A bibliometric analysis of Kawasaki disease from 1974 to 2022.

Objective: To analyse the research history, development trends and current status of relevant literature in the field of Kawasaki disease, and to provide the basis for future directions in Kawasaki disease (KD) research. Methods: Literature on Kawasaki disease published between January 1974 and December 2022 was searched for in the Web of Science database, and CiteSpace was used to perform visual analyses. Results: The search yielded a total of 6950 articles. The number of publications related to Kawasaki disease showed an increasing trend. A collaborative network analysis revealed that the United States, Japan and mainland China were the most influential countries in this field. The University of California system contributed the most publications and the journal with the most publications was Circulation. JW Newburger was an authoritative author in this field. "Coronary artery lesion", "Intravenous immunoglobulin" (IVIG) and "Risk factor" were three prominent keywords. Keyword bursts changed from "TNF" and "IVIG", which focused on aetiology and treatment, to "Long term management", which emphasized the recovery period, and to "Kawasaki-like disease" and "Multisystem inflammatory syndrome" during the novel coronavirus pandemic. Trends of highly cited references indicated that landmark articles in different periods focused on Kawasaki disease guidelines, gene polymorphisms and multisystem inflammatory syndrome caused by the novel coronavirus. Conclusion: The aetiology of Kawasaki disease remains unclear, but viral infection is likely to play an important role. The combination of evolving sequencing technologies, large-scale epidemiological investigations and prospective cohort studies is likely to be important in exploring Kawasaki disease and improving its prognosis in future.

Improving anion sensing ability of the indolocarbazole-based fluorescence turn-on sensor by increasing salicylaldehyde response unit.

Detection abilities on tested subjects of sensors should be closely connected to the sensing unit numbers. Herein, two anion sensors ICZ-o-1S and ICZ-o-2S were synthesized by using indolo (2,3-a) carbazoles as fluorescent chromophore and salicylaldehyde as recognition site. Though UV-Vis and fluorescent ways, it demonstrated that F- can induce the sensor solutions becoming colored from colorless to yellow green, and can endow them with bright green turn-on fluorescence, proving their sensitive and selective sensing on F-. Accordingly, the F ion sensing studies including anti-interference abilities against to other anions on fluorescence response, stoichiometric ratios of sensor-F- in 1 : 1 and 1 : 2, -OH deprotonation sensing mechanism confirmed by 1H NMR titration and theoretical calculation were fully covered. Most importantly, fluoride ion detection limits achieved by ICZ-o-1S and ICZ-o-2S were 1.8 × 10-7 M and 6.0 × 10-8 M, respectively, the latter with two sensing units exhibited 3 times lower detection limit outcompeted to the former with only one sensing unit, rendering the sensor design strategy of improving detecting ability by increasing sensing unit number was rational. The practical application of F- detection in water-containing environment calibrated from the standard curve between the fluorescence intensity of sensor-F- system and the changing F- concentration was conducted. In addition, the accuracy of the sensor on detecting F- was evaluated by the spiked recovery experiment, therefore, the fast and convenient F- concentration detection based on the fluorescence color RGB values of the tested sensor-sample mixture was investigated. Consequently, the results obtained by these two sensors should deliver effective supports on designing high-performance sensors featuring naked-eye and fluorescence turn-on anion sensing by altering the response unit numbers.

The protective effect of inhibiting mitochondrial fission on the juvenile rat brain following PTZ kindling through inhibiting the BCL2L13/LC3 mitophagy pathway.

