Effect of weight loss on proteinuria in adults with type 2 diabetes: A real-world study.

AIMS: To assess the impact of weight loss on proteinuria in patients with type 2 diabetes (T2DM) in real-world settings. METHODS: A total of 1054 participants were categorized based on weight change from baseline to one-year follow-up: weight gain (≥3%), stable weight, or weight loss (≥3%). Proteinuria outcomes were defined as urinary albumin/creatinine ratio (UACR) progression (≥30 % increase), UACR regression (≥30 % reduction), or UACR stable. Ordered logistic regression analysis evaluated the relationship between weight loss and UACR regression. RESULTS: Of the 1054 participants, 44.5 % were overweight, and 24.1 % were obese. Patients with obesity were at higher risk of developing proteinuria (OR, 1.783; 95 %CI, 1.195 to 2.659). Weight loss was associated with an 83.3 % increase in UACR regression compared to weight gain (OR, 1.833; 95 % CI, 1.262 to 2.663; P = 0.001). This association remained consistent across most subgroups and stronger in males (P for interaction = 0.023), with a 6 % UACR regression for every 1 kg weight loss (OR, 1.06; 95 % CI, 1.02 to 1.10; P = 0.003). CONCLUSIONS: Our real-world study reveals that weight reduction is associated with UACR regression in patients with T2DM, regardless of the approach used for weight management, and the association was much stronger in males.

Relationship between the expression level of miRNA-4485 and the severity of depressive symptoms in major depressive disorder patients

Background and objectives: Despite the growing pieces of evidence on the relationship between the altered expression level of miRNAs and major depressive disorder (MDD), few studies have focused on the relationship between the altered expression of miRNAs and the severity of depressive symptoms. This study aimed to investigate the relationship between the expression level of miRNA-4485 and the severity of depressive symptoms in major depressive disorder (MDD) patients.MethodsEighty MDD patients without antidepressants and 45 healthy controls were placed and tested for the expression level of miRNA-4485 using quantitative RT‒PCR. At the same time, the Hamilton Depression Scale (HAMD) was used to assess depression symptoms for MDD patients. Twenty-nine out of 80 MDD patients were selected for miRNA expression level testing and symptomatology assessments before and after three weeks of treatment.ResultsThe expression level of miRNA-4485 in the MDD group was significantly overexpressed compared to that in healthy controls (P < 0.05), and the expression level of miRNA-4485 in the higher HAMD group was also much higher than that in the lower HAMD group and healthy controls (P < 0.05). The expression level of miRNA-4485 in MDD patients was negatively correlated with HAMD total score, anxiety/somatization, and bodyweight factor score (P < 0.05), accounting for 9.4%, 12.4% and 5.7%, respectively. MiRNA-4485 significantly predicted MDD and the severity of depressive symptoms (P < 0.05). Compared with that before treatment, the expression level of miRNA-4485 was significantly downregulated after treatment, while the patient's depressive symptoms were improved (p < 0.05). The improvement in depressive symptoms was positively correlated with the downregulation of miRNA-4485, which could significantly predict the effects of antidepressant treatment on MDD (P < 0.05). (AU)

A stratified analysis of a deep learning algorithm in the diagnosis of diabetic retinopathy in a real-world study.

