Potential therapeutic strategies to halt viral neuroinvasion.

The viral infection of the central nervous system is a significant public health concern. So far, most clinical cases of viral neuroinvasion are dealt with supportive and/or symptomatic treatments due to the unavailability of specific treatments. Thus, developing specific therapies is required to alleviate neurological symptoms and disorders. In this review, we shed light on molecular aspects of viruses' entry into the brain which upon targeting with specific drugs have shown promising efficacy in vitro and in preclinical in vivo model systems. Further assessing the therapeutic potential of these drugs in clinical trials may offer opportunities to halt viral neuroinvasion in humans.

Japanese encephalitis virus NS1 and NS1' protein disrupts the blood-brain barrier through macrophage migration inhibitory factor-mediated autophagy.

Flaviviruses in the Japanese encephalitis virus (JEV) serogroup, such as JEV, West Nile virus, and St. Louis encephalitis virus, can cause severe neurological diseases. The nonstructural protein 1 (NS1) is a multifunctional protein of flavivirus that can be secreted by infected cells and circulate in the host bloodstream. NS1' is an additional form of NS1 protein with 52 amino acids extension at its carboxy-terminal and is produced exclusively by flaviviruses in the JEV serogroup. In this study, we demonstrated that the secreted form of both NS1 and NS1' can disrupt the blood-brain barrier (BBB) of mice, with NS1' exhibiting a stronger effect. Using the in vitro BBB model, we found that treatment of soluble recombinant JEV NS1 or NS1' protein increases the permeability of human brain microvascular endothelial cells (hBMECs) and leads to the degradation of tight junction proteins through the autophagy-lysosomal pathway. Consistently, NS1' protein exhibited a more pronounced effect compared to NS1 in these cellular processes. Further research revealed that the increased expression of macrophage migration inhibitory factor (MIF) is responsible for triggering autophagy after NS1 or NS1' treatment in hBMECs. In addition, TLR4 and NF-κB signaling was found to be involved in the activation of MIF transcription. Moreover, administering the MIF inhibitor has been shown to decrease viral loads and mitigate inflammation in the brains of mice infected with JEV. This research offers a novel perspective on the pathogenesis of JEV. In addition, the stronger effect of NS1' on disrupting the BBB compared to NS1 enhances our understanding of the mechanism by which flaviviruses in the JEV serogroup exhibit neurotropism.IMPORTANCEJapanese encephalitis (JE) is a significant viral encephalitis worldwide, caused by the JE virus (JEV). In some patients, the virus cannot be cleared in time, leading to the breach of the blood-brain barrier (BBB) and invasion of the central nervous system. This invasion may result in cognitive impairment, behavioral disturbances, and even death in both humans and animals. However, the mechanism by which JEV crosses the BBB remains unclear. Previous studies have shown that the flavivirus NS1 protein plays an important role in causing endothelial dysfunction. The NS1' protein is an elongated form of NS1 protein that is particularly produced by flaviviruses in the JEV serogroup. This study revealed that both the secreted NS1 and NS1' of JEV can disrupt the BBB by breaking down tight junction proteins through the autophagy-lysosomal pathway, and NS1' is found to have a stronger effect compared to NS1 in this process. In addition, JEV NS1 and NS1' can stimulate the expression of MIF, which triggers autophagy via the ERK signaling pathway, leading to damage to BBB. Our findings reveal a new function of JEV NS1 and NS1' in the disruption of BBB, thereby providing the potential therapeutic target for JE.

Revealing the mechanism of central pain hypersensitivity in primary dysmenorrhea: evidence from neuroimaging.

