Association of sleep disturbances with diminished ovarian reserve in women undergoing infertility treatment.

With an aging population seeking infertility treatment, diminished ovarian reserve (DOR) is a prevalent indication for assisted reproductive technology (ART). This study aims to investigate the relationship between sleep parameters and DOR among women attending an infertility clinic. Methods We consecutively enrolled women attending an infertility clinic from July 2020 to June 2021. Participants completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale(ESS), and STOP-Bang Questionnaire to assess self-reported sleep quality. DOR-related indices including antral follicle count, anti-Müllerian hormone(AMH), follicle-stimulating hormone (FSH) were evaluated. A total of 979 women were enrolled, with 148 classified into the DOR group and 831 in the non-DOR group. The DOR group was notably older compared to the non-DOR group. Analysis showed that the DOR group exhibited significantly shorter sleep onset latency (p = 0.001) and shorter total sleep duration (p = 0.014) compared to the non-DOR group. Logistic regression analysis identified age, PSQI-sleep latency, and PSQI score as independent factors associated with an increased risk of DOR(all p < 0.05). Furthermore, stratified analysis by age group revealed that snoring and PSQI-sleep latency were particularly notable risk factors for DOR among women aged 35 years and older (OR = 2.489, p = 0.040; OR = 2.007, p = 0.008, respectively). Our study highlights that shorter sleep onset latency and shorter total sleep duration may be associated with DOR among women undergoing ART treatments. Particularly noteworthy, snoring and sleep latency were identified as additional risk factors for DOR among women aged 35 years and older.

Axial Shortening Effects of Repeated Low-level Red-light Therapy in Children with High Myopia: A Multicenter Randomized Controlled Trial.

PURPOSE: To evaluate the effectiveness and safety of RLRL in delaying the progression of high myopes -6.00 D or worse. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial. PARTICIPANTS: Two hundred and two high myopic children aged 7 to 12 years with cycloplegia spherical equivalent refraction (SE) ≤ -6.00 D, astigmatism less than 2.50 D, anisometropia of 1.50 D or less were enrolled from March 2022 to December 2022. Follow-up was completed in December 2023. METHODS: Eligible participants were randomly allocated to either the intervention (RLRL + single vision spectacle [SVS]) or the control group (SVS). The RLRL treatment was administered every day for 3 minutes, twice a day, with an interval of at least 4 hours. MAIN OUTCOMES MEASURES: The primary outcome was the change in axial length (AL) at 12 months compared to baseline. Secondary outcomes included changes in SE, changes of choroidal thickness (ChT) and retinal thickness (RT) in different circle sectors. Outcomes were analyzed by means of intention-to-treat and per-protocol methods. RESULTS: After 12-month treatment, AL and SE changes were -0.11 ± 0.25 mm and 0.18 ± 0.63 D for RLRL group and 0.32 ± 0.09 mm and -0.80 ± 0.42 D for control group. Axial shortening > 0.05 mm was observed to 59% in the RLRL and 0% in the control group at 12 months. ChT and RT from a single center were analyzed. In the RLRL group, ChT were thickened in all sectors at 12 months. RT was increased in parafoveal and perifoveal circles. In the control group, all sectors of ChT and only perifoveal RT were significantly thinner at 12 months. The multivariate linear regression model revealed significant correlations between changes in ChT central foveal circle and RT perifoveal circle at 1 month and AL changes at 12 months. No fundus structure changes, afterimage exceeding 6 minutes nor best corrected visual acuity decreased reported. CONCLUSIONS: RLRL could effectively shorten the AL and inhibit the progression of myopia in high myopic patients -6.00 D or worse. AL shortening is sustained over 12 months of treatment. These observed changes appeared to be associated with increases in ChT and RT.

Single-cell RNA sequencing reveals intratumoral heterogeneity and multicellular community in primary hepatocellular carcinoma underlying microvascular invasion.

