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Children and adults differ significantly in physiology, biochemistry and immune function, which leads to significant differences in blood transfusion strategies between children and adults. To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children, the National Health Commission organized the formulation and release of the health industry standard Guideline for Pediatric Transfusion (WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard, and explain and interpret the preparation of the " scope", " general provisions" and " factors to consider" of the Standard, hoping to contribute to the understanding and implementation of the Standard.

Abstract Therapeutic agents targeting cytokine-cytokine receptor (CK-CKR) interactions lead to the disruption in cellular signaling and are effective in treating many diseases including tumors. However, a lack of universal and quick access to annotated structural surface regions on CK/CKR has limited the progress of a structure-driven approach in developing targeted macromolecular drugs and precision medicine therapeutics. Herein we develop CytoSIP (Single nucleotide polymorphisms (SNPs), Interface, and Phenotype), a rich internet application based on a database of atomic interactions around hotspots in experimentally determined CK/CKR structural complexes. CytoSIP contains: (1) SNPs on CK/CKR; (2) interactions involving CK/CKR domains, including CK/CKR interfaces, oligomeric interfaces, epitopes, or other drug targeting surfaces; and (3) diseases and phenotypes associated with CK/CKR or SNPs. The database framework introduces a unique tri-level SIP data model to bridge genetic variants (atomic level) to disease phenotypes (organism level) using protein structure (complexes) as an underlying framework (molecule level). Customized screening tools are implemented to retrieve relevant CK/CKR subset, which reduces the time and resources needed to interrogate large datasets involving CK/CKR surface hotspots and associated pathologies. CytoSIP portal is publicly accessible at https://CytoSIP.biocloud.top , facilitating the panoramic investigation of the context-dependent crosstalk between CK/CKR and the development of targeted therapeutic agents.

Abstract With the rapid development of machine learning technology, it has become possible to automatically identify cultural heritage elements in traditional buildings. This research aimed to develop a machine learning model based on the YOLOv4 architecture to identify the traditional Chinese porcelain inlay pattern in the Lingnan region. The researchers collected and annotated a large quantity of Lingnan Chinese porcelain inlay image data and then used these data to train the studied model. The research results show that (1) the model in this study was specifically adjusted to effectively identify a variety of Chinese porcelain inlay pattern types, including traditional patterns such as plum blossoms and camellias. (2) In the 116th epoch, the model showed excellent generalization ability, and the verification loss reached the lowest value of 0.88. The lowest training loss in the 195th epoch was 0.99, indicating that the model reached an optimal balance point for both recognition accuracy and processing speed. (3) By comparing different models for detecting Chinese porcelain inlay images across 581 pictures, our YOLOv4 model demonstrated greater accuracy in most classification tasks than did the YOLOv8 model, especially in the classification of chrysanthemums, where it achieved an accuracy rate of 87.5%, significantly outperforming YOLOv8 by 58.82%. However, the study also revealed that under certain conditions, such as detecting apples and pears in low-light environments, YOLOv8 showed a lower missing data rate, highlighting the limitations of our model in dealing with complex detection conditions.

Background Lupus nephritis (LN) is an autoimmune-related kidney disease with a poor prognosis, however the potential pathogenic mechanism remains unclear and there is a lack of precise biomarkers. Therefore, a thorough screening and identification of renal markers in LN are immensely beneficial to the research on its pathogenic mechanisms and treatment strategies. Methods We utilized bioinformatics to analyze the differentially expressed genes (DEGs) at the transcriptome level of three clusters: total renal, glomeruli, and renal tubulointerstitium in the GEO database to discover potential renal biomarkers of LN. We utilized NephroSeq datasets and measured mRNA and protein levels in the kidneys of MRL/lpr mice to confirm the expression of key DEGs. Results Seven significantly differential genes (EGR1, MME, PTPRC, RORC, MX1, ZBTB16, FKBP5) were revealed from the transcriptome database of GSE200306, which were mostly enriched in the pathway of the hematopoietic cell lineage and T cell differentiation respectively by KEGG and GO analysis. The seven hot differential genes were verified to have consistent change trends using three datasets from NephroSeq database. The receiver operating characteristic (ROC) curve indicated that five DEGs (PTPRC, MX1, EGR1, MME and RORC) exhibited a higher diagnostic ROC value in both the glomerulus and tubulointerstitium group. Validation of core genes using MRL/lpr mice showed that MME and PTPRC exhibit significantly differential mRNA and protein expression patterns in mouse kidneys like the datasets. Conclusions This study identified seven key renal biomarkers through bioinformatics analysis using the GEO and NephroSeq databases. It was identified that MME and PTPRC may have a high predictive value as renal biomarkers in the pathogenesis of LN, as confirmed by animal validation.

Abstract This study aimed to investigate the risk factors for the onset of subsequent primary breast cancer (SPBC) in women with a previous diagnosis of early‐stage breast cancer (BC) and to construct a prognostic prediction model for patients with SPBC. Using the Surveillance, Epidemiology, and End Results‐17 (SEER‐17) database, we conducted a retrospective cohort analysis on women with initial primary early‐stage BC from 2004 to 2015. Standardized incidence ratio (SIR) was calculated to determine the risk of subsequent primary cancer (SPC). A competing risk model was built to identify the risk factors for the onset of SPBC. And risk factors associated with breast cancer‐specific mortality in SPBC patients were evaluated and presented in the form of nomogram. Compared with the general population, the overall risk of SPC for all sites was significantly elevated in women with early‐stage BC (SIR = 1.21, 95% CI: 1.20–1.23), and breast is the most frequent site. Age, race and ethnicity, year of diagnosis, history of other tumors, histological type, surgery, radiation, chemotherapy, tumor size, positive lymph nodes numbers and ER status were independent risk factors (p

The COVID-19 outbreak has been declared the sixth Public Health Emergency of International Concern certified by the World Health Organization. With the extensive application of COVID-19 vaccines, rare but serious adverse reactions have gradually emerged, among which systemic capillary leak syndrome (SCLS) deserves our attention. SCLS is difficult to diagnose. Not only can it exacerbate various diseases, but also can lead to pulmonary edema, kidney failure, and even death. We summarized and discussed case reports of SCLS induced by COVID-19 vaccines to raise awareness of COVID-19 vaccine-associated rare diseases. We conducted a comprehensive search in Web of Science, PubMed and Embase and collected case reports of SCLS induced by COVID-19 vaccine before February 19, 2024. We identified and analyzed 12 articles, encompassing 15 cases. We synthesized the data to summerize possible mechanisms of SCLS, clinical manifestations, differential diagnoses, and therapeutic approaches. Most SCLS occurred after vaccination with the Pfe-Biontech mRNA vaccine (9/15) and following the second vaccination (10/15). Almost all patients experienced hypotension (13/15) and tachycardia (11/15). Most patients received intravenous fluids (9/15) and corticosteroids (9/15). 11 patients were recovered and were discharged, while 4 patients died. Inflammation and endothelial cell damage may be linked to SCLS and COVID-19 vaccines. These findings highlight the necessity of focusing on serious adverse reactions of COVID-19 vaccines and the urgency to reconsider the safety of COVID-19 vaccines.

Kounis syndrome is an acute coronary syndrome triggered by allergic mediators that induce coronary vasoconstriction and thrombosis, leading to further myocardial damage and anaphylactic shock. Kounis syndrome is also a rare but severe adverse reaction to the COVID-19 vaccine, a phenomenon that underscores the importance of collecting and analyzing similar cases to improve treatment and prognosis. Through comprehensive searches of the Web of Science, Embase, and PubMed databases, this study aimed to gather detailed patient data on patients who developed Kounis syndrome after receiving the COVID-19 vaccine and to further investigate the possible underlying mechanisms using currently available studies. A total of 15 patients (8 females, 7 males) were found. We analyzed comprehensive patient data, including demographics, vaccination details, time of onset of illness after vaccination, clinical manifestations, treatment and outcomes, duration of illness, and relevant examination results. Analysis of these data combined with known allergy-related mechanisms indicated that, regardless of the vaccine type, the first dose of the vaccine was more likely to cause Kounis syndrome than subsequent doses. Therefore, early diagnosis and clinical symptomatic treatment are particularly crucial for managing the severity of Kounis syndrome and preventing further cardiac complications. Additionally, when an unusual and severe allergic reaction occurs within a few hours after vaccination, it is important to closely monitor the development of cardiac-related symptoms and prepare clinically for the potential onset of Kounis syndrome.

