Suppression of innate and acquired immunity in severe hand foot and mouth disease caused by EV71 infections in children.

Hand, foot, and mouth disease (HFMD) is a common children infectious disease caused by human enteroviruses. Most of the cases have minimal symptoms, however, some patients may develop serious neurological, cardiac complications, or even death. The pathological mechanism leading to severe HFMD is not clearly understood, and the immunological status of the individual patient may play an important role. Transcriptomes of peripheral blood mononuclear cells from EV71-infected patients (n = 45) and healthy controls (n = 36) were examined. Immune pathways were up-regulated in patients with mild disease symptoms (n = 11, M) compared to the healthy controls (n = 36, H), demonstrating an effective anti-viral response upon EV71 infection. However, in patients with severe symptoms (n = 23, S) as well as severe patients following treatment (n = 11, A), their innate and acquired immune pathways were down-regulated, indicating a global immunity suppression. Such immune suppression characteristics could thus provide an opportunity for early EV-71 infection prognosis prediction. Based on our cohort, an SVM model using RNA-seq expression levels of five genes (MCL1, ZBTB37, PLEKHM1P, IFNAR2 and YEATS2) was developed and achieved a high ROC-AUC (91·3%) in predicting severe HFMD. Meanwhile, qPCR fold-changes method was performed based three genes (MCL1, IFNAR2 and YEATS2) on additional cohort. This qPCR method achieved a ROC-AUC of 78.6% in predicting severe HFMD, which the patients could be distinguished in 2-3 h. Therefore, our models demonstrate the possibility of HFMD severity prediction based on the selected biomarkers that predict severe HFMD effectively.

Intestinal microbiota has important effect on severity of hand foot and mouth disease in children.

BACKGROUND: The incidence of hand foot and mouth disease (HFMD) has increased in recent years, making it a very common childhood illness worldwide. The relationship between different enterovirus genotypes and disease severity is not clearly understood. Given that enteroviruses are transmitted through the gastrointestinal tract, we hypothesized that variation in intestinal microorganisms of the host might play a role in the prognosis of HFMD. METHODS: We carried out a meta-transcriptomic-wide association study of fecal samples obtained from a cohort of children (254 patients, 227 tested positive for enterovirus, including 16 patients co-infectied with 2 kinds of enterovirus) with mild and severe HFMD and healthy controls. RESULTS: We found there was no significant difference in the amount of each virus type between the mild and severe cases. Genes of enterovirus 71 (EV71) and coxsackievirus A (CV-A) from the severe and mild cases did not show significant clustering. Clostridium sp. L2-50 and Bacteroides stercoris ATCC 43183 were enriched in the guts of children with severe HFMD and KEGG enrichment was found between mild and severe cases. CONCLUSIONS: Intestinal microorganisms appear to interact with enterovirus to determine the progression of HFMD. Genes of Bacteroides and Clostridium may be used as predictive markers for a more efficient prognosis and intervention. The enrichment of intestinal bacteria genes with functions may facilitate the development of severe symptoms for HFMD patients.

Impacts of cigarette smoking on liver fibrosis and its regression under therapy in male patients with chronic hepatitis B.