Background: Primary dysmenorrhea (PDM) is the most common problem in menstruating women. A number of functional magnetic resonance imaging (fMRI) study have revealed that the brain plays a crucial role in the pathophysiology of PDM. However, these results have been inconsistent, and there is a lack of a comprehensive fMRI study to clarify the onset and long-term effects of PDM. The aim of this study was thus to investigate the onset and long-term effects of PDM in a cohort of patients with PDM. Methods: This study employed a cross-sectional design with prospective data collection, in which 25 patients with PDM and 20 healthy controls (HCs) were recruited. The patients with PDM underwent fMRI scans both during the PDM during the pain phase (PDM-P) and nonpain phase (PDM-NP). The long-term effects of PDM on the brain was assessed by comparing PDM-NP findings with those of HCs, and the central mechanism of PDM was assessed by comparing the PDM-P findings with those of PDM-NP. To identify changes in brain function, the amplitude of low-frequency fluctuations and the regional homogeneity (ReHo) were measured. To assess changes in brain structure, voxel-based morphometry (VBM) was applied. The periaqueductal gray (PAG) was set as a region of for conducting seed-based whole-brain functional connectivity (FC) analysis. Subsequently, Pearson correlation analyses were employed to evaluate the associations between the abnormal brain region and the clinical information of the patients. Results: There were neither functional nor structural differences between patients in the PDM-NP and HCs. Compared with those in PDM-NP, those in PDM-P showed increased ReHo in the left dorsolateral prefrontal cortex (DLPFC) but decreased FC between PAG and right superior parietal gyrus, bilateral inferior parietal gyrus, right calcarine gyrus, left superior occipital gyrus, left precentral gyrus, right DLPFC, and left crus I of the cerebellar hemisphere. Conclusions: The results from this study suggest that the mechanism of central pain hypersensitivity of PDM may be related to the disorder of the FC between the PAG and descending pain modulation system, default mode network (DMN), and occipital lobe. These findings could help us better understand the pathophysiology of PDM from a neuroimaging perspective.

The accumulation of active ingredients of Polygonatum cyrtonema Hua is associated with soil characteristics and bacterial community.

Introduction: With the increasing demand for health products derived from Polygonati rhizoma (PR), people begin to artificially plant Polygonatum cyrtonema Hua (P. cyrtonema) in the middle and lower reaches of the Yangtze River. To promote P. cyrtonema cultivation and increase farmers' income, efforts are needed to understand the ways to obtain high-quality PR under artificial cultivation conditions. Methods: Rhizomes of artificial planting P. cyrtonema and rhizosphere soils were collected across five regions in Zhejiang Province, China. Subsequently, the contents of the main active ingredients of P. cyrtonema and soil properties were analyzed, and both rhizosphere and endophytic bacteria of P. cyrtonema were detected by 16S rDNA sequencing. The relationship between the active ingredients and soil properties, and the dominant bacteria were investigated by correlation analysis. Results: The content of active ingredients of P. cyrtonema from the five regions varied significantly, especially polysaccharides and saponins. High-throughput sequencing demonstrated that Proteobacteria was the dominant bacterial phylum in all samples, and Burkholderia-Caballeronia-Paraburkholderia was the main endophytic bacterial genus in rhizome. In addition, the bacterial diversity and richness of rhizosphere soil samples were higher than those of rhizome samples. Soil physicochemical properties and enzyme activities were significantly different across regions, leading to notable variations in the community structures of rhizosphere and endophytic bacteria. Redundancy analysis (RDA) displayed that pH and urease (UE) were the major factors altering shifting rhizosphere bacteria community structure. Moreover, the composition and diversity of rhizome endophytic bacteria were principally affected by both soil physicochemical properties and soil enzyme activities. Soil properties and bacteria from rhizosphere soil and rhizome had a considerable impact on certain active ingredients in P. cyrtonema under artificial cultivation conditions after Pearson correlation analysis. Polysaccharides were significantly correlated with nutrient-rich soil and endophytic bacteria, such as Burkholderia-Caballeronia-Paraburkholderia, Pseudomonas, Ralstonia, and Bacillus. However, flavonoids were associated with nutrient-poor soil. Saponins were positively correlated with OM and available phosphorous (AP) and were significantly negatively affected by rhizosphere bacterial communities. Conclusion: The study demonstrated that bacterial microorganisms were involved in the accumulation of active ingredients of P. cyrtonema together with soil physicochemical properties and enzyme activities, which provided a theoretical basis for the scientific and effective artificial cultivation of high-quality P. cyrtonema.

An Asynchronous Spiking Neural Membrane System for Edge Detection.

Spiking neural membrane systems (SN P systems) are a class of bio-inspired models inspired by the activities and connectivity of neurons. Extensive studies have been made on SN P systems with synchronization-based communication, while further efforts are needed for the systems with rhythm-based communication. In this work, we design an asynchronous SN P system with resonant connections where all the enabled neurons in the same group connected by resonant connections should instantly produce spikes with the same rhythm. In the designed system, each of the three modules implements one type of the three operations associated with the edge detection of digital images, and they collaborate each other through the resonant connections. An algorithm called EDSNP for edge detection is proposed to simulate the working of the designed asynchronous SN P system. A quantitative analysis of EDSNP and the related methods for edge detection had been conducted to evaluate the performance of EDSNP. The performance of the EDSNP in processing the testing images is superior to the compared methods, based on the quantitative metrics of accuracy, error rate, mean square error, peak signal-to-noise ratio and true positive rate. The results indicate the potential of the temporal firing and the proper neuronal connections in the SN P system to achieve good performance in edge detection.

