Establishment of Galectin-3 Time-resolved Fluoroimmunoassay and its Application in Idiopathic Membranous Nephropathy.

The aim of this study was to establish a time-resolved fluorescent immunoassay (TRFIA) for the detection of serum Galectin-3 (Gal-3) and apply this method to evaluate the clinical significance of serum Gal-3 in predicting Idiopathic Membranous Nephropathy (IMN) progression. The Gal-3-TRFIA was established using the double antibody sandwich method, with the capture antibodies coated on a 96-well microplate and the detection antibodies chelated with Europium (III) (Eu3+). Serum Gal-3 was detected in 81 patients with IMN and 123 healthy controls to further evaluate the value of the Gal-3 in staging of IMN. The sensitivity of the Gal-3-TRFIA assay was 0.85 ng/mL, and the detection range was 0.85-1000 ng/mL. The Gal-3 intra-batch and inter-batch coefficients of variation were 3.45% and 5.12%, respectively. The correlation coefficient (R) between the Gal-3-TRFIA assay and commercially available enzyme-linked immunosorbent assay kits was 0.83. The serum Gal-3 concentration was higher in patients with IMN (65.57 ± 55.90 ng/mL) compared to healthy controls (16.29 ± 9.91 ng/mL, P < 0.0001). In this study, a wide detection range Gal-3-TRFIA assay was developed using lanthanide (Eu3+) chelates for the detection of Gal-3 concentrations in serum. Gal-3 concentration is elevated in patients with IMN.

Forest fire monitoring via uncrewed aerial vehicle image processing based on a modified machine learning algorithm.

Forests are indispensable links in the ecological chain and important ecosystems in nature. The destruction of forests seriously influences the ecological environment of the Earth. Forest protection plays an important role in human sustainable development, and the most important aspect of forest protection is preventing forest fires. Fire affects the structure and dynamics of forests and also climate and geochemical cycles. Using various technologies to monitor the occurrence of forest fires, quickly finding the source of forest fires, and conducting early intervention are of great significance to reducing the damage caused by forest fires. An improved forest fire risk identification algorithm is established based on a deep learning algorithm to accurately identify forest fire risk in a complex natural environment. First, image enhancement and morphological preprocessing are performed on a forest fire risk image. Second, the suspected forest fire area is segmented. The color segmentation results are compared using the HAF and MCC methods, and the suspected forest fire area features are extracted. Finally, the forest fire risk image recognition processing is conducted. A forest fire risk dataset is constructed to compare different classification methods to predict the occurrence of forest fire risk to improve the backpropagation (BP) neural network forest fire identification algorithm. An improved machine learning algorithm is used to evaluate the classification accuracy. The results reveal that the algorithm changes the learning rate between 0.1 and 0.8, consistent with the cross-index verification of the 10x sampling algorithm. In the combined improved BP neural network and support vector machine (SVM) classifier, forest fire risk is recognized based on feature extraction and the BP network. In total, 1,450 images are used as the training set. The experimental results reveal that in image preprocessing, image enhancement technology using the frequency and spatial domain methods can enhance the useful information of the image and improve its clarity. In the image segmentation stage, MCC is used to evaluate the segmentationresults. The accuracy of this algorithm is high compared with other algorithms, up to 92.73%. Therefore, the improved forest fire risk identification algorithm can accurately identify forest fire risk in the natural environment and contribute to forest protection.

Clinical value of the sTim­3 level in chronic kidney disease.

Chronic kidney disease (CKD) is a global disease that is harder to treat at a later stage. Therefore, early diagnosis and monitoring of CKD are crucial. T cell immunoglobulin and mucin domain molecule 3 (Tim-3) is a negative regulator of the T cell responses and it is involved in the immunomodulation of kidney disease. To date, only a small number of reports regarding serum soluble Tim-3 (sTim-3) in CKD are available. In the present study, the serum levels of sTim-3 in patients with CKD at different stages and the levels of sTim-3 in the early diagnosis and monitoring of CKD were analyzed. A highly sensitive time-resolved fluorescence immunoassay was performed to quantify sTim-3 levels in 318 patients with CKD and 114 healthy individuals. The serum levels of sTim-3 in patients with CKD (33.47±20.77 ng/ml) were significantly higher than those in the healthy individuals group (8.32±3.23 ng/ml; P<0.0001). As CKD progressed from stage G1 to G5, the serum sTim-3 level gradually increased (P<0.0001). A cut-off value of 13.63 ng/ml for the sTim-3 concentration was effective in diagnosing patients with CKD (area under the receiver operating characteristic curve, 0.9176; sensitivity, 79.87%; specificity, 96.49%). At this critical value, the positive detection rate of CKD in the early stages (G1 + G2), G3, G4 and G5 was 55.70, 77.78, 84.44 and 92.86%, respectively. In conclusion, the serum sTim-3 levels in patients with CKD were significantly higher than those in the healthy individuals group. As CKD progressed from G1 to G5, the serum sTim-3 concentration gradually increased, facilitating the monitoring of the progression of CKD. In addition, serum sTim-3 had an auxiliary effect that was useful in the early diagnosis of CKD. The positive detection rate of CKD in the early stages was 55.70%, which can assist other clinically common kidney disease indicators.