Maintaining the balance of mitochondrial fission and mitochondrial autophagy on seizures is helpful to find a solution to control seizures and reduce brain injuries. The present study is to investigate the protective effect of inhibiting mitochondrial fission on brain injury in juvenile rat epilepsy induced by pentatetrazol (PTZ) by inhibiting the BCL2L13/LC3-mediated mitophagy pathway. PTZ was injected (40 mg/kg) to induce kindling once every other day, for a total of 15 times. In the PTZ + DMSO (DMSO), PTZ + Mdivi-1 (Mdivi-1), and PTZ + WY14643 (WY14643) groups, rats were pretreated with DMSO, Mdivi-1 and WY14643 for half an hour prior to PTZ injection. The seizure attacks of young rats were observed for 30 min after model establishment. The Morris water maze (MWM) was used to test the cognition of experimental rats. After the test, the numbers of NeuN(+) neurons and GFAP(+) astrocytes were observed and counted by immunofluorescence (IF). The protein expression levels of Drp1, BCL2L13, LC3 and caspase 3 in the hippocampus of young rats were detected by immunohistochemistry (IHC) and Western blotting (WB). Compared with the PTZ and DMSO groups, the seizure latency in the Mdivi-1 group was longer (P < 0.01), and the severity degree and frequency of seizures were lower (P < 0.01). The MWM test showed that the incubation periods of crossing the platform in the Mdivi-1 group was significantly shorter. The number of platform crossings, the platform stay time, and the ratio of residence time/total stay time were significantly increased in the Mdivi-1 group (P < 0.01). The IF results showed that the number of NeuN(+) neurons in the Mdivi-1 group was greater, while the number of GFAP(+) astrocytes was lower. IHC and WB showed that the average optical density (AOD) and relative protein expression levels of Drp1, BCL2L13, LC3 and caspase 3 in the hippocampi of rats in the Mdivi-1 group were higher (P < 0.05). The above results in the WY14643 group were opposite to those in the Mdivi-1 group. Inhibition of mitochondrial fission could reduce seizure attacks, protect injured neurons, and improve cognition following PTZ-induced epilepsy by inhibiting mitochondrial autophagy mediated by the BCL2L13/LC3 mitophagy pathway.

The efficacy and safety of acupuncture in the treatment of taste disorders after rehabilitation from COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Since the outbreak of the new crown pneumonia epidemic, although it has had a serious impact on people's lives and health in itself, the sequelae that accompany coronavirus disease 2019 (COVID-19) have also had a serious impact on people's mental health and quality of life. Taste disorder (TD) is one of the sequelae of COVID-19. Patients may experience reduced or even absent taste sensation, which seriously affects their real life. The efficacy of acupuncture in the treatment of taste disorders has been well reported, but there is a lack of evidence-based medical evidence. Therefore, this study set out to systematically evaluate the efficacy and safety of acupuncture in the treatment of post-COVID-19 taste disorder. METHODS: According to the retrieval strategies, randomized controlled trials on the acupuncture for COVID-19 TD were obtained from Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database and the Wanfang Database, regardless of publication date, or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the studies. The meta-analysis was performed using Review Manager (RevMan 5.4) and StataSE 15.0 software. Ultimately, the evidentiary grade for the results will be evaluated. This systematic evaluation protocol is registered in PROSPERO under the registration ID CRD42022364653. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This meta-analysis will evaluate the effect of acupuncture and moxibustion on TD caused by sequelae of COVID-19, providing evidence as to the treatment in these patients.

Prediction Model Risk-of-Bias Assessment Tool for coronary artery lesions in Kawasaki disease.

Objective: To review and critically appraise articles on prediction models for coronary artery lesions (CALs) in Kawasaki disease included in PubMed, Embase, and Web of Science databases from January 1, 1980, to December 23, 2021. Materials and methods: Study screening, data extraction, and quality assessment were performed by two independent reviewers, with a statistics expert resolving discrepancies. Articles that developed or validated a prediction model for CALs in Kawasaki disease were included. The Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies checklist was used to extract data from different articles, and Prediction Model Risk-of-Bias Assessment Tool (PROBAST) was used to assess the bias risk in different prediction models. We screened 19 studies from a pool of 881 articles. Results: The studies included 73-5,151 patients. In most studies, univariable logistic regression was used to develop prediction models. In two studies, external data were used to validate the developing model. The most commonly included predictors were C-reactive protein (CRP) level, male sex, and fever duration. All studies had a high bias risk, mostly because of small sample size, improper handling of missing data, and inappropriate descriptions of model performance and the evaluation model. Conclusion: The prediction models were suitable for the subjects included in the studies, but were poorly effective in other populations. The phenomenon may partly be due to the bias risk in prediction models. Future models should address these problems and PROBAST should be used to guide study design.

Taurine supplementation improves hippocampal metabolism in immature rats with intrauterine growth restriction (IUGR) through protecting neurons and reducing gliosis.

