LncRNA HOXC-AS3 accelerates malignant proliferation of cervical cancer cells via stabilizing KDM5B.

BACKGROUND: Cervical cancer (CC) is a common malignancy amongst women globally. Ubiquitination plays a dual role in the occurrence and development of cancers. This study analyzed the mechanism of long noncoding RNA HOXC cluster antisense RNA 3 (lncRNA HOXC-AS3) in malignant proliferation of CC cells via mediating ubiquitination of lysine demethylase 5B (KDM5B/JARID1B). METHODS: The expression patterns of lncRNA HOXC-AS3 and KDM5B were measured by real-time quantitative polymerase chain reaction or Western blot analysis. After transfection with lncRNA HOXC-AS3 siRNA and pcDNA3.1-KDM5B, proliferation of CC cells was assessed by the cell counting kit-8, colony formation, and 5-Ethynyl-2'-deoxyuridine staining assays. The xenograft tumor model was established to confirm the impact of lncRNA HOXC-AS3 on CC cell proliferation in vivo by measuring tumor size and weight and the immunohistochemistry assay. The subcellular location of lncRNA HOXC-AS3 and the binding of lncRNA HOXC-AS3 to KDM5B were analyzed. After treatment of lncRNA HOXC-AS3 siRNA or MG132, the protein and ubiquitination levels of KDM5B were determined. Thereafter, the interaction and the subcellular co-location of tripartite motif-containing 37 (TRIM37) and KDM5B were analyzed by the co-immunoprecipitation and immunofluorescence assays. RESULTS: LncRNA HOXC-AS3 and KDM5B were upregulated in CC tissues and cells. Depletion of lncRNA HOXC-AS3 repressed CC cell proliferation and in vivo tumor growth. Mechanically, lncRNA HOXC-AS3 located in the nucleus directly bound to KDM5B, inhibited TRIM37-mediated ubiquitination of KDM5B, and upregulated the protein levels of KDM5B. KDM5B overexpression attenuated the inhibitory role of silencing lncRNA HOXC-AS3 in CC cell proliferation in vivo and in vitro. CONCLUSION: Nucleus-located lncRNA HOXC-AS3 facilitated malignant proliferation of CC cells via stabilization of KDM5B protein levels.

The Association Between Functional Variants in Long Non-coding RNAs and the Risk of Autism Spectrum Disorder Was Not Mediated by Gut Microbiota.

The effect of functional variants in long non-coding RNA (lncRNA) gene regions on autism spectrum disorder (ASD) remains unclear. The present study aimed to investigate the association of functional variants located in lncRNA genes with the risk of ASD and explore whether gut microbiota would mediate the relationship. A total of 87 cases and 71 healthy controls were enrolled in the study. MassARRAY platform and 16S rRNA sequencing were respectively applied to assess the genotype of candidate SNPs and gut microbiota of children. The logistic regression models showed that the association between rs2295412 and the risk of ASD was statistically significant after Bonferroni adjustments. The risk of ASD decreased by 19% for each additional C allele carried by children in multiplicative models (OR = 0.81, 95% CI, 0.69-0.94, P = 0.007). Although we identified significant correlations between rs8113922 polymorphisms, Bifidobacteriales, and ASD, the mediating effect of gut microbiota on the relationship of the polymorphisms with the risk of ASD was not significant. The findings demonstrated that functional variants in lncRNA genes play an important role in ASD and gut microbiota could not mediate the association. Future studies are warranted to verify the results and search for more possible mechanisms of variants located in lncRNA genes implicated in ASD.

Recanalization of a long segment occluded superior vena cava by puncturing the remnant calcified fibrin sheath of the internal jugular vein: A case report.

A fibrin sheath with central venous occlusion is a common complication after central venous catheterization, and these patients often experience catheter dysfunction. A calcified fibrin sheath can cause a catheter to be stuck, and typically necessitates catheter removal or replacement. From another point of view, a calcified fibrin sheath can be seen in ultrasound and computed tomography, and the original fibrin sheath channel between the internal jugular vein and the atrium is unusually strong. When central vein occlusion occurs, the remnant calcified fibrin sheath of the internal jugular vein can be punctured under ultrasound guidance, allowing the guidewire to enter the atrium directly through the fibrin sheath. Here, we report a case in which we achieved easy recanalization of a long segment occluded superior vena cava by puncturing the remnant calcified fibrin sheath of the internal jugular vein.