Background: Microvascular invasion (MVI) is associated with an unfavorable prognosis and early recurrence of hepatocellular carcinoma (HCC), which is the crucial pathological hallmark of immunotherapy. While microvascular invasion (MVI) in hepatocellular carcinoma (HCC) currently lacks a detailed single-cell analysis of the tumor microenvironment (TME), it holds significant promise for immunotherapy using immune checkpoint inhibitors (ICI). Methods: We performed single-cell RNA sequencing (scRNA-seq) on 3 MVI positive (MVIP) and 14 MVI-negative (MVIN) tumor tissues, as well as their paired adjacent non-tumoral tissues. Results: We identified SPP1+ macrophages and CD4+ proliferative T cells as intertumoral populations critical for the formation of cold tumors and immunosuppressive environments in MVI-positive patients and verified their prognostic value in correlation with MVIP HCC patients. Additionally, we identified SPP1+ dominated interactions between SPP1+ macrophages and the immunosuppressive T population as contributors to MVI destruction and tumorigenesis. Conclusions: We provide a comprehensive single-cell atlas of HCC patients with MVI, shedding light on the immunosuppressive ecosystem and upregulated signaling associated with MVI. These findings demonstrate that intercellular mechanisms drive MVI and provide a potential immunotherapeutic target for HCC patients with HCC and underlying MVI.

Genome-Wide Survey of the Potential Function of CrLBDs in Catharanthus roseus MIA Biosynthesis.

Catharanthus roseus (C. roseus) can produce over 150 types of monoterpenoid indole alkaloids (MIAs), including vinblastine and vincristine, which are currently the primary sources of these alkaloids. Exploring the complex regulatory mechanisms of C. roseus is significant for resolving MIA biosynthesis. The Lateral Organ Boundaries Domain (LBD) is a plant-specific transcription factor family that plays crucial roles in the physiological processes of plant growth, stress tolerance, and specialized metabolism. However, the LBD gene family has not been extensively characterized in C. roseus, and whether its members are involved in MIA biosynthesis is still being determined. A total of 34 C. roseus LBD (CrLBD) genes were identified. RNA-Seq data were investigated to examine the expression patterns of CrLBD genes in various tissues and methyl jasmonate (MeJA) treatments. The results revealed that the Class Ia member CrLBD4 is positively correlated with iridoid biosynthetic genes (p < 0.05, r ≥ 0.8); the Class IIb member CrLBD11 is negatively correlated with iridoid biosynthetic genes (p < 0.05, r ≤ -0.8). Further validation in leaves at different growth stages of C. roseus showed that CrLBD4 and CrLBD11 exhibited different potential expression trends with iridoid biosynthetic genes and the accumulation of vindoline and catharanthine. Yeast one-hybrid (Y1H) and subcellular localization assays demonstrated that CrLBD4 and CrLBD11 could bind to the "aattatTCCGGccgc" cis-element and localize to the nucleus. These findings suggest that CrLBD4 and CrLBD11 may be potential candidates for regulating MIA biosynthesis in C. roseus. In this study, we systematically analyzed the CrLBD gene family and provided insights into the roles of certain CrLBDs in the MIA biosynthesis of C. roseus.

Effect of snoring on pregnant women and fetal outcomes: a cross sectional study.

PURPOSE: Snoring frequently occurs among pregnant women, particularly in the later stages of pregnancy. It often signals obstructive sleep apnea (OSA), which could potentially affect pregnancy outcomes negatively. Hence, our study aimed to investigate how snoring influences the likelihood of pregnancy complications and fetal outcomes in a cohort of expectant mothers. METHODS: We enrolled pregnant women in their second and third trimesters and had them fill out a questionnaire concerning sleep-related symptoms such as snoring, excessive daytime sleepiness, and frequency of nighttime awakenings, along with anthropometric measurements. Subsequently, the participants were divided into snorers and non-snorers, and the occurrence of pregnancy complications and fetal outcomes was monitored. RESULTS: The study enrolled a total of 212 pregnant women, among whom 35 were identified as snorers and 177 as non-snorers during mid to late pregnancy. This indicated a snoring prevalence of 16.5% in our sample. Significant differences were noted between the two groups regarding the occurrence of oligohydramnios (11.43% vs. 2.82%, p = 0.044) and fetal distress (28.57% vs. 8.47%, p = 0.003). Logistic regression analyses revealed that snoring was independently associated with fetal distress (odds ratio [OR] = 4.99, 95% confidence interval [CI] 1.88-13.23, p = 0.001). CONCLUSIONS: Our findings suggest that habitual snoring was the independent risk factor fetal distress after adjusting for potential confounders, indicating that habitual snoring may have a detrimental effect during mid to late pregnancy.