Comprehensive Evaluation of the Nutritional Properties of Different Germplasms of Polygonatum cyrtonema Hua.

Polygonatum cyrtonema Hua, an edible resource and medical material, is mainly consumed as a food in China. However, few published studies have comprehensively assessed its nutritional components. In this study, the proximate, carbohydrate, and dietary fiber contents as well as the mineral, vitamin, and amino acid compositions of five sources of P. cyrtomena grown in Yuhang district, Hangzhou city, Zhejiang province, were investigated. The nutritional profile of the five germplasms was investigated using analytical chemistry methods. All germplasms had a low starch content and contained greater amounts of carbohydrates (23.25-34.29%), protein (2.96-5.40%), Ca (195.08-282.08 mg/100 g), Fe (29.68-59.37 mg/100 g), and vitamin C (60.49-149.86 mg/100 g) in comparison to ginger, yam, and potatoes. The polysaccharide content ranged from 16.92% to 28.48%, representing the main source of carbohydrates. Fructose, a desirable sweetener, was the most abundant monosaccharide, representing 1.06% to 4.88% of the content. P. cyrtonema was found to be high in dietary fiber, with pectin and resistant starch being the major soluble components and hemicellulose being the dominant insoluble dietary fiber. A correlation analysis (CA) revealed significant correlations for the carbohydrate components and dietary fiber fractions with other nutrients. A principal component analysis (PCA) identified significant differences between the nutritional characteristics of the five germplasms, with Huanggang having the highest comprehensive quality scores. Moreover, ten nutrient components were selected as potential indicators that could be used to further evaluate the nutritional quality of P. cyrtomena. Our results demonstrate the rich nutrient composition and characteristics of P. cyrtonema and provide a valuable reference for the future development and utilization of Polygonatum.

Serum response factor promoting axonal regeneration by activating the Ras-Raf-Cofilin signaling pathway after the spinal cord injury.

INTRODUCTION: Serum response factor (SRF) is important in muscle development, tissue repair, and neuronal regulation. OBJECTIVES: This research aims to thoroughly examine the effects of SRF on spinal cord injury (SCI) and its ability to significantly impact the recovery and regeneration of neuronal axons. METHODS: The researchers created rat models of SCI and scratch injury to primary spinal cord neurons to observe the expression of relevant factors after neuronal injury. RESULTS: We found that the SRF, Ras, Raf, and cofilin levels increased after injury and gradually returned to normal levels. Afterward, researchers gave rats with SCI an SRF inhibitor (CCG1423) and studied the effects with nuclear magnetic resonance and transmission electron microscopy. The SRF inhibitor rodents had worse spinal cord recovery and axon regrowth than the control group. And the apoptosis of primary neurons after scratch injury was significantly higher in the SRF inhibitor group. Additionally, the researchers utilized lentiviral transfection to modify the SRF expression in neurons. SRF overexpression increased neuron migration while silencing SRF decreased it. Finally, Western blotting and RT-PCR were conducted to examine the expression changes of related factors upon altering SRF expression. The results revealed SRF overexpression increased Ras, Raf, and cofilin expression. Silencing SRF decreased Ras, Raf, and Cofilin expression. CONCLUSION: Based on our research, the SRF promotes axonal regeneration by activating the "Ras-Raf-Cofilin" signaling pathway.

Analysis of Nonhomologous End Joining and Homologous Recombination Efficiency in HEK-293T Cells using GFP Based Reporter Systems.

