Clinical and epidemiological characteristics of 96 pediatric human metapneumovirus infections in Henan, China after COVID-19 pandemic: a retrospective analysis.

BACKGROUND: In the aftermath of the COVID-19 pandemic, there has been a surge in human metapneumovirus (HMPV) transmission, surpassing pre-epidemic levels. We aim to elucidate the clinical and epidemiological characteristics of HMPV infections in the post-COVID-19 pandemic era. METHODS: In this retrospective single-center study, participants diagnosed with laboratory confirmed HMPV infection through Targeted Next Generation Sequencing were included. The study encompassed individuals admitted to Henan Children's Hospital between April 29 and June 5, 2023. Demographic information, clinical records, and laboratory indicators were analyzed. RESULTS: Between April 29 and June 5, 2023, 96 pediatric patients were identified as infected with HMPV with a median age of 33.5 months (interquartile range, 12 ~ 48 months). The majority (87.5%) of infected children were under 5 years old. Notably, severe cases were statistically younger. Predominant symptoms included fever (81.3%) and cough (92.7%), with wheezing more prevalent in the severe group (56% vs 21.1%). Coinfection with other viruses was observed in 43 patients, with Epstein-Barr virus (EBV) (15.6%) or human rhinovirus A (HRV type A) (12.5%) being the most common. Human respiratory syncytial virus (HRSV) coinfection rate was significantly higher in the severe group (20% vs 1.4%). Bacterial coinfection occurred in 74 patients, with Haemophilus influenzae (Hin) and Streptococcus pneumoniae (SNP) being the most prevalent (52.1% and 41.7%, respectively). Severe patients demonstrated evidence of multi-organ damage. Noteworthy alterations included lower concentration of IL-12p70, decreased lymphocytes percentages, and elevated B lymphocyte percentages in severe cases, with statistical significance. Moreover, most laboratory indicators exhibited significant changes approximately 4 to 5 days after onset. CONCLUSIONS: Our data systemically elucidated the clinical and epidemiological characteristics of pediatric patients with HMPV infection, which might be instructive to policy development for the prevention and control of HMPV infection and might provide important clues for future HMPV research endeavors.

Current status of hand-foot-and-mouth disease.

Hand-foot-and-mouth disease (HFMD) is a viral illness commonly seen in young children under 5 years of age, characterized by typical manifestations such as oral herpes and rashes on the hands and feet. These symptoms typically resolve spontaneously within a few days without complications. Over the past two decades, our understanding of HFMD has greatly improved and it has received significant attention. A variety of research studies, including epidemiological, animal, and in vitro studies, suggest that the disease may be associated with potentially fatal neurological complications. These findings reveal clinical, epidemiological, pathological, and etiological characteristics that are quite different from initial understandings of the illness. It is important to note that HFMD has been linked to severe cardiopulmonary complications, as well as severe neurological sequelae that can be observed during follow-up. At present, there is no specific pharmaceutical intervention for HFMD. An inactivated Enterovirus A71 (EV-A71) vaccine that has been approved by the China Food and Drug Administration (CFDA) has been shown to provide a high level of protection against EV-A71-related HFMD. However, the simultaneous circulation of multiple pathogens and the evolution of the molecular epidemiology of infectious agents make interventions based solely on a single agent comparatively inadequate. Enteroviruses are highly contagious and have a predilection for the nervous system, particularly in child populations, which contributes to the ongoing outbreak. Given the substantial impact of HFMD around the world, this Review synthesizes the current knowledge of the virology, epidemiology, pathogenesis, therapy, sequelae, and vaccine development of HFMD to improve clinical practices and public health efforts.

The role of unconventional lymph node metastasis in neck recurrence among patients with tongue cancer.

