Sodium selenite inhibits cervical cancer progression via ROS-mediated suppression of glucose metabolic reprogramming.

AIMS: This study aims to explore the inhibitory effect of selenium on cervical cancer through suppression of glucose metabolic reprogramming and its underlying mechanisms. METHODS: Sodium selenite (SS) treated HeLa and SiHa cells were assessed for proliferation using the CCK-8 assay and immunofluorescence. DNA synthesis was measured with the EdU assay. A nude mouse xenograft model evaluated SS's anti-cervical cancer effects. Reactive oxygen species (ROS) and mitochondrial membrane potential were measured using flow cytometry, DCFH-DA, and JC-1 probes, respectively. Apoptosis was detected via Annexin V/PI staining and Western blot. Glucose uptake, lactate production, and ATP generation were determined using 2-NBDG probes and assay kits. The mRNA and protein levels of glycolysis-related genes HK2, GLUT1, and PDK1 were measured using RT-qPCR and Western blot. KEY FINDINGS: SS inhibited HeLa and SiHa cells viability in a dose- and time-dependent manner. Intraperitoneal injection of SS in nude mice significantly inhibited HeLa cell xenograft growth without evident hepatotoxicity or nephrotoxicity. SS inhibited glucose metabolic reprogramming in cancer cells primarily via ROS-mediated AKT/mTOR/HIF-1α pathway inhibition. Pretreatment with N-acetylcysteine (NAC) or MHY1485 (an mTOR activator) partially reversed the inhibitory effects of SS on glucose metabolic reprogramming, cell proliferation, and migration, as well as its pro-apoptotic effects. SIGNIFICANCE: SS exhibited anti-cervical cancer effects, likely through the induction of ROS generation and inhibition of glucose metabolic reprogramming in cervical cancer cells, thereby inhibiting cell proliferation and promoting apoptosis. These findings provide new insights into understanding the molecular mechanisms underlying SS for potential new drug development for cervical cancer.

Video laryngoscopy may improve the intubation outcomes in critically ill patients: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The role of video laryngoscopy in critically ill patients requiring emergency tracheal intubation remains controversial. This systematic review and meta-analysis aimed to evaluate whether video laryngoscopy could improve the clinical outcomes of emergency tracheal intubation. METHODS: We searched the PubMed, Embase, Scopus and Cochrane databases up to 5 September 2024. Randomised controlled trials comparing video laryngoscopy with direct laryngoscopy for emergency tracheal intubation were analysed. The primary outcome was the first-attempt success rate, while secondary outcomes included intubation time, glottic visualisation, in-hospital mortality and complications. RESULTS: Twenty-six studies (6 in prehospital settings and 20 in hospital settings) involving 5952 patients were analysed in this study. Fifteen studies had low risk of bias. Overall, there was no significant difference in first-attempt success rate between two groups (RR 1.05, 95% CI 0.97 to 1.13, p=0.24, I2=89%). However, video laryngoscopy was associated with a higher first-attempt success rate in hospital settings (emergency department: RR 1.13, 95% CI 1.03 to 1.23, p=0.007, I2=85%; intensive care unit: RR 1.16, 95% CI 1.05 to 1.29, p=0.003, I2=68%) and among inexperienced operators (RR 1.15, 95% CI 1.03 to 1.28, p=0.01, I2=72%). Conversely, the first-attempt success rate with video laryngoscopy was lower in prehospital settings (RR 0.75, 95% CI 0.57 to 0.99, p=0.04, I2=95%). There were no differences for other outcomes except for better glottic visualisation (RR 1.11, 95% CI 1.03 to 1.20, p=0.005, I2=91%) and a lower incidence of oesophageal intubation (RR 0.42, 95% CI 0.24 to 0.71, p=0.001, I2=0%) when using video laryngoscopy. CONCLUSIONS: In hospital settings, video laryngoscopy improved first-attempt success rate of emergency intubation, provided superior glottic visualisation and reduced incidence of oesophageal intubation in critically ill patients. Our findings support the routine use of video laryngoscopy in the emergency department and intensive care units. PROSPERO REGISTRATION NUMBER: CRD 42023461887.