ABSTRACTConsidering the widespread use of COVID-19 vaccines as a preventive measure against the spread of the virus, it’s necessary to direct attention to the adverse effects associated with vaccines in a limited group of populations. Multiple evanescent white dot syndrome (MEWDS) following COVID-19 vaccination is a rare adverse reaction associated with COVID-19 vaccines. In this systematic review, we collected 19 articles with 27 patients up to November 1, 2023, summarizing the basic information, clinical manifestations, examinations, treatments, and recoveries of the 27 patients. The 27 enrolled patients (6 males, 21 females) had a median age of 34.1 years (15–71 years old) and were mainly from 5 regions: Asia (8), the Mediterranean region (8), North America (7), Oceania (3) and Brazil (1). Symptoms occurred post-first dose in 9 patients, post-second dose in 14 (1 with symptoms after both), post-third dose in 1, and both post-second and booster doses in 1, while details on 2 cases were not disclosed. Treatments included tapered oral steroids (6), topical steroids (3), tapered prednisone with antiviral drugs and vitamins (1), and valacyclovir and acetazolamide (1), while 16 received no treatment. All patients experienced symptom improvement, and nearly all patients ultimately recovered. Moreover, we summarized possible hypotheses concerning the mechanism of COVID-19 vaccine-associated MEWDS. The findings provide insights into the clinical aspects of COVID-19 vaccine-associated MEWDS. More attention should be given to patients with vaccine-associated MEWDS, and necessary treatment should be provided to patients experiencing a substantial decline in visual acuity to improve their quality of life.

ABSTRACTTo prevent COVID-19, the COVID-19 vaccine has been widely administered worldwide, but various complications accompany this vaccine. The aim of this study was to investigate the demographic patterns, clinical features, diagnostic findings, and treatment outcomes associated with shoulder injury related to vaccine administration (SIRVA). This study examined 22 patients with SIRVA following COVID-19 vaccination from the Web of Science (WOS) and PubMed databases. The patients were categorized based on sex, age, type of COVID-19 vaccine received, dose administered, latency of symptom onset, and the presence of specific clinical manifestations. Patients, evenly distributed by sex (12 females, 10 males), and aged 21 to 84 years (mean age 46.6), were analyzed. SIRVA cases were reported across all age groups. The Pfizer – BioNTech COVID-19 vaccine had the highest incidence (n = 8), followed by the Oxford/AstraZeneca COVID-19 vaccine (n = 4). Symptoms, primarily shoulder pain (n = 22) and shoulder mobility disorders (n = 18), occurred within three days post-vaccination. Some patients also reported shoulder swelling (n = 5) and fever (n = 2). Imaging revealed nonspecific X-ray findings, supraspinatus tendon calcification (n = 2), and shoulder edema and inflammation on MRI (n = 12). This study provides insights into the clinical aspects of SIRVA related to COVID-19 vaccination. Recognition and appropriate management of these complications are crucial for optimal patient outcomes.

BackgroundOne of the primary reasons for tumor invasion and metastasis is anoikis resistance. Biochemical recurrence (BCR) of prostate cancer (PCa) serves as a harbinger of its distant metastasis. However, the role of anoikis in PCa biochemical recurrence has not been fully elucidated.MethodsDifferential expression analysis was used to identify anoikis-related genes based on the TCGA and GeneCards databases. Prognostic models were constructed utilizing LASSO regression, univariate and multivariate Cox regression analyses. Moreover, Gene Expression Omnibus datasets (GSE70770 and GSE46602) were applied as validation cohorts. Gene Ontology, KEGG and GSVA were utilized to explore biological pathways and molecular mechanisms. Further, immune profiles were assessed using CIBERSORT, ssGSEA, and TIDE, while anti-cancer drugs sensitivity was analyzed by GDSC database. In addition, gene expressions in the model were examined using online databases (Human Protein Atlas and Tumor Immune Single-Cell Hub).Results113 differentially expressed anoikis-related genes were found. Four genes (EEF1A2, RET, FOSL1, PCA3) were selected for constructing a prognostic model. Using the findings from the Cox regression analysis, we grouped patients into groups of high and low risk. The high-risk group exhibited a poorer prognosis, with a maximum AUC of 0.897. Moreover, larger percentage of immune infiltration of memory B cells, CD8 Tcells, neutrophils, and M1 macrophages were observed in the high-risk group than those in the low-risk group, whereas the percentage of activated mast cells and dendritic cells in the high-risk group were lower. An increased TIDE score was founded in the high-risk group, suggesting reduced effectiveness of ICI therapy. Additionally, the IC50 results for chemotherapy drugs indicated that the low-risk group was more sensitive to most of the drugs. Finally, the genes EEF1A2, RET, and FOSL1 were expressed in PCa cases based on HPA website. The TISCH database suggested that these four ARGs might contribute to the tumor microenvironment of PCa.ConclusionWe created a risk model utilizing four ARGs that effectively predicts the risk of BCR in PCa patients. This study lays the groundwork for risk stratification and predicting survival outcomes in PCa patients with BCR.

BackgroundThe development and marketing of Bedaquiline (BDQ) represent significant advancements in treating tuberculosis, particularly multidrug-resistant forms. However, comprehensive research into BDQ’s real-world safety remains limited.PurposeWe obtained BDQ related adverse event (AE) information from the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) to assess its safety and inform drug usage.MethodsThe AE data for BDQ from 2012 Q4 to 2023 Q3 was collected and standardized. Disproportionality analysis, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multi-item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN) was used to quantify signals of BDQ-related AEs. Logistic regression was used to analyze the individual data of hepatotoxicity and drug-induced liver injury, and multiple linear regression models were established. Additionally, network pharmacology was employed to identify the potential biological mechanisms of BDQ-induced liver injury.ResultsWe identified 2017 case reports directly related to BDQ. Our analysis identified 341 Preferred Terms (PTs) characterizing these AEs across 27 System Organ Classes (SOC). An important discovery was the identification of AEs associated with ear and labyrinth disorders, which had not been documented in the drug’s official leaflet before. Subgroup analysis revealed a negative correlation between BDQ-related liver injury and females (OR: 0.4, 95%CI: 0.3–0.6). In addition, via network pharmacology approach, a total of 76 potential targets for BDQ related liver injury were predicted, and 11 core target genes were selected based on the characterization of protein-protein interactions. The pathway linked to BDQ-induced liver injury was identified, and it was determined that the PI3K-Akt signaling pathway contained the highest number of associated genes.ConclusionThe analysis of the FAERS database revealed adverse events linked to BDQ, prompting the use of a network pharmacology approach to study the potential molecular mechanism of BDQ-induced liver injury. These findings emphasized the significance of drug safety and offered understanding into the mechanisms behind BDQ-induced liver injury. BDQ demonstrated distinct advantages, including reduced incidence of certain adverse events compared to traditional treatments such as injectable agents and second-line drugs. However, it is important to acknowledge the limitations of this analysis, including potential underreporting and confounding factors. This study provides valuable insights into the safety of BDQ and its role in the management of MDR-TB, emphasizing the need for continued surveillance and monitoring to ensure its safe and effective use.

BackgroundFor children with severe aplastic anemia, if the first immunosuppressive therapy (IST) fails, it is not recommended to choose a second IST. Therefore, for patients without matched sibling donor (MSD) and matched unrelated donor (MUD), haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) can be chosen as a salvage treatment. This article aims to explore the comparison between upfront Haplo-HSCT and salvage Haplo-HSCT after IST.Methods29 patients received salvage Haplo-HSCT, and 50 patients received upfront Haplo-HSCT. The two groups received Bu (Busulfan, 3.2mg/kg/d*2d on days -9 to-8), CY (Cyclophosphamide, 60mg/kg/d*2d on days -4 to-3), Flu (fludarabine, 40mg/m2/d*5d on days -9 to -5) and rabbit ATG (Anti-thymocyte globulin, total dose 10mg/kg divided into days -4 to -2).ResultsThe OS of the salvage Haplo-HSCT group showed no difference to the upfront Haplo-HSCT group (80.2 ± 8.0% vs. 88.7 ± 4.8%, p=0.37). The FFS of the salvage Haplo-HSCT group also showed no difference to the frontline Haplo-HSCT group (75 ± 8.2% vs. 84.9 ± 5.3%, p=0.27). There was no significant difference in the incidence of other complications after transplantation between the two groups, except for thrombotic microangiopathy (TMA). In the grouping analysis by graft source, the incidence of II-IV aGVHD in patients using PBSC ± BM+UCB was lower than that in the PBSC ± BM group (p=0.010)ConclusionUpfront Haplo-HSCT and salvage Haplo-HSCT after IST in children with acquired severe aplastic anemia have similar survival outcomes. However, the risk of TMA increases after salvage Haplo-HSCT. This article provides some reference value for the treatment selection of patients. In addition, co-transplantation of umbilical cord blood may reduce the incidence of GVHD.