Improving iconic memory through contrast detection training with HOA-corrected vision.

Iconic memory and short-term memory are not only crucial for perception and cognition, but also of great importance to mental health. Here, we first showed that both types of memory could be improved by improving limiting processes in visual processing through perceptual learning. Normal adults were trained in a contrast detection task for ten days, with their higher-order aberrations (HOA) corrected in real-time. We found that the training improved not only their contrast sensitivity function (CSF), but also their iconic memory and baseline information maintenance for short-term memory, and the relationship between memory and CSF improvements could be well-predicted by an observer model. These results suggest that training the limiting component of a cognitive task with visual perceptual learning could improve visual cognition. They may also provide an empirical foundation for new therapies to treat people with poor sensory memory.

Peripheral myopic defocus signal affects the efficiency of visual information processing in myopic children.

PURPOSE: Spectacle lenses with peripheral lenslets have shown promise for myopia control by providing peripheral myopic defocus signals. Here, we aimed to investigate the impact of prolonged exposure (>6 months) to peripheral myopic defocus on visual information processing in myopic children. METHODS: The study included 30 myopic children who habitually wore spectacle lenses with highly aspherical lenslets (HAL group) and 34 children who habitually wore single-vision (SV group) spectacles. The quick contrast sensitivity function (qCSF) was used to measure contrast sensitivity (CS) under conditions of no or high noise. Both groups were tested with HAL and SV lenses. The perceptual template model was utilised to fit the contrast sensitivity function (CSF) and determine differences in information processing efficiency through internal additive noise ( N add ) and perceptual template gain (ß). RESULTS: The areas under the log CSF in the SV group were significantly higher than for the HAL group in both zero-noise conditions with the SV test lens (p = 0.03) and high-noise conditions with the HAL test lens (p = 0.02). For 2 cycle per degree (cpd) stimuli, ß was significantly higher in the SV group with the HAL test lens than in the HAL group (p = 0.02), while there was a trend towards a significant difference in ß for 6 cpd stimuli (p = 0.07). However, there were no significant differences in N add between the two groups, with or without noise interference. CONCLUSION: The reduced CS observed in myopic children wearing HAL lenses for 6 months or more may be due to decreased ß. This suggests that prolonged use of spectacle lenses with peripheral myopic defocus signals may compromise the central visual system's ability to process additional external noise, resulting in decreased efficiency in visual information processing.

Highly Dispersed Mn-Doped Ceria Supported on N-Doped Carbon Nanotubes for Enhanced Oxygen Reduction Reaction.

The weak adsorption of oxygen on transition metal oxide catalysts limits the improvement of their electrocatalytic oxygen reduction reaction (ORR) performance. Herein, a dopamine-assisted method is developed to prepare Mn-doped ceria supported on nitrogen-doped carbon nanotubes (Mn-Ce-NCNTs). The morphology, dispersion of Mn-doped ceria, composition, and oxygen vacancies of the as-prepared catalysts were analyzed using various technologies. The results show that Mn-doped ceria was formed and highly dispersed on NCNTs, on which oxygen vacancies are abundant. The as-prepared Mn-Ce-NCNTs exhibit a high ORR performance, on which the average electron transfer number is 3.86 and the current density is 24.4% higher than that of commercial 20 wt % Pt/C. The peak power density of Mn-Ce-NCNTs is 68.1 mW cm-2 at the current density of 138.9 mA cm-2 for a Zn-air battery, which is close to that of 20 wt % Pt/C (69.4 mW cm-2 at 106.1 mA cm-2). Density functional theory (DFT) calculations show that the oxygen vacancy formation energies of Mn-doped CeO2(111) and pure CeO2(111) are -0.55 and 2.14 eV, respectively. Meanwhile, compared with undoped CeO2(111) (-0.02 eV), Mn-doped CeO2(111) easily adsorbs oxygen with the oxygen adsorption energy of only -0.68 eV. This work provides insights into the synergetic effect of Mn-doped ceria for facilitating oxygen adsorption and enhancing ORR performance.

Visual Tracking in Amblyopia: A Continuous Psychophysical Approach.