BACKGROUND & AIMS: The role of cigarette smoking in the development of chronic hepatitis B (CHB) remains poorly understood. We assessed the potential contributions of cigarette smoking to liver fibrosis and its regression after starting antiviral therapy in CHB patients. METHODS: In this cohort study, 2144 consecutive male CHB patients under no antiviral therapy were evaluated and 206 patients with significant liver fibrosis (≥F2) initiating antiviral therapy had longitudinal follow-up. Liver fibrosis was measured by liver stiffness measurement using transient elastography. To adjust for imbalances between smoking history and never smoking groups, propensity score (PS) matching model with 1:1 ratios were performed. Cigarette smoking history and intensity (pack-years) were collected and documented using a standardized questionnaire. RESULTS: Before PS matching, 432/2144 patients had advanced fibrosis in prevalence cohort. Patients with smoking history (n = 1002) had a greater prevalence of advanced fibrosis than those without (n = 1142) (24.4% vs 16.5%, P = 0.001). Multivariate logistic regression analysis demonstrated that smoking contributed to advanced fibrosis (OR, 1.458; 95% CI, 1.114-1.908). In longitudinal cohort, multivariate logistic regression analysis demonstrated retarded fibrosis regression in patients with history of smoking ≥10 pack-years (OR, 0.288; 95% CI, 0.1-0.825). After PS matching, patients with smoking history had higher prevalence of advanced fibrosis (22.8% vs 18%, P = 0.024) than those non-smokers. In post-PS-matching logistic regression, the effect of smoking on advanced fibrosis persisted (OR, 1.415; 95% CI, 1.047-1.912; P = 0.024). CONCLUSIONS: Cigarette smoking in male CHB patients aggravated liver fibrosis prior to and delayed fibrosis regression under antiviral therapy.

[Effects of thymectomy on bone age and height development in juvenile myasthenia gravis].

OBJECTIVE: To explore the effects of clinical indicators, particularly thymectomy on the development of juvenile myasthenia gravis (JMG) through the developmental status of bone age (BA) and height. METHODS: A cross-sectional study of 80 JMG patients was recruited to examine whether JMG patients had the abnormalities of height and bone development according to the distribution of height standard deviation score (Ht SDS) and BA. RESULTS: The mean BA was delayed by (0.15 ± 1.32) years compared with patient chronological age (CA). The mean Ht SDS (HtCA SDS -1.25 ± 1.03) was also lower than healthy controls. In multivariate analysis, the age at onset was negatively associated with delayed BA (P=0.007) whereas the cumulative intake of prednisone was negatively associated with HtCA SDS (P=0.043). No significant correlation existed between thymectomy and delayed BA or HtCA SDS. Delayed BA and slow growth existed in JMG patients. The age at onset of JMG was a correlative factor for delayed BA. And the intake of cumulative prednisone might be a determinant of height retardation. Thymectomy had no impact on the development of bone and height. CONCLUSION: We should pay more attention to monitoring BA and height in JMG patients to take appropriate therapeutic interventions.

Epidemic features and megagenomic analysis of childhood Mycoplasma pneumoniae post COVID-19 pandemic: a 6-year study in southern China.

With the atypical rise of Mycoplasma pneumoniae infection (MPI) in 2023, prompt studies are needed to determine the current epidemic features and risk factors with emerging trends of MPI to furnish a framework for subsequent investigations. This multicentre, retrospective study was designed to analyse the epidemic patterns of MPI before and after the COVID-19 pandemic, as well as genotypes and the macrolide-resistance-associated mutations in MP sampled from paediatric patients in Southern China. Clinical data was collected from 1,33,674 patients admitted into investigational hospitals from 1 June 2017 to 30 November 2023. Metagenomic next-generation sequencing (mNGS) data were retrieved based on MP sequence positive samples from 299 paediatric patients for macrolide-resistance-associated mutations analysis. Pearson's chi-squared test was used to compare categorical variables between different time frames. The monthly average cases of paediatric common respiratory infection diseases increased without enhanced public health measures after the pandemic, especially for influenza, respiratory syncytial virus infection, and MPI. The contribution of MPI to pneumoniae was similar to that in the outbreak in 2019. Compared to mNGS data between 2019-2022 and 2023, the severity of MP did not grow stronger despite higher rates of macrolide-resistance hypervariable sites, including loci 2063 and 2064, were detected in childhood MP samples of 2023. Our findings indicated that ongoing surveillance is necessary to understand the impact of post pandemic on MP transmission disruption during epidemic season and the severity of clinical outcomes in different scenarios.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

Intelligent pH indicator composite film based on pectin/chitosan incorporated with black rice anthocyanins for meat freshness monitoring.