A deep learning system for myopia onset prediction and intervention effectiveness evaluation in children.

The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p < 0.001) in both test sets. In an emulated randomized controlled trial (eRCT) on the Shanghai outdoor cohort (n = 3303) where DeepMyopia showed effectiveness in myopia prevention compared to NonCyc-based model, with an adjusted relative reduction (ARR) of -17.8%, 95% CI: -29.4%, -6.4%. DeepMyopia-assisted interventions attained quality-adjusted life years (QALYs) of 0.75 (95% CI: 0.53, 1.04) per person and avoided blindness years of 13.54 (95% CI: 9.57, 18.83) per 1 million persons compared to natural lifestyle with no active intervention. Our findings demonstrated DeepMyopia as a reliable and efficient AI-based decision support system for intervention guidance for children.

Efficacy of weekly dose of 1% atropine for myopia control in Chinese children.

PURPOSE: To assess the effect of weekly 1% atropine use on children's myopia progression and whether the effect is sustainable. METHODS: Medical records of myopic children aged 3-15 years receiving weekly 1% atropine for more than 1 year were retrospectively reviewed. Axial length (AL) and spherical equivalent refraction (SER) at every visit were collected. The changes in AL or SER over time were analysed using generalised estimating equation. The related factors of myopic progression were performed by multiple linear regression. The performance of short-term AL change to predict atropine-poor responders (AL change >0.2 mm/year) was assessed using receiver operating characteristic analysis. RESULTS: A total of 694 participants with a mean age of 8.83 years were included. The participants with follow-up time reached 1, 2, 3 and 4 years were 256 (36.9%), 250 (36.0%), 143 (20.6%) and 45 (6.5%) separately. The cumulative change in AL was 0.05 mm, 0.24 mm, 0.47 mm, 0.56 mm separately for 1-year, 2-year, 3-year and 4- year treatment. Approximate 0.20 mm elongation per year was observed since the second-year of the treatment. Older age and lower initial myopic refraction were independently associated with less myopic progression. A decrease in AL of more than 0.04 mm during the initial 2 months could serve as an indicator for identifying fast progressors (AL change >0.2 mm/year) over a 2-year period, with sensitivity and specificity rates of 0.78 and 0.73, respectively. CONCLUSION: Weekly 1% atropine may be a potentially effective treatment with longer lasting effects for children with myopia control especially in those with older age and lower myopia.

Smartwatch Measures of Outdoor Exposure and Myopia in Children.

Importance: Time spent outdoors has been proven effective in preventing myopia, but little is known about the association of outdoor exposure patterns with myopia. Objective: To examine the association of outdoor exposure patterns with myopic shift in children. Design, Setting, and Participants: This 1-year prospective cohort study from December 2017 to December 2018 was a secondary analysis of a cluster-randomized trial (Shanghai Time Outside to Reduce Myopia [STORM]). STORM was a school-based intervention study, recruiting 16 schools from 8 districts in Shanghai, from October 2016 to December 2018. Children without myopia at baseline who consistently wore a smartwatch for a minimum of 6 hours daily, sustained for at least 90 days, and who had complete information were included. Data analysis was performed from December 2017 to December 2018. Exposures: The outdoor exposure pattern was defined as the episode of time outdoors and instant sunlight intensity over a continuous period. Main Outcomes and Measures: Myopic shift was defined as the absolute change in refraction between the initial spherical equivalence and the follow-up spherical equivalence. Results: This study included 2976 students (mean [SD] age, 7.2 [0.6] years; 1525 girls [51.2%]). The mean (SD) daily time outdoors was 90 (28) minutes, and the mean (SD) sunlight intensity was 2345 (486) lux. Of the 12 outdoor exposure patterns, the major outdoor exposure patterns were time outdoors with at least 15 minutes, accounting for 74.9% of minutes (33 677 584 of 45 016 800 minutes). Only patterns with at least 15 minutes accompanied with no less than 2000 lux were associated with less myopic shift in refraction (for ≥15 minutes and 2000 to 3999 lux, -0.007 diopter [D] [95% CI, -0.011 to -0.002 D]; for ≥15 minutes and ≥4000 lux, -0.006 D [95% CI, -0.010 to -0.002 D]). The isotemporal substitution of patterns with at least 15 minutes and 2000 lux for other outdoor exposure patterns was positively associated with less myopic shift. Conclusions and Relevance: In this 1-year prospective cohort study of children with smartwatches, continuous outdoor exposure with at least 15 minutes accompanied with no less than 2000 lux sunlight intensity was associated with less myopic shift. These findings suggest that future outdoor interventions should focus not only on the overall time outdoors but also on the effective outdoor exposure patterns, as a means to effectively prevent myopia in children.