Nanoconfined Supercooled Water in Hydrated Two-Dimensional Polyaniline for Sub-Zero Solid-State Zinc-Ion Hybrid Capacitor.

Solid-state electrochemical energy systems have attracted numerous attentions for their excellent performance, high safety, and low cost. Recently, ice of aqueous electrolytes is reported as a new kind solid-state electrolyte for low-temperature solid-state devices. However, the lack of kinetically favorable electrodes hampers the performance of this new class of icy electrolyte-based solid-state devices at sub-zero temperatures. In this work, a hydrated layered polyaniline cathode active material (h-LPANi) with nanoconfined supercooled water by metatungstate clusters is utilized to improve the performance of sub-zero solid-state zinc ion hybrid capacitors (ZIHCs). The interlayer confined hydrated network of h-LPANi improves kinetics, surpassing pristine polyaniline and conventional porous carbon-based active materials. At -15 °C, the solid-state iced ZIHCs with h-LPANi cathode demonstrate an areal energy density of 580.0 µWh cm-2 at 1.1 mW cm-2 and 155.7 µWh cm-2 at 43.3 mW cm-2, surpassing other low-temperature solid-state ZIHCs with conventional cathodes.

Fundus morphological characteristics assesment in high myopia patients with or without posterior scleral staphyloma by optical coherence tomography.

OBJECTIVE: To observe the morphological characteristics of posterior scleral staphyloma (PSS) with or without macular retinoschisis (MRS) using optical coherence tomography (OCT). Additionally, the incidence and severity of other pathologic myopic maculopathy associated with posterior scleral staphyloma was also evaluated. METHODS: General information and OCT imaging data from 440 patients with posterior scleral staphyloma (PSS) and the PSS curvature > 20×10-3 µm-1 were collected. These patients visited the Department of Ophthalmology at the First Affiliated Hospital of Harbin Medical University from January 2013 to June 2021. The obtained OCT images of PSS were analyzed using the Image J software to measure the curvature along the Bruch's membrane. The measured curvature was divided into four levels using the quartile method. The classification of macular retinoschisis (MRS) was based on the anatomical structure of the retina and the location of macular retinoschisis. Patients with PSS accompanied by MRS were assigned to the MRS group, while PSS patients without MRS were assigned to the non-MRS group. Additionally, typical OCT changes in other pathologic myopic maculopathy diseases, such as myopic choroidal neovascularization (mCNV), myopic traction maculopathy (MTM), and myopic foveoschisis (MF), were recorded and evaluated. RESULTS: A total of 615 eyes (328 right eyes, 287 left eyes) from 440 patients (80 males and 360 females) were recruited in this study. The MRS group consisted of 159 patients (36.1%) with 190 eyes (30.9%), while the non-MRS group consisted of 281 patients (63.9%) with 425 eyes (69.1%). Both groups had a significantly higher proportion of female patients compared to male patients, and the right eye was more commonly affected than the left eye. In the MRS group, the prevalence of MRS increased progressively with the severity of PSS. Among the common posterior pole diseases, epiretinal membrane had the highest prevalence (33.2%), while lamellar macular hole had the lowest prevalence (5.3%). In the non-MRS group, the proportion of PSS in each group decreased progressively (except for an equal prevalence in the third and fourth levels) with increasing severity of PSS. Among the common posterior pole diseases, choroidal neovascularization had the highest prevalence (41.4%), while lamellar macular hole had the lowest prevalence (6.5%). When comparing the two groups, there were no significant differences in age, gender, and eye distribution. The MRS group had a higher prevalence of macular schisis, retinal detachment, and dome-shaped macula (17.9%, 14.2%, 14.8%) compared to the non-MRS group (11.3%, 9.2%, 9.6%). The non-MRS group had a significantly higher prevalence of choroidal neovascularization (41.4%) compared to the MRS group (12.6%), while there were no significant differences in the prevalence of epiretinal membrane and lamellar macular hole between the two groups. CONCLUSION: The prevalence of MRS increased progressively with the severity of PSS, and the MRS occurrence was positively correlated with PSS, which indicated that PSS may lead to MRS, while the proportion of PSS in each group decreases gradually with the severity of PSS in the non-MRS group decreased progressively (except for an equal prevalence in the third and fourth levels). In the MRS group, outer macular retinoschisiss were most relevant to posterior scleral staphyloma, and the prevalence of macular holes and retinal detachments was higher in the MRS group compared to the non-MRS group, indicating that MRS may further turn into complications such as macular holes and retinal detachments, which can significantly affect vision or lead to blindness. The prevalence of choroidal neovascularization (CNV) was significantly higher in the non-MRS group compared to the MRS group, suggesting that PSS with lower severity is more prone to develop into CNV. Dome-shaped macula (DSM) seems to play a protective role in the development of pathologic myopia, and abnormal changes in posterior scleral staphyloma curvature may be an important factor affecting the development and shape of DSM.