DNA double-strand breaks (DSBs) represent the most perilous DNA lesions, capable of inducing substantial genetic information loss and cellular demise. In response, cells employ two primary mechanisms for DSB repair: nonhomologous end joining (NHEJ) and homologous recombination (HR). Quantifying the efficiency of NHEJ and HR separately is crucial for exploring the relevant mechanisms and factors associated with each. The NHEJ assay and HR assay are established methods used to measure the efficiency of their respective repair pathways. These methods rely on meticulously designed plasmids containing a disrupted green fluorescent protein (GFP) gene with recognition sites for endonuclease I-SceI, which induces DSBs. Here, we describe the extrachromosomal NHEJ assay and HR assay, which involve co-transfecting HEK-293T cells with EJ5-GFP/DR-GFP plasmids, an I-SceI expressing plasmid, and an mCherry expressing plasmid. Quantitative results of NHEJ and HR efficiency are obtained by calculating the ratio of GFP-positive cells to mCherry-positive cells, as counted by flow cytometry. In contrast to chromosomally integrated assays, these extrachromosomal assays are more suitable for conducting comparative investigations involving multiple established stable cell lines.

Manipulation of Electronic States of Pt Sites via d-Band Center Tuning for Enhanced Oxygen Reduction Reaction in Proton Exchange Membrane Fuel Cells.

Expediting the torpid kinetics of the oxygen reduction reaction (ORR) at the cathode with minimal amounts of Pt under acidic conditions plays a significant role in the development of proton exchange membrane fuel cells (PEMFCs). Herein, a novel Pt-N-C system consisting of Pt single atoms and nanoparticles anchored onto the defective carbon nanofibers is proposed as a highly active ORR catalyst (denoted as Pt-N-C). Detailed characterizations together with theoretical simulations illustrate that the strong coupling effect between different Pt sites can enrich the electron density of Pt sites, modify the d-band electronic environments, and optimize the oxygen intermediate adsorption energies, ultimately leading to significantly enhanced ORR performance. Specifically, the as-designed Pt-N-C demonstrates exceptional ORR properties with a high half-wave potential of 0.84 V. Moreover, the mass activity of Pt-N-C reaches 193.8 mA gPt-1 at 0.9 V versus RHE, which is 8-fold greater than that of Pt/C, highlighting the enormously improved electrochemical properties. More impressively, when integrated into a membrane electrode assembly as cathode in an air-fed PEMFC, Pt-N-C achieved a higher maximum power density (655.1 mW cm-2) as compared to Pt/C-based batteries (376.25 mW cm-2), hinting at the practical application of Pt-N-C in PEMFCs.

Prevalence of surgical site infection and risk factors in patients after foot and ankle surgery: A systematic review and meta-analysis.

The present systematic review and meta-analysis aimed to determine the prevalence of surgical site infection (SSI) and related factors in patients after foot and ankle surgery. A comprehensive, systematic search was conducted in different international electronic databases, such as Scopus, PubMed, Web of Science and Persian electronic databases such as Iranmedex and Scientific Information Database (SID) using keywords extracted from Medical Subject Headings such as 'Prevalence', 'Surgical wound infection', 'Surgical site infection' and 'Orthopaedics' from the earliest to 1 June 2023. The appraisal tool for cross-sectional studies (AXIS tool) evaluates the quality of the included studies. A total of 10 447 patients undergoing foot and ankle surgery participated in nine studies. The pooled prevalence of SSI in patients who underwent foot and ankle surgery was reported in nine studies was 4.2% (95% CI: 2.4%-7.2%; I2 = 96.793%; p < 0.001). The odds ratio of SSI prevalence in men was higher than that of women and was significant (OR: 1.335; 95% CI: 1.106-1.612; Z = 3.009; p = 0.003). The pooled prevalence of SSI in patients with hindfoot fracture sites reported in five studies was 4.9% (95% CI: 2.6%-8.9%; I2 = 90.768%; p < 0.001). The pooled prevalence of SSI in patients with diabetes mellitus (DM) reported in six studies was 9.1% (95% CI: 5.6%-14.6%; I2 = 73.957%; p = 0.002). The pooled prevalence of SSI in patients with hypertension (HTN) reported in five studies was 5.5% (95% CI: 2.5%-11.6%; I2 = 91.346%; p < 0.001). The pooled prevalence of SSI in patients with tobacco use reported in eight studies was 6.6% (95% CI: 4.1%-10.4%; I2 = 85.379%; p < 0.001). In general, the existing differences in the prevalence of SSI after foot and ankle surgery in different studies can be based on different risk factors such as comorbidities and gender. Therefore, it is suggested to design appropriate interventions to reduce SSI in these patients.

Altered brain function and structure pre- and post- COVID-19 infection: a longitudinal study.

