Akt/mTOR signaling pathway， as well as the expression of yeast Atg6 homolog （Beclin1） and microtubule-associated protein 1 light chain 3 （LC3） in the renal tissue were analyzed by Western blot. ResultCompared with the control group， the model group showcased increased 24 h UTP， SCr， BUN， TG， and TC levels and decreased Alb level （P<0.01）. After modeling， the rats showed granulosity of epithelial cells of renal tubules， thickening of capillary basement membrane， proliferation of mesangial cells， and sclerosis of glomerulus. Furthermore， modeling down-regulated the expression of nephrin and podocin in the podocyte hiatus of glomerulus （P<0.01） as well as the protein levels of p-PI3K， p-Akt， and p-mTOR and the autophagy markers LC3 and Beclin1 in renal tissue （P<0.01）. Compared with model group， irbesartan and HQS decreased the 24 h UTP， Cr， BUN， TG， and TC levels， increased the Alb level， and alleviated the pathological damage of kidney. Moreover， they up-regulated the expression of Nephrin and Podocin in the podocyte hiatus of glomerulus， as well as the protein levels of p-PI3K， p-Akt， p-mTOR， LC3， and Beclin1 in renal tissue （P<0.05， P<0.01）. ConclusionHQS may inhibit the PI3K/Akt/mTOR signaling pathway to enhance podocyte autophagy and protect the glomerulus， thus slowing down the development of DN.

miR-720 Regulates Insulin Secretion by Targeting Rab35.

miRNAs pose a good prospect in the diagnosis and treatment of type 2 diabetes (T2D). This study is aimed at investigating whether miR-720 targets Rab35 to regulate insulin secretion in MIN6 cells and its molecular mechanism and the clinical value of miR-720 as a specific biomarker of T2D. Fifty-five samples of new diagnosis T2D patients and normal control were collected. Levels of miR-720, fasting blood glucose, insulin, and other indicators of glucose and lipid metabolism were determined. We increased and decreased the miR-720 expression using miR-720 mimic and inhibitor to identify the effect of miR-720 on insulin secretion in MIN6 cells, respectively. Then, we used miR-720 mimic, miR-720 inhibitor, and dual luciferase reporter gene assays to prove miR-720 which regulates insulin secretion by targeting Rab35 in MIN6 cells. In addition, we overexpressed and silenced the Rab35 gene to detect the expression of PI3K, Akt, and mTOR in MIN6 cells by RT-PCR and western blot. In this study, circulating miR-720 was significantly higher in the T2D group than the control group, and miR-270 was positive correlated with FBG, while negatively correlated with FINS. The overexpression of miR-720 inhibited insulin secretion, and miR-720 downregulation promoted insulin secretion. miR-720 regulated insulin secretion by targeting Rab35 in MIN6 cells. Compared with the control group, the expression of PI3K, Akt, and mTOR was significantly decreased by the overexpression of the Rab35 gene, while the silencing Rab35 gene could induce the expression of PI3K, Akt, and mTOR. Furthermore, miR-720 mimic could activate the PI3K pathway. We conclude that miR-720 may be a potential biomarker for the diagnosis of T2D. Increase of miR-720 reduced the Rab35 expression then activate the PI3K/Akt/mTOR signal pathway, thus inhibiting insulin secretion.

Self-Amplification of Coherent Energy Modulation in Seeded Free-Electron Lasers.

The spectroscopic techniques for time-resolved fine analysis of matter require coherent x-ray radiation with femtosecond duration and high average brightness. Seeded free-electron lasers (FELs), which use the frequency up-conversion of an external seed laser to improve temporal coherence, are ideal for providing fully coherent soft x-ray pulses. However, it is difficult to operate seeded FELs at a high repetition rate due to the limitations of present state-of-the-art laser systems. Here, we report a novel self-modulation method for enhancing laser-induced energy modulation, thereby significantly reducing the requirement of an external laser system. Driven by this scheme, we experimentally realize high harmonic generation in a seeded FEL using an unprecedentedly small external laser-induced energy modulation. An electron beam with a laser-induced energy modulation as small as 1.8 times the slice energy spread is used for lasing at the seventh harmonic of a 266-nm seed laser in a single-stage high-gain harmonic generation (HGHG) setup and the 30th harmonic of the seed laser in a two-stage HGHG setup. The results mark a major step toward a high-repetition-rate, fully coherent x-ray FEL.