With the improvement of consumer awareness of food safety and the increasing concern about plastic pollution, the development of novel intelligent packaging film is imminent. This project aims to develop an environmentally friendly pH-sensitive intelligent food packaging film for meat freshness monitoring. In this study, anthocyanin-rich extract from black rice (AEBR) was added to composite film formed by the co-polymerisation of pectin and chitosan. AEBR showed strong antioxidant activity, and different colour responses to different conditions. The mechanical properties of the composite film remarkably improved when AEBR was incorporated into. Besides, the introduction of anthocyanins enables the colour of composite film to change from red to blue with the degree of meat spoilage increased which shows the indicative effect of composite films on meat putrification. Therefore, the AEBR-loaded pectin/chitosan film could be used as an indicator to monitor meat freshness in real-time.

Polysaccharides as antioxidants and prooxidants in managing the double-edged sword of reactive oxygen species.

Polysaccharides, a class of naturally occurring carbohydrates, were widely presented in animals, plants, and microorganisms. Recently, health benefits of polysaccharides have attracted much attention due to their unique characteristics in reactive oxygen species (ROS) management. ROS, by-products of aerobic metabolism linked to food consumption, exhibited a dual role in protecting cells and fostering pathogenesis collectively termed double-edged sword. Some interesting studies reported that polysaccharides could behave as prooxidants under certain conditions, besides antioxidant capacities. Potentiation of the bright side of ROS could contribute to the host defense that was vitally important for the polysaccharides acting as biological response modifiers. Correspondingly, disease prevention of polysaccharides linked to the management of ROS production was systematically described and discussed in this review. Furthermore, major challenges and future prospects were presented, aiming to provide new insight into applying polysaccharides as functional food ingredients and medicine.

3D printed pore morphology mediates bone marrow stem cell behaviors via RhoA/ROCK2 signaling pathway for accelerating bone regeneration.

Bone bionics and structural engineering have sparked a broad interest in optimizing artificial scaffolds for better bone regeneration. However, the mechanism behind scaffold pore morphology-regulated bone regeneration remains unclear, making the structure design of scaffolds for bone repair challenging. To address this issue, we have carefully assessed diverse cell behaviors of bone mesenchymal stem cells (BMSCs) on the ß-tricalcium phosphate (ß-TCP) scaffolds with three representative pore morphologies (i.e., cross column, diamond, and gyroid pore unit, respectively). Among the scaffolds, BMSCs on the ß-TCP scaffold with diamond pore unit (designated as D-scaffold) demonstrated enhanced cytoskeletal forces, elongated nucleus, faster cell mobility, and better osteogenic differentiation potential (for example, the alkaline phosphatase expression level in D-scaffold were 1.5-2 times higher than other groups). RNA-sequencing analysis and signaling pathway intervention revealed that Ras homolog gene family A (RhoA)/Rho-associated kinase-2 (ROCK2) has in-depth participated in the pore morphology-mediated BMSCs behaviors, indicating an important role of mechanical signaling transduction in scaffold-cell interactions. Finally, femoral condyle defect repair results showed that D-scaffold could effectively promote endogenous bone regeneration, of which the osteogenesis rate was 1.2-1.8 times higher than the other groups. Overall, this work provides insights into pore morphology-mediated bone regeneration mechanisms for developing novel bioadaptive scaffold designs.

White hyacinth bean polysaccharide ameliorates diabetes via microbiota-gut-brain axis in type 2 diabetes mellitus rats.