BACKGROUND: Evidence indicates that the SARS-CoV-2 virus can infect the brain, resulting in central nervous system symptoms. However, there is a lack of a longitudinal imaging study investigating the impact of Coronavirus disease 2019 (COVID-19) infection on brain function. Consequently, this study aimed to fill this knowledge gap using functional magnetic resonance imaging (fMRI). METHODS: Twenty-one participants underwent two resting-state fMRI scans before and after infection. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were assessed to identify the brain function changes. Additionally, voxel-based morphometry (VBM) was utilized to assess changes in brain structure. Subsequently, brain regions that showed significant differences were identified as regions of interest (ROI) in functional connectivity analysis (FC). RESULTS: After infection, ALFF was increased in the bilateral paracentral lobe and postcentral gyrus while decreased in the bilateral precuneus. Moreover, ReHo was decreased in the cerebellar vermis, accompanied by a decrease in FC with the bilateral postcentral gyrus. Furthermore, gray matter volume (GMV) reduction was observed in the left thalamus. The results of the correlation analysis revealed a negative correlation between ALFF values in the bilateral precuneus and scores on the self-rating anxiety scale (SAS) in pre- and post-infection datasets. CONCLUSION: Neuroimaging alterations may occur before the manifestation of clinical symptoms, indicating that the functioning of the motor and sensory systems, as well as their connection, might be affected following infection. This alteration can potentially increase the potential of maladaptive responses to environmental stimuli. Furthermore, patients may be susceptible to future emotional disorders.

FAM21 interacts with Ku to promote the localization of WASH to DNA double strand break sites.

Cytoplasmic FAM21 works as a guiding protein in Wiskott-Aldrich Syndrome Protein and SCAR Homolog (WASH) complex by linking WASH complex to endosomes through its interaction with retromer. Recently, we have reported that nuclear WASH localizes to DNA double strand break (DSB) sites to promote DNA repair through non-homologous end-joining (NHEJ). However, whether FAM21, the close partner of WASH, is involved in the nuclear WASH localization and DNA repair remains to be clarified. Here, we show that FAM21 interacts with Ku and the interaction between C-terminal FAM21 and Ku is essential for its recruitment to DSB sites. Moreover, FAM21 depletion led to decreases in WASH recruitment to damaged DNA and repair capacity upon DNA damage. Taken together, these results reveal that FAM21 promotes DNA repair by orchestrating the recruitment of WASH to DSB sites, providing a mechanistic insight into WASH-dependent DNA DSB repair.

Electrical impedance tomography: a review on hardware systems and circuits.

Electrical impedance tomography (EIT) is a widely used functional imaging technology in the field of biomedical engineering with the characteristics of non-radiation, high temporal resolution, real-time, miniaturization, and low cost, but with relatively poor spatial resolution, which makes it become an effective complementary imaging alternative in conjunction with structural imaging technologies such as MRI and CT for bedside monitoring. The hardware systems and circuits (HSC) are the physical basis for EIT, and have major impacts on imaging speed, accuracy, cost and other key performance specifications. This review attempts to provide researchers with a relatively comprehensive picture of HSC for different EIT systems, which is organized as follows. Firstly, the general EIT hardware systems are classified as serial, fully parallel and semi-parallel types, respectively, according to their hardware architecture. Secondly, the main analogy front-end circuits of EIT hardware systems are summarized, in which the current drive circuits are divided into open loop, linear closed-loop and nonlinear closed-loop based on different feedback types. Thirdly, the common error sources and evaluation indicators on EIT measurements are summarized. Finally, the future development trends and research challenges of EIT are discussed. This review is expected to promote the development of EIT technology, especially on the design of HSC.

The relationship between a growth mindset and the learning engagement of nursing students: A structural equation modeling approach.

AIMS: To explore the relationship among a growth mindset, well-being and learning engagement of nursing students and the mediating effect of well-being. BACKGROUND: Reduced well-being and learning burnout are common among nursing students. From the perspective of positive psychology, a positive education can help students obtain well-being, improve their academic performance and be actively involved in learning. The core of positive education is a growth mindset. However, few studies have explored the causal relationship among a growth mindset, learning engagement and well-being. DESIGN: Correlational design based on cross-sectional data from a multicenter survey study. METHODS: A web-based survey was completed by 1065 nursing students from 5 schools in China between August 2022 and December 2022. The Growth Mindset Scale, the PERMA profiler and the Learning Engagement Scale were used to investigate the effect of a growth mindset on learning engagement and the mediating effect of well-being. RESULTS: Both a growth mindset (r = 0.272, p < 0.01) and well-being (r = 0.693, p < 0.01) were positively correlated with learning engagement, and a growth mindset (r = 0.363, p < 0.01) was positively correlated with well-being. Well-being completely mediated the relationship between a growth mindset and learning engagement. CONCLUSIONS: The growth mindset and well-being of nursing students are related to learning engagement. Therefore, schools can change students' thinking mode by carrying out positive education to enable students to acquire the ability to maintain their well-being and to improve their well-being and learning engagement.