Variations in Irisin, Bone Mineral Density, Bone Mineral Content, and Body Composition After Laparoscopic Bariatric Procedures in Obese Adults.

INTRODUCTION: This study was aimed to assess irisin levels in obesity (OB) and T2DM individuals and investigate the dynamic changes of irisin, bone mineral density (BMD), bone mineral content, and body composition in 19 OB patients after laparoscopic bariatric procedures, and also to evaluate the correlation of irisin, with BMD and body composition. METHODS: Forty-five OB, 20 T2DM, and 20 healthy adults had been recruited. Levels of irisin were measured in all subjects. Metabolic characteristics were obtained from OB and T2DM patients. Nineteen patients were randomly assigned to be received Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) procedure and to be completed 6-month follow-up. Irisin, BMD, bone mineral content, and body composition were measured at each visit. RESULTS: Significantly higher circulating irisin levels were measured in the OB group compared with T2DM and control groups. FINS, C-P, HOMA-IR, FBCI, HBCI, ALT, AST, and UA levels of OB were significantly higher than those of T2DM patients. While FBG and HbA1c of the OB were significantly lower than T2DM group. There were significant differences among circulating irisin, BMD, and body composition after laparoscopic bariatric surgery. Levels of irisin were decreased after operations including both LRYGB and LSG surgery compared with preoperation. At each time point (1, 3, and 6 months) of postoperation, there was no significant difference in percentage of total weight loss between LSG and LRYGB group. The positive correlation of irisin levels with total BMD, muscle, and fat masses were found during 6-month follow-up after surgery. CONCLUSIONS: The levels of irisin were higher in OB patients. There were positive correlations of irisin levels with total BMD, muscle, and fat masses during 6-month follow-up after surgery. Irisin may be involved in the occurrence and development of obese and it is related to BMD and body composition. Both LRYGB and LSG operations could decrease the circulating levels of irisin.

Slippage boosted spectral cleaning in a seeded free-electron laser.

The realization of fully coherent light sources at extreme ultraviolet to x-ray region has been a long-standing challenge for laser technologies. While modern single pass free-electron lasers (FELs) hold the ability to produce very intense x-ray radiation on few-femtosecond timescale, the output radiation pulses usually have noisy spectra and limited temporal coherence since the amplification starts from electron noise. A promising way for producing stable transform-limited pulses is based on the harmonic up-conversion techniques with a conventional laser as the seed. However, it is found that the insignificant phase error in the seed laser may be eventually multiplied by the harmonic number, leading to a degradation of the output temporal coherence at x-ray wavelength. Here, we report for the first time on the demonstration of a slippage boosted spectral cleaning technique to mitigate the impact of seed laser induced phase errors and to significantly improve the temporal coherence of a seeded FEL with large phase errors in the seed laser. Experimental results indicate the possibility of generating fully coherent x-ray radiation pulses with this technique.

Atom-economic synthesis of cyclobuta[a]naphthalen-4-ols via a base-promoted [2 + 2] cycloaddition/1,6-nucleophilic addition cascade.

A first atom-economic [2 + 2] cycloaddition/1,6-conjugate addition cascade of yne-allenones with C-nucleophiles including 1,3-dicarbonyls and α,α-dicyanoolefins under base-promoted conditions has been established, enabling the direct construction of C(sp3)-C(sp3) bonds to generate cyclobuta[a]naphthalen-1-ols with generally good yields. These resulting products have a cyclobutene unit that contains both an aryl and alkyl group.

Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes.