Gut played a potent role in onset and progression of metabolic disorders, presenting an exciting direction for diabetes prevention. Here, the anti-diabetic effects of White hyacinth bean polysaccharides (WHBP) were observed, including the reduction of blood glucose levels and improvement of intestinal impairment in type 2 diabetes mellitus (T2DM) rats. Further data concerning intestinal protection suggested that WHBP restored intestinal barrier, as evidenced by inhibition of intestinal pathological damage, up-regulation of Zonula occluden-1 expression and manipulation of the redox system in T2DM rats. Moreover, WHBP-mediated anti-diabetic effects were in parallel with the adjustment of changes in gut microbiota composition of T2DM rats. Meanwhile, hypersecretion of corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone levels, which were critical coordinators of the hypothalamic-pituitary-adrenal (HPA) axis, were suppressed in T2DM rats exposed to WHBP, indicating that WHBP-mediated health benefits were referring to regulate brain feedback in reduction of HPA axis. Concomitantly, further suggested and expanded on gut-brain communication by data of microbial metabolites short-chain fatty acids, mediators of gut-brain interactions, were remarkably raised in cecum contents of T2DM rats subjected to WHBP. Collectively, WHBP performed anti-diabetic effects were associated with control of microbiota-gut-brain axis implicated in intestinal barrier, HPA axis, gut microbiota and their metabolites.

Integrated transcriptome and hormone analyses provide insights into silver thiosulfate-induced "maleness" responses in the floral sex differentiation of pumpkin (Cucurbita moschata D.).

The perfect mating of male and female flowers is the key to successful pollination. The regulation of ethylene with chemicals is a good option for inducing staminate or female flowers. Silver thiosulfate is often used to induce the formation of male flowers in subgynoecious and gynoecious crops, which is important to maintain their progenies. However, its effects on flower sex differentiation in pumpkin (Cucurbita moschata Duch.) and the underlying mechanism remain unclear. In this study, the application of silver thiosulfate to pumpkin seedlings significantly delayed the occurrence of the first female flower and increased the number of male flowers. We next investigated the underlying mechanism by employing transcriptome and endogenous hormone analyses of the treated plants. In total, 1,304 annotated differentially expressed genes (DEGs)were identified by comparing silver thiosulfate-treated and control plants. Among these genes, 835 were upregulated and 469 were downregulated. The DEGs were mainly enriched in the phenylpropanoid biosynthesis and metabolism pathways (phenylalanine ammonia-lyase, peroxidase) and plant hormone signal transduction pathways (auxin signaling, indole-3-acetic acid-amido synthetase, ethylene response factor). Silver thiosulfate significantly reduced the levels of 2-oxindole-3-acetic acid, para-topolin riboside, dihydrozeatin-O-glucoside riboside, and jasmonoyl-l-isoleucine but increased the levels of trans-zeatin-O-glucoside, cis-zeatin riboside, and salicylic acid 2-O-ß-glucoside. The levels of auxin and jasmonic acid were decreased, whereas those of salicylic acid were increased. Different trends were observed for different types of cytokinins. We concluded that silver thiosulfate treatment not only affects the expression of auxin synthesis and signaling genes but also that of ethylene response factor genes and regulates the levels of auxin, salicylic acid, jasmonic acid, and cytokinins, which together might contribute to the maleness of pumpkin. This study provides useful information for understanding the mechanism underlying the effect of silver thiosulfate on floral sex differentiation in pumpkin, a widely cultivated vegetable crop worldwide, and gives a production guidance for the induction of maleness using STS for the reproduction of gynoecious lines of Cucurbitaceae crops.

The defining of the reference range of liver stiffness and fat attenuation parameter for healthy Chinese children.

AIMS: We aimed to establish the basal reference levels of liver stiffness and accumulated fat in healthy Chinese children. METHODS: To obtain the liver stiffness measurement (LSM) and the fat attenuation parameter (FAP) levels, the transient elastography (FibroTouch) was used in pediatric patients aged 0 to 18 years. The patients were divided into groups as follows: newborns/infants (0-2 years), preschool children (3-5 years), elementary school children (6-11 years), and adolescents/teenagers (12-18 years). The weight, height and fasting liver function tests were performed. FibroTouch and abdominal ultrasonography were performed. RESULTS: The livers of 521 out of 1362 children (329 male; median age, 4.6 years; age range 0.2-17.6 years) were examined with the FibroTouch. The LSM reference range was 1.5-5.9 kPa, and the FAP reference range was 159.6-217.1 dB/m in healthy children from 0 to 18 years of age. The median LSM value was higher in males than that in females (3.5 vs. 3.2 kPa, respectively; P = 0.01). CONCLUSION: For healthy children from 0 to 18 years in southern China, the LSM reference range was 1.5-5.9 kPa, and the FAP reference range was 159.6-217.1 dB/m. The LSM values were age-dependent in children from 3 to 18 years old, and the FAP values were age-independent in children from 0 to18 years old.