Objective. We conducted a meticulous bioinformatics analysis leveraging expression data of 226 PANRGs obtained from previous studies, as well as clinical data from AML patients derived from the HOVON database. Methods. Through meticulous data analysis and manipulation, we were able to categorize AML cases into two distinct PANRG clusters and subsequently identify differentially expressed genes (PRDEGs) with prognostic significance. Furthermore, we organized the patient data into two corresponding gene clusters, allowing us to investigate the intricate relationship between the risk score, patient prognosis, and the immune landscape. Results. Our findings disclosed significant associations between the identified PANRGs, gene clusters, patient survival, immune system, and cancer-related biological processes and pathways. Importantly, we successfully constructed a prognostic signature comprising nineteen genes, enabling the stratification of patients into high-risk and low-risk groups based on individually calculated risk scores. Furthermore, we developed a robust and practical nomogram model, integrating the risk score and other pertinent clinical features, to facilitate accurate patient survival prediction. Our comprehensive analysis demonstrated that the high-risk group exhibited notably worse prognosis, with the risk score proving to be significantly correlated with infiltration of most immune cells. The qRT-PCR results revealed significant differential expression patterns of LGR5 and VSIG4 in normal and human leukemia cell lines (HL-60 and MV-4-11). Conclusions. Our findings underscore the potential utility of PANoptosis-based molecular clustering and prognostic signatures as predictive tools for assessing patient survival in AML.

Organic fertilizers produced from agricultural waste materials using earthworms have many advantages. The impact of vermicompost bio-organic fertilizer (VcF) prepared from waste mushroom bran on the quality of Chinese herbal medicine and soil health deserves attention. We conducted a field experiment to explore the quality of Rhizoma atractylodis and soil, using chemical fertilizer and VcF at dosages of 30 t·ha−1 and 40 t·ha−1. The results demonstrated that VcF significantly increased the contents of atractylenolide II, β-eudesmol, atractylenol, and atractylenolone by 34%, 175%, 72%, and 24%, respectively, along with a 70% increase in yield compared to the control. VcF significantly increased the available phosphorus content and the activity of the soil enzymes (α-Galactosidase, β-Galactosidase, and peroxidase), while reducing the nitrate nitrogen content. The addition of vermicompost did not change the soil bacterial diversity, while it significantly increased the soil fungal diversity. VcF improved the soil fungal diversity and significantly enhanced the relative abundance of the bacterial phylum Actinobacteriota and WPS-2, as well as the fungal phylum Ascomycota. Vermicompost significantly increased the relative abundance of bacteria phylum Actinobacteriota and WPS-2, as well as the fungi phylum Ascomycota. Actinobacteria mainly participate in the decomposition of detritus and the heterotrophic nutrient cycle. A Principal Coordinates Analysis of the soil bacterial and fungi communities suggested a significant impact of vermicompost application on the community structure of the soil bacteria. Conversely, no significant variance was detected in the bacterial community composition across the two levels of vermicompost. This study contributes to the enhancement of fertilization strategies for Atractylodes macrocephala, broadens the application scope of vermicompost, and advances the growth of organic agriculture.

The breeding of laying hens and broilers in China has increased tremendously. Wet organic fertilizer prepared from hen manure using high-temperature container fermentation preserves high levels of nutrients and a diverse microbial community. We applied low doses of organic fertilizer to peanuts in the black soil area of China’s northeastern region. Based on the calculation of nitrogen content, treatments were set as follows: chemical fertilizer (PCF), organic fertilizer (POF, 4500 kg·ha−1), and replacement of 50% chemical fertilizer with organic fertilizer (PR, 2250 kg·ha−1). Compared to the plots with chemical fertilizers, the use of organic fertilizer and replacing 50% of the chemical fertilizers with organic fertilizer significantly increased peanut yields. Both the organic fertilizer and replacing 50% of the chemical fertilizers with organic fertilizer did not significantly affect the activities of the most tested soil enzymes related to carbon transformation and the absolute abundance of microorganisms. However, they did significantly enhance soil dehydrogenase and α-glucosidase. The community abundance ratio of fungi/bacteria trended downward, leading to soil with a high-fertility bacterial composition. The replacement of 50% chemical fertilizer with organic fertilizer significantly enhanced the species richness and diversity of the bacterial and fungal communities. Organic fertilizer treatment significantly increased the relative abundance of Gemmatimonas and Sphingomonas. The relative abundance of Mycobacterium in the treatment where 50% of the chemical fertilizers were replaced with organic fertilizer was significantly lower than that in the organic fertilizer treatment. PCoA results showed that the low-dose organic fertilizer treatment, replacing 50% of the chemical fertilizers with organic fertilizer, had a significant impact on the composition of soil bacterial communities.

Damaged skin cannot prevent harmful bacteria from invading tissues, causing infected wounds or even severe tissue damage. In this study, we developed a controlled-release antibacterial composite hydrogel system that can promote wound angiogenesis and inhibit inflammation by sustained releasing Cu-Epigallocatechin-3-gallate (Cu-EGCG) nano-capsules. The prepared SilMA/HAMA/Cu-EGCG hydrogel showed an obvious inhibitory effect on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). It could also promote the proliferation and migration of L929 fibroblasts. In vivo full-thickness infected wound healing experiments confirmed the angiogenesis and inflammation regulating effect. Accelerate collagen deposition and wound healing speed were also observed in the SilMA/HAMA/Cu-EGCG hydrogel treated group. The findings of this study show the great potential of this controlled-release antibacterial composite hydrogel in the application of chronic wound healing.

The Coronavirus Disease 2019 (COVID-19) pandemic has now persisted globally for four years, resulting in a staggering death toll of over 4 million individuals. The COVID-19 vaccine has emerged as a highly effective tool in controlling the spread of this virus. However, as the number of individuals receiving COVID-19. In this context, the investigation of adverse reactions related to COVID-19 vaccines holds paramount importance in relevant research. The purpose is to evaluate the current research status regarding adverse reactions associated with COVID-19 vaccines, offering insights for future research. A total of 3,746 articles were included in this analysis, and there has been a notable upward trajectory in the volume of published articles. The CiteSpace v6.1.R6, VOSviewer, SCImago Graphica, and Excel 2019 were employed to analyze and visualize the results. The institutions, countries, journals, authors, co-cited references, and keywords of these articles were analyzed. Furthermore, this study delves into the characteristics of articles on adverse reactions associated with COVID-19 vaccines. It was observed that the number of studies on COVID-19 vaccines has increased year by year since 2019 and witnessed a surge in output in 2021. The vast majority of studies have affirmed the overall safety of COVID-19 vaccines, with adverse reactions tending to be more concentrated in specific diseases. These findings provide valuable ideas for future research in this field and suggest the importance of strengthening international cooperation on adverse reactions to COVID-19 vaccines.

AbstractBackground & Objective The systemic immune-inflammation indicator (SII) has been extensively employed in various diseases for course change, treatment efficacy, or prediction, whereas whether it applies to iron overload or iron deficiency remains unclear. This study aimed at investigating the correlation between SII and serum ferritin in people aged over 20 in the US.Methods The measurements of the systemic immune-inflammation indicator (SII = platelet count × neutrophil-to-lymphocyte ratio) and serum ferritin of 5491 participants in the NHANES database served as the independent and dependent variables for the present cross-sectional study, respectively. Moreover, the correlation was investigated through and used multiple linear regression, smooth curve fitting, and threshold effect.Results After rigorous inclusion and exclusion of 19,225 participants, a grand total of 5,491 participants conforming to the requirements were covered for relevant analysis. SII showed a significant negative correlation with serum ferritin in unregulated ([β=-0.05,p

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have an irreplaceable role in the treatment of myocardial infarction (MI), which can be injected into the transplanted area with new cardiomyocytes (Cardiomyocytes, CMs), and improve myocardial function. However, the immaturity of the structure and function of iPSC-CMs is the main bottleneck at present. Since collagen participates in the formation of extracellular matrix (ECM), we synthesized nano colloidal gelatin (Gel) with collagen as the main component, and confirmed that the biomaterial has good biocompatibility and is suitable for cellular in vitro growth. Subsequently, we combined the PI3K/AKT/mTOR pathway inhibitor BEZ-235 with Gel and found that the two combined increased the sarcomere length and action potential amplitude (APA) of iPSC-CMs, and improved the Ca2+ processing ability, the maturation of mitochondrial morphological structure and metabolic function. Not only that, Gel can also prolong the retention rate of iPSC-CMs in the myocardium and increase the expression of Cx43 and angiogenesis in the transplanted area of mature iPSC-CMs, which also provides a reliable basis for the subsequent treatment of mature iPSC-CMs.