OBJECTIVES: Statistics on the rate of unconventional lymph node metastases (ULNM) at the time of one-stage radical surgery in tongue cancer patients. To assess whether an extended neck dissection group with additional removal of ULNs has a lower rate of neck recurrence compared to the traditional neck dissection group. MATERIALS AND METHODS: A total of 336 patients with TSCC who underwent radical surgery were recruited and underwent traditional or extended neck dissection. Compared to traditional neck dissection, the aim of extended neck dissection is designed to additional resect ULNs. RESULTS: In total, 180 patients underwent extended neck dissection, while 156 underwent traditional neck dissection. The incidence of ULNM was 11.67% (21/180) in patients treated with extended neck dissection. The incidence of ipsilateral neck recurrence was 9.49% and 0.56% in patients who underwent traditional and extended neck dissection, respectively (p = 0.0001). CONCLUSIONS: Extended neck dissection is effective for preventing neck recurrence in TSCC patients with ULNs. CLINICAL RELEVANCE: ULNM may be the main cause of neck recurrence after neck dissection in patients with tongue cancer. A better prognosis may be achieved by additional resection of ULNs on the basis of traditional neck dissection.

Protein interaction interface region prediction by geometric deep learning.

MOTIVATION: Protein-protein interactions drive wide-ranging molecular processes, and characterizing at the atomic level how proteins interact (beyond just the fact that they interact) can provide key insights into understanding and controlling this machinery. Unfortunately, experimental determination of three-dimensional protein complex structures remains difficult and does not scale to the increasingly large sets of proteins whose interactions are of interest. Computational methods are thus required to meet the demands of large-scale, high-throughput prediction of how proteins interact, but unfortunately, both physical modeling and machine learning methods suffer from poor precision and/or recall. RESULTS: In order to improve performance in predicting protein interaction interfaces, we leverage the best properties of both data- and physics-driven methods to develop a unified Geometric Deep Neural Network, 'PInet' (Protein Interface Network). PInet consumes pairs of point clouds encoding the structures of two partner proteins, in order to predict their structural regions mediating interaction. To make such predictions, PInet learns and utilizes models capturing both geometrical and physicochemical molecular surface complementarity. In application to a set of benchmarks, PInet simultaneously predicts the interface regions on both interacting proteins, achieving performance equivalent to or even much better than the state-of-the-art predictor for each dataset. Furthermore, since PInet is based on joint segmentation of a representation of a protein surfaces, its predictions are meaningful in terms of the underlying physical complementarity driving molecular recognition. AVAILABILITY AND IMPLEMENTATION: PInet scripts and models are available at https://github.com/FTD007/PInet. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Update on Omicron variant and its threat to vulnerable populations.

Objective: To reduce the incidence of severe illness and fatalities, and promote the awareness of protection and precaution, increased vaccination, strengthen the physical fitness, frequent ventilation, and health education should be enhanced among vulnerable populations as essential measures for the future control of COVID-19. Study design: Systematic review. Method: The search was done using PubMed, EMBASE and Web of Science for studies without language restrictions, published up through March 2023, since their authoritative and comprehensive literature search database. Eighty articles were included. Extraction of articles and quality assessment of included reviews was performed independently by two authors using the AMSTAR 2 score. Results: The articles in the final data set included research on epidemiological characteristics, pathogenicity, available vaccines, treatments and epidemiological features in special populations including the elders, pregnant women, kids, people with chronic diseases concerning Omicron. Conclusion: Although less pathogenic potential is found in Omicron, highly mutated forms have enhanced the ability of immune evasion and resistance to existing vaccines compared with former variants. Severe complications and outcomes may occur in vulnerable populations. Infected pregnant women are more likely to give birth prematurely, and fatal implications in children infected with Omicron are hyperimmune response and severe neurological disorders. In immunocompromised patients, there is a greater reported mortality and complication compared to patients with normal immune systems. Therefore, maintain social distancing, wear masks, and receive vaccinations are effective long-term measures.

Adjunctive Chinese medicine therapy reduces relapse of psoriasis vulgaris after discontinuation of biologics: a prospective registry-based cohort study.