Increase in Serum Soluble Tim-3 Level Is Related to the Progression of Diseases After Hepatitis Virus Infection.

Background: Viral hepatitis is a widespread and serious infectious disease, and most patients with liver cirrhosis and hepatocellular carcinoma are prone to viral infections. T cell immunoglobulin-and mucin-domain-containing molecule-3 (Tim-3) is an immune checkpoint molecule that negatively regulates T cell responses, playing an extremely important role in controlling infectious diseases. However, reports about the role of serum soluble Tim-3 (sTim-3) in hepatitis virus infection are limited. Therefore, this study explored changes in sTim-3 levels in patients infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV). Methods: This study applied high-sensitivity time-resolved fluorescence immunoassay for the detection of sTim-3 levels. A total of 205 cases of viral hepatitis infection (68 cases of HBV infection, 60 cases of HCV infection, and 77 cases of HEV virus infection) and 88 healthy controls were quantitatively determined. The changes in serum sTim-3 level and its clinical value in hepatitis virus infection were analyzed. Results: Patients with HBV infection (14.00, 10.78-20.45 ng/mL), HCV infection (15.99, 11.83-27.00 ng/mL), or HEV infection (19.09, 10.85-33.93 ng/mL) had significantly higher sTim-3 levels than that in the healthy control group (7.69, 6.14-10.22 ng/mL, P < 0.0001). Patients with hepatitis and fibrosis infected with HBV (22.76, 12.82-37.53 ng/mL), HCV (33.06, 16.36-39.30 ng/mL), and HEV (28.90, 17.95-35.94 ng/mL) had significantly higher sTim-3 levels than patients with hepatitis without fibrosis (13.29, 7.75-17.28; 13.86, 11.48-18.64; 14.77, 9.79-29.79 ng/mL; P < 0.05). Conclusion: sTim-3 level was elevated in patients infected with HBV, HCV, or HEV and gradually increased in patients with either hepatitis or hepatitis with hepatic fibrosis. It has a certain role in the evaluation of the course of a disease after hepatitis virus infection.

Development of a time-resolved fluorescence immunoassay based on immunomagnetic beads for gastrin-17.

OBJECTIVE: In this study, a novel, simple, and rapid immunoassay for the determination of gastrin-17 (G-17) in human serum was established by combining immunomagnetic beads with time-resolved fluorescence immunoassay (TRFIA). METHODS: Immunomagnetic beads were coated with anti-G-17 M01 antibody, anti-G-17 M02 antibody was labeled with Eu3+ chelates. The concentration of G-17 in the serum was detected with the double-antibody sandwich method. RESULTS: The limit of background(LOB), limit of detection (LOD), and limit of quantification (LOQ) were 0.09, 0.104, and 0.39 pmol/L, respectively. The detection range of G-17-TRFIA was 0.39-100 pmol/L. The average intra- and inter-assay coefficients of variation (CV) were 5.95%-9.07% and 6.09%-8.14%, respectively. The recoveries for the serum samples ranged from 94.70% to 100.95%. The specificity of our G-17-TRFIA was acceptable. The correlation coefficient between G-17-TRFIA and commercial G-17-ELISA methods was R2 = 0.9092. CONCLUSIONS: A novel G-17-TRFIA detection method was successfully established to provide a reference for the early diagnosis of patients with atrophic gastritis in clinical research.

Clinical Value of Combined Detection of Serum sTim-3 and Pepsinogen for Gastric Cancer Diagnosis.