Sodium Selenite Induces Autophagy and Apoptosis in Cervical Cancer Cells via Mitochondrial ROS-Activated AMPK/mTOR/FOXO3a Pathway.

Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been fully explored. This study found that sodium selenite (SS) inhibits the viability of HeLa and SiHa cells in a dose- and time-dependent manner. Intraperitoneal injection of 3 and 6 mg/kg SS for 14 days in female nude mice significantly inhibited the growth of HeLa cell xenografts without evident hepatotoxicity or nephrotoxicity. RNA sequencing results indicated that the AMP-activated protein kinase (AMPK), Forkhead box protein O (FOXO), and apoptosis signaling pathways are key regulatory pathways in SS's anti-CC effects, and SS's inhibition of HeLa cell proliferation may be related to autophagy and ROS-induced apoptosis. Further research has revealed that SS induces cell autophagy and apoptosis through the AMPK/mTOR/FOXO3a pathway, characterized by the upregulation of p-AMPK/AMPK, FOXO3a, LC3-II, cleaved-caspase3, and cleaved-PARP and the downregulation of p-mTOR/mTOR and p62. Additionally, SS impaired mitochondrial function, including decreased mitochondrial membrane potential, mitochondrial Ca2+ overload, and accumulation of mitochondrial reactive oxygen species (mtROS). Pretreatment with Mitoquinone mesylate (Mito Q) and compound C partially reversed SS-induced apoptosis, autophagy, and proliferation inhibition. Pretreatment with 3-methyladenine (3-MA) enhances SS-induced apoptosis and proliferation inhibition in HeLa cells but reverses these effects in SiHa cells. In summary, SS induces apoptosis, autophagy, and proliferation inhibition in HeLa and SiHa cells through the activation of the AMPK/mTOR/FOXO3a signaling pathway via mtROS. Autophagy activation may be a major risk factor for SS-induced apoptosis in SiHa cells but can protect HeLa cells from SS-induced apoptosis. These findings provide new evidence for understanding the molecular mechanisms underlying SS in potential new drug development for CC.

Short-term effects of sunlight exposure on fundus blood flow perfusion in children: a randomised controlled trial.

AIM: To evaluate the short-term effects of different sunlight exposure on fundus blood flow perfusion (BFP) after near work. METHODS: In this parallel randomised controlled trial, 81 students aged 7-15 with spherical equivalent refraction between -2.00 and +3.00 diopters were randomly assigned to either a low-illuminance (4k lux) group (N=40) or high-illuminance (10k lux) (N=41). Following 1 hour indoor reading, participants had sunlight exposure matching their group's intensity for 15 minutes. BFPs in the superficial retina, deep retina and choroid were measured at four time points: pre-reading, post-reading, 5th-minute and 15th-minute sunlight exposure. RESULTS: Within the initial 5 minutes of sunlight exposure, the 10k lux group showed a tendency for decreased BFP, particularly in the choroid (superficial retina: -0.2, 95% CI -0.9 to 0.5; deep retina: -0.1, 95% CI -0.6 to 0.4; choroid: -0.4, 95% CI -0.8 to 0.0), while the 4k lux group exhibited an increase (superficial retina: 0.7, 95% CI 0.1 to 1.3; deep retina: 0.3, 95% CI -0.2 to 0.8; choroid: 0.1, 95% CI -0.2 to 0.5). From 5 to 15 minutes, BFP decreased in both groups. At the 5th-minute mark, the 10k lux group exhibited a greater decrease in choroid (10k -0.4 vs 4k 0.1, p=0.051). No significant difference was observed after 15 minutes of exposure. CONCLUSION: Higher illuminance sunlight exposure can restore fundus BFP more rapidly than lower; however, duration remains pivotal. To prevent myopia, continuous sunlight exposure for over 15 minutes is recommended to aid in reinstating the fundus BFP increased by near work. TRIAL REGISTRATION NUMBER: NCT05594732.