Taurine as an essential amino acid in the brain could play an important role in protecting the fetal brain of intrauterine growth restriction (IUGR). The hippocampus with IUGR showed neural metabolic disorder and structure changed that affected memory and learning ability. This study was aimed to identify the effect of taurine supplementation on the metabolism alterations and cellular composition changes of the hippocampus in IUGR immature rats. Metabolite concentrations were determined by magnetic resonance spectroscopy (MRS) in the hippocampus of juvenile rats with IUGR following taurine supplementation with antenatal or postnatal supply. The composition of neural cells in the hippocampus was observed by immunohistochemical staining (IHC) and western blotting (WB). Antenatal taurine supplementation increased the ratios of N-acetylaspartate (NAA) /creatine (Cr) and glutamate (Glu) /Cr of the hippocampus in the IUGR immature rats, but reduced the ratios of choline (Cho) /Cr and myoinositol (mI) /Cr. At the same time, the protein expression of NeuN in the IUGR rats was increased through intrauterine taurine supplementation, and the GFAP expression was reduced. Especially the effect of antenatal taurine was better than postpartum. Furthermore, there existed a positive correlation between the NAA/Cr ratio and the NeuN protein expression (R = 0.496 p < 0.001 IHC; R = 0.568 p < 0.001 WB), the same results existed in the relationship between the mI/Cr ratio and the GFAP protein expression (R = 0.338 p = 0.019 IHC; R = 0.440 p = 0.002 WB). Prenatal taurine supplementation can better improve hippocampal neuronal metabolism by increasing NAA / Cr ratio related to the number of neurons and reducing Cho / Cr ratio related to the number of glial cells.

The role of FOXO4/NFAT2 signaling pathway in dysfunction of human coronary endothelial cells and inflammatory infiltration of vasculitis in Kawasaki disease.

Aims: The Ca+/NFAT (Nuclear factor of activated T cells) signaling pathway activation is implicated in the pathogenesis of Kawasaki disease (KD); however, we lack detailed information regarding the regulatory network involved in the human coronary endothelial cell dysfunction and cardiovascular lesion development. Herein, we aimed to use mouse and endothelial cell models of KD vasculitis in vivo and in vitro to characterize the regulatory network of NFAT pathway in KD. Methods and Results: Among the NFAT gene family, NFAT2 showed the strongest transcriptional activity in peripheral blood mononuclear cells (PBMCs) from patients with KD. Then, NFAT2 overexpression and knockdown experiments in Human coronary artery endothelial cells (HCAECs) indicated that NFAT2 overexpression disrupted endothelial cell homeostasis by regulation of adherens junctions, whereas its knockdown protected HCAECs from such dysfunction. Combined analysis using RNA-sequencing and transcription factor (TF) binding site analysis in the NFAT2 promoter region predicted regulation by Forkhead box O4 (FOXO4). Western blotting, chromatin immunoprecipitation, and luciferase assays validated that FOXO4 binds to the promoter and transcriptionally represses NFAT2. Moreover, Foxo4 knockout increased the extent of inflamed vascular tissues in a mouse model of KD vasculitis. Functional experiments showed that inhibition NFAT2 relieved Foxo4 knockout exaggerated vasculitis in vivo. Conclusions: Our findings revealed the FOXO4/NFAT2 axis as a vital pathway in the progression of KD that is associated with endothelial cell homeostasis and cardiovascular inflammation development.

Taurine improves the differentiation of neural stem cells in fetal rats with intrauterine growth restriction via activation of the PKA-CREB-BDNF signaling pathway.

Intrauterine growth restriction (IUGR) affects brain neural stem cell (NSC) differentiation. In the present study, we investigated whether taurine supplementation may improve NSC differentiation in IUGR fetal rats via the protein kinase A-cyclic adenosine monophosphate (cAMP) response element protein-brain derived neurotrophic factor (PKA-CREB-BDNF) signaling pathway. The IUGR fetal rat model was established with a low-protein diet. Fresh subventricular zone (SVZ) tissue from the fetuses on the 14th day of pregnancy was microdissected and dissociated into single-cell suspensions, then was cultured to form neurospheres. The neurospheres were divided into the control group, the IUGR group, the IUGR+taurine (taurine) group, the IUGR+H89 (H89) group and the IUGR+taurine+H89 (taurine+H89) group. The mRNA and protein expression levels of PKA, CREB and BDNF were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting (WB). Tuj-1-positive neurons and GFAP-positive glial cells were detected by immunofluorescence. The total number of proliferating NSCs and the percentage of Tuj-1-positive neurons in the IUGR group were lower than those in the control group, but the percentage of GFAP-positive cells was higher in the IUGR group than in the control group. Taurine supplementation increased the total number of neural cells and the percentage of Tuj-1-positive neurons, and reduced the percentage of GFAP-positive cells among differentiated NSCs after IUGR. H89 reduced the total number and percentage of Tuj-1-positive neurons and increased the percentage of GFAP-positive cells. The mRNA and protein levels of PKA, CREB, and BDNF were lower in the IUGR group. The mRNA and protein expression levels of these factors were increased by taurine supplementation but reduced by the addition of H89. Taurine supplementation increased the ratio of neurons to glial cells and prevented gliosis in the differentiation of NSCs in IUGR fetal rats by activating the PKA-CREB-BDNF signaling pathway.