PURPOSE: The present study aimed to evaluate the clinical value of the combined detection of soluble T cell immunoglobulinand mucin domain molecule 3 (sTim-3) and pepsinogen (PG) in sera for gastric cancer (GC) diagnosis. PATIENTS AND METHODS: The double antibody sandwich method was used to establish a highly sensitive time-resolved fluorescence immunoassay for the detection of sTim-3. Serum sTim-3, PGI, and PGII levels in 149 GC patients (123 first-diagnosis GC patients and 26 post-GC patients), 81 patients with benign gastric disease (BGD), and 73 healthy controls were quantitatively detected. The clinical diagnostic value of the combined detection of sTim-3 and PG in GC was analyzed. RESULTS: Serum sTim-3 levels in GC (20.41 ± 9.55 ng/mL) and BGD (16.50 ± 9.76 ng/mL) patients were significantly higher (P < 0.001) than those in healthy controls (9.22 ± 3.40 ng/mL). Combined detection of sTim-3 and PGI/PGII (AUC: 0.9330, sensitivity: 86.44%, and specificity: 91.78%) showed a high diagnostic value for GC. When the level of PGI/PGII was less than 12.11 and that of sTim-3 was greater than 14.30 ng/mL, the positive rate of the control group was reduced to 0%, and the positive detection rate of GC was 54.47%. In addition, in post-operative patients, serum sTim-3 levels in the recurrence group (33.56 ± 4.91 ng/mL) were significantly higher than those in the no recurrence group (11.95 ± 5.16 ng/mL). CONCLUSION: sTim-3 levels in BGD and GC sera were significantly higher than those in the control group sera. Additionally, sTim-3 serum levels can predict recurrence in post-operative patients. Compared with PG alone, the combined detection of serum PG and sTim-3 can significantly improve the detection sensitivity and specificity of BGD and GC.

[The application of noninvasive urodynamics in early detection of diabetic cystopathy].

OBJECTIVE: To evaluate the early detection of diabetic cystopathy (DCP) with the technology of noninvasive urodynamics. METHODS: 70 patients with type 2 diabetes mellitus (DM) and 30 normal control subjects were checked with the technology of noninvasive urodynamics. Based on their disease course of less or more than 5 years, the DM patients were divided into two groups. Maximal flow rate, average flow rate, the volume leading to first bladder sensation and residual urine volume were measured by using noninvasive urodynamic technology. RESULTS: Among the 70 DM patients, 34 were detected to have bladder residual urine, so the DCP detection rate was 48.6%. In the patients with DCP, the average residual urine volume was 7-139 ml (30.1 +/- 27.1) ml, while there was no residual urine in the normal control group. As compared with the normal control group, maximal flow rate and average flow rate were decreased in all the patients with DM and those with DCP (P < 0.01). After follow up of the disease, the patients with a course of more than five years of disease control had even lower maximal flow rate and average flow rate. CONCLUSION: Maximal flow rate decrease and bladder residual urine detected with the technology of noninvasive urodynamics may be widely used in early detection and early diagnosis of DCP.

Attention-deficit hyperactivity disorder in elementary school students in Shantou, China: prevalence, subtypes, and influencing factors.

Attention-deficit hyperactivity disorder (ADHD) is a frequent childhood-onset psychiatric condition and categorized into three subtypes of predominantly inattentive (ADHD-I), hyperactive impulsive (ADHD-H), and combined (ADHD-C). The prevalence and subtypes of ADHD vary considerably. The primary aim of this study was to provide a prevalence estimate of ADHD in elementary school students living in Shantou, a district of China, and in addition to examine the influence of informants, age, and gender on the prevalence. A total of 3,497 students aged 7-12 years were enrolled by random and stratified sampling. In stage I, teachers and parents of all participating students in randomly selected schools were asked to complete Chinese versions of the Conners' 10-item scale. In stage II, students with high scores (>15) were interviewed by a psychiatrist for a diagnosis with or without ADHD. Parents rated many more students with high scores than teachers did in stage I. The prevalence of ADHD determined by Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) was 5.91% (5.27%-6.55%), which is comparable to the rates reported in previous studies with Chinese children. This hits the low border of the ADHD prevalence range from 5.9 to 7.1% worldwide, and is lower than that of Chinese children living in Hong Kong, suggesting an important influence of Chinese culture on the diagnosis of ADHD. The constituent ratios of ADHD-I, ADHD-C, and ADHD-H subtypes were 67.43, 24.57, and 8.00%, respectively. The rate of ADHD-H decreased with age, whereas that of ADHD-I remained at the highest levels in all age groups, suggesting that symptoms in the inattention domain are the most persistent and refractory.