AimsUnderstanding the cellular mechanisms underlying early allograft rejection is crucial for the development of effective immunosuppressant strategies. This study aims to investigate the cellular composition of graft-infiltrating cells during the early rejection stage at a single-cell level and identify potential therapeutic targets.MethodsA heterotopic heart transplant model was established using enhanced green fluorescent protein (eGFP)-expressing mice as recipients of allogeneic or syngeneic grafts. At 3 days post-transplant, eGFP-positive cells infiltrating the grafts were sorted and subjected to single-cell RNA-seq analysis. Potential molecular targets were evaluated by assessing graft survival and functions following administration of various pharmacological inhibitors.ResultsA total of 27,053 cells recovered from syngrafts and allografts were classified into 20 clusters based on expression profiles and annotated with a reference dataset. Innate immune cells, including monocytes, macrophages, neutrophils, and dendritic cells, constituted the major infiltrating cell types (>90%) in the grafts. Lymphocytes, fibroblasts, and endothelial cells represented a smaller population. Allografts exhibited significantly increased proportions of monocyte-derived cells involved in antigen processing and presentation, as well as activated lymphocytes, as compared to syngrafts. Differential expression analysis revealed upregulation of interferon activation-related genes in the innate immune cells infiltrating allografts. Pro-inflammatory polarization gene signatures were also enriched in these infiltrating cells of allografts. Gene profiling and intercellular communication analysis identified natural killer cells as the primary source of interferon-γ signaling, activating inflammatory monocytes that displayed strong signals of major histocompatibility complexes and co-stimulatory molecules. The inflammatory response was also associated with promoted T cell proliferation and activation in allografts during the early transplant stages. Notably, caspase-1 exhibited specific upregulation in inflammatory monocytes in response to interferon signaling. The regulon analysis also revealed a significant enrichment of interferon-related motifs within the transcriptional regulatory network of downstream inflammatory genes including caspase-1. Remarkably, pharmacological inhibition of caspase-1 was shown to reduce immune infiltration, prevent acute graft rejection, and improve cardiac contractile function.ConclusionThe single-cell transcriptional profile highlighted the crucial role of caspase-1 in interferon-mediated inflammatory monocytes infiltrating heart transplants, suggesting its potential as a therapeutic target for attenuating rejection.

Vogt-Koyanagi-Harada (VKH) disease is a rare and serious ocular adverse reaction following COVID-19 vaccination. This study aimed to evaluate the clinical features, diagnosis and management of COVID-19 vaccine-associated VKH disease. Case reports of VKH disease after COVID-19 vaccination were collected up to February 11, 2023 for retrospective analysis. Twenty-one patients (9 males and 12 females) were included, with a median age of 45 years (range 19–78), from three main regions, Asia (12/21), the Mediterranean region (4/21), and South America (5/21). Fourteen patients developed symptoms after the first dose of the vaccine, and 8 after the second dose. Vaccines included mRNA vaccine (10 cases), virus vector vaccine (6 cases), and inactivated vaccine (5 cases). The average time interval from vaccination to onset of symptoms was 7.5 days (range 12 hours to 4 weeks). All 21 patients experienced visual impairment after vaccination, with 20 cases involving both eyes. Sixteen patients showed symptoms of meningitis. Serous retinal detachment was observed in 16 patients, choroidal thickening was observed in 14, aqueous cell in 9, and subretinal fluid in 6. CSF pleocytosis was detected in 7 patients and skin symptoms were found in 3 patients. All patients received corticosteroid therapy, and 8 also received immunosuppressive agents. All patients recovered well, with a mean recovery time of 2 months. Early diagnosis and early treatment are crucial to the prognosis of patients with VKH after vaccination with COVID-19 vaccine. The risk of vaccination against COVID-19 in patients with a history of VKH disease should be evaluated clinically.

Since COVID-19 became a global pandemic in 2020, the development and application of SARS-CoV-2 vaccines has become an important task to prevent the spread of the epidemic. In addition to the safety and efficacy of COVID-19 vaccines, the adverse reactions caused by vaccines in a small number of people also deserve our attention. We aimed to discuss and analyze the possible causes of Sweet syndrome caused by the COVID-19 vaccine by integrating the effective information from 16 patients and combining it with the latest views on the innate immune mechanism. We searched the PubMed and Embase databases for published patient reports on the occurrence or recurrence of Sweet syndrome after COVID-19 vaccination. We summarized the basic information of the patients, the type of vaccination, the presence of underlying diseases, and the clinical manifestations, clinical treatment and prognosis of the patients. The results were reported in narrative methods and were sorted into tables. We initially identified 53 studies. 16 articles were included through full-text screening. Based on the table we compiled, we generally concluded that the first dose of any type of COVID-19 vaccine was more likely to cause Sweet syndrome than subsequent doses. Sweet syndrome may occur after COVID-19 vaccination. Clinicians should consider Sweet syndrome in addition to common adverse reactions such as anaphylaxis and infection when a patient presents with acute fever accompanied by nodular erythema, pustules, and edematous plaques after COVID-19 vaccination.

BackgroundGlobally, chronic kidney disease (CKD) is a growing public health concern. Serum uric acid (SUA) is an easily detectable and readily available biochemical indicator that has long been recognized as an independent risk factor for CKD. In addition, studies have indicated a potential relationship between SUA and body mass index (BMI). However, studies on the effect of SUA levels on the estimated glomerular filtration rate (eGFR) in adolescents with different BMIs are very rare.MethodsWeighted multiple regression analysis was used to estimate the independent relationship between SUA and log-transformed eGFR. Additionally, we used a weighted generalized additive model and smooth curve fitting to describe the nonlinear relationships in the subgroup analysis.ResultsFirst, SUA was negatively associated with log-transformed eGFR even after adjusting for all covariates (β=-0.0177, 95% CI: -0.0203-0.0151, P

Abstract Background and objectives Vaccine is the most essential avenue to prevent hepatitis B virus (HBV) infection in infants and preschool children in China, with the largest populations carrying HBV in the world. This study aimed to evaluate the factors associating the response level of anti-HBs in children, providing instructions for HBV prevention clinically. Methods The children taking physical examinations in the Third Xiangya Hospital from January 2013 to April 2020 were recruited. Telephone follow-up were adopted to collect further information. Univariate logistic regression was used to analyse the relationship between age and anti-HBs expression. Grouping by age and anti-HBs expression, we used chi-square test and T test to compare qualitative and quantitative data between positive group and negative group in each age subgroup. The meaningful variables (P

Abstract Sepsis is a life-threatening syndrome with disturbed host responses to severe infections, accounting for the majority of death in hospitalized patients. However, effective medicines are currently scant in clinics due to the poor understanding of the exact underlying mechanism. We previously found that blocking caspase-11 pathway (human orthologs caspase-4/5) is effective to rescue coagulation-induced organ dysfunction and lethality in sepsis models. Herein, we screened our existing chemical pools established in our lab using bacterial outer membrane vesicle (OMV)-challenged macrophages, and found 7-(diethylamino)-1-hydroxy-phenothiazin-3-ylidene-diethylazanium chloride (PHZ-OH), a novel phenothiazinium-based derivative, was capable of robustly dampening caspase-11-dependent pyroptosis. The in-vitro study both in physics and physiology showed that PHZ-OH targeted AP2-associated protein kinase 1 (AAK1) and thus prevented AAK1-mediated LPS internalization for caspase-11 activation. By using a series of gene-modified mice, our in-vivo study further demonstrated that administration of PHZ-OH significantly protected mice against sepsis-associated coagulation, multiple organ dysfunction, and death. Besides, PHZ-OH showed additional protection on Nlrp3 −/− and Casp1 −/− mice but not on Casp11 −/− , Casp1/11 −/− , Msr1 −/− , and AAK1 inhibitor-treated mice. These results suggest the critical role of AAK1 on caspase-11 signaling and may provide a new avenue that targeting AAK1-mediated LPS internalization would be a promising therapeutic strategy for sepsis. In particular, PHZ-OH may serve as a favorable molecule and an attractive scaffold in future medicine development for efficient treatment of bacterial sepsis.