BACKGROUND: The aim of our research was to prospectively explore the clinical value of a deep learning algorithm (DLA) to detect referable diabetic retinopathy (DR) in different subgroups stratified by types of diabetes, blood pressure, sex, BMI, age, glycosylated hemoglobin (HbA1c), diabetes duration, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR) at a real-world diabetes center in China. METHODS: A total of 1147 diabetic patients from Shanghai General Hospital were recruited from October 2018 to August 2019. Retinal fundus images were graded by the DLA, and the detection of referable DR (moderate nonproliferative DR or worse) was compared with a reference standard generated by one certified retinal specialist with more than 12 years of experience. The performance of DLA across different subgroups stratified by types of diabetes, blood pressure, sex, BMI, age, HbA1c, diabetes duration, UACR, and eGFR was evaluated. RESULTS: For all 1674 gradable images, the area under the receiver operating curve, sensitivity, and specificity of the DLA for referable DR were 0.942 (95% CI, 0.920-0.964), 85.1% (95% CI, 83.4%-86.8%), and 95.6% (95% CI, 94.6%-96.6%), respectively. The DLA showed consistent performance across most subgroups, while it showed superior performance in the subgroups of patients with type 1 diabetes, UACR ≥ 30 mg/g, and eGFR < 90 mL/min/1.73m2 . CONCLUSIONS: This study showed that the DLA was a reliable alternative method for the detection of referable DR and performed superior in patients with type 1 diabetes and diabetic nephropathy who were prone to DR.

Association of the Non-Alcoholic Fatty Liver Disease Fibrosis Score with subclinical myocardial remodeling in patients with type 2 diabetes: A cross-sectional study in China.

AIMS/INTRODUCTION: Non-alcoholic fatty liver disease, especially with liver fibrosis, is associated with cardiovascular diseases. The Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS), a non-invasive marker of advanced fibrosis, was found to be associated with cardiovascular diseases in different populations. The aim of the present study was to determine whether the NFS is associated with subclinical myocardial remodeling in type 2 diabetes patients. MATERIALS AND METHODS: A cross-sectional study was carried out in type 2 diabetes patients. The NFS derived from available parameters was calculated, and the participants were divided according to the quartiles of the NFS and grades of the NFS (low, intermediate and high). Fibrosis-4 and Aspartate Aminotransferase to Platelet Ratio Index, another two liver fibrosis scores, were also calculated. Subclinical myocardial remodeling was examined by echocardiography, and its associations with NFS, Fibrosis-4 and Aspartate Aminotransferase to Platelet Ratio Index were analyzed. RESULTS: A total of 1,878 type 2 diabetes patients were enrolled in the present study. The NFS was independently associated with sex, age, body mass index, low-density lipoprotein cholesterol and glycated hemoglobin in type 2 diabetes patients. Parameters of subclinical myocardial remodeling including left atrial dimension, interventricular septum thickness, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular posterior wall thickness (LVPWT) and left ventricular mass index were all gradually increased with the increment of the NFS. Linear regression analysis further showed that the NFS was positively associated with left atrial dimension, interventricular septum thickness, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, LVPWT and left ventricular mass index after adjustment for the confounding factors. Similarly, Fibrosis-4 was associated with left atrial dimension, interventricular septum thickness, LVPWT and left ventricular mass index. In contrast, the Aspartate Aminotransferase to Platelet Ratio Index was only associated with LVPWT. CONCLUSIONS: Non-invasive liver fibrosis scores, especially the NFS, are independently associated with subclinical myocardial remodeling in type 2 diabetes patients.

Rapid Detection of Alternaria Species Involved in Pear Black Spot Using Loop-Mediated Isothermal Amplification.

Alternaria species are the most important fungal pathogens that attack various crops as well as fruit trees such as pear and cause black spot disease. Here, a loop-mediated isothermal amplification (LAMP) assay is developed for the detection of Alternaria species. A. alternata cytochrome b (cyt-b) gene was used to design two pairs of primers and amplified a 229-bp segment of Aacyt-b gene. The results showed that LAMP assay is faster and simpler than polymerase chain reaction (PCR). LAMP assay is highly sensitive method for the detection of about 1 pg of genomic DNA of A. alternata by using optimized concentration of MgCl2 (4 mM) in final LAMP reaction. In contrast, the limit of detection was 1 ng of target DNA via conventional PCR. Among the genomic DNA of 46 fungal species, only the tubes containing DNA of Alternaria spp. except A. porri, A. solani, and A. infectoria changed color from orange to yellowish green with SYBR Green I including the main pathogens of pear black spot. The yellowish green color was indicative of DNA amplification. Moreover, LAMP assay was used for testing infected tissues among 22 healthy and diseased pear tissues; the orange color changed to yellowish green for infected tissues only. Altogether, we conclude that cyt-b gene can be used for the detection of Alternaria spp. via LAMP assay, which is involved in pear black spot disease.