Spatiotemporal Epidemiological Trends of Mpox in Mainland China: Spatiotemporal Ecological Comparison Study.

BACKGROUND: The World Health Organization declared mpox an international public health emergency. Since January 1, 2022, China has been ranked among the top 10 countries most affected by the mpox outbreak globally. However, there is a lack of spatial epidemiological studies on mpox, which are crucial for accurately mapping the spatial distribution and clustering of the disease. OBJECTIVE: This study aims to provide geographically accurate visual evidence to determine priority areas for mpox prevention and control. METHODS: Locally confirmed mpox cases were collected between June and November 2023 from 31 provinces of mainland China excluding Taiwan, Macao, and Hong Kong. Spatiotemporal epidemiological analyses, including spatial autocorrelation and regression analyses, were conducted to identify the spatiotemporal characteristics and clustering patterns of mpox attack rate and its spatial relationship with sociodemographic and socioeconomic factors. RESULTS: From June to November 2023, a total of 1610 locally confirmed mpox cases were reported in 30 provinces in mainland China, resulting in an attack rate of 11.40 per 10 million people. Global spatial autocorrelation analysis showed that in July (Moran I=0.0938; P=.08), August (Moran I=0.1276; P=.08), and September (Moran I=0.0934; P=.07), the attack rates of mpox exhibited a clustered pattern and positive spatial autocorrelation. The Getis-Ord Gi* statistics identified hot spots of mpox attack rates in Beijing, Tianjin, Shanghai, Jiangsu, and Hainan. Beijing and Tianjin were consistent hot spots from June to October. No cold spots with low mpox attack rates were detected by the Getis-Ord Gi* statistics. Local Moran I statistics identified a high-high (HH) clustering of mpox attack rates in Guangdong, Beijing, and Tianjin. Guangdong province consistently exhibited HH clustering from June to November, while Beijing and Tianjin were identified as HH clusters from July to September. Low-low clusters were mainly located in Inner Mongolia, Xinjiang, Xizang, Qinghai, and Gansu. Ordinary least squares regression models showed that the cumulative mpox attack rates were significantly and positively associated with the proportion of the urban population (t0.05/2,1=2.4041 P=.02), per capita gross domestic product (t0.05/2,1=2.6955; P=.01), per capita disposable income (t0.05/2,1=2.8303; P=.008), per capita consumption expenditure (PCCE; t0.05/2,1=2.7452; P=.01), and PCCE for health care (t0.05/2,1=2.5924; P=.01). The geographically weighted regression models indicated a positive association and spatial heterogeneity between cumulative mpox attack rates and the proportion of the urban population, per capita gross domestic product, per capita disposable income, and PCCE, with high R2 values in north and northeast China. CONCLUSIONS: Hot spots and HH clustering of mpox attack rates identified by local spatial autocorrelation analysis should be considered key areas for precision prevention and control of mpox. Specifically, Guangdong, Beijing, and Tianjin provinces should be prioritized for mpox prevention and control. These findings provide geographically precise and visualized evidence to assist in identifying key areas for targeted prevention and control.

Quantification of Fundus Tessellation Reflects Early Myopic Maculopathy in a Large-Scale Population of Children and Adolescents.