Umbilical cord mesenchymal stem cells (UCMSCs) transplantation has been proposed as a promising treatment modality for myocardial infarction (MI), but the low retention rate remains a considerable challenge. Injectable natural polymer hydrogels with conductivity ability are highly desirable as cell delivery vehicles to repair infarct myocardium and restore the cardiac function. In this work, we developed a hydrogel system based on gelatin methacrylate (GelMA) and oxidized dextran (ODEX) as cell delivery vehicles for MI. And dopamine could be used as a reductant of graphene oxide (GO) to form reductive GO (rGO). By adjusting the amount of rGO, the conductivity of hydrogels with 0.5 mg/mL rGO concentration (≈10−4 S/cm) was similar to that of natural heart tissue. In vitro cell experiments showed that the prepared hydrogels had excellent biocompatibility and cell delivery ability of UCMSCs. More importantly, GelMA-O5/rGO hydrogel could promote UCMSCs growth and proliferation, improve the myocardial differentiation ability of UCMSCs, and up-regulate the expression of cTnI and Cx43. Further in vivo experiments demonstrated that GelMA-O5/rGO/UCMSCs Hydrogel could significantly improve the ejection fraction (EF) of rats and significantly reduce myocardial infarct area compared to PBS group, promote the survival of UCMSCs, enhance the expression level of cTnI and Cx43, and decrease the expression level of caspase-3. The findings of this study suggested that the injectable conductive GelMA-O5/rGO hydrogel encapsulating UCMSCs could improve damaged myocardial tissue and reconstruct myocardial function, which will be a promising therapeutic strategy for cardiac repair.

Summary: Urinary tract infection (UTI) is a pervasive health problem worldwide. Patients with a history of UTIs suffer increased risk of recurrent infections, a major risk of antibiotic resistance. Here, we show that bladder infections induce expression of Ezh2 in bladder urothelial cells. Ezh2 is the methyltransferase of polycomb repressor complex 2 (PRC2)—a potent epigenetic regulator. Urothelium-specific inactivation of PRC2 results in reduced urine bacterial burden, muted inflammatory response, and decreased activity of the NF-κB signaling pathway. PRC2 inactivation also facilitates proper regeneration after urothelial damage from UTIs, by attenuating basal cell hyperplasia and increasing urothelial differentiation. In addition, treatment with Ezh2-specific small-molecule inhibitors improves outcomes of the chronic and severe bladder infections in mice. These findings collectively suggest that the PRC2-dependent epigenetic reprograming controls the amplitude of inflammation and severity of UTIs and that Ezh2 inhibitors may be a viable non-antibiotic strategy to manage chronic and severe UTIs.

Kidney disease has become a global public health problem affecting over 750 million people worldwide and imposing a heavy economic burden on patients. The complex architecture of the human kidney makes it very difficult to study the pathophysiology of renal diseases in vitro and to develop effective therapeutic options for patients. Even though cell lines and animal models have enriched our understanding, they fail to recapitulate key aspects of human kidney development and renal disease at cellular and functional levels. Organoids can be derived from either pluripotent stem cells or adult stem cells by strictly regulating key signalling pathways. Today, these self-differentiated organoids represent a promising technology to further understand the human kidney, one of the most complex organs, in an unprecedented way. The newly established protocols improved by organ-on-chip and coculture with immune cells will push kidney organoids towards the next generation. Herein, we focus on recent achievements in the application of kidney organoids in disease modelling, nephrotoxic testing, precision medicine, biobanking, and regenerative therapy, followed by discussions of novel strategies to improve their utility for biomedical research. The applications we discuss may help to provide new ideas in clinical fields.

Abstract Chronic wounds represent a major challenge to the present healthcare system. In recent decades, many topical therapies have been investigated for the treatment of chronic wounds, including different types of wound dressings, antimicrobial agents, and cell therapy. Platelet-derived growth factor (PDGF) plays an important role in wound healing and has been approved for treatment of wounds related to diabetes mellitus. However, the high cost and short retention time of PDGF protein have limited its wide application. To overcome this challenge, we designed a PDGF-mimicking peptide by connecting PDGF epitope VRKIEIVRKK and self-assembling motif derived from β-amyloid peptide. The resultant peptide can self-assemble into a fibril-rich network and leads to supramolecular hydrogelation with good stability. The hydrophilic epitope can be exposed on the surface of nanofibrils, which might contribute to the binding and activation of PDGF receptors. The forming hydrogel is able to induce the growth and migration of vascular endothelial cells and promote the formation of vascular branches. In the full-thickness skin wounds of healthy mice, after the application of the hydrogel, the density of neovascularization marked by CD31 was greater than that in the control group on Day 3. Larger collagen deposition and a thicker epidermis were observed on Day 12. These results demonstrate that the hydrogel can stimulate collagen deposition and angiogenesis, enhance skin regeneration, and show an excellent therapeutic effect. Taken together, this work not only provides new insight into the design of bioactive peptides but also offers a promising biomaterial for wound healing.

BackgroundAn increasing number of studies have focused on the role of gut microbiota in the treatment of ADHD, but its related molecular mechanisms are not yet clear, and there is still room for development of studies targeting this area. This study analyzes publications from 2012 to 2021 in a comprehensive and multi-faceted visualization, with the aim of grasping the existing research profile and guiding scholars to make more in-depth studies.MethodsThe 1,677 articles and 298 review articles on gut microbiota in ADHD were retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, Microsoft Excel 2019, Scimago Graphica, Bibliometrix and Pajek metrics software were used for visualization and analysis of the included literature.ResultsOn August 3, 2022, a total of 1975 English-language articles on gut microbiota in ADHD were retrieved from Web of Science Core Collection (WoSCC) from January 2012 to December 2021, with a steady upward trend in the number of articles published in this field over the decade. The top three countries in terms of the number of articles published are the United States, China, and Spain. Meanwhile, CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS CSIC, UNIV OF CALIFORNIA SYSTEM, and UDICE FRENCH RESEARCH UNIV have made significant contributions in this field. In the analysis of the published journals, PLoS One was not only the first in terms of number of articles published but also the most cited. Wang J was the most prolific author and CAPORASO JG ranked first in terms of co-cited authors. In addition, “Diet rapidly and reproducibly alters the human gut microbiome,” published by David LA et al., has the highest citation frequency in this field. The most frequently occurring keyword was “gut microbiota.”ConclusionThe results of this paper clarify the current status of research on gut microbiota in ADHD. Based on the research on the mechanism of gut microbiota in other diseases, there is reason to believe that the exploration of gut microbiota in ADHD must be increasingly mature. And the study speculates that future research may focus on “nutrition supplements,” “lipid metabolism,” and “gut brain axis.” It is imperative to promote a closer international cooperation among scholars in this field.

ObjectiveThis study aimed to investigate the international scientific output regarding the relationship between COVID-19 and cardiovascular diseases (CVDs) through a bibliometric analysis and explore research hotspots in this field.MethodsWe searched the Web of Science Core Collection for publications and used different types of software, such as R, CiteSpace, and VOSviewer, to analyze and visualize the data.ResultsA total of 10,055 publications were retrieved as of the 13 December 2022, based on the inclusion criteria after screening. The USA and China lead in the quantity and quality of publications in this field. Based on Bradford's law, 63 journals were considered core journals in the field. Co-cited references and keywords analysis indicated that researchers paid particular attention to cardiovascular comorbidities, outcomes, and COVID-19 regenerative medicine. In summary, with increasing COVID-19 research related to CVD, more attention might be drawn to the relationship between these two diseases.ConclusionThe hotspots in this field may continue to revolve around cardiovascular comorbidities, outcomes, and COVID-19 regenerative medicine. Owing to the different situations faced by different groups with COVID-19, further exploration of the related factors specific to each of these groups, e.g., history or no history of heart failure, is needed, with a view to providing a reference for intervention measures in COVID-19 research.

BackgroundHydrogen sulfide (H2S) is known for its unpleasant odor and severe toxicity. However, an in-depth study of H2S showed that it can be used as an important messenger, which can play important physiological and pathological roles in vitro and in vivo. In recent years, the application of H2S in the field of cardiac preservation has attracted the interest and attention of scholars worldwide. H2S plays an effective and protective role in cardiac ischemia/reperfusion injury through antioxidant, anti-inflammatory, and antiapoptotic mechanisms.ObjectiveThe purpose of this study is to analyze the current scientific achievements on the application of H2S in the field of cardiac preservation and to provide new ideas for further research.MethodsTS = (“hydrogen sulfide” OR “hydrogen sulfide”) AND TS = (“cardiac” OR “heart” OR “myocardium” OR “hearts”) AND TS = (“reperfusion” or “transplantation” or “implanted” or “transplant” or “implantation” or “migration” or “preservation” or “grafting” OR “ischemia” OR “perfusion” or “conservation” or “preserve” or “reservation”) AND DT = (Article OR Review) AND LA = (English) were used as search strategies for data collection from the Science Citation Index-Expanded database of the Web of Science Core Collection. CiteSpace 5.8. R3 and Microsoft Office Excel 2019 were used for data analysis.ResultsA total of 429 related articles were included, and the total number of articles showed a fluctuating upward trend. We used CiteSpace 5.8. R3 and Microsoft Excel 2019 to evaluate and visualize the results, analyzing institutions, countries, journals, authors, co-cited references, and keywords.ConclusionsAs increasing evidence shows that H2S plays an indispensable role in the field of cardiac preservation, its mechanistic research and clinical application may become the main focus of future research.