Postpartum assessment of the beta cell function and insulin resistance for Chinese women with previous gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) imparts a high risk of developing postpartum diabetes and is considered to be an early stage of type 2 diabetes mellitus (T2DM). In this study, a 75-g oral glucose tolerance test was performed on 472 women with GDM at 6-8 weeks after delivery. The clinical and metabolic characteristics were compared between the patients with normal glucose tolerance (NGT) and abnormal glucose metabolism (AGM). These data were then compared between pre-diabetic and diabetic patients. A total of 37.7% of the women with GDM continued to have abnormal glucose levels after delivery. Compared with the women who reverted to normal, HOMA-IR was significantly higher in AGM. A multiple stepwise regression analysis revealed that age, the postpartum body mass index (BMI), low density lipoprotein-cholesterol (LDL-C), 2 h glucose load plasma glucose (2 h PG), triglycerides (TG), hemoglobin A1c (HbA1c), 1 h glucose load plasma insulin (INS) level, and 2 h INS level were independent risk factors for the development of insulin resistance after delivery. This study has identified a high prevalence of AGM after GDM. Insulin resistance appears to be the major contributor. Any treatment to reduce the postpartum BMI and lipids level may be beneficial to decrease insulin resistance.

Rapid Detection of Ustilaginoidea virens from Rice using Loop-Mediated Isothermal Amplification Assay.

Ustilaginoidea virens is an important fungus that causes rice false smut disease. This disease significantly reduces both grain yield and quality. Various methods have been developed for the detection of U. virens but most of these methods need sophisticated equipment such as a thermal cycler. Here, we present a loop-mediated isothermal amplification (LAMP) assay for the specific detection of U. virens. This assay used a specific region of the UvG-ß1 gene (212-bp region) to design six LAMP primers. The LAMP assay was optimized by the combination of rapidity, simplicity, and high sensitivity for the detection of about 1 pg of target genomic DNA in the reaction whereas, with polymerase chain reaction (PCR), there was no amplification of DNA with concentrations less than 1 ng. Among the genomic DNA of 22 fungus species and two strains of U. virens, only the tube containing the DNA of U. virens changed to yellowish green with SYBR Green I. The color change was indicative of DNA amplification. No DNA was amplified from either the other 22 fungus species or the negative control. Moreover, 20 spikelets and 22 rice seed samples were used for the detection of rice false smut via LAMP. The results were comparable with conventional PCR. We conclude that gene UvG-ß1 coupled with LAMP assay, can be used for the detection and identification of U. virens gene via LAMP.

Development of a nested-PCR assay for the rapid detection of Pilidiella granati in pomegranate fruit.

Pilidiella granati, a causal agent of twig blight and crown rot of pomegranate, is an emerging threat that may cause severe risk to the pomegranate industry in the future. Development of a rapid assay for the timely and accurate detection of P. granati will be helpful in the active surveillance and management of the disease caused by this pathogen. In this study, a nested PCR method was established for the detection of P. granati. Comparative analysis of genetic diversity within 5.8S rDNA internal transcribed spacer (ITS) sequences of P. granati and 21 other selected fungal species was performed to design species-specific primers (S1 and S2). This primer pair successfully amplified a 450 bp product exclusively from the genomic DNA of P. granati. The developed method can detect 10 pg genomic DNA of the pathogen in about 6 h. This technique was successfully applied to detect the natural infection of P. granati in the pomegranate fruit. The designed protocol is rapid and precise with a high degree of sensitivity.