Triglyceride-glucose index and combined indicators: effective indicators for screening NAFLD in snoring patients.

AIMS: Nonalcoholic fatty liver disease (NAFLD) is a common complication in snoring patients, especially in patients with obstructive sleep apnea syndrome (OSA). Triglyceride-glucose (TyG) index was a simple indicator of metabolic status and a surrogate marker of insulin resistance. This study aimed to explore the relationship between NAFLD and TyG index in snoring patients. METHODS: A retrospective study was conducted. The successive snoring patients enrolled in the Sleep Center of the First Affiliated Hospital of Fujian Medical University and had abdominal ultrasonography were included. The clinical characteristics of patients in different quartile TyG groups were compared. The relationship of the TyG index and NAFLD were valued via logistic regression models and restricted cubic spline analysis. The value of TyG index in predicting NAFLD was determined by receiver operating characteristic curve (ROC curve). RESULTS: A total of 463 NAFLD cases were found among the 654 snoring patients. TyG index was a risk factor of NAFLD in snoring patients (OR = 2.38, 95% CI = 1.71-3.36). The risk of NAFLD was much higher in patients with the highest quartile of TyG index (OR = 5.12, 95% CI = 2.85-9.22), compared with the lowest quartile group. Restricted cubic spline (RCS) analysis showed a significant dose-response relationship between TyG index and risk of NAFLD (p for non-linearity < 0.001). A combination of TyG, neck circumference and ESS score presented the acceptable AUC for the detection of NAFLD in snoring patients (0.746, 95% CI 0.701-0.790, p < 0.001). CONCLUSION: The TyG index was a risk factor of NAFLD in snoring patients. A combination of TyG, neck circumferences and ESS score could act as a convenient and effective indicator for screening NAFLD in snoring patients.

Quantum Molecular Docking with a Quantum-Inspired Algorithm.

Molecular docking (MD) is a crucial task in drug design, which predicts the position, orientation, and conformation of the ligand when it is bound to a target protein. It can be interpreted as a combinatorial optimization problem, where quantum annealing (QA) has shown a promising advantage for solving combinatorial optimization. In this work, we propose a novel quantum molecular docking (QMD) approach based on a QA-inspired algorithm. We construct two binary encoding methods to efficiently discretize the degrees of freedom with an exponentially reduced number of bits and propose a smoothing filter to rescale the rugged objective function. We propose a new quantum-inspired algorithm, hopscotch simulated bifurcation (hSB), showing great advantages in optimizing over extremely rugged energy landscapes. This hSB can be applied to any formulation of an objective function under binary variables. An adaptive local continuous search is also introduced for further optimization of the discretized solution from hSB. Concerning the stability of docking, we propose a perturbation detection method to help rank the candidate poses. We demonstrate our approach on a typical data set. QMD has shown advantages over the search-based Autodock Vina and the deep-learning DIFFDOCK in both redocking and self-docking scenarios. These results indicate that quantum-inspired algorithms can be applied to solve practical problems in drug discovery even before quantum hardware become mature.