Purpose: This study investigated the distribution of fundus tessellation density (FTD) in a Chinese pediatric population and its potential in reflecting early myopic maculopathy (tessellated fundus). Methods: Participants were enrolled from kindergartens, primary schools, and middle schools, with cluster sampling in Shanghai, China. A series of ophthalmic examinations was conducted. Based on fundus photograph, FTD was quantitatively assessed using an artificial intelligence algorithm, and tessellated fundus was diagnosed by well-trained ophthalmologists. Results: A total of 14,234 participants aged four to 18 years were included, with 7421 boys (52.1%). Tessellated fundus was observed in 2200 (15.5%) participants. The median of FTD was 0.86% (range 0.0-42.1%). FTD increased with age and axial length. In the logistics regression, larger FTD was independently associated with tessellated fundus (P < 0.001). The area under curves of receiver operating characteristic curve for categorizing tessellated fundus using FTD was 0.774, and the cutoff point of FTD was 2.22%. Conclusions: The density of fundus tessellation was consistent with the severity of myopia. FTD could help diagnose the early stage of myopic maculopathy, tessellated fundus, providing a new pattern for myopia screening and detection of early myopic fundus changes. Translational Relevance: Quantification of fundus tessellation with artificial intelligence could help detect early myopic maculopathy.

Long-term relatively high dietary manganese intake could decrease the risk of hyperuricemia: Twelve-year distinct dietary manganese consumption trajectories and the China Health and Nutrition Survey.

BACKGROUND AND AIM: Currently, the relationship between dynamic changes in dietary manganese (Mn) intake and risk of hyperuricemia (HU) is still unclear. This study aimed to identify dietary Mn consumption trajectories in the Chinese adults and assess their relation with the risk of HU. METHODS AND RESULTS: Cohort data from the China Health and Nutrition Survey (CHNS) 1997-2009 were employed in this study. Overall, 6886 adult participants were included. Participants were designated into subgroups based on the trajectories of dietary Mn consumption by sex. Cox proportional hazard models were used to explore the associations between different trajectories and the risk of HU. For men, compared with low stable trajectory group, moderate to high trajectory group was significantly related to reduced risk of HU (HR = 0.61, 95% CI: 0.38 to 0.98) with adjustment for covariates. TC, HDL-C, ApoB, and TG exerted partial regulation function between trajectories and HU. For women, compared with low stable trajectory group, high stable trajectory group was significantly related to reduced risk of HU (HR = 0.76, 95% CI: 0.60 to 0.95) with adjustment for covariates. Similarly, TC, HDL-C, ApoB, and ApoA exerted partial regulation function between trajectories and HU. CONCLUSIONS: Long-term relatively high dietary Mn consumption may have a protective effect against HU in Chinese adults. The differences in HU-related factors among different dietary Mn intake trajectories partially regulated the association between these trajectories and HU.

Development and validation of a smartwatch algorithm for differentiating physical activity intensity in health monitoring.

To develop and validate a machine learning based algorithm to estimate physical activity (PA) intensity using the smartwatch with the capacity to record PA and determine outdoor state. Two groups of participants, including 24 adults (13 males) and 18 children (9 boys), completed a sequential activity trial. During each trial, participants wore a smartwatch, and energy expenditure was measured using indirect calorimetry as gold standard. The support vector machine algorithm and the least squares regression model were applied for the metabolic equivalent (MET) estimation using raw data derived from the smartwatch. Exercise intensity was categorized based on MET values into sedentary activity (SED), light activity (LPA), moderate activity (MPA), and vigorous activity (VPA). The classification accuracy was evaluated using area under the ROC curve (AUC). The METs estimation accuracy were assessed via the mean absolute error (MAE), the correlation coefficient, Bland-Altman plots, and intraclass correlation (ICC). A total of 24 adults aged 21-34 years and 18 children aged 9-13 years participated in the study, yielding 1790 and 1246 data points for adults and children respectively for model building and validation. For adults, the AUC for classifying SED, MVPA, and VPA were 0.96, 0.88, and 0.86, respectively. The MAE between true METs and estimated METs was 0.75 METs. The correlation coefficient and ICC were 0.87 (p < 0.001) and 0.89, respectively. For children, comparable levels of accuracy were demonstrated, with the AUC for SED, MVPA, and VPA being 0.98, 0.89, and 0.85, respectively. The MAE between true METs and estimated METs was 0.80 METs. The correlation coefficient and ICC were 0.79 (p < 0.001) and 0.84, respectively. The developed model successfully estimated PA intensity with high accuracy in both adults and children. The application of this model enables independent investigation of PA intensity, facilitating research in health monitoring and potentially in areas such as myopia prevention and control.