Marker-assisted breeding of the rice restorer line Wanhui 6725 for disease resistance, submergence tolerance and aromatic fragrance.

BACKGROUND: Rice is a staple food crop in the world. With the increase in world population and economic development, farmers need to produce more rice in limited field. However, the rice production is frequently affected by biotic and abiotic stresses. The use of natural disease resistance and stress tolerance through genetic breeding is the most efficient and economical way to combat or acclimate to these stresses. In addition, rice with aromatic fragrance can significantly increase market value for its good grain quality. Mianhui 725 (MH725) is an elite restorer line that has been widely used to produce three-line hybrid rice in China. We previously introduced rice bacterial blight resistance genes Xa4 and Xa21 into MH725 and obtained an introgression rice line Wanhui 421 (WH421), which theoretically possesses 96.9% genetic background of MH725. RESULTS: Here we report the introduction and pyramiding of disease resistance genes Xa27 and Pi9, submergence tolerance gene Sub1A and aromatic fragrance gene badh2.1 in WH421 through backcrossing and marker-assisted selection. The newly developed introgression rice line was designated as Wanhui 6725 (WH6725), which theoretically possesses 95.0% genetic background of MH725. WH6725 and its hybrid rice conferred disease resistance to both blast and bacterial blight diseases and showed tolerance to submergence for over 14 days without significant loss of viability. Compared with non-aromatic rice MH725, WH6725 has strong aromatic fragrance. The major important agronomic traits and grain quality of WH6725 and its hybrid rice obtained in field trials were similar to those of MH725 and the control hybrid rice, indicating that WH6725 is as good as MH725 when it is used as a restorer line for three-line hybrid rice production. CONCLUSION: We have successfully developed a new restorer line WH6725 with disease resistance to rice blast and bacterial blight, tolerance to submergence and aromatic fragrance, which can be used to replace MH725 for hybrid rice production.

Simple and rapid detection of Tilletia horrida causing rice kernel smut in rice seeds.

A simple and rapid method for the detection of Tilletia horrida, the causal agent of rice kernel smut, in rice seeds is developed based on specific polymerase chain reaction (PCR). To design the specific primers for the detection of T. horrida, partial sequences of internal transcribed spacer (ITS) DNA region of T. horrida, T. controversa, T. walkeri, T. ehrhartae, T. indica and T. caries were analyzed and compared. A 503-bp fragment was amplified with the designed primers from the T. horrida genomic DNA. However, no PCR product was obtained from the DNA of other five Tilletia species and 22 fungal plant pathogens tested in the present work indicating the specificity of the primers for the detection of T. horrida. The PCR was performed by directly using the spores, isolated from the 21 different rice seed samples, as template DNA. The T. horrida was detected in 6 of the samples, indicating that 28.6% of the rice samples were contaminated with the kernel smut pathogen. This simple PCR based diagnostic assay can be applied for the direct and rapid detection and identification of T. horrida to screen large numbers of rice seed samples.

Genotypes and Phenotypic Characterization of Field Fusarium asiaticum Isolates Resistant to Carbendazim in Anhui Province of China.

Fusarium asiaticum is a causal agent of Fusarium head blight (FHB) of wheat in the southern part of China. Carbendazim has been extensively used for controlling FHB for more than 30 years, leading to the widespread carbendazim-resistant isolates in all major wheat-producing provinces in China, especially in Anhui Province. F. asiaticum isolates were collected throughout Anhui Province between 2010 and 2012 to monitor their sensitivity to carbendazim. In total, 74 of 899 single-spore isolates F. asiaticum were found to be resistant to carbendazim. Resistant isolates were collected from all of the sampled sites except Hefei of Anhui Province. The overall frequency of carbendazim resistance was shown to be 8.2%. Of the 74 isolates, 1, 68, and 5 had low resistance (LR), moderate resistance (MR) ,and high resistance (HR), respectively, to carbendazim. Five types of point mutations (F167Y, E198L, E198K, F200Y, and E198Q) in the ß2-tubulin gene conferring resistance to carbendazim were detected in the field-resistant isolates with frequencies of 89.2, 2.7, 4.1, 2.7, and 1.4%, respectively. The point mutations at codon 167, 198, or 200 of the ß2-tubulin gene were correlated with different levels of carbendazim resistance. Some of the sensitive and resistant isolates appeared to possess different biological characteristics; however, these might not be due to resistance. Because carbendazim resistance was generally widespread throughout Anhui Province, the sensitivity of F. asiaticum populations to carbendazim should be constantly monitored for the development of carbendazim resistance in natural populations.