BACKGROUND: Biologics have revolutionized psoriasis treatment; however, relapse of psoriasis after discontinuation of biologics remains unresolved. OBJECTIVE: To assess the impact of adjunctive Chinese medicine (CM) therapy on relapse of psoriasis vulgaris (PV) after discontinuation of biologics. METHODS: We constructed a prospective cohort study through a psoriasis case registry platform that enrolled patients treated with biologics (in combination with or without CM). The endpoint event was relapse, defined as loss of psoriasis area and severity index (PASI) 75. RESULTS: A total of 391 patients completed the study and were included in the analysis, of whom 169 (43.2%) experienced relapse during follow-up. To minimize the bias, a 1:1 propensity score matching (PSM) was performed, generating matched cohorts of 156 individuals per group. Adjuvant CM therapy significantly associated with reduced incidence of relapse (HR =0.418, 95% CI = 0.289 ∼ 0.604, p < 0.001), and the protective effect of CM in the subgroup analysis was significant. In addition, PASI 90 response and disease duration were associated with relapse (p < 0.05). CONCLUSION: Adjunctive CM therapy is associated with reduced relapse incidence in PV after discontinuation of biologics.

Evaluation of the Mechanism of Yishan Formula in Treating Breast Cancer Based on Network Pharmacology and Experimental Verification.

BACKGROUND: Yishan formula (YSF) has a significant effect on the treatment of breast cancer, which can improve the quality of life and prolong the survival of patients with breast cancer; however, its mechanism of action is unknown. OBJECTIVE: In this study, network pharmacology and molecular docking methods have been used to explore the potential pharmacological effects of the YSF, and the predicted targets have been validated by in vitro experiments. METHODS: Active components and targets of the YSF were obtained from the TCMSP and Swiss target prediction website. Four databases, namely GeneCards, OMIM, TTD, and DisGeNET, were used to search for disease targets. The Cytoscape v3.9.0 software was utilized to draw the network of drug-component-target and selected core targets. DAVID database was used to analyze the biological functions and pathways of key targets. Finally, molecular docking and in vitro experiments have been used to verify the hub genes. RESULTS: Through data collection from the database, 157 active components and 618 genes implicated in breast cancer were obtained and treated using the YSF. After screening, the main active components (kaempferol, quercetin, isorhamnetin, dinatin, luteolin, and tamarixetin) and key genes (AKT1, TP53, TNF, IL6, EGFR, SRC, VEGFA, STAT3, MAPK3, and JUN) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the YSF could affect the progression of breast cancer by regulating biological processes, such as signal transduction, cell proliferation and apoptosis, protein phosphorylation, as well as PI3K-Akt, Rap1, MAPK, FOXO, HIF-1, and other related signaling pathways. Molecular docking suggested that IL6 with isorhamnetin, MAPK3 with kaempferol, and EGFR with luteolin have strong binding energy. The experiment further verified that YSF can control the development of breast cancer by inhibiting the expression of the hub genes. CONCLUSION: This study showed that resistance to breast cancer may be achieved by the synergy of multiple active components, target genes, and signal pathways, which can provide new avenues for breast cancer-targeted therapy.

Epidemiology and etiology of hand, foot, and mouth disease in Zhengzhou, China, from 2009 to 2021.

Background: Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by a variety of enteroviruses (EVs). To explore the epidemiological characteristics and etiology of HFMD in Zhengzhou, China, we conducted a systematic analysis of HFMD surveillance data from Zhengzhou Center for Disease Control and Prevention from January 2009 to December 2021 (https://wjw.zhengzhou.gov.cn/). Methods: Surveillance data were collected from Zhengzhou Center for Disease Control and Prevention from January 2009 to December 2021 (https://wjw.zhengzhou.gov.cn/). Cases were analyzed according to the time of onset, type of diagnosis, characteristics, viral serotype, and epidemiological trends. Results: We found that the primary causative agent responsible for the HFMD outbreaks in Zhengzhou was Enterovirus A71 (EVA-71) (48.56%) before 2014. After 2015, other EVs gradually became the dominant strains (57.68%). The data revealed that the HFMD epidemics in Zhengzhou displayed marked seasonality, with major peaks occurring from April to June, followed by secondary peaks from October to November, except in 2020. Both the severity and case-fatality ratio of HFMD decreased following the COVID-19 pandemic (severity ‰: 13.46 vs. 0.17; case-fatality ‰: 0.21 vs. 0, respectively). Most severe cases were observed in patients aged 1 year and below, accounting for 45.81%. Conclusions: Overall, the incidence rate of HFMD decreased in Zhengzhou following the introduction of the EVA-71 vaccine in 2016. However, it is crucial to acknowledge that HFMD prevalence continues to exhibit a distinct seasonal pattern and periodicity, and the occurrence of other EV infections poses a new challenge for children's health.