Efficient molecular conformation generation with quantum-inspired algorithm.

CONTEXT: Conformation generation, also known as molecular unfolding (MU), is a crucial step in structure-based drug design, remaining a challenging combinatorial optimization problem. Quantum annealing (QA) has shown great potential for solving certain combinatorial optimization problems over traditional classical methods such as simulated annealing (SA). However, a recent study showed that a 2000-qubit QA hardware was still unable to outperform SA for the MU problem. Here, we propose the use of quantum-inspired algorithm to solve the MU problem, in order to go beyond traditional SA. We introduce a highly compact phase encoding method which can exponentially reduce the representation space, compared with the previous one-hot encoding method. For benchmarking, we tested this new approach on the public QM9 dataset generated by density functional theory (DFT). The root-mean-square deviation between the conformation determined by our approach and DFT is negligible (less than about 0.5Å), which underpins the validity of our approach. Furthermore, the median time-to-target metric can be reduced by a factor of five compared to SA. Additionally, we demonstrate a simulation experiment by MindQuantum using quantum approximate optimization algorithm (QAOA) to reach optimal results. These results indicate that quantum-inspired algorithms can be applied to solve practical problems even before quantum hardware becomes mature. METHODS: The objective function of MU is defined as the sum of all internal distances between atoms in the molecule, which is a high-order unconstrained binary optimization (HUBO) problem. The degree of freedom of variables is discretized and encoded with binary variables by the phase encoding method. We employ the quantum-inspired simulated bifurcation algorithm for optimization. The public QM9 dataset is generated by DFT. The simulation experiment of quantum computation is implemented by MindQuantum using QAOA.

Biochemical targets of the micropeptides encoded by lncRNAs.

Long non-coding RNAs (lncRNAs) are a group of transcripts longer than 200 nucleotides, which play important roles in regulating various cellular activities by the action of the RNA itself. However, about 40% of lncRNAs in human cells are potentially translated into micropeptides (also referred to as microproteins) usually shorter than 100 amino acids. Thus, these lncRNAs may function by both RNAs directly and their encoded micropeptides. The micropeptides encoded by lncRNAs may regulate transcription, translation, protein phosphorylation or degradation, or subcellular membrane functions. This review attempts to summarize the biochemical targets of the micropeptides-encoded by lncRNAs, which function by both RNAs and micropeptides, and discuss their associations with various diseases and their potentials as drug targets.

Effectiveness of repeated low-level red light in myopia prevention and myopia control.

BACKGROUND/AIMS: To compare the effects of repeated low-level red light (RLRL) treatment on axial length growth and refractive error changes in myopic and premyopic children. METHODS: Subjects were assigned randomly to four subgroups: myopia-RLRL group (M-RL), myopia-control group (M-C), premyopia-RLRL group (PM-RL) and premyopia-control group (PM-C). Subjects in the RLRL group completed a 12-month treatment composed of a 3 min RLRL treatment session twice daily, with an interval of at least 4 hours, for 7 days per week. Visits were scheduled before and at 1-month, 3-month, 6-month, 9-month and 12-month follow-up after the treatment. Repeated-measures analysis of variance was used to compare the spherical equivalent refractive errors (SE) and axial length (AL) changes between the groups across the treatment period. RESULTS: After 12 months of treatment, in the myopia group, SE and AL changes were -0.078±0.375 D and 0.033±0.123 mm for M-RL and -0.861±0.556 D and 0.415±0.171 mm for M-C; in the premyopia group, the progression of SE and AL was -0.181±0.417 D and 0.145±0.175 mm for PM-RL and -0.521±0.436 D and 0.292±0.128 mm for PM-C. PM-RL indicated a lower myopia incidence than PM-C (2.5% vs 19.4%). Additionally, the percentage of AL shortening in the M-RL was higher than that in the PM-RL before the 9-month follow-up. CONCLUSION: RLRL effectively delayed myopia progression in children with myopia and reduced the incidence of myopia in premyopic children. Moreover, RLRL exhibited a stronger impact on myopic children compared with premyopic individuals.