Purpose: This study aimed to explore the underlying mechanisms of the observed visuomotor deficit in amblyopia. Methods: Twenty-four amblyopic (25.8 ± 3.8 years; 15 males) and 22 normal participants (25.8 ± 2.1 years; 8 males) took part in the study. The participants were instructed to continuously track a randomly moving Gaussian target on a computer screen using a mouse. In experiment 1, the participants performed the tracking task at six different target sizes. In experiments 2 and 3, they were asked to track a target with the contrast adjusted to individual's threshold. The tracking performance was represented by the kernel function calculated as the cross-correlation between the target and mouse displacements. The peak, latency, and width of the kernel were extracted and compared between the two groups. Results: In experiment 1, target size had a significant effect on the kernel peak (F(1.649, 46.170) = 200.958, P = 4.420 × 10-22). At the smallest target size, the peak in the amblyopic group was significantly lower than that in the normal group (0.089 ± 0.023 vs. 0.107 ± 0.020, t(28) = -2.390, P = 0.024) and correlated with the contrast sensitivity function (r = 0.739, P = 0.002) in the amblyopic eyes. In experiments 2 and 3, with equally visible stimuli, there were still differences in the kernel between the two groups (all Ps < 0.05). Conclusions: When stimulus visibility was compensated, amblyopic participants still showed significantly poorer tracking performance.

Association of IL-6-572 polymorphism with sepsis: An updated meta-analysis.

OBJECTIVES: To analyze the relationship between IL and 6 572C/G polymorphism with sepsis. METHODS: Searching 8 databases the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Chongqing VIP, Embase, PubMed, WanFang Data, and Web of Science from inception to October 1, 2023. Meta-analysis was performed by using Review Manager 5.4 and STATA 15.0. RESULTS: 9 studies were included, 1 study was excluded from the previous meta-analysis, and 6 studies were added. Sensitivity analysis suggested that the results were relatively robust. The P values of Egger test indicated that no conspicuous publication bias was found. CONCLUSION: According to the meta-analysis results of existing studies, the IL-6 572C/G GG genotype and G allele are risk factors for sepsis, this result changes the previous conclusion that the IL-6 572 polymorphism is not related to sepsis. However, the results still need to be conservatively treated due to the sample size was not large enough.

Association between the trajectory of ideal cardiovascular health metrics and incident chronic kidney disease among 27,635 older adults in northern China-a prospective cohort study.

BACKGROUND: There is a lack of relevant studies evaluating the long-term impact of cardiovascular health factor (CVH) metrics on chronic kidney disease (CKD). OBJECTIVE: This study investigates the long-term change in CVH metrics in older people and explores the relationship between CVH metrics trajectory and CKD. METHODS: In total, 27,635 older people aged over 60 from the community-based Tianjin Chronic Kidney Disease Cohort study were enrolled. The participants completed five annual physical examinations between January 01, 2014, and December 31, 2018, and a subsequent follow-up between January 01, 2019, and December 31, 2021. CVH metrics trajectories were established by the group-based trajectory model to predict CKD risk. The relationships between baseline CVH, CVH change (ΔCVH), and CKD risk were also explored by logistic regression and restricted cubic spline regression model. In addition, likelihood ratio tests were used to compare the goodness of fit of the different models. RESULTS: Six distinct CVH metrics trajectories were identified among the participants: low-stable (11.19%), low-medium-stable (30.58%), medium-stable (30.54%), medium-high-decreased (5.46%), medium-high-stable (18.93%), and high-stable (3.25%). After adjustment for potential confounders, higher CVH metrics trajectory was associated with decreased risk of CKD (P for trend < 0.001). Comparing the high-stable with the low-stable group, the risk of CKD decreased by 46%. All sensitivity analyses, including adjusting for baseline CVH and removing each CVH component from the total CVH, produced consistent results. Furthermore, the likelihood ratio test revealed that the model established by the CVH trajectory fit better than the baseline CVH and Δ CVH. CONCLUSION: The higher CVH metrics trajectory and improvement of CVH metrics were associated with decreased risk of CKD. This study emphasized the importance of improving CVH to achieve primary prevention of CKD in older people.

Predictive factors for lung metastasis in pediatric differentiated thyroid cancer: a clinical prediction study.