Background: In recent years, there has been an increasing interest in using extracellular vesicles (EVs) as potential therapeutic agents or natural drug delivery systems in kidney-related diseases. However, a detailed and targeted report on the current condition of extracellular vesicle research in kidney-related diseases is lacking. Therefore, this prospective study was designed to investigate the use of bibliometric analysis to comprehensively overview the current state of research and frontier trends on extracellular vesicle research in kidney-related diseases using visualization tools.Methods: The Web of Science Core Collection (WoSCC) database was searched to identify publications related to extracellular vesicle research in kidney-related diseases since 1999. Citespace, Microsoft Excel 2019, VOSviewer software, the R Bibliometrix Package, and an online platform were used to analyze related research trends to stratify the publication data and collaborations.Results: From 1 January 1999 to 26 June 2022, a total of 1,122 EV-related articles and reviews were published, and 6,486 authors from 1,432 institutions in 63 countries or regions investigated the role of extracellular vesicles in kidney-related diseases. We found that the number of articles on extracellular vesicles in kidney-related diseases increased every year. Dozens of publications were from China and the United States. China had the most number of related publications, in which the Southeast University (China) was the most active institution in all EV-related fields. Liu Bi-cheng published the most papers on extracellular vesicles, while Clotilde Théry had the most number of co-citations. Most papers were published by The International Journal of Molecular Sciences, while Kidney International was the most co-cited journal for extracellular vesicles. We found that exosome-related keywords included exosome, exosm, expression, extracellular vesicle, microRNA, microvesicle, and liquid biopsy, while disease- and pathological-related keywords included biomarker, microRNA, apoptosis, mechanism, systemic lupus erythematosus, EGFR, acute kidney injury, and chronic kidney disease. Acute kidney disease (AKI), CKD, SLE, exosome, liquid biopsy, and extracellular vesicle were the hotspot in extracellular vesicle and kidney-related diseases research.Conclusion: The field of extracellular vesicles in kidney-related disease research is rapidly growing, and its domain is likely to expand in the next decade. The findings from this comprehensive analysis of extracellular vesicles in kidney-related disease research could help investigators to set new diagnostic, therapeutic, and prognostic ideas or methods in kidney-related diseases.

Background: Hydrogen is a chemical substance that has yet to be widely used in medicine. However, recent evidence indicates that hydrogen has multi-faceted pharmacological effects such as antioxidant, anti-inflammatory, and antiapoptotic properties. An increased number of studies are being conducted on the application of hydrogen in various diseases, especially those affecting the renal system. Summary: Hydrogen can be inhaled, as a gas or liquid, and can be administered orally, intravenously, or locally. Hydrogen can rapidly enter suborganelles such as mitochondria and nucleus by simple diffusion, producing reactive oxygen species (ROS) and triggering DNA damage. Hydrogen can selectively scavenge hydroxyl radical (•OH) and peroxynitrite (ONOO−), but not other reactive oxygen radicals with physiological functions, such as peroxyanion (O2−) and hydrogen peroxide (H2O2). Although the regulatory effect of hydrogen on the signal transduction pathway has been confirmed, the specific mechanism of its influence on signal molecules remains unknown. Although many studies have investigated the therapeutic and preventive effects of H2 in cellular and animal experiments, clinical trials are few and still far behind. As a result, more clinical trials are required to investigate the role of hydrogen in kidney disease, as well as the effect of its dose, timing, and form on the overall efficacy. Large-scale randomized controlled clinical trials will be required before hydrogen can be used to treat renal illnesses. Key Messages: This article reviews the mechanisms of hydrogen in the treatment of renal disease and explores the possibilities of its use in clinical practice.

Abstract Clinically, steroid-resistant nephrotic syndrome (SRNS) is always prolonged and difficult to treat and easily develops into end-stage renal disease, resulting in a low survival rate. Strategies to reverse steroid resistance and reduce the long-term use of high doses of steroid medicines are urgently needed. In this study, a novel nanoparticle drug system (Pm-GCH) with a core–shell structure was designed. Metal–organic frameworks, synthesized by glycyrrhizic acid (G) and calcium ions (Ca2+) loaded with hydrocortisone (H) were the core of the nanoparticles. Platelet membrane vesicles were the shells. The natural platelet membrane endows Pm-GCH with good biocompatibility and the ability to promote immune escape. In addition, under the chemotaxis of inflammatory factors, platelet membranes assist Pm-GCH in nonspecific targeting of the inflammatory sites of the kidney. Under an inflammatory acid environment, GCH slowly degrades and releases glycyrrhizic acid and hydrocortisone. Glycyrrhizic acid inhibits the inactivation of hydrocortisone, jointly inhibits the activity of phospholipase A2 (PLA2) and the classic activation pathway of complement C2, blocks the production of inflammatory factors, plays an anti-inflammatory role, and enhances the efficacy of hydrocortisone in the treatment of SRNS. Moreover, glycyrrhizic acid alleviates osteoporosis induced by long-term use of glucocorticoids. These results indicate that Pm-GCH is a promising treatment strategy for SRNS. Graphical Abstract

ContextThe development and progression of Non-alcoholic Fatty Liver Disease (NAFLD) is associated with type 2 diabetes mellitus (T2DM), but there are no studies to demonstrate whether blood glucose levels are associated with the progression of NAFLD.ObjectiveAlterations in glucose metabolism may cause hepatic steatosis and inflammatory responses, leading to hepatocyte damage and promoting NAFLD’s progression. Since glycohemoglobin reflects current blood glucose levels and is easily detectable, the present study aimed to investigate whether glycohemoglobin is associated with liver stiffness in patients with NAFLD.MethodsWe studied 1510 NAFLD patients aged 20-80 in NHANES 2017- March 2020, who were defined using the controlled attenuation parameter (CAP) ≥263 dB/m. Multivariable linear regressions were used to assess the independent association between glycohemoglobin and median liver stiffness measurements (LSM) after adjusting for potential confounders. Subsequently, they were subjected to curve fitting and threshold effect analysis. Stratified analysis was used to find the variables affecting the relationship.ResultsGlycohemoglobin and median LSM showed a positive correlation in different models (β (95% CI): Crude Model: 1.460 (1.053, 1.867); Model 1: 1.476 (1.066, 1.885); Model 2: 1.517 (0.919, 2.115)), and this correlation disappeared when glycohemoglobin ≥8.6%. Furthermore, this correlation was more pronounced in the non-diabetic and former smoking subgroups.ConclusionIn patients with NAFLD, glycohemoglobin may reflect the degree of liver stiffness, and preventing excessive glycohemoglobin may have a positive effect on slowing the progression of NAFLD especially in non-diabetic and former smokers.

ObjectiveThe purpose of this study was to investigate the international scientific output on mental health of students during COVID-19 from 2020 to 2022 through a bibliometric analysis and to explore trend and research hotspots in this field.MethodsWe searched the Web of Science Core Collection for publications and used a variety of software to analyze and visualize the data such as R, CiteSpace, VOSviewer and Scimago.ResultsA total of 2,734 publications were retrieved as of June 4, 2022, published by 3,894 institutions from 120 countries/regions. China and the United States lead in the quantity and quality of publications in this field. According to Bradford’s Law, 16 journals are considered core journals in the field. Co-cited references indicate the main psychological problems of students under the epidemic revolve around anxiety, poor sleep and financial difficulty. Their behavior might also be influenced by increased internet and alcohol use.ConclusionMental health of students during COVID-19 is attracting increasing attention. It is identified that the research hotspots in this field continue to revolve around emotional anxiety and unhealthy behaviors. Due to the different troubles faced by different groups under COVID-19, further exploration of the relevant factors specific for students are needed, with a hopeful view to providing ideas for intervention measures.