The dose of focused ultrasound ablation surgery (FUAS) for unresectable pancreatic cancer is predictable: A multicenter retrospective study.

To analyze the influencing factors of energy efficiency factors (EEF) in focused ultrasound ablation surgery (FUAS) for unresectable pancreatic cancer and build a dosimetry model. The patients with unresectable pancreatic cancer that underwent FUAS were enrolled from 3 clinical centers between June 2015 and June 2022 for retrospective analysis. The significance of the factors with the potential to affect the EEF was assessed, correlations among the factors were analyzed, and the accuracy of the prediction models established by the factors containing different imaging features was compared. From a total of 236 cases, 215 cases were screened for study, EEF was significantly correlated with mode of anesthesia, grayscale change, tumor volume, tumor location, the distance from the tumor center to skin, contrast-enhanced computer tomography enhancement type, T2-weighted imaging fat suppression signal intensity and contrast-enhanced T1-weighted imaging enhancement type on magnetic resonance imaging. The resultant multiple regression models of EEF achieved significance, contains predictors of Tumor volume, the distance from tumor center to skin, T2-weighted imaging fat suppression signal intensity, and contrast-enhanced T1-weighted imaging enhancement type had better goodness of fit. Compared with CT, the EEF prediction model established by adding magnetic resonance imaging features showed better prediction in FUAS treatment of unresectable pancreatic cancer.

A prospective study on the endometrium properties and the pregnancy rate of infertile women with thin endometrium receiving Fructus ligustri lucidi used in traditional Chinese medicine.

OBJECTIVE: To evaluate whether Zi Gui Nv Zhen capsules (ZGNZC) can increase the fertility rate of Chinese women with infertility due to thin endometrium. METHODS: Prospective, randomized, open-labeled 3-monthly study; 104 patients (aged 20-40 years) receiving either ZGNZC (experimental group, n = 55) or not (control group, n = 49). Main outcomes: thickness/type of the endometrium during ovulation and pregnancy rate. Between-group analysis (A) compares the experimental vs. control group, and within-group analysis (B) compares data at baseline and after study in the experimental group. RESULTS: (A) Between-group-analysis: Patients with ZGNZC had a higher endometrium thickness (0.8 ± 0.27 vs. 0.68 ± 0.10; p < .05) and higher type A endometrium rates (34.2% vs. 13.2%; p < .05) than the control group. Pregnancy rates were higher in the experimental than in the control group (43.6% vs. 22.4%; p < .05). (B) Within-group-analysis: ZGNZC increased endometrium thickness (0.58 ± 0.13 vs. 0.87 ± 0.24 vs. 0.83 ± 0.26 vs. 0.80 ± 0.27), and type A endometrium rates (10.9% vs. 60.0% vs. 49.0% vs. 34.2%) (all p < .05). Univariate analysis of pregnancy with other study parameters showed positive and significant correlations between pregnancy and administration of ZGNZC (p < .05). All hepato-renal biomarkers remained within the norm. There were no adverse events. CONCLUSIONS: In infertile women with thin endometrium who wish to conceive, two months' application of ZGNZC can improve endometrial properties and proliferation, which is necessary for a healthy pregnancy, and increase the clinical pregnancy rate in our prospective randomized observational study.

Cost-effectiveness of cytomegalovirus vaccination for females in China: A decision-analytical Markov study.