OBJECTIVES: The objective of this study was to develop and evaluate the efficacy of a nomogram for predicting lung metastasis in pediatric differentiated thyroid cancer. METHODS: The SEER database was utilized to collect a dataset consisting of 1,590 patients who were diagnosed between January 2000 and December 2019. This dataset was subsequently utilized for the purpose of constructing a predictive model. The model was constructed utilizing a multivariate logistic regression analysis, incorporating a combination of least absolute shrinkage feature selection and selection operator regression models. The differentiation and calibration of the model were assessed using the C-index, calibration plot, and ROC curve analysis, respectively. Internal validation was performed using a bootstrap validation technique. RESULTS: The results of the study revealed that the nomogram incorporated several predictive variables, namely age, T staging, and positive nodes. The C-index had an excellent calibration value of 0.911 (95 % confidence interval: 0.876-0.946), and a notable C-index value of 0.884 was achieved during interval validation. The area under the ROC curve was determined to be 0.890, indicating its practicality and usefulness in this context. CONCLUSIONS: This study has successfully developed a novel nomogram for predicting lung metastasis in children and adolescent patients diagnosed with thyroid cancer. Clinical decision-making can be enhanced by assessing clinicopathological variables that have a significant predictive value for the probability of lung metastasis in this particular population.

Mast cell in infantile hemangioma.

Infantile hemangioma (IH) is the most common benign vascular tumor characterized by three phases - proliferation, early involution and late involution. Mast cells (MCs) play an important role in allergic reactions and numerous diseases, including tumors. While the mechanisms underlying MCs migration, activation and function in the life cycle of IH remain unclear, previous studies suggested that MCs circulate through the vasculature and migrate into IH, and subsequently mature and get activated. Estradiol (E2) emerges as a potential attractant for MC migration into IH and their subsequent activation. In various stages of IH, activated MCs secrete both proangiogenic and anti-angiogenic modulators, absorbed by various cells adjacent to them. Imbalances in these modulators may contribute to IH proliferation and involution.

Effect of myopia-control lenses on central and peripheral visual performance in myopic children.

PURPOSE: To evaluate the short-term effects of three myopia-control lenses, which impose peripheral myopic defocus while providing clear central vision, on central and peripheral visual performance in myopic children. METHODS: Twenty-one myopic children were enrolled in the study. Central visual performance was assessed using the quick contrast sensitivity function. Peripheral visual performance was evaluated by measuring peripheral contrast threshold and global motion perception, while subjects maintained fixation through the central portion of the lens. Single-vision spectacle lenses (SVL), spectacle lenses with highly aspherical lenslets (HAL) and defocus-incorporated soft contact (DISC) lenses were evaluated in random order, followed by orthokeratology (OK) lenses. All tests were performed monocularly on the right eye. RESULTS: The area under the log contrast sensitivity function (AULCSF) with DISC lenses was lower than that with SVL (1.14 vs. 1.40, p < 0.001) and HAL (1.14 vs. 1.33, p = 0.001). HAL increased the temporal visual field contrast threshold compared with OK lenses (p = 0.04), and OK lenses decreased the superior visual field contrast threshold compared with that of SVL (p = 0.04) and HAL (p = 0.005). HAL also increased the peripheral coherence threshold for identifying the contraction movement compared with OK lenses (p = 0.01). CONCLUSIONS: The short-term use of these optical interventions for myopia control exhibited measurable differences in central and peripheral visual performance. Relevant attention could be paid to these differences, especially when children switch to different treatments. DISC lenses exhibited worse central contrast sensitivity than SVL and HAL. Imposing peripheral defocus signals did not affect children's peripheral visual performance compared with SVL. However, considering the poorer peripheral visual performance provided by HAL, OK lenses are recommended for children if there are specific demands for global scene recognition and motion perception.

Perceptual learning changes the amplitude not the shape of the temporal window of visual processing.

Perceptual learning (PL) can significantly improve human performance in perceptual tasks primarily through template reweighting. Previous studies have documented how PL changes perceptual template in stimulus feature space. We investigated how PL reweights visual information in time. With a dynamic external noise paradigm and the elaborated perceptual template model (ePTM) analysis, we found that training with an orientation identification task in the zero external noise condition reduced contrast thresholds in both zero and high external noise conditions, whereas training in the high external noise condition only reduced contrast thresholds in high external noise conditions. The ePTM analysis showed that training in both zero and high external noise changed the overall amplitude, but not the shape of the temporal window of the perceptual template to exclude external noise across time, and training in zero external noise additionally reduced additive internal noise. Our results provided additional constraints for models of PL. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Analysis of enhanced CT imaging signs and clinicopathological prognostic factors in hepatoid adenocarcinoma of stomach patients with radical surgery: a retrospective study.