The retinol-binding protein 4 (RBP4) has been postulated to play a role in glucose homeostasis, insulin resistance, and diabetes mellitus in human and animal studies. The aim of the present study was to evaluate the role of RBP4 in Chinese patients with type 2 diabetes mellitus with and without diabetic retinopathy (DR). Plasma RBP4 concentrations were tested in 287 patients with type 2 diabetes. At baseline, demographic and clinical information including presence of DR and vision-threatening DR (VTDR) was collected. The relationship between RBP4 and DR (VTDR) was investigated using logistic regression. Patients with DR or VTDR had significantly higher plasma levels of RBP4 on admission (P<0.0001). Receiver operating characteristics (ROCs) to predict DR and VDTR demonstrated areas under the curve for RBP4 of 0.79 (95% confidence interval (CI): 0.73-0.85) and 0.90 (95% CI: 0.85-0.94), respectively, which were superior to other factors. For each 1 µg/ml increase in plasma level of RBP4, the unadjusted and adjusted risk of DR would be increased by 8% (with the odds ratio (OR) of 1.08 (95% CI: 1.05-1.13), P<0.001) and 5% (1.05 (1.02-1.11), P=0.001), respectively. It was 12% (with the OR of 1.12 (95% CI: 1.07-1.18), P<0.001) and 9% (1.09 (1.05-1.15), P<0.001) for VTDR. The present study shows that elevated plasma levels of RBP4 were associated with DR and VDTR in Chinese patients with type 2 diabetes, suggesting a possible role of RBP4 in the pathogenesis of DR complications. Lowering RBP4 could be a new strategy for treating type 2 diabetes with DR.

Intravoxel incoherent motion (IVIM) at 3.0 T: evaluation of early renal function changes in type 2 diabetic patients.

PURPOSE: The purpose of this study was to evaluate the utility of intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) parameters in identifying early renal function changes in diabetics. METHODS: A total of 40 patients with type 2 diabetes mellitus and 20 healthy control subjects underwent multiple b value DWI. The diabetic patients were stratified into two groups based on albuminuria category: NAU (normal to mildly increased albuminuria; ACR < 30 mg/g) and MAU (moderately increased albuminuria; 30 ≤ ACR < 300 mg/g). The mean cortical and medullary IVIM parameters (D, D*, f, and ADC) were calculated and compared among the different groups, and the correlation of ACR and eGFR was also calculated. RESULTS: The present study revealed the limited water molecule diffusion and hyperperfusion of renal cortex and medulla in diabetic patients before proteinuria detection. Mean cortical and medullary D values negatively correlated with the ACR values in diabetics with 30 ≤ ACR < 300 mg/g, whereas no correlation was found between ACR values and other IVIM parameters. CONCLUSION: IVIM DWI might be helpful in noninvasively identifying early-stage DN. The IVIM parametric values are more sensitive than the ACR in detecting early-stage kidney changes.

Analysis of islet beta cell functions and their correlations with liver dysfunction in patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD).

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) primarily manifests in neonates or infants with hepatomegaly, liver dysfunction, and hypoglycemia. This study investigated the functions of islet beta cells and their correlations with liver dysfunction in NICCD patients.We retrospectively analyzed clinical data on liver function and islet beta cell functions for 36 patients diagnosed with NICCD and 50 subjects as the control group. The NICCD group had significantly higher total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate amino transferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) and alpha-fetoprotein (AFP) levels and albumin/globulin ratio (A/G) (P < .05), and lower ALB and GLB levels than the control group (P < .05). The differences in fasting blood glucose (FBG), fasting insulin, C-peptide (C-P), the homeostasis model of assessment for the insulin resistance index (HOMA-IR), fasting beta cell function (FBCI), and the HOMA beta cell function index (HBCI) between the NICCD and control groups were not significant (P > .05). A linear correlation was found between FBG and fasting insulin (P < .001) and between FBG and C-P in the NICCD patients (P = .001). Fasting insulin (P = .023), HOMA-IR (P = .023), FBCI (P = .049), and HBCI (P = .048) were positively correlated with increases in the ALT level. There was no difference in islet beta cell functions between the NICCD and control groups. The liver dysfunction may be correlated with islet beta cell functions in NICCD patients.