Impaired ß cell function in Chinese newly diagnosed type 2 diabetes mellitus with hyperlipidemia.

The objective is to explore the effects of hyperlipidemia on ß cell function in newly diagnosed type 2 diabetes mellitus (T2DM). 208 patients were enrolled in the study and were divided into newly diagnosed T2DM with hyperlipidemia (132 patients) and without hyperlipidemia (76 patients). Demographic data, glucose levels, insulin levels, lipid profiles, homeostasis model assessment for ß cell function index (HOMA-ß ), homeostasis model assessment for insulin resistance index (HOMA-IR), and quantitative insulin-sensitivity check index (QUICKI) were compared between the two groups. We found that comparing with those of normal lipid levels, the subjects of newly diagnosed T2DM with hyperlipidemia were younger, and had declined HOMA-ß . However, the levels of HOMA-ß were comparable regardless of different lipid profiles (combined hyperlipidemia, hypertriglyceridemia, and hypercholesterolemia). Multiple stepwise linear regression analysis showed that high fasting plasma glucose (FPG), decreased fasting insulin level (FINS), and high triglyceride (TG) were independent risk factors of ß cell dysfunction in newly diagnosed T2DM. Therefore, the management of dyslipidemia, together with glucose control, may be beneficial for T2DM with hyperlipidemia.

Protective effect of α-lipoic acid on islet cells co-cultured with 3T3L1 adipocytes.

Obesity and ß-cell dysfunction due to oxidative stress impact the pathogenesis of type 2 diabetes mellitus. We co-cultured 3T3L1 adipocytes and islet cells in the presence or absence of the antioxidant α-lipoic acid (LA) and assayed the effects of the adipocytes and LA on the secretion of insulin by the islet cells and on the activities of factors involved in secretion and oxidative stress. At low glucose concentrations (2.8 mmol/l), the presence of adipocytes (co-culture) increased insulin secretion compared with islet cells cultured alone (control) and this increase was diminished by LA (co-culture plus LA). At high glucose concentrations (22 mmol/l), insulin secretion levels were similar for all islet groups, resulting in a restoration of the stimulation index in the presence of LA. The mRNA levels of the glucose-stimulated insulin secretion (GSIS) genes glucokinase, glucose transporter 2 and Kir6.2 were downregulated under co-culture and co-culture plus LA conditions. Protein and tyrosine phosphorylation levels of insulin receptor-ß and insulin receptor substrate-1 were decreased under co-culture conditions and were restored by LA treatment. Cellular malondialdehyde levels increased in the co-cultured islets and this increase was blocked by LA. The mRNA levels of superoxide dismutase and catalase were reduced under co-culture conditions and these reductions were eliminated by the addition of LA. In conclusion, 3T3L1 adipocytes disturb insulin secretion and induce islet dysfunction. The effects may be mediated by multiple pathways, which include downregulation of GSIS gene expression, suppression of islet cell insulin signaling and the induction of oxidative stress. LA may protect islet cells via activation of islet cell insulin signaling and the mRNA expression of antioxidant enzymes.

Integrated Use of Pyraclostrobin and Epoxiconazole for the Control of Fusarium Head Blight of Wheat in Anhui Province of China.