Preparation of acylated blueberry anthocyanins through an enzymatic method in an aqueous/organic phase: effects on their colour stability and pH-response characteristics.

To explore the potential of anthocyanins in pH-colour responsive intelligent packaging and improve the stability of the pigments, 3,4,5-trimethoxybenzoic acid and gallic acid were grafted onto blueberry anthocyanins via enzyme-catalysed grafting. The structural analysis based on UV-vis and IR spectroscopy showed that the two acids were successfully grafted onto the blueberry anthocyanins. The acylation degrees of the 3,4,5-trimethoxybenzoic acid-acylated anthocyanin (Tr-An) and gallic acid-acylated anthocyanin (Ga-An) were 6.38% and 6.51%, respectively. The results from the DPPH radical scavenging assay and ferric reducing antioxidant power assay implied that the antioxidant capacity of Tr-An was worse than that of natural anthocyanin (Na-An), but the antioxidant capacity of Ga-An was stronger than that of Na-An. The grafting of the two acids enhanced the stability of the blueberry anthocyanins and had little effect on the pH-colour response characteristics of the blueberry pigments.

Preparation of Lipid-Soluble Bilberry Anthocyanins through Acylation with Cinnamic Acids and their Antioxidation Activities.

To enable the use of anthocyanins in food with high oil content, bilberry anthocyanins were acylated with cinnamic acids to address their poor lipid solubility. Structural analyses based on Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and 1H nuclear magnetic resonance analyses indicated that cinnamic acids were efficiently grafted onto 6-OH of glucoside and galactoside and 5-OH of arabinose through an esterification reaction. The higher the dose of the acylating agent, the higher the acylation degree (AD) and the lower the total anthocyanidin content (TAC) of bilberry anthocyanins. An-Ci4 presented the highest AD value (6.61%), and An-Ci3 exhibited the lowest TAC value (50.16 mg/g). After acylating with lipophilic cinnamic acids, the lipid solubility of acylated bilberry anthocyanins significantly improved. The color of the native bilberry anthocyanin solution dissolved in ethyl acetate and dioxane was transparent. By contrast, the acylated anthocyanin solution dissolved in these solvents was unmistakably red. In terms of the antioxidant activity, acylated bilberry anthocyanins demonstrated inferior performance in 2,2-diphenyl-1-picrylhydrazyl (DPPH) clearance but a better inhibition ratio in ß-carotene bleaching assay compared with native bilberry anthocyanins. As AD value increased, the DPPH clearance of acylated anthocyanins decreased and their inhibition ratio increased in ß-carotene bleaching assay.

Influence of Gender and Reproductive Factors on Liver Fibrosis in Patients With Chronic Hepatitis B Infection.