BACKGROUND: The global burden of disease caused by congenital cytomegalovirus (CMV) infection is high. Previous modeling studies have suggested that CMV vaccination may be cost-effective in developed countries. Congenital CMV infection is more likely driven by maternal non-primary infection in China. We aimed to measure the effectiveness and cost-effectiveness of population-level CMV vaccination in Chinese females. METHODS: A decision tree Markov model was developed to simulate potential CMV vaccination strategies in a multi-cohort setting, with a population size of 1,000,000 each for the infant, adolescent (10-year-old) and young adult (20-year-old) cohorts. The hypothetical vaccines were assumed to have 50% efficacy, 20 years of protection, 70% coverage, at a price of US$120/dose for base-case analysis. Costs and disability-adjusted life years (DALYs) were discounted by 3% per year and the vaccination would be considered cost-effective if an incremental cost-effectiveness ratio (ICER) was lower than 2021 Chinese per capita GDP (US$12,500). FINDINGS: For the pre-infection (PRI) vaccine efficacy type, the adolescent strategy was the most cost-effective, with an ICER of US$12,213 (12,134 to 12,291) pre DALY averted, compared with the next best strategy (young adult strategy). For pre- and post-infection (P&PI) efficacy type, the young adult strategy was the most cost-effective as it was cost-saving. In one-way analysis varying the PRI vaccine price, the infant strategy, adolescent strategy and the young adult strategy would be a dominant strategy over others if the vaccine cost ≤US$60, US$61-121 and US$122-251 per dose respectively. In contrast, the young adult strategy continued to be the preferred strategy until the P&PI vaccine price exceeded US$226/dose. Our main results were robust under a wide variety of sensitivity analyses and scenario analyses. INTERPRETATION: CMV vaccination for females would be cost-effective and even cost-saving in China. Our findings had public health implications for control of CMV diseases.

Novel biallelic variants in the PLEC gene are associated with severe hearing loss.

Pediatric auditory neuropathy spectrum disorder is a particular type of hearing loss caused by abnormal sound transmission from the cochlea to the brain. It is due to defective peripheral synaptic function or improper neuronal conduction. Using trio whole-exome sequencing, we have identified novel biallelic variants in the PLEC gene in three individuals with profound deafness from two unrelated families. Among them, one pediatric patient diagnosed with auditory neuropathy spectrum disorder had a good cochlear implantation outcome. The other two adult patients were diagnosed with non-syndromic hearing loss. Studies in mice and zebrafish confirmed that plectin is developmentally expressed in the inner ear. Moreover, plectin's knockdown resulted in a reduction of synaptic mitochondrial potential and loss of ribbon synapses, reinforcing the idea of a role for plectin in neuronal transmission. Altogether, the results presented here, point to a new unconventional role for plectin in the inner ear. Contrary to the well-characterized association of plectin to skin and muscle diseases, we found that specific plectin mutations can result in hearing loss with no other clinical manifestations. This is important because 1) it provides evidence of plectin's involvement in inner ear function and 2) it will help clinicians at the time of diagnosis and treatment.

Moderate elevation of serum uric acid levels improves short-term functional outcomes of ischemic stroke in patients with type 2 diabetes mellitus.

BACKGROUND: Serum uric acid (SUA), an end-product of purine catabolism diffused in the blood, is positively associated with the risk of type 2 diabetes mellitus (T2DM). However, in the T2DM population, the association of SUA fluctuation ([Formula: see text]SUA) with the functional outcome of ischemic stroke (IS) is still unclear. Accordingly, this study aimed to assess the correlation between [Formula: see text]SUA and short-term IS functional outcomes in T2DM patients. METHODS: All T2DM patients diagnosed with IS in the China National Stroke Registry III were included. [Formula: see text]SUA, which was defined as the difference between the SUA levels at baseline and 3 months after symptom onset, was classified into two groups, i.e., elevated [Formula: see text]SUA ([Formula: see text]SUA > 0) and reduced [Formula: see text]SUA ([Formula: see text]SUA [Formula: see text] 0). The outcomes measured using the Modified Rankin Scale (mRS) were scored from 0 to 6, and poor functional outcome was defined as an mRS score of 3-6 at 3 months after IS. RESULTS: Among the 1255 participants (mean age: 61.6 ± 9.8 years), 64.9% were men. Patients with elevated [Formula: see text]SUA had a lower incidence of poor functional outcomes at 3 months. Compared with reduced [Formula: see text]SUA, elevated [Formula: see text]SUA at 0-50 µmol/L (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.28-0.78, p = 0.004) and 50-100 µmol/L (OR = 0.40, 95% CI = 0.21-0.77, p = 0.006) was significantly correlated with a reduced risk of poor functional outcomes at 3 months. CONCLUSION: This study showed that a moderate increase in [Formula: see text]SUA in the range of 0-100 µmol/L at 3 months after IS might be beneficial in T2DM adults and more studies are warranted to confirm this.