Response of Psoriasis with Systemic Lupus Erythematosus to Secukinumab: A Case Report and Review of the Literature.

Although psoriasis and systemic lupus erythematosus are both immune abnormalities, there are few reports on Ps combined with SLE in China and abroad. We present a case of a 23-year-old female with a 10-year history of psoriasis, who had a relapse with significant joint symptoms and a PASI score of 35.6, along with several positive antibodies, including antinuclear antibodies, elevated CRP and ESR, and was diagnosed with psoriasis and SLE. She has been treated with secukinumab 300 mg subcutaneously, improving her condition. She is currently being followed up. The PubMed, SCOPUS, and ISI Web of Science databases were thoroughly searched for English studies reporting psoriasis with systemic lupus erythematosus and treated using biologics. Three case reports/series were included after the screening. Our case report provides a reference for clinicians using secukinumab to treat psoriasis combined with SLE. However, further research is needed to determine whether it can be widely used or if there are common signaling pathways that can be interfered with the pathogenesis of the diseases.

Arising Concerns of Atypical Manifestations in Patients with Hand, Foot, and Mouth Disease.

Hand, foot, and mouth disease (HFMD) is a mild exanthematous, febrile disease, but it also remains a threat to global public health. HFMD is characterized by a brief febrile illness in children and with a typical skin rash of the hand and foot, with or without mouth ulcers. However, the morphology and distribution of vesicles, as well as accompanying symptoms, are varied among atypical HFMD. An upsurge in atypical presentations of HFMD caused by Coxsackievirus A6 (CVA6), including Gianotti-Crosti-like eruptions, eczema coxsackium, petechial/purpuric eruption, and vesiculobullous exanthema, can be difficult to diagnose clinically as it may mimic other severe skin diseases, such as eczema herpeticum, varicella, disseminated zoster, and erythema multiforme major. The recognition of the distinguishing features of atypical HFMD is vital for an accurate and timely diagnosis, as is initiating appropriate laboratory evaluation and supportive care. Clinicians must identify the wide range of cutaneous and mucosal alterations caused by atypical HFMD. A systemic, high-quality overview of atypical HFMD is needed for advances in better strategies for clinical diagnosis and treatment. Hence, this review is aimed at summarizing the available data on clinical investigations and differential diagnostics to provide a scientific guide for the timely diagnosis of HFMD for preventing serious complications.

Mandibular resection and defect reconstruction guided by a contour registration-based augmented reality system: A preclinical trial.