INTRODUCTION: The role of reproductive factors in the development of chronic hepatitis B (CHB) remains unknown. We assessed the potential contributions of gender, menopausal status, and menarche age to liver fibrosis in CHB. METHODS: A cross-sectional prospective study included 716 women and 716 age-matched men with CHB who were not currently receiving antiviral therapy. Liver stiffness measurement using transient elastography was used to stage liver fibrosis as F0-F1 (<7.2 kPa), F ≥ 2 (7.2 kPa), F ≥ 3 (9.4 kPa), and F = 4 (12.2 kPa). Female patients were asked regarding their age at menarche and menopausal status using a questionnaire. RESULTS: Of the 716 women, 121 (16.9%) were postmenopausal, and 80 (11.2%) had advanced liver fibrosis. Multivariate logistic regression analysis showed that the postmenopausal status compared with the premenopausal status (odds ratio [OR] = 3.65-8.83; P < 0.05) and age at menarche of >14 years compared with <13 years (OR = 2.85-3.95; P < 0.05) were significantly associated with advanced fibrosis. Compared with premenopausal women, age-matched men had a higher OR for advanced fibrosis (P < 0.05). Compared with postmenopausal women, age-matched men did not show a significant difference in the degree of liver fibrosis (P > 0.05). Longitudinal data analysis showed that postmenopausal women (n = 31) were significantly less likely to undergo regression of liver fibrosis after antiviral treatment vs premenopausal women (n = 19) (26.3% vs 74.2%, respectively; P < 0.001). DISCUSSION: Menopause and late menarche aggravated liver fibrosis in untreated CHB, besides menopause delayed fibrosis regression under antiviral therapy. The protective effect of female gender against fibrosis was lost for postmenopausal women. TRANSLATIONAL IMPACT: It is important to consider menopausal status and age at menarche in establishing surveillance strategies among CHB females. Postmenopausal estrogen therapy may be considered for the prevention or treatment of liver fibrosis.

[Analysis of clinical characteristics of the 12 cases of neonatal dengue fever in Guangzhou in 2014 and literatures review].

OBJECTIVE: To explore the clinical manifestations and laboratory examination characteristics of neonatal dengue fever. METHOD: A retrospective analysis of 12 cases of neonatal dengue fever treated in the Guangdong Women and Children's Hospital and Guangzhou Women and Children's Medical Center was conducted, and related literature was reviewed. RESULT: Twelve cases of neonatal dengue fever included 9 males and 3 females; their age was 30 min after birth to 29 d, the age of onset was 30 min-24 d. (1) CLINICAL FEATURES: fever was present in 11 cases, rash in 6 cases, bleeding in 1 case, jaundice in 5 cases, cough in 1 case, coagulopathy in 2 cases. (2) Mothers' perinatal conditions: 7 mothers were confirmed to have dengue fever, 2 mothers had suspected dengue fever, and in 3 mothers the dengue fever was excluded. Eight mothers prenatally had fever. (3) LABORATORY TESTS: Thrombocytopenia was found in 11 cases (19×10(9)-156×10(9)/L), activated partial thromboplastin time prolonged in 11 cases (44.0-89.8 s), fibrinogen decreased in 5 cases (1.17-3.02 g/L), aspartate aminotransferase (AST) increased in 5 cases (28-78 U/L), creatine kinase (CK-MB) increased in 4 cases (13-86 U/L), hypokalemia in 1 case (2.8-5.1 mmol/L ), C- reactive protein (CRP) increased in 6 cases (0.04-46.05 mg/L). (4) Treatment and prognosis: platelet transfusion was used in 2 cases, anti-infective therapy was given to 6 cases, intravenous gamma globulin treatment was used in 5 cases, hospitalization was 4-17 d, 10 cases were cured, 2 cases were discharged after condition was improved. Literature search was performed with "neonatal dengue" as keywords at Wanfang, Weipu, and CNKI, no relevant reports were found. Pubmed search was done with "neonatal dengue" and "case report" as keywords, 15 reports were retrieved during 1990 and 2014, which reported 30 cases, all acquired the disease via vertical transmission; the main clinical manifestations were fever, rash, petechiae, anemia, jaundice, tachycardia, and hepatomegaly; laboratory test: all had visible purpura due to thrombocytopenia; anti-infective treatment, platelet transfusion and symptomatic treatment were given, and all the 30 cases of infants were cured. CONCLUSION: The clinical manifestations of neonatal dengue fever are characterized by fever and the disorder of blood coagulation system. The course of disease is mild, lack of specific clinical symptoms, and the prognosis is good. Mother to infant vertical transmission of dengue virus is one of the ways of transmission.