The Clinical Significance of Nasal Nitric Oxide Concentrations in Preschool Children with Nasal Inflammatory Disease.

BACKGROUND: Allergic rhinitis is an allergic inflammation of the nasal airways, and chronic rhinosinusitis is an inflammation of the paranasal sinuses. It can be induced by infection, allergy, or autoimmune problems. Diagnosis of these two diseases is made primarily based on clinical symptoms, allergen test, and imaging. The allergen test is invasive and expensive. The imaging test is harmful to children. Measurement of nasal nitric oxide (NNO) was noninvasive, without radiation, and inexpensive. This study was to evaluate the clinical significance of NNO in preschool children with nasal inflammatory diseases. METHODS: A total of 55 cases of allergic rhinitis, including 35 mild cases and 20 moderate to severe cases, and 33 cases of chronic rhinosinusitis, including 18 mild cases and 15 moderate to severe cases were selected as the experimental group. Fifty healthy preschool children were chosen as the control group. The levels of NNO in all children were measured. The differences in the levels of NNO among allergic rhinitis, chronic rhinosinusitis, and the control group were compared. The levels of NNO in the control group were also analyzed. RESULTS: The levels of NNO were significantly higher in preschool children with allergic rhinitis than in the control group, and the differences were significant. However, the levels of NNO in preschool children with chronic rhinosinusitis were lower than in the control group. In the control group, the levels of NNO were not significantly different between genders, and no significant correlation between NNO levels and the children's height was found. CONCLUSION: As a noninvasive method for detecting nasal inflammatory diseases, measuring the levels of NNO had a high clinical significance in preschool children.

Obesity is associated with Henoch-Schönlein Purpura Nephritis and development of end-stage renal disease in children.

Objectives: To explore the association of obesity with the occurrence of Henoch-Schönlein Purpura Nephritis (HSPN) and development of end-stage renal disease (ESRD) in children with Henoch-Schönlein Purpura (HSP).Methods: This was a retrospective study of 446 pediatric patients with diagnosed HSP. All patients' demographic characteristics, clinical features, and laboratory data were collected from the electronic medical records in hospitals from January 2008 to December 2014, and the prognosis was followed up till December 2018. Multivariate logistic regression and the Cox proportional hazard regression were employed for exploring the potential risk factors for occurrence of HSPN and development of ESRD, respectively.Results: It is reported that 35.2% (n = 157) of HSP patients had HSPN. The multivariate logistic regression showed that obesity (OR = 3.82; 95% CI: 1.92-7.49; p < .01), age over 6 years old at onset (OR = 2.24; 95% CI: 1.32-4.87; p < .01) and angioedema (OR = 1.72; 95% CI: 1.25-4.02; p < .01) were significantly associated with the occurrence of HSPN. During a median follow-up of 52.0 months, 5.2% (n = 23) of HSP patients developed ESRD. The Cox proportional hazard regression indicated that obesity (HR = 3.27; 95% CI: 2.01-6.37; p < .01) and International Study of Kidney Disease of Children (ISKDC) III (HR= 2.88; 95% CI: 1.96-3.80; p < .01) were predictors for the development of ESRD in patients with HSP.Conclusions: Obesity is associated with an increased risk of renal involvement and contributes to the development of ESRD in pediatric patients with HSP.

Early prediction of preeclampsia and small-for-gestational-age via multi-marker model in Chinese pregnancies: a prospective screening study.