BACKGROUND: To investigate the association between CT signs and clinicopathological features and disease recurrence in patients with hepatoid adenocarcinoma of stomach (HAS). METHODS: Forty nine HAS patients undergoing radical surgery were retrospectively collected. Association between CT and clinicopathological features and disease recurrence was analyzed. Multivariate logistic model was constructed and evaluated for predicting recurrence by using receiver operating characteristic (ROC) curve. Survival curves between model-defined risk groups was compared using Kaplan-Meier method. RESULTS: 24(49.0%) patients developed disease recurrence. Multivariate logistic analysis results showed elevated serum CEA level, peritumoral fatty space invasion and positive pathological vascular tumor thrombus were independent factors for disease recurrence. Odds ratios were 10.87 (95%CI, 1.14-103.66), 6.83 (95%CI, 1.08-43.08) and 42.67 (95%CI, 3.66-496.85), respectively. The constructed model showed an area under ROC of 0.912 (95%CI,0.825-0.999). The model-defined high-risk group showed poorer overall survival and recurrence-free survival than the low-risk group (both P < 0.001). CONCLUSIONS: Preoperative CT appearance of peritumoral fatty space invasion, elevated serum CEA level, and pathological vascular tumor thrombus indicated poor prognosis of HAS patients.

Two new flavanones from Polytrichum commune Hedw.

Seven flavanones, including two new compounds coupled with styryl units, communins C (1) and D (2), as well as five known compounds, were isolated from Polytrichum commune Hedw. The planar structures of all compounds were determined using extensive spectroscopic analysis. The absolute configurations of two new compounds were assigned by comparing experimental ECD with calculated ECD. The cytotoxicity of all isolates against HCT-116, BGC803, MCF7 and PANC-1 cell lines was evaluated. Communin D exhibited significant cytotoxic activity on BGC803 cells with an IC50 value of 9.3 µM.

Association of cumulative resting heart rate exposure with rapid renal function decline: a prospective cohort study with 27,564 older adults.

OBJECTIVE: To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. METHODS: In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m2 and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m2 or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. RESULTS: During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. CONCLUSIONS: The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

Trilobatin rescues fulminant hepatic failure by targeting COX2: Involvement of ROS/TLR4/NLRP3 signaling.

BACKGROUND: Fulminant hepatic failure (FHF) lacks efficient therapies notwithstanding increased comprehending of the inflammatory response and oxidative stress play crucial roles in the pathogenesis of this type of hepatic damage. Trilobatin (TLB), a naturally occurring food additive, is endowed with anti-inflammation and antioxidant properties. PURPOSE: In current study, we evaluated the effect of TLB on FHF with a mouse model with d-galactosamine/lipopolysaccharide (GalN/LPS)-induced FHF and LPS-stimulated Kupffer cells (KCs) injury. METHODS: Mice were randomly divided into seven groups: control group, TLB 40 mg/kg + control group, GalN/LPS group, TLB 10 mg/kg + GalN/LPS group, TLB 20 mg/kg + GalN/LPS group, TLB 40 mg/kg + GalN/LPS group, bifendate 150 mg/kg + GalN/LPS group. The mice were administered intragastrically TLB (10, 20 and 40 mg/kg) for 7 days (twice a day) prior to injection of GalN (700 mg/kg)/LPS (100 µg/kg). The KCs were pretreated with TLB (2.5, 5, 10 µM) for 2 h or its analogue (10 µM) or COX2 inhibitor (10 µM), and thereafter challenged by LPS (1 µg/ml) for 24 h. RESULTS: TLB effectively rescued GalN/LPS-induced FHF. Furthermore, TLB inhibited TLR 4/NLRP3/pyroptosis pathway, and caspase 3-dependent apoptosis pathway, along with reducing excessive cellular and mitochondrial ROS generation and enhancing mitochondrial biogenesis. Intriguingly, TLB directly bound to COX2 as reflected by transcriptomics, molecular docking technique and surface plasmon resonance assay. Furthermore, TLB failed to attenuate LPS-induced inflammation and oxidative stress in KCs in the absence of COX2. CONCLUSION: Our findings discover a novel pharmacological effect of TLB: protecting against FHF-induced pyroptosis and apoptosis through mediating ROS/TLR4/NLRP3 signaling pathway and reducing inflammation and oxidative stress. TLB may be a promising agent with outstanding safety profile to treat FHF.

Safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing progression to diabetes in a Chinese population with impaired glucose regulation: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Impaired glucose regulation (defined as either impaired glucose tolerance or impaired fasting glucose) is an important risk factor for the development of diabetes. We aimed to evaluate the safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing diabetes in Chinese participants with impaired glucose regulation. METHODS: We did a multicentre, open-label, randomised controlled trial at 43 endocrinology departments in general hospitals across China. Eligible participants were individuals with impaired glucose regulation (ie, impaired glucose tolerance or impaired fasting glucose, or both), men or women aged 18-70 years with a BMI of 21-32 kg/m2. Eligible participants were randomly assigned (1:1) via a computer-generated randomisation to receive either standard lifestyle intervention alone or metformin (850 mg orally once per day for the first 2 weeks and titrated to 1700 mg orally per day [850 mg twice per day]) plus lifestyle intervention. Block randomisation was used with a block size of four, stratified by glucose status (impaired fasting glucose or impaired glucose tolerance), hypertension, and use of any anti-hypertensive medication. Lifestyle intervention advice was given by investigators at all participating sites. The primary endpoint was the incidence of newly diagnosed diabetes at the end of the 2-year follow-up. Analysis was done using the full analysis set and per-protocol set. This study is registered with ClinicalTrials.gov, number NCT03441750, and is completed. FINDINGS: Between April, 2017, and June, 2019, 3881 individuals were assessed for eligibility, of which 1678 (43·2%) participants were randomly assigned to either the metformin plus lifestyle intervention group (n=831) or the lifestyle intervention alone group (n=847) and received the allocated intervention at least once. During a median follow-up of 2·03 years, the incidence rate of diabetes was 17·27 (95% CI 15·19-19·56) per 100 person-years in the metformin plus lifestyle intervention group and 19·83 (17·67-22·18) per 100 person-years in the lifestyle intervention alone group. The metformin plus lifestyle intervention group showed a 17% lower risk of developing diabetes than the lifestyle intervention alone group (HR 0·83 [95% CI 0·70-0·99]; log-rank p=0·043). A higher proportion of participants in the metformin plus lifestyle intervention group reported adverse events than in the lifestyle intervention alone group, primarily due to more gastrointestinal adverse events. The percentage of participants reporting a serious adverse event was similar in both groups. INTERPRETATION: Metformin plus lifestyle intervention further reduced the risk of developing diabetes than lifestyle intervention alone in Chinese people with impaired glucose regulation, showing additional benefits of combined intervention in preventing progression to diabetes without new safety concerns. FUNDING: Merck Serono China, an affiliate of Merck KGaA, Darmstadt, Germany. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Decomposing the Response Time in Amblyopia: A Drift Diffusion Model Analysis.

Purpose: Amblyopes are known to have delayed response times (RT) in various visual tasks. We aim to investigate whether any factor other than the sensory deficit contributes to the delayed RT in amblyopia. Method: Fifteen amblyopic (26.0 ± 4.50 years) and 15 normal (25.6 ± 2.90 years) participants took part in this study. The responses and RTs in an orientation identification task were collected for each participant with stimulus contrast adjusted to the multiples of individual's threshold. A drift diffusion model was used to fit to the response and RT data and to estimate the RT components. Result: There was a significant difference in the RT between the amblyopic and normal groups (F(1, 28) = 6.75, P = 0.015) but no difference in the accuracy (F(1, 28) = 0.028, P = 0.868). The drift rate function in the amblyopic eye had a larger threshold (P = 0.001) and shallower slope (P = 0.006) than that of the fellow eye. The amblyopic group has a longer non-decision time than the normal group (F(1, 28) = 8.02, P = 0.008). The drift rate threshold correlated with the contrast sensitivity (P = 1.71 × 10-18) but the non-decision time did not (P = 0.393). Conclusions: Both sensory and post-sensory factors contributed to the delayed RT in amblyopia. The effect of the sensory loss in V1 on RT can be compensated by increasing stimulus contrast, and the post-sensory delay provides evidence for higher-level deficits in amblyopia.