The aim of this study was to verify the feasibility and accuracy of a contour registration-based augmented reality (AR) system in jaw surgery. An AR system was developed to display the interaction between virtual planning and images of the surgical site in real time. Several trials were performed with the guidance of the AR system and the surgical guide. The postoperative cone beam CT (CBCT) data were matched with the preoperatively planned data to evaluate the accuracy of the system by comparing the deviations in distance and angle. All procedures were performed successfully. In nine model trials, distance and angular deviations for the mandible, reconstructed fibula, and fixation screws were 1.62 ± 0.38 mm, 1.86 ± 0.43 mm, 1.67 ± 0.70 mm, and 3.68 ± 0.71°, 5.48 ± 2.06°, 7.50 ± 1.39°, respectively. In twelve animal trials, results of the AR system were compared with the surgical guide. Distance deviations for the bilateral condylar outer poles were 0.93 ± 0.63 mm and 0.81 ± 0.30 mm, respectively (p = 0.68). Distance deviations for the bilateral mandibular posterior angles were 2.01 ± 2.49 mm and 2.89 ± 1.83 mm, respectively (p = 0.50). Distance and angular deviations for the mandible were 1.41 ± 0.61 mm, 1.21 ± 0.18 mm (p = 0.45), and 6.81 ± 2.21°, 6.11 ± 2.93° (p = 0.65), respectively. Distance and angular deviations for the reconstructed tibiofibular bones were 0.88 ± 0.22 mm, 0.84 ± 0.18 mm (p = 0.70), and 6.47 ± 3.03°, 6.90 ± 4.01° (p = 0.84), respectively. This study proposed a contour registration-based AR system to assist surgeons in intuitively observing the surgical plan intraoperatively. The trial results indicated that this system had similar accuracy to the surgical guide.

Drought resistance index screening and evaluation of lettuce under water deficit conditions on the basis of morphological and physiological differences.

Introduction: Water is one of the important factors affecting the yield of leafy vegetables. Lettuce, as a widely planted vegetable, requires frequent irrigation due to its shallow taproot and high leaf evaporation rate. Therefore, screening drought-resistant genotypes is of great significance for lettuce production. Methods: In the present study, significant variations were observed among 13 morphological and physiological traits of 42 lettuce genotypes under normal irrigation and water-deficient conditions. Results: Frequency analysis showed that soluble protein (SP) was evenly distributed across six intervals. Principal component analysis (PCA) was conducted to transform the 13 indexes into four independent comprehensive indicators with a cumulative contribution ratio of 94.83%. The stepwise regression analysis showed that root surface area (RSA), root volume (RV), belowground dry weight (BDW), soluble sugar (SS), SP, and leaf relative water content (RWC) could be used to evaluate and predict the drought resistance of lettuce genotypes. Furthermore, the drought resistance ranks of the genotypes were similar according to the drought resistance comprehensive evaluation value (D value), comprehensive drought resistance coefficient (CDC), and weight drought resistance coefficient (WDC). The cluster analysis enabled the division of the 42 genotypes into five drought resistance groups; among them, variety Yidali151 was divided into group I as a strongly drought-resistant variety, group II included 6 drought-resistant genotypes, group III included 16 moderately drought-resistant genotypes, group IV included 12 drought-sensitive genotypes, and group V included 7 highly drought-sensitive genotypes. Moreover, a representative lettuce variety was selected from each of the five groups to verify its water resistance ability under water deficit conditions. In the drought-resistant variety, it was observed that stomatal density, superoxide anion (O2.-wfi2) production rate, and malondialdehyde (MDA) content exhibited a low increase rate, while catalase (CAT), superoxide dismutase (SOD), and that peroxidase (POD) activity exhibited a higher increase than in the drought-sensitive variety. Discussion: In summary, the identified genotypes are important because their drought-resistant traits can be used in future drought-resistant lettuce breeding programs and water-efficient cultivation.

Concentrated Growth Factors Promote hBMSCs Osteogenic Differentiation in a Co-Culture System With HUVECs.

Osteogenesis is a complex physiologic process that occurs during bone regeneration. This process requires several growth factors that act on bone marrow-derived mesenchymal stem cells (BMSCs). Concentrated growth factor (CGF) is a new-generation platelet-rich derivative that is an appealing autologous material for application in tissue repair and bone regenerative medicine because it contains a variety of fibrin and growth factors. In this study, the effects of CGF on the proliferation and osteogenic differentiation of hBMSCs and human umbilical vein endothelial cells (HUVECs) were explored with in vitro cell co-culture experiments. HBMSCs and HUVECs were directly co-cultured at the ratio of 1:2 under different concentrations (0, 2, 5, 10, 20%) of CGF for 7 days. Alkaline phosphatase (ALP) staining and quantitative reverse transcription polymerase chain reaction were used to detect the effects of CGF on the expression of osteogenic genes (ALP, osteocalcin [OCN], type I collagen [COL-1], Runt-related transcription factor 2 [RUNX2]) and connexin 43 (CX43). RNA sequencing was used to explore potential regulated genes and signaling pathways that affect the osteogenesis of co-cultured hBMSCs exposed to CGF. The results showed higher expressions of ALP, COL-1, RUNX2, OCN, and CX43 in the direct co-culture group containing 10% CGF compared to the direct co-culture group without CGF and the indirect co-culture group. In summary, 10% CGF can significantly promote osteogenesis in hBMSCs directly co-cultured with HUVECs. Intercellular communication between the direct co-culture of hBMSCs and HUVECs through CX43 may be one of the main regulatory mechanisms.