Impact of COVID-19 Nonpharmaceutical Interventions on Respiratory Syncytial Virus Infections in Hospitalized Children.

BACKGROUND: Nonpharmaceutical interventions (NPIs) targeted at SARS-CoV-2 have remarkably affected the circulation of other respiratory pathogens, including respiratory syncytial virus (RSV). This study aimed to assess the changes in epidemiological and clinical characteristics of RSV infections in hospitalized children before and during the pandemic in Suzhou, China. METHODS: We prospectively enrolled children aged < 18 years who were hospitalized in Soochow University Affiliated Children's Hospital with acute lower respiratory infection (ALRIs) from January 2018 to July 2022. Changes in epidemiological and clinical characteristics of RSV infections were analyzed. RESULTS: Compared with the same period in 2018-2019, the difference in the overall positive rate of RSV was not statistically significant in 2020, while it increased significantly in 2021 (11.8% [662/5621] vs. 20.8% [356/1711], p < 0.001) and 2022 (9.0% [308/3406] vs. 18.9% [129/684], p < 0.001). Specifically, the positive rates declined considerably from October to December 2020 but sharply increased during the summer of 2021. Compared to prepandemic period, RSV infections were more frequently observed in older children during the pandemic. RSV-positive children exhibited milder clinical characteristics during the COVID-19 pandemic, including decreased proportion of patients with hospital stay ≥ 11 days (10.3% vs. 6.7%, p < 0.05), less requirement for oxygen therapy (13.7% vs. 6.9%, p < 0.001), and fewer cases of polypnea (12.2% vs. 9.7%, p < 0.05) and wheeze (50.1% vs. 42.9%, p < 0.001). CONCLUSIONS: The implementation of multilayered NPIs targeted at COVID-19 has affected the activity of RSV. Ongoing monitoring of RSV is warranted as the changing RSV epidemiology can provide valuable insights for future healthcare system planning.

Heterostructured WOx/W2C Nanocatalyst for Li2S Oxidation in Lithium-Sulfur Batteries with High-Areal-Capacity.

Lithium-sulfur (Li-S) batteries show extraordinary promise as a next-generation battery technology due to their high theoretical energy density and the cost efficiency of sulfur. However, the sluggish reaction kinetics, uncontrolled growth of lithium sulfide (Li2S), and substantial Li2S oxidation barrier cause low sulfur utilization and limited cycle life. Moreover, these drawbacks get exacerbated at high current densities and high sulfur loadings. Here, a heterostructured WOx/W2C nanocatalyst synthesized via ultrafast Joule heating is reported, and the resulting heterointerfaces contribute to enhance electrocatalytic activity for Li2S oxidation, as well as controlled Li2S deposition. The densely distributed nanoparticles provide abundant binding sites for uniform deposition of Li2S. The continuous heterointerfaces favor efficient adsorption and promote charge transfer, thereby reducing the activation barrier for the delithiation of Li2S. These attributes enable Li-S cells to deliver high-rate performance and high areal capacity. This study provides insights into efficient catalyst design for Li2S oxidation under practical cell conditions.

The Unneglectable Disease Burden of Otitis Media Among Children in China: A Systematic Review and Meta-analysis.