Blood glucose and insulin and correlation of SLC25A13 mutations with biochemical changes in NICCD patients.

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a hereditary metabolic disease arising from biallelic mutations of SLC25A13. This study aimed to explore the characteristics of fasting blood glucose (FBG), fasting insulin (FINS) and C-peptide (C-P) levels in NICCD infants, analyze their SLC25A13 genetic mutations and further discuss the correlation between SLC25A13 genetic mutations and biochemical changes. Seventy-two cases of infants with cholestasis disease were gathered. Among them, 36 cases with NICCD diagnosis were case group. Meanwhile, 36 cases with unknown etiology but excluded NICCD were control group. FBG, FINS, C-P, ALT, AST, GGT, ALP, TG, HDL-C, LDL-C and Non-HDL-C were collected from all subjects, and DNA was extracted from venous blood for SLC25A13 mutations detection. The incidence of hypoglycemia was 3% in NICCD group. There were no significant statistical difference of FBG, FINS and C-P between NICCD and INC groups ( P > 0.05). ALT, LDL-C and Non-HDL-C levels in NICCD group were lower than the INC group, while SLC25A13 mutations were associated with the level of GGT ( P < 0.05). Ten different SLC25A13 genetic mutations were detected, among which, 851del4, IVS16ins3kb, IVS6+5 G > A and 1638ins23 mutations made up 82% of all mutations. The incidence of hypoglycemia may be higher in small gestational age infants with NICCD. Low LDL-C may be one of the characteristics of dyslipidemia in NICCD infants. There was a correlation between SLC25A13 gene mutations distribution and the GGT level, but the meaning of this finding remains to be further in-depth study. Impact statement This study aims to compare FBG, FINS, C-P, other biochemical and clinical manifestations between NICCD and non-NICCD infants, and discuss differential diagnosis of NICCD and INC beyond the genetic analysis. And investigate the correlation between SLC25A13 genetic mutations and biochemical changes. This work presented that incidence of hypoglycemia may be higher in small gestational age infants with NICCD. Low LDL-C may be one of the characteristics of dyslipidemia in NICCD infants. There was a correlation between SLC25A13 gene mutations distribution and the GGT level.

Urinary Smad1 is a new biomarker for diagnosis and evaluating the severity of diabetic nephropathy.

The aim of this study was to analyze urinary Smad1 level in patients with type 2 diabetes, explore the possibility of Smad1 being a biomarker for early diagnosis and evaluation of severity of diabetic nephropathy, and explore the impact factors affecting urinary Smad1 concentration. In this study, 132 subjects with type 2 diabetes and 50 healthy volunteers were enrolled. Subjects were grouped according to urine albumin to creatinine ratio (ACR) into: normal albumin in urine (NAU), low albumin in urine (LAU), high albumin in urine (HAU), and very high albumin in urine (VHAU). Among those, LAU, HAU, and VHAU were regarded as the diabetic nephropathy group (DN group), NAU was regarded as nondiabetic nephropathy (non-DN group), and the healthy volunteers were the controls. Enzyme-linked immunosorbent assay was used to detect the urinary Smad1 concentration, urinary Smad1 to creatinine ratio (SCR) was used as the standard reference. Compared with non-DN group, SCR of DN group was higher (P < 0.05), while there was no difference between the non-DN group and controls (P > 0.05). There was no significant difference for SCR between LAU and NAU groups (P > 0.05). The SCR was higher in VHAU group than those in HAU and LAU groups, and higher in HAU than that in LAU group (P < 0.05). Pearson correlation analysis showed that SCR measures were positively correlated to ACR, duration and diabetic retinopathy of the disease (r = 0.285, 0.230, 0.202; P = 0.001, 0.008, 0.019, respectively). Multiple linear regression analysis showed that ACR and duration were independent impact factors for SCR (P < 0.05). This is the first known study examining the correlation of Smad1 and DN in clinical practice. It suggested that the urinary Smad1 may be a potential diagnostic parameter for DN and may be used to evaluate the severity of DN. However, it cannot predict those in patients with the earliest DN and low urine albumin concentration. Furthermore, ACR and duration may be independent impact factors for urinary Smad1.