Fusarium asiaticum and F. graminearum are the primary causal agents of Fusarium head blight (FHB) of wheat in China. Carbendazim (a benzimadazole fungicide, MBC), has been extensively used for the control of FHB, resulting in severe MBC resistance in China. This article presents the baseline sensitivity of F. asiaticum and F. graminearum isolates from Anhui Province of China to fungicides pyraclostrobin (a quinone outside inhibitor) and epoxiconazole (a sterol demethylation inhibitor). In the presence of salicylhydroxamic acid, the 50% effective concentration (EC50) values for pyraclostrobin in inhibiting mycelial growth of the 126 F. asiaticum isolates and 63 F. graminearum isolates were 0.012 to 0.135 µg/ml and 0.010 to 0.105 µg/ml, and the EC50 values for pyraclostrobin in inhibiting conidium germination of the F. asiaticum and F. graminearum populations were 0.047 to 0.291 and 0.042 to 0.255 µg/ml, respectively. The EC50 values for epoxiconazole in inhibiting mycelial growth of the F. asiaticum and F. graminearum populations were 0.12 to 0.95 and 0.16 to 0.93 µg/ml, respectively. All of the baseline sensitivity curves were unimodal. This study also suggested that there was no cross-resistance between MBC and pyraclostrobin or epoxiconazole. In the protective and curative tests, pyraclostrobin and epoxiconazole applied at 200 and 300 µg/ml exhibited over 75% protective and curative control efficacy in all treatments. In field trials, both pyraclostrobin and epoxiconazole at 225 g a.i./ha provided over 80% efficacy in 2010 and 2011 at both sites where MBC resistance occurred, suggesting excellent activity against FHB. Interestingly, integrated use of pyraclostrobin + epoxiconazole applied at 150 + 150 g a.i./ha provided over 85% efficacy at both sites in 2010 and 2011. Pyraclostrobin and epoxiconazole should be good alternatives to MBC for the control of FHB, and integrated use of these two fungicides might achieve greater efficacy.

[3T3L1 adipocytes induce rat beta-cell dysfunction].

OBJECTIVE: To investigate the integrated effects of adipocytes on rat beta-cells, differentiated 3T3L1 adipocytes and rat islet cells co-culture system was established. METHODS: There were two groups: control group (SD rat islet cells) and co-culture group (islet cells and 3T3L1 adipocytes coculture system). Islet cells were obtained for determination of (1) insulin secretion and insulin content; (2) mRNA expressions of GLUT2, GCK and Kir6.2; (3) protein expressions of IR-beta, IRS-1 and their tyrosine phosphorylation level. RESULTS: (1) At low glucose, insulin secretion of co-culture group increased compared with that of control group (0.79 +/- 0.35) ng x h(-1) x ml(-1) islet vs. (0.38 +/- 0.09) ng x h(-1) x ml(-1) x islet, P = 0.028. At high glucose, insulin secretion of those two groups was almost at the same level (P = 0.760). Compared with control group (2.84 +/- 0.92), stimulation index (SI, insulin release at high glucose/ low glucose) of co-culture system decreased to (1.57 +/- 0.61, P = 0.04). And the insulin content of the both groups was almost at the same level (P = 0.102). (2) The mRNA of GCK, GLUT2 and Kir6.2 in co-culture group downregulated to (0.27 +/- 0.11, P = 0.01), (0.34 +/- 0.24, P = 0.009) and (0.41 +/- 0.09, P = 0.003) compared with control group (mRNA = 1). (3) The protein levels of IR-beta, IRS-1 and their tyrosine phosphorylation decreased in co-culture system. CONCLUSIONS: 3T3L1 adipocytes are involved in beta-cell dysfunction, which may facilitate the development of type 2 diabetes. The effects may be mediated by multiple pathways, which include downregulation of GSIS related gene expressions and suppression of islet cell insulin signaling.