Introgression of OsAP47 by marker-assisted selection enhanced resistance against southern rice black-streaked dwarf virus disease.

Southern rice black-streaked dwarf virus disease (SRBSDVD) is the most destructive viral disease in rice. In order to breeding resistant cultivars, Insertion-Deletion (InDel) markers were developed linked to OsAP47, the first isolated major resistance gene against SRBSDVD. Marker-assisted selection (MAS) was conducted to introduce this gene into the commercial variety. A rice line carrying homozygous resistance allele of OsAP47 was selected and named Kanghei No. 201 (KH201). Evaluated by artificial inoculation, KH201 showed significantly higher resistance than the recurrent parent Suxiu No.867 (SX867). And no significant differences were detected for KH201 in the yield-related components, including spikelets per panicle (SPP), ripened grains per panicle (RGPP), 1000-grain weight (TGW) and panicles per square meter (PPSM), leading to stable theoretical yield. The results indicated that introgression of OsAP47 improved rice resistance and can avoid yield losses produced by SRBSDVD. KH201 was demonstrated as a resistance material that could be used in rice breeding.

Investigation and characterization of rice dwarfing epidemic caused by southern rice black-streaked dwarf virus in Jiangsu in 2023.

During the field surveys in Jiangsu Province, China, contiguous patches of rice plants with varying degrees of dwarfing, wax-white or dark brown enations at the base of stems, and abnormal heading symptoms were observed in the fields located in Jiangning District in Nanjing City, Jurong County in Zhenjiang City, and Zhangjiagang County in Suzhou City. Through molecular analyses, the presence of southern rice black-streaked dwarf virus was confirmed in symptomatic rice plants. The infections of other rice viruses that cause dwarfing were also ruled out. Additionally, Koch's postulates were fulfilled, further validating SRBSDV as the causal agent for the observed dwarfing disease epidemic. Furthermore, the phylogenetic analyses revealed that the SRBSDV prevalent in Jiangsu in 2023 may originate from multiple regions in Vietnam. Our study has documented the emergence of an SRBSDV epidemic in Jiangsu in 2023, marking the first incidence of southern rice black-streaked dwarf disease in this region.

Effect modification of time spent outdoors on the association between early childhood overweight and myopia: a one-year follow-up study.

BACKGROUND: This study examined the moderating role of outdoor time on the relationship between overweight and myopia. METHODS: The data for this study was obtained from a prospective study in Shanghai, where non-myopic children wore wristwear and were followed up for 1 year. Eye examinations were performed at each visit. The modification effect was assessed on the additive scale using multivariable logistic regression, and relative excess risk due to interaction was used to calculate the modification effect. RESULTS: A total of 4683 non-myopic children were included with 32.20% being overweight at baseline. Following a 1-year period, 17.42% of children had myopia. When compared to those who spent <90 minutes outdoors, children who spent >120 had a relative risk of myopia onset that was reduced to 0.61. As time spent outdoors decreased, more risks of myopia onset were identified among overweight children than among normal children, the modification effect on the additive scale was -0.007, with ~70% of this effect attributed to the modifying influence of outdoor time. CONCLUSIONS: Increasing outdoor time can reduce myopia more among overweight children than normal. Future interventions should focus on outdoor activities among overweight children to reduce myopia risks.

Cutoff values of axial length/corneal radius ratio for determining myopia vary with age among 3-18 years old children and adolescents.