Experimental demonstration of longitudinal beam phase-space linearizer in a free-electron laser facility by corrugated structures.

Removal of the undesired time-energy correlations in the electron beam is of paramount importance for efficient lasing of a high-gain free-electron laser. Recently, it has been theoretically and experimentally demonstrated that the longitudinal wakefield excited by the electrons themselves in a corrugated structure allows for precise control of the electron beam phase space. In this Letter, we report the first utilization of a corrugated structure as a beam linearizer in the operation of a seeded free-electron laser driven by a 140 MeV linear accelerator, where a gain of ∼10 000 over spontaneous emission was achieved at the second harmonic of the 1047 nm seed laser, and a free-electron laser bandwidth narrowing by 50% was observed, in good agreement with the theoretical expectations.

[Clinical features and COMP gene mutation in a family with a pseudoachondroplasia child].

This study aimed to report the clinical characteristics and COMP gene mutation of a family with pseudoachondroplasia (PSACH), a relatively rare spinal and epiphyseal dysplasia that is inherited as an autosomal dominant trait. Clinical information on a 5-year-2-month-old PSACH child and his parents was collected and analyzed. Diagnosis was confirmed by PCR amplification and direct sequencing of all the 19 exons and their flanking sequences of COMP gene, and the mutation was further ascertained by cloning analysis of exon 10. The child presented with short and stubby fingers, bow leg, short limb dwarfism and metaphysic broadening in long bone as well as lumbar lordosis. A mutation c.1048_1116del (p.Asn350_Asp372del) in exon 10, inherited from his father who did not demonstrate any phenotypic feature of PSACH, was detected in the child. PSACH was diagnosed definitively by means of COMP mutation analysis, on the basis of the child's clinical and imaging features. The non-penetrance phenomenon of COMP mutation was described for the first time in PSACH.

Wnt/ß-catenin signaling may be involved with the maturation, but not the differentiation, of insulin-producing cells.

Wnt/ß-catenin signaling (WNT) has widespread roles during stem cell differentiation. Whether WNT suppresses or promotes insulin-producing cell (IPC) differentiation and function is still not known. In this study, we investigated the role of WNT signaling during human adipose-derived stem cell (hADSC) differentiation into IPCs. Western blot analysis revealed that several key components of WNT were dynamically regulated in a 12-day IPC differentiation assay. Specifically, protein levels of Wnt1, ß-catenin, and GSK3ß steadily increased from day 0 to day 9 and rapidly decreased by day 12 of differentiation. Similarly, endonuclear ß-catenin levels peaked at day 9 and then, fell to pre-differentiation levels. The expression of two WNT pathway targets, TCF-1 and cyclin D1, closely followed the same pattern of regulation, confirming that WNT signaling was transiently activated during IPC differentiation. Interestingly, the inhibition of WNT signaling did not block IPC differentiation; instead, it resulted in the upregulation of IPC-specific markers, including PDX-1, insulin, IRS-1, and IRS-2. Notably, another IPC marker, glucokinase, remained downregulated since it is a direct target of WNT signaling. Next, we examined the effect of maintaining active WNT signaling from day 9 to day 12 of IPC differentiation. Differentiating cells were treated with Wnt1 on day 9, when WNT signaling is typically turned off, and subjected to gene expression analysis on day 12. Remarkably, Wnt1 treatment resulted in reduced expression of IPC-specific markers. Taken together, these data indicate that WNT may not be necessary for IPC differentiation but may be involved in IPC maturation.