A randomized clinical trial of the safety and efficacy of sitagliptin in patients with type 2 diabetes mellitus inadequately controlled by acarbose alone.

OBJECTIVE: To evaluate the safety and efficacy of sitagliptin when added to the treatment of patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on acarbose monotherapy. RESEARCH DESIGN AND METHODS: This was a multicenter, randomized, placebo-controlled, double-blind clinical trial. Patients (N = 381) with T2DM and inadequate glycemic control (glycated hemoglobin [HbA1c] ≥ 7.0% and ≤10.0%) on acarbose monotherapy (at least 50 mg three times daily) were randomized in a 1:1 ratio to receive the addition of sitagliptin 100 mg or matching placebo once daily for 24 weeks. MAIN OUTCOME MEASURES: Changes from baseline in HbA1c and fasting plasma glucose (FPG) at Week 24. RESULTS: The mean baseline HbA1c in randomized patients was 8.1%. At Week 24, the placebo-controlled, least squares mean changes from baseline (95% confidence interval) in HbA1c and FPG in the sitagliptin group were -0.62% and -0.8 mmol/L (p < .001), respectively. At Week 24, 37.8% of patients in the sitagliptin group were at HbA1c goal of <7% compared with 17.2% in the placebo group (p < .001). Sitagliptin was generally well tolerated, and there were no significant between-group differences in prespecified safety parameters (symptomatic hypoglycemia, diarrhea, abdominal pain, nausea, vomiting). A higher incidence of serious adverse events was observed in the sitagliptin group (5.2%) relative to placebo (0.5%); all but one, in the sitagliptin group, were not considered related to drug. CONCLUSIONS: Sitagliptin was generally well tolerated and provided statistically superior and clinically meaningful improvements in glycemic control after 24 weeks of treatment compared to placebo when added to treatment of patients with inadequate glycemic control on acarbose monotherapy. Clinicaltrials.gov: NCT01177384.

Polyethylene glycol loxenatide injections added to metformin effectively improve glycemic control and exhibit favorable safety in type 2 diabetic patients.

BACKGROUND: The aim of the present study was to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEX168) injections in Chinese type 2 diabetic (T2D) patients. METHODS: The present multicenter randomized double-blind parallel placebo-controlled clinical trial enrolled patients who had been treated with a stable dose of metformin (≥1500 mg/day) for ≥12 weeks and had an HbA1c level between 7% and 11%. Subjects were randomly divided into three groups (1: 1: 1) and were treated with once weekly subcutaneous injections of either placebo or 100 or 200 µg PEX168 for 12 weeks. All subjects continued to receive metformin daily. RESULTS: After 12 weeks treatment, the adjusted least-squares mean of HbA1c reductions from baseline values in the 100 and 200 µg PEX168 groups were significantly higher than in the placebo group (-1.02% [95% confidence interval {CI} -1.33, -0.71), -1.36% [95% CI -1.68, -1.04], and 0.13% [95% CI -0.20, 0.45], respectively; P < 0.05). After treatment, 50% and 60.5% of subjects in the 100 and 200 µg PEX168 groups, respectively, achieved HbA1c levels <7% (P < 0.01 for both vs placebo [HbA1c 11.1%]). The most frequent adverse reactions in the PEX168 groups were mild to moderate dose-dependent gastrointestinal reactions. There were no reports of hypoglycemia or pancreatitis in any of the groups. CONCLUSIONS: Continuous 12 week treatment with PEX168 showed excellent safety and efficacy in T2D patients whose glucose was not well controlled with metformin alone.

Association of the Transcription Factor 7 Like 2 (TCF7L2) Polymorphism With Diabetic Nephropathy Risk: A Meta-Analysis.