PURPOSE: To investigate the effectiveness and cutoffs of axial length/corneal radius (AL/CR) ratio for myopia detection in children by age. METHODS: Totally, 21 kindergartens and schools were enrolled. Non-cycloplegic autorefraction (NCAR), axial length (AL), horizontal and vertical meridian of corneal radius (CR1, CR2), and cycloplegic autorefraction were measured. Receiver operating characteristic (ROC) curve was used to obtain the effectiveness and cutoff for myopia detection. RESULTS: Finally, 7803 participants aged 3-18 years with mean AL/CR ratio of 2.99 ± 0.16 were included. Area under the ROC curve (AUC) of AL/CR ratio for myopia detection (0.958 for AL/CR1, 0.956 for AL/CR2, 0.961 for AL/CR) was significantly larger than that of AL (0.919, all P < 0.001), while AUCs of the three were similar with different cutoffs (> 2.98, > 3.05, and > 3.02). When divided by age, the ROC curves of AL/CR ratio in 3- to 5-year-olds showed no significance or low accuracy (AUCs ≤ 0.823) in both genders. In ≥ 6-year-olds, the accuracies were promising (AUCs ≥ 0.883, all P < 0.001), the cutoffs basically increased with age (from > 2.93 in 6-year-olds to > 3.07 in 18-year-olds among girls, and from > 2.96 in 6-year-olds to > 3.07 in 18-year-olds among boys). In addition, boys presented slightly larger cutoffs than girls in all ages except for 16 and 18 years old. For children aged 3-5 years, AL/CR ratio or AL combined with NCAR increased AUC to > 0.900. CONCLUSION: AL/CR ratio provided the best prediction of myopia with age-dependent cutoff values for all but preschool children, and the cutoffs of boys were slightly larger than those of girls. For preschool children, AL/CR ratio or AL combined with NCAR is recommended to achieve satisfactory accuracy. AL/CR ratio calculated by two meridians showed similar predictive power but with different cutoffs.

Anisometropia and its association with refraction development in highly myopic children.

CLINICAL RELEVANCE: Anisometropia can affect visual development in children. Investigations of anisometropia in high myopes would explore potential causes related to anisometropia, highlighting the management of anisometropia in high myopia. BACKGROUND: The prevalence of anisometropia ranged from 0.6% to 4.3% in general paediatric population and from 7% to 14% in myopes. Anisometropia is regarded as an associated factor for myopia development, while myopia progression is a stimulus driving anisometropic development. The purpose of this study was to investigate the prevalence of anisometropia and its association with refraction development in Chinese children with high myopia. METHODS: In the cohort study, a total of 1,577 highly myopic (spherical equivalent ≤-5.0D) children aged 4-18 years were included. Refractive parameters (dioptre of sphere, dioptre of cylinder, corneal curvature radius, and axial length) of both eyes were measured after cycloplegia. The prevalence and degree of anisometropia were compared among refractive groups (non-parametric tests or chi-square tests), and regression analyses were used to determine associated factors of anisometropia. The statistical significance was set to P < 0.05 (two-tailed). RESULTS: In highly myopic children with a mean (standard deviation) age of 13.06 (2.80) years, the proportions of spherical equivalent anisometropia, cylindrical anisometropia and spherical anisometropia ≥1.00 D were 34.5%, 21.9% and 39.9%, respectively. There was more spherical equivalent anisometropia associated with more severe astigmatism (P for trend <0.001). In the multivariate regression analysis, more spherical equivalent anisometropia, cylindrical anisometropia and spherical anisometropia were associated with higher degrees of astigmatism (standard beta = -0.175, -0.148 and -0.191, respectively). More spherical anisometropia was associated with better spherical power (standard beta = 0.116). CONCLUSION: The proportion of anisometropia in highly myopic children was high, compared with previously reported general population, and more severe anisometropia was associated with higher degree of cylindrical power, but not spherical power.

Activation of MAPK-mediated immunity by phosphatidic acid in response to positive-strand RNA viruses.