HOXC10 promotes migration and invasion via the WNT-EMT signaling pathway in oral squamous cell carcinoma.

As a master regulator of embryonic morphogenesis, homeodomain-containing gene 10 (HOXC10) has been found to promote progression of human cancers and indicate poor survival outcome. Therefore, we concentrate on elucidating the role of HOXC10 in progression of oral squamous cell carcinoma (OSCC). In our study, the expression of HOXC10 was significantly increased in human OSCC samples and was significantly correlated with TNM stage and lymph node metastasis. Upregulation of HOXC10 indicated a poor overall survival of OSCC patients according to the Kaplan-Meier survival curves. Furthermore, HOXC10-knockdown dramatically suppressed migration, invasion, and expression of N-Cadherin, Vimentin and Snail, as well as increased E-cadherin level both in vivo and in vitro. Bioinformatics and cellular study further confirmed that HOXC10 may promote invasion and migration of OSCC cells by regulating the WNT/epithelial-mesenchymal transition (EMT) signaling pathway. These findings suggest that HOXC10 plays a pivotal role in the metastasis of OSCC and highlight its usefulness as a potential prognostic marker or therapeutic target in human OSCC.

The importance of forgetting: Limiting memory improves recovery of topological characteristics from neural data.

We develop of a line of work initiated by Curto and Itskov towards understanding the amount of information contained in the spike trains of hippocampal place cells via topology considerations. Previously, it was established that simply knowing which groups of place cells fire together in an animal's hippocampus is sufficient to extract the global topology of the animal's physical environment. We model a system where collections of place cells group and ungroup according to short-term plasticity rules. In particular, we obtain the surprising result that in experiments with spurious firing, the accuracy of the extracted topological information decreases with the persistence (beyond a certain regime) of the cell groups. This suggests that synaptic transience, or forgetting, is a mechanism by which the brain counteracts the effects of spurious place cell activity.

A Changeable Lab-on-a-Chip Detector for Marine Nonindigenous Microorganisms in Ship's Ballast Water.

The spread and invasion of many nonindigenous species in the ship's ballast water around the world has been a hazard and threat to ecology, economy, and human health. The rapid and accurate detection of marine invasive species in ship's ballast water is essential. This article is aimed at analysing ballast water quality by means of a changeable microfluidic chip detector thus comply with the D-2 standard of ship's ballast water management and sediment convention. The detection system was designed through the integration of microfluidic chip technology, the impedance pulse sensing and LED light induced chlorophyll fluorescence (LED-LICF) detection. This system can measure the number, size, shape, and volume of targeted microorganisms, and it can also determine the chlorophyll fluorescence intensity, which is an important factor in analysing the activity of phytoplankton. The targeted samples were Chlorella volutis, Dunaliella salina, Platymonas subcordiformis, Chrysophytes, Escherichia coli, and Enterococci. The whole detection or operation can be accomplished through online detection in a few minutes with using micron volume of the sample solution. The valid data outputs are simultaneously displayed in terms of both impedance pulse amplitudes and fluorescent intensity signals. The detection system is designed for multi-sizes real time detection through changing the microchannel sizes on the microfluidic chip. Because it can successfully detect the label-free microorganisms, the system can be applicable to in-situ detections with some modifications to the system.