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Abstract Background Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare single-gene X-linked immunodeficiency disease caused by mutations in the forkhead box protein 3 (FOXP3) gene. The typical clinical manifestations of IPEX mainly include severe atopic dermatitis, insulin-dependent type 1 diabetes mellitus, and intractable diarrhea. Case presentation Here, we report a boy with intractable diarrhea diagnosed with early-onset IPEX syndrome due to the c.434C > T (p.Ala145Val) mutation in exon 4 of the FOXP3 gene. The patient experienced intractable diarrhea and severe weight loss, and his clinical symptoms could not be alleviated by conventional supportive and anti-infection treatment. Sirolimus, an immunosuppressant, preferentially inhibits effector T cells while allowing the proliferation of Tregs and is used to treat IPEX patients and alleviate intractable diarrhea. Conclusion We reviewed the literature on the use of sirolimus for the treatment of IPEX syndrome over the past two decades.

Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide and in recent years its incidence is increasing rapidly in China, which constitutes a major public health burden. Almost 90% of CRC cases develop from precursor adenomatous polyps, through a series of genetic changes known as adenoma-carcinoma sequence during at least 10 years. Detection and removal of colorectal adenoma (CRA) could reduce CRC mortality risk by colonoscopy, but the recurrence rate is high. Our previous RCT study (NCT02226185) found that oral Berberine (BBR), a natural isoquinoline alkaloid extracted from the Chinese herb Coptis chinensis for 2 years significantly reduced recurrence after endoscopic removal of CRA (RR 0.77, 95% CI 0.66-0.91; p=0.001). The study recruited 895 participants who had undergone complete polypectomy within 6 months in seven hospital centers across six provinces in China between Nov 14, 2014, and Dec 30, 2016. Participants were randomly assigned (1:1) to receive BBR (0·3 g twice daily) or placebo tablets via block randomization for 2 years. After the end of randomized treatment, we continued this Follow-up Study to track adenoma recurrence for an average of 6 years till Sep 30, 2024. Besides 114 participants lost to follow up, we obtained follow-up information for 781 participants, 648 of whom underwent at least one colonoscopy after the end of study treatment and were included in this analysis. Mantel-Haenszel test was used to compute relative risks (RRs) and 95% confidence intervals (CIs) for the effect of BBR on risk of adenoma recurrence. Cox proportional-hazards model and Andersen-Gill model were used to analyze multi-recurrence by time. The study is registered with ClinicalTrials.gov, number NCT06629051. During the average 6 years follow up, we found that participants in the BBR group still had a substantially and statistically significantly lower risk of CRA than those in the placebo group (34.7% versus 52.1%; adjusted RR = 0.639, 95% CI = 0.508 to 0.785, P

Background: The variations in non-coding RNA alterations and the host immune response between patients with bacterial and non-bacterial sepsis, along with their clinical characteristics, are largely unknown. Methods: The landscape of long non-coding RNA (lncRNA) and mRNA in whole blood cells from pediatric patients with bacterial sepsis or non-bacterial sepsis were characterized using an Arraystar human LncRNA microarray. Weighted correlation network analysis (WGCNA) were conducted to identify immune-related LncRNA-mRNA signatures. Least absolute shrinkage and selection operator (Lasso) regression and Ridge regression analysis were employed to develop a specific LncRNA-mRNA signature, serving as a discriminant classifier for bacterial and non-bacterial sepsis in children. Results: A total of 33 differentially expressed lncRNAs and 52 mRNAs were identified in pediatric patients with either bacterial sepsis or non-bacterial sepsis. Among these, 69 lncRNAs and mRNAs were pinpointed using WGCNA and found to be significantly correlated with clinical parameters. Further intersection analysis identified 12 lncRNAs and 16 mRNAs as immune-related signature for discerning bacterial infections in children with sepsis. Additionaly, the lncRNA-mRNA co-expression network highlighted the key lncRNAs (AC090159.1 and AC080129.2) and mRNAs (S100A8 and TCF7L2) as an infection score model. Lasso regression analysis revealed that this infection score model achieved an area under the received operating curve (AUROC) of 0.96 in the training set and 0.86 in the validation set. Ultimately, the expression levels of these 4 key lncRNAs and mRNAs showed significant correlation with CRP or PCT levels. Conclusion: The machine learning model, developed utilizing key lncRNAs (AC090159.1 and AC080129.2) and mRNAs (S100A8 and TCF7L2), demonstrates robust discrimination and calibration capabilities for distinguishing between bacterial and non-bacterial sepsis in children.

Abstract Background To explore a method for screening and diagnosing neonatal congenital heart disease (CHD) applicable to grassroots level, evaluate the prevalence of CHD, and establish a hierarchical management system for CHD screening and treatment at the grassroots level. Methods A total of 24,253 newborns born in Tang County between January 