Increasing evidence suggests that mitogen-activated protein kinase (MAPK) cascades play a crucial role in plant defense against viruses. However, the mechanisms that underlie the activation of MAPK cascades in response to viral infection remain unclear. In this study, we discovered that phosphatidic acid (PA) represents a major class of lipids that respond to Potato virus Y (PVY) at an early stage of infection. We identified NbPLDα1 (Nicotiana benthamiana phospholipase Dα1) as the key enzyme responsible for increased PA levels during PVY infection and found that it plays an antiviral role. 6K2 of PVY interacts with NbPLDα1, leading to elevated PA levels. In addition, NbPLDα1 and PA are recruited by 6K2 to membrane-bound viral replication complexes. On the other hand, 6K2 also induces activation of the MAPK pathway, dependent on its interaction with NbPLDα1 and the derived PA. PA binds to WIPK/SIPK/NTF4, prompting their phosphorylation of WRKY8. Notably, spraying with exogenous PA is sufficient to activate the MAPK pathway. Knockdown of the MEK2-WIPK/SIPK-WRKY8 cascade resulted in enhanced accumulation of PVY genomic RNA. 6K2 of Turnip mosaic virus and p33 of Tomato bushy stunt virus also interacted with NbPLDα1 and induced the activation of MAPK-mediated immunity. Loss of function of NbPLDα1 inhibited virus-induced activation of MAPK cascades and promoted viral RNA accumulation. Thus, activation of MAPK-mediated immunity by NbPLDα1-derived PA is a common strategy employed by hosts to counteract positive-strand RNA virus infection.

Impact of the COVID-19 Pandemic on the Professional Attitudes of Medical Students: A Pre-Post-Like Study.

OBJECTIVE: This study assesses the difference in professional attitudes among medical students, both before and after coronavirus disease 2019 (COVID-19), and identifies the determinants closely associated with it, while providing precise and scientific evidence for implementing precision education on such professional attitudes. METHODS: A pre-post-like study was conducted among medical students in 31 provinces in mainland China, from March 23, to April 19, 2021. RESULTS: The proportion of medical students whose professional attitudes were disturbed after the COVID-19 pandemic, was significantly lower than before the COVID-19 pandemic (χ2 = 15.6216; P < 0.0001). Compared with the "undisturbed -undisturbed" group, the "undisturbed-disturbed" group showed that there was a 1.664-fold risk of professional attitudes disturbed as grade increased, 3.269-fold risk when others suggested they choose a medical career rather than their own desire, and 7.557-fold risk for students with COVID-19 in their family, relatives, or friends; while the "disturbed-undisturbed" group showed that students with internship experience for professional attitudes strengthened was 2.933-fold than those without internship experience. CONCLUSIONS: The professional attitudes of medical students have been strengthened during the COVID-19 pandemic. The results provide evidence of the importance of education on professional attitudes among medical students during public health emergencies.

Yield components affected by rice black-streaked dwarf virus disease in rice cultivars with different resistance levels.

Introduction: Rice black-streaked dwarf virus disease (RBSDVD) is one of the most destructive rice viral diseases, leading to severe yield losses in rice production. However, little is known about the yield-related components associated with the disease and no resistance cultivars have been successfully used in rice breeding. Methods: Seven rice cultivars were analyzed in this study, including six commercial rice varieties and a new line Zhongjian No. 201 (ZJ201) containing the resistance gene OsAP47. Resistance levels of these cultivars were evaluated by artificial inoculation and yield components were collected, including panicle length (PL), spikelets per panicle (SPP), ripened grains per panicle (RGPP), as well as panicles per square meter (PPSM) and 1000-grain weight (TGW). Seed setting rate (SSR) were calculated with the data of SPP and RGPP. Results and discussion: The results showed that ZJ201 displayed the highest resistance level and most of the commercial rice cultivars exhibited susceptible to RBSDVD. Yields of all the rice cultivars were significantly declined except ZJ201 and yield losses produced by RBSDVD were mainly due to the reduction of PL, SPP, RGPP, and TGW, suggesting that developments of these traits are associated with RBSDV infection. Resistant rice cultivar could reduce yield losses by maintaining normal development of these traits. Significant correlations were identified between resistance levels and the yield components except SSR and PPSM. The results provided useful clues for understanding the mechanisms of RBSDV invasion and its effect on rice production. ZJ201 was demonstrated as a resistance material that could be used in rice breeding.