It is assumed that genetic factors may participate in the development of diabetic nephropathy (DN). The association between TCF7L2 gene polymorphism and DN risk is still unclear. To evaluate the relationship, we performed this meta-analysis. Eligible relevant studies were searched and selected from PubMed, Embase, and ISI Web of Science. Summary effect estimates were derived using a random effects model, with attention to study quality and publication bias. Ethnical approval was not necessary, because this meta-analysis was based on published articles, and did not involve patient consent. A total of 7 studies were identified. Analysis of all studies indicated significant association between TCF7L2 gene polymorphism and DN risk (odds ratio [OR] = 1.31, 95% confidence interval (CI) = 1.10-1.56, Pheterogeneity < 0.00001, P = 0.002). Subgroup analysis showed similar results in Asian (OR = 1.33, 95% CI = 1.10-1.62, Pheterogeneity = 0.03, P = 0.004), in Caucasian (OR = 2.27, 95% CI = 1.78-2.90, Pheterogeneity = 0.17, P < 0.00001), in rs7903146 mutation (OR = 1.61, 95% CI = 1.25-2.07, Pheterogeneity < 0.00001, P = 0.0002), However, no association was observed in Negroid (OR = 1.10, 95% CI = 0.90-1.35, Pheterogeneity < 00001, P = 0.36). Our results suggest that TCF7L2 gene polymorphism may contribute to the risk of DN. However, more studies should be launched in the future.

Effects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double-blind, controlled trial.

AIMS/INTRODUCTION: To assess the efficacy and safety of acetyl-L-carnitine (ALC) on diabetic peripheral neuropathy compared with methylcobalamin (MC). MATERIALS AND METHODS: This was a multicenter, randomized, parallel-group, double-blind, double-dummy, positive-controlled, non-inferior phase II clinical trial. Diabetic patients with abnormal nerve conduction test results were randomized in a 1:1 ratio to receive oral ALC 500 mg t.i.d. or MC 0.5 mg t.i.d. for 24 weeks. The neuropathy symptom score, neuropathy disability score and neurophysiological parameters were measured during follow up. RESULTS: A total of 232 patients were randomized (ALC n = 117, MC n = 115), 88% of which completed the trial. At week 24, patients from both groups had significant reductions in both neuropathy symptom score and neuropathy disability score with no significant difference between two groups (neuropathy symptom score reduction: ALC vs MC 2.35 ± 2.23, P < 0.0001 vs 2.11 ± 2.48, P < 0.0001, intergroup P = 0.38; neuropathy disability score reduction ALC vs MC 1.66 ± 1.90, P < 0.0001 vs 1.35 ± 1.65, P < 0.0001, intergroup P = 0.23). Neurophysiological parameters were also improved in both groups. No significant difference was found between groups in the development of adverse events. CONCLUSIONS: ALC is as effective as MC in improving clinical symptoms and neurophysiological parameters for patients with diabetic peripheral neuropathy over a 24-week period with good tolerance.

Randomized clinical trial of the safety and efficacy of sitagliptin and metformin co-administered to Chinese patients with type 2 diabetes mellitus.

INTRODUCTION: The results of a clinical trial to evaluate the efficacy and safety of initial combination therapy with sitagliptin and metformin in Chinese patients with type 2 diabetes and inadequate glycemic control are reported here. MATERIALS AND METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, parallel group, 24-week clinical trial carried out in China. Patients (n = 744) with type 2 diabetes and inadequate glycemic control (glycated hemoglobin ≥7.5 and ≤11.0%) who were either drug-naïve or washed out of previous therapy were randomized in equal ratios to sitagliptin 100 mg once daily (q.d.; S100), metformin 500 mg twice daily (b.i.d.; M1000), metformin 850 mg b.i.d. (M1700), sitagliptin 50 mg b.i.d. plus metformin 500 mg b.i.d. (S100/M1000), sitagliptin 50 mg b.i.d. plus metformin 850 mg b.i.d. (S100/M1700), or placebo. RESULTS: The mean baseline glycated hemoglobin in randomized patients was 8.7%. Least squares mean changes from baseline in glycated hemoglobin were -0.59% (placebo), -0.99% (S100), -1.29% (M1000), -1.56% (M1700), -1.67% (S100/M1000) and -1.83% (S100/M1700) (P < 0.05 for each active group vs placebo, for S100/M1700 and S100/M1000 vs S100, and for S100/M1000 vs M1000). All treatments were generally well-tolerated. The overall incidence of hypoglycemia (symptomatic or asymptomatic) was higher in the two co-administration groups (S100/M1700 and S100/M1000) compared with the placebo. The incidence of symptomatic hypoglycemia was low, and similar, across all treatment groups. The incidences of gastrointestinal adverse events were generally higher in high-dose metformin groups than in the placebo group. CONCLUSIONS: In Chinese patients with type 2 diabetes, initial combination therapy with sitagliptin and metformin was generally well-tolerated, and provided improvement in glycemic control.