BACKGROUND: Otitis media (OM) is one of the most commonly diagnosed infections among children yet with obscure disease burden. METHODS: The literature published from 1980 to 2022 was retrieved in PubMed, Ovid-EMBASE, Web of Science, CNKI, Wanfang and VIP. Literature screening, quality assessment and data extraction were conducted by 2 independent reviewers. Heterogeneity and publication bias were detected by I2 , Egger's and Begg's tests. The data were pooled using the random-effects model. The number of OM cases was estimated by the multiplied model based on pooled results and the 2020 China census data. RESULTS: A total of 28,378 literatures were identified with 67 finally included for data analysis. The OM incidence among children was 7.89% [95% confidence interval (CI): 5.43%-11.33%] and the prevalence of OM was 5.13% (95% CI: 3.49%-7.49%). The most common pathogen of the OM cases was Streptococcus pneumoniae ( S. pneumoniae ), with a positive rate of 33.52% (95% CI: 26.55%-41.29%). The most common serotypes of S. pneumoniae isolated from OM cases were serotypes 19F, 19A, 6B, 23F and 3, with 85.8% covered by the PCV13. We estimated that there were 8,950,797 (95% CI: 6,080,533-12,928,051) OM cases among under-fives in China in 2020, of which 3,374,451 (95% CI: 1,698,901-6,277,862) cases of OM were caused by S. pneumoniae . CONCLUSIONS: The burden of OM in China was considerable yet neglected. To date, S. pneumoniae was the most frequently detected bacterial pathogen of OM. Vaccination may be effective to protect young children from OM.

The Effects of Repeated Low-Level Red-Light Therapy on the Structure and Vasculature of the Choroid and Retina in Children with Premyopia.

INTRODUCTION: The purpose of this study was to explore the effects of repeated low-level red-light (RLRL) therapy on the structure and vasculature of the choroid and retina in Chinese children with premyopia. METHODS: This study was a single-center randomized clinical trial. A total of 94 children with premyopia (- 0.50 D < spherical equivalent [SE] ≤ + 0.75 D) were randomly assigned to either the RLRL therapy or control group. Follow-up visits were planned at 1, 3, 6, 9, and 12 months. Optical coherence biometry was used to measure axial length (AL) and anterior segment parameters. Choroidal thickness (CT), retinal thickness (RT), superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), choriocapillaris perfusion area (CCPA), and choroidal vessel volume (CVV) were measured by optical coherence tomography angiography, centered on the foveal, parafoveal (ParaF), and perifoveal (PeriF) regions. RESULTS: The thickening of the choroid was observed across the entire macular region at different time points in the RLRL therapy group. Relative to the baseline measurement, foveal CT significantly increased at the 1-month follow-up with RLRL therapy, with a mean (± standard deviation [SD]) adjusted change of 16.96 ± 19.87 µm. The greatest magnitude of foveal CT changes was observed at the 3-month visit (an increase of 19.58 ± 20.59 µm), with a slight reduction in the extent of foveal CT increase at the 6-month visit (an increase of 15.85 ± 23.77 µm). The second greatest CT increase was observed at the 9-month visit (an increase of 19.57 ± 35.51 µm), after which the extent of CT increase gradually decreased until the end of the study at the 12-month visit (an increase of 11.99 ± 32.66 µm). We also observed a significant increase in CT in the ParaF and PeriF areas in the RLRL group over 12 months. In contrast, CT across the entire macular region in the control group significantly decreased throughout the follow-up visits (all P < 0.05). Regarding the vascular parameters of the choroid, significant increases in CVV were observed primarily in the ParaF and PeriF regions of the choroid in the RLRL group. In comparison, the control group exhibited decreases in CVV throughout the entire area. Furthermore, notable elevations in CCPA were detected in the PeriF area of the choroid in the RLRL group during the 1-month (an increase of 0.40 mm2), 3-month (an increase of 0.25 mm2), and 12-month visits (an increase of 0.42 mm2) (all P < 0.05). In addition, no notable differences were observed between the groups regarding foveal RT and retinal vascular parameters throughout the 12 months (P > 0.05). Notably, RLRL therapy achieved a notable reduction in SE shift by 73.8%, a substantial decrease in AL change by 67.9%, and a significant reduction in myopia incidence by 45.1% within 1 year. CONCLUSION: Our study demonstrated a significant increase in CT and flow in the RLRL-treated eyes throughout the 12-months of the study. Combined with its reduction in spherical equivalent progression and axial elongation, RLRL could be used as an effective therapy for preventing progression in premyopes. TRIAL REGISTRATION: ChiCTR2200062028.