Abstract Nanomaterials' unique structures at the nanometer level determine their incredible functions, and based on this, they can be widely used in the field of nanomedicine. However, nanomaterials do possess disadvantages that cannot be ignored, such as burst release, rapid elimination, and poor bioadhesion. Hydrogels are scaffolds with three‐dimensional structures, and they exhibit good biocompatibility and drug release capacity. Hydrogels are also associated with disadvantages for biomedical applications such as poor anti‐tumor capability, weak bioimaging capability, limited responsiveness, and so on. Incorporating nanomaterials into the 3D hydrogel network through physical or chemical covalent action may be an effective method to avoid their disadvantages. In nanocomposite hydrogel systems, multifunctional nanomaterials often work as the function core, giving the hydrogels a variety of properties (such as photo‐thermal conversion, magnetothermal conversion, conductivity, targeting tumor, etc.). While, hydrogels can effectively improve the retention effect of nanomaterials and make the nanoparticles have good plasticity to adapt to various biomedical applications (such as various biosensors). Nanocomposite hydrogel systems have broad application prospects in biomedicine. In this review, we comprehensively summarize and discuss the most recent advances of nanomaterials composite hydrogels in biomedicine, including drug and cell delivery, cancer treatment, tissue regeneration, biosensing, and bioimaging, and we also briefly discussed the current situation of their commoditization in biomedicine.

Background: Ferroptosis, a form of regulatory cell death, has been linked to the development of various tumors. Peripheral neuroblastoma (NB) is one of the most common extracranial solid tumors in children, and it has been proposed that regulating tumor cell ferroptosis may be a future treatment for NB. However, it is unclear how ferroptosis contributes to NB development.Methods: Expression data were collected from two independent cohorts (GEO and Arrayexpress databases). Univariate Cox analysis, multivariate Cox analysis, and the least absolute shrinkage and selection operator (Lasso) algorithm were applied to create a prognostic signature, whose performance was quantified using the area under the receiver operating characteristic curve (AUC) and Kaplan–Meier curves. A prognostic meta-analysis was used to test the suitability and stability of the FRG signature. Drug sensitivity analyses were performed using the data collected from Cell Miner™.Results:PROM2, AURKA, STEAP3, CD44, ULK2, MAP1LC3A, ATP6V1G2, and STAT3 are among the eight genes in the FRG prognostic signature, all of which were highly expressed in stage 1 NB, except AURKA. Furthermore, the high-risk group, which was stratified by signature, had a lower overall survival rate than the low-risk group. GSEA revealed that high-risk groups have more biological processes related to ferroptosis.Conclusion: Ferroptosis-related genes are expressed differently between stages 1 and 4 NB. The FRG signature successfully stratified NB patients into two risk groups and can accurately predict the overall survival in NB. In addition, we found that the gene AURKA might have the potential to be a prognostic marker in NB.

BackgroundEarly identification and treatment are paramount for intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). Unfortunately, there is no single crucial biomarker to identify these patients in a timely manner, which makes KD the most common cause of acquired heart disease in children in developed countries. Recently, many studies have focused on the association between serum ferritin (SF), IVIG resistance, and CALs in KD. We thus performed a systematic review and meta-analysis to ascertain the diagnostic and prognostic values of SF in predicting IVIG resistance and CALs in KD in the acute phase.MethodsThe pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) were extracted from the data to evaluate the SF levels in KD. The hazard ratios (HRs) of related risk factors and their corresponding 95% confidence intervals (CIs) were applied to compute the pooled assessments of the outcomes.ResultsA total of 11 eligible articles were included in this meta-analysis, including twenty studies for diagnosis and five studies for prognosis. In terms of diagnostic values, SF could identify KD patients in the overall studies with a relatively high pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of 0.76 (95% CI: 0.69–0.82), 0.82 (95% CI: 0.76–0.88), 4.33 (95% CI: 3.07–6.11), 0.29 (95% CI: 0.22–0.38), 15.0 (95% CI: 9.00–25.00), and 0.86 (95% CI: 0.83–0.89), respectively. In studies comparing KD patients and controls, there were a relatively high pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of 0.79 (95% CI: 0.72–0.84), 0.84 (95% CI: 0.79–0.91), 4.61 (95% CI: 3.27–6.51), 0.26 (95% CI: 0.20–0.34), 20.82 (95% CI: 11.83–36.64), and 0.89 (95% CI: 0.86–0.91), respectively. For the prognostic values, we found poor survival outcomes based on KD patients (HR = 1.31, 95% CI: 1.07–1.59, P = 0.008).ConclusionOur meta-analysis suggests that SF may be used as a workable and critical biomarker for the diagnosis and prognosis of IVIG resistance and CALs in patients with KD. We also propose that maintaining the dynamic balance between iron, SF, and ferroptosis will be an important therapeutic strategy to reduce the morbidity of CALs.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022279157].

No Abstract

BackgroundStage IV Thyroid cancer (TC) has a relatively poor prognosis and lacks a precise and efficient instrument to forecast prognosis. Our study aimed to construct a nomogram for predicting the prognosis of patients with stage IV TC based on data from the SEER programme.MethodsWe enrolled patients diagnosed with TC from 2004 to 2015 in the study. Furthermore, the median survival time (MST) for the patients equalled 25 months. The patients were split into two groups: the training group and validation group. We used descriptive statistics to calculate demographic and clinical variables, Student’s t test was used to describe continuous variables, and the chi-square test was used to describe classified variables. We used the concordance index (C-index) to evaluate discrimination ability and calibration plots to evaluate calibration ability. The improvement of the nomogram compared with the AJCC TNM system was evaluated by the net weight classification index (NRI), comprehensive discriminant rate improvement (IDI) and decision curve analysis (DCA).ResultsThere were 3501 patients contained within our cohort, and the median follow-up was 25 months [quartile range (IQR): 6-60] in the whole population, 25 months (IQR: 6-60) in the training cohort, and 25 months (IQR: 5-59) in the validation cohort. The C-index value of the training cohort equalled 0.86 (95% CI: 0.85-0.87), and the value of the validation cohort equalled 0.85 (95% CI: 0.84-0.86). The NRI values were as follows: training queue: 1.16 for three-year and 1.12 for five-year OS prediction; authentication group: 1.22 for three-year and 1.21 for five-year OS prediction. The IDI values were as follows: training cohort: 0.25 for three-year and 0.21 for five-year OS prediction; validation cohort: 0.27 for three-year and 0.21 for five-year OS prediction. The DCA diagram showed that the nomogram was superior in predicting the three-year and five-year trends.ConclusionsOur nomogram can be used to forecast the survival of patients with stage IV TC.

Human anatomy is an important medical subject that includes abstract content and strong operability. The lack of specimens required for anatomical experimental teaching and unclear observation of fine structures of specimens lead to difficulties for students in learning. As a new technology in the field of computers, virtual reality (VR) has been widely used in the medical field and has great development potential and application value. Its use in the teaching of human anatomy has received increasing attention. This technology increases the sense of reality of medical students in learning and improves the learning effect, including initiative and enthusiasm of students. Publications were obtained from the Web of Science (WoS) Core Collection on April 30, 2022, with the following retrieval strategy: [(TS = VR) OR (TS = virtual reality)] AND (TS = anatomy) AND [(TS = education) OR (TS = train*) OR (TS = teach*) OR (TS = learn*) OR (TS = study*)] NOT TS = (surgery), and the time frame was from 1999 to 2022. Then, VOSviewer software, Excel and GraphPad Prism 9 were used to analyze the data. The keywords included cocitations, countries/territories, publication numbers, institutions, authors and journals of publications. A series of scientometric and visualized analyses were conducted, and a table for a detailed analysis of the application of VR in anatomy teaching was created. This paper mainly analyses the application status and progress of VR technology in anatomy teaching, which is shown to improve the anatomical learning effect of medical students. In conclusion, the application of VR technology in human anatomy has great potential.

Cardiovascular disease is still one of the leading causes of death in the world, and heart transplantation is the current major treatment for end-stage cardiovascular diseases. However, because of the shortage of heart donors, new sources of cardiac regenerative medicine are greatly needed. The prominent development of tissue engineering using bioactive materials has creatively laid a direct promising foundation. Whereas, how to precisely pattern a cardiac structure with complete biological function still requires technological breakthroughs. Recently, the emerging three-dimensional (3D) bioprinting technology for tissue engineering has shown great advantages in generating micro-scale cardiac tissues, which has established its impressive potential as a novel foundation for cardiovascular regeneration. Whether 3D bioprinted hearts can replace traditional heart transplantation as a novel strategy for treating cardiovascular diseases in the future is a frontier issue. In this review article, we emphasize the current knowledge and future perspectives regarding available bioinks, bioprinting strategies and the latest outcome progress in cardiac 3D bioprinting to move this promising medical approach towards potential clinical implementation.