BACKGROUND: Recent evidence suggests early screening of preeclampsia and small-for-gestational-age (SGA) would benefit pregnancies followed by subsequent prophylactic use of aspirin. Multi-marker models have shown capability of predicting preeclampsia and SGA in first trimester. Yet the clinical feasibility of combined screening model for Chinese pregnancies has not been fully assessed. The aim of this study is to evaluate the applicability of a multi-marker screening model to the prediction of preeclampsia and SGA in first trimester particularly among Chinese population. METHODS: Three thousand two hundred seventy pregnancies meeting the inclusion criteria took first-trimester screening of preeclampsia and SGA. A prior risk based on maternal characteristics was evaluated, and a posterior risk was assessed by combining prior risk with multiple of median (MoM) values of mean arterial pressure (MAP), serum placental growth factor (PLGF) and pregnancy associated plasma protein A (PAPP-A). Both risks were calculated by Preeclampsia PREDICTOR™ software, Perkin Elmer. Screening performance of prior and posterior risks for early and late preeclampsia by using PREDICTOR software was shown by Receiver Operating Characteristics (ROC) curves. The estimation of detection rates and false positive rates of delivery with both preeclampsia and SGA was made. RESULTS: Eight cases developed early preeclampsia (0.24%) and 35 were diagnosed as late preeclampsia (1.07%). Five with early preeclampsia and ten with late preeclampsia later delivered SGA newborns (0.46%); 84 without preeclampsia gave birth to the SGAs (2.57%). According to ROC curves, posterior risks performed better than prior risks in terms of preeclampsia, especially in early preeclampsia. At 10% false positive rate, detection rates of early and late preeclampsia were 87.50 and 48.57%, detection rates of early and late SGA were 41.67 and 28.00%, respectively. For SGA, detection rates in cases with preeclampsia were much higher than those in absence of it. CONCLUSIONS: This study demonstrates that combined screening model could be useful for predicting early preeclampsia in Chinese pregnancies. Furthermore, the performance of SGA screening by same protocol is strongly associated with preeclampsia.

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion of corpus callosum in Chinese children.

OBJECTIVE: To investigate the characteristics and etiology of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in Chinese children. METHODS: We collected ten pediatric MERS patients from local hospital and enrolled another nineteen patients by reviewing the available literatures. The information of enrolled patients about clinical features, laboratory data, treatment strategies and prognoses were collected for further analysis. RESULTS: A total of 29 children, the median age of twenty-nine patients was (4.09±3.64) years old. The male-to-female ratio was 1.42:1.0. The major cause of MERS was viral infection. 18 patients had consciousness disturbance which was the most prominent syndrome. 18 patients had transient seizures and only one needed anticonvulsant treatment for long. 9 patients were observed serum sodium levels <135mEq/L. The cells and protein of cerebral spinal fluid (CSF) were increased in 3 patients. In all patients, brain MRI evaluation revealed typical lesion in splenium of the corpus callosum (SCC). 5 patients had additional lesions involving the periventricular white matter or bilateral centrum semiovale diagnosed. 3 patients were treated with antivirus treatment because of virus infection. 7 patients received corticosteroid. 2 patients received intravenous IVIG. As a result, all patients had fully recovered without neurological residual. CONCLUSIONS: The result of present study suggests that Chinese children with MERS might have favorable prognosis, although there is still no guideline for treatment.

Establishment of trimester-specific thyroid stimulating hormone and free thyroxine reference interval in pregnant Chinese women using the Beckman Coulter UniCel™ DxI 600.

BACKGROUND: Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals are essential for screening and diagnosing thyroid dysfunction during pregnancy. The aim of this study was to establish method- and trimester-specific TSH and FT4 reference intervals in pregnant Chinese women using the Beckman Coulter UniCel™ DxI 600. METHODS: A cross-sectional dataset analysis was performed. A total of 3507 participants were recruited, and 2743 were eligible for analysis to set reference intervals. TSH, FT4, and thyroid peroxidase antibody (TPOAb) levels were analyzed with the Beckman Coulter UniCel™ DxI 600 Access® immunoassay system. Ranges between the 2.5th and 97.5th percentiles were defined as reference intervals for TSH and FT4. RESULTS: The calculated reference intervals for the first, second, and third trimesters were TSH: 0.06-3.13, 0.07-4.13 and 0.15-5.02 mIU/L, respectively, and FT4: 8.72-15.22, 7.10-13.55 and 6.16-12.03 pmol/L, respectively. CONCLUSIONS: Our reference intervals for TSH and FT4 are distinct from the ranges reported in the DxI 600 instruction manual and previously reported data, confirming the importance of method-specific reference intervals.