Modeling the optimal seasonal monoclonal antibody administration strategy for respiratory syncytial virus (RSV) prevention based on age-season specific hospitalization rate of RSV in Suzhou, China, 2016-2022.

BACKGROUND: The approval of nirsevimab brings light to reducing the heavy disease burden caused by respiratory syncytial virus (RSV). Considering the seasonality of RSV, the timing of administrating monoclonal antibody (mAb) is critical to maximize health utility. This study aimed to model and seek the optimal seasonal mAb administration strategy for preventing RSV-associated hospitalization. METHODS: Age-season specific hospitalization rates for RSV-associated acute lower respiratory infection (RSV-ALRI) were estimated from a hospital-based birth cohort. Using these rates, we simulated and evaluated the effect of diverse mAb administration strategies on preventing RSV-ALRI hospitalization. Optimal strategies were selected based on their effectiveness and relative cost-effectiveness. RESULTS: Compared with the year-round strategy of administration mAb at birth for all children, 291 out of the 854 candidate strategies, featuring diverse administration timing and age thresholds, demonstrated a greater number of averted RSV-ALRI hospitalizations and a lower number needed to treat (NNT). The NNT represents the number of mAb doses needed to prevent one case of RSV-ALRI hospitalization. Among the 291 strategies, administration mAb to children born in July-January or August-January at birth and administrating to the remaining <12 months old children in September, exhibited the highest increase in averted RSV-ALRI hospitalizations than the year-round strategy, with a magnitude of 23 %, while also achieve an 18 % reduction in NNT. CONCLUSION: Administrating monoclonal antibodies to children born in July to January at birth, and administrating to the remaining <1-year-old children in September or October would be the optimal seasonal mAb administration strategy for children in Suzhou, China.

Disease Burden of Meningitis Caused by Streptococcus pneumoniae Among Under-Fives in China: A Systematic Review and Meta-analysis.

INTRODUCTION: Streptococcus pneumoniae is the leading cause of meningitis, with a case fatality of up to about 50%. Children younger than 5 years are at greater risk for pneumococcal meningitis compared with other populations. It is of significant importance to provide a comprehensive understanding of the burden of pneumococcal meningitis among under-fives in the low pneumococcal conjugate vaccine (PCV) coverage period in China. METHODS: A systematic review was conducted. We searched both English (PubMed, Ovid-EMBASE, Biosis, Web of Science, and Cochrane) and Chinese (CNKI, Wanfang, and ViP) databases for studies on bacterial meningitis in China published between January 1980 and July 2022. Ineligible studies were excluded based on study design and data integrity. Heterogeneity was assessed with I2 and estimates of bacterial meningitis morbidity and mortality were pooled using random-effects models. Subgroup analysis was conducted to trace the source of the heterogeneity and summarize average estimates. RESULTS: A total of 13,082 studies were identified in the literature, and 56 studies were finally included for data analysis. The estimated incidence of pneumococcal meningitis was 2.10 cases per 100,000 children younger than 5 years each year (95% CI: 0.59-7.46), with a pooled case fatality rate of 24.59% (95%CI: 19.35-30.28%) in China. It was estimated that 1617.16 (95% CI: 454.35-5744.78) pneumococcal meningitis cases and 548.86 (95% CI: 474.80-627.62) deaths occurred among under-fives in China in 2020. Streptococcus pneumoniae played an important role in the etiology of confirmed bacterial meningitis cases, with a pooled proportion of 22.05% (95% CI: 17.83-26.27%). The most prevalent serotypes were 6B, 14, 19F, 19A, and 23F, which were preventable with a vaccine. CONCLUSIONS: Pneumococcal meningitis remains one of the most important health problems among children younger than 5 years in China. Immunization programs should be promoted to avoid preventable cases and deaths.