Background: Nanocomposite hydrogels (NHs) are stable composite materials formed by dispersing nanomaterials in hydrogels and have broad development prospects in the biomedical field. In this study, we aimed to systematically and comprehensively evaluate the trends and hot spots of biomedical applications of NHs from 2010 to 2022.Methods: In total, 713 articles and reviews related to NH applications in the biomedical field from 2010 to 2022 were retrieved from the Web of Science Core Collection (WOSCC). Two scientometric software programs, VOSviewer and Microsoft Excel 2019, were used to visually perform bibliometric analysis in terms of research trends, sources, the contribution of journals, co-citation, and the co-occurrence of keywords.Results: From 1 January 2010 to 3 February 2022, the number of annual scientific publications about NHs exhibited an upward trend, and research articles were published in a larger proportion (more than 77%). The top three countries in NH research were China, the United States, and India. Meanwhile, Tabriz University of Medical Sciences, the Chinese Academy of Sciences, and Tshwane University of Technology were the most active and contributive. In the contribution of journals, the journal Advanced Functional Materials had the highest number of publications, and the journal Int J Biol Macro had the most citations. Varaprasad K was the most prolific author, and Haraguchi K ranked first among co-cited authors. In the ranking of frequency in the co-cited references, Nanocomposite Hydrogels for Biomedical Applications, published by Gaharwar AK, was the most frequently cited reference. The keyword with the highest frequency was “drug delivery.”Conclusion: This study performed a full overview of NHs using bibliometrics and identified current trends and hot spots. This information may help researchers focusing on NHs to identify developments in this field.

PurposeThis study aimed to evaluate the effect and influence of the undergraduate tutor system on the undergraduate stage of Chinese 8-year medical program students in scientific research.MethodsWe collected related data from 194 medical students in the Xiangya Medical School of Central South University. The questionnaire was composed of three parts, namely, eight questions for basic information about individual and undergraduate tutor system, five questions for the subjective feeling impact of the undergraduate tutor system, and 22 questions for accessing the scientific research ability and academic results. The students were mainly divided into three groups to compare different kinds of undergraduate tutor systems, namely, single tutor for multiple students' system (group A), multiple tutors for multiple students' system (group B), and no tutor system for comparison (group C).ResultsThe type of tutorial system, the frequency of guidance, and the way of guidance were independent influence factors of the view of 8-year medical students on scientific research. Group B behaved better than group C in literature processing (P = 0.012), experimental operation (P < 0.001), statistical analysis (P < 0.001), and manuscript producing (P = 0.019). Group A and B joined in more National college students' innovation and entrepreneurship training programs (P = 0.003, P < 0.001). The most popular types of articles published by students were bioinformatics, meta-analysis, and reviews.ConclusionUndergraduate tutor system has made tremendous achievements in cultivating students' scientific research capacity; however, implement improvement should be considered to better educate students.

Abstract Bacterial infection is one of the most frequent complications in the burn and chronic wounds. Inspired by natural existing superhydrophobic surface structures, a novel asymmetric wettable membrane was prepared using the electrospinning technique for facilitating the bacteria‐infected wound healing. Herein, the prepared membrane consists of two layers: The hydrophobic outer layer was composed of poly (lactic‐co‐glycolic) acid (PLGA) and black phosphorus‐grafted chitosan (HACC‐BP), while the hydrophilic inner layer was composed by using a mixture of gelatin (Gel) with ginsenoside Rg1 (Rg1). Biological studies in vitro showed BP@PLGA/Gel (BP@BM) membrane with excellent antibacterial activity could significantly inhibit the adhesion of bacteria, and Rg1 could facilitate the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Compared to Aquacel Ag dressing, the result in vivo revealed that the Rg1/BP@BM could facilitate better wound healing by triggering phosphoinositide 3‐kinase (P‐PI3K/PI3K) and phosphorylation of protein kinase B (P‐AKT/AKT) signaling pathways, upregulating Ki67, CD31, α‐SMA, and TGF‐β1, and downregulating TNF‐α, IL‐1β, and IL‐6, promoting M2 polarization (IL‐10, CD206, and Arg‐1) of macrophages, inhibiting M1 polarization (iNOS) of macrophages. These findings suggested that the asymmetric wettable membrane have the huge potential for wound healing.

BackgroundSex hormones are recognized to play a significant role in increasing bone mineral density (BMD) and promoting bone maturation during adolescence. The purpose of our study was to use a database with large population data to evaluate the association of BMD with sex hormones (including testosterone and estradiol) and sex hormone-binding globulin (SHBG) in adolescent boys and girls aged 12–19 years.MethodsThe data for our study were taken from the National Health and Nutrition Examination Survey 2013-2016, and we used weighted multiple linear regression models to assess the relationship between testosterone, estradiol, and SHBG and total BMD. We use weighted generalized additive models and smooth curve fitting to discover underlying nonlinear relationships.ResultsA total of 1648 teenagers (853 boys, 795 girls) were selected for the final analysis. In boys, testosterone and estradiol levels were positively associated with total BMD, whereas SHBG levels were negatively associated with total BMD after adjusting for covariates [P < 0.05; 95% confidence interval (CI)]. In addition, there was a point between estradiol and total BMD, after which the positive correlation between estradiol and total BMD was relatively insignificant in boys. In girls, there was a positive association between estradiol and total BMD (P < 0.05; 95% CI), but there was no significant association between the testosterone (β 0.0004; 95% CI -0.0001 to 0.0008) or SHBG (β -0.0001; 95% CI -0.0002 to 0.0001) levels and total BMD. We also found an inverted U-shaped association between testosterone and total BMD with the inflection point at 25.4 ng/dL of testosterone.ConclusionsWe found differences in the association of sex hormones with total BMD in boys and girls. Based on our findings, an appropriate increase in serum testosterone levels may be beneficial for skeletal development in girls because of the inverted U-shaped relationship (with the inflection point at 25.4 ng/dL of testosterone), and a high testosterone level might be detrimental to BMD. Furthermore, keeping estradiol levels below a certain level in boys (24.3 pg/mL) may be considered.

ObjectiveThe aim was to investigate the distribution and correlation of Ca, Mg, Zn, Cu, Fe, Pb, and Cd in the blood of children aged 0–14 years in Hunan, China, which may serve to provide a basis for clinical guidance on child health.Study DesignA retrospective analysis was carried out. Concentrations of all elements were determined by atomic absorption spectrophotometry. Distributions were analyzed and compared among different age, sex, and year groups by the Kruskal–Wallis test, the chi-square test, and the Fisher's exact test. Spearman's rank correlation coefficient was used to evaluate the association between every pair of elements.ResultsA total of 46,951 children were involved in this study from 2013 to 2019. The median blood levels of elements were 13.51 μmol/L (Cu), 58.69 μmol/L (Zn), 1.70 mmol/L (Ca), 1.40 mmol/L (Mg), 7.46 mmol/L (Fe), 35.00 μg/L (Pb), and 1.00 μg/L (Cd). Girls had a higher level of Ca and lower levels of Pb and Cd than boys. Cu and Ca showed an upward trend, and Mg and Pb showed a downward trend by year. Zn and Fe increased and Ca decreased significantly with age. The deficiency rates of Fe and Zn decreased significantly by year, while Ca and Cu increased significantly by year. Cd exposure in this area was relatively low.ConclusionMost children had normal levels of the essential elements Ca, Cu, and Mg and the toxic elements Pb and Cd. Severe deficiencies in Zn and Fe were observed in the relatively younger children but improved with age. Persistent efforts in reducing Pb exposure might still be needed.

Background It is necessary and urgent to vaccinate 245 million Chinese children against influenza pandemics. The main purpose of this study was to evaluate different psychological and demographic factors that influence parental willingness to vaccinate their children against influenza. Methods A hybrid theoretical framework was expanded and verified with 462 sample data collected from four cities in China. Structural equation models were used to test nine theoretical hypotheses, and the non-standardized coefficient method was used to discuss the moderating effects among demographic variables. Results Knowledge is considered to be the significant factor of performance expectancy (β = 0.228), effort expectancy (β = 0.227) and perceived risk (β = −0.138), and social influence also has the significant impacts on the above three variables, with β values of 0.437, 0.386, and −0.172. Performance expectancy (β = 0.402), effort expectancy (β = 0.343), and perceived risk (β = −0.244) thus significantly affect parental behavioral intention regarding children’s influenza vaccination. Gender, education, and kids’ gender are demographic variables with significant moderating effects, while age, income, number of kids are not significant. Conclusion To improve the acceptability of influenza vaccination among Chinese children, the promoting policies should emphasize on public knowledge and social influence, as well as effectiveness, affordability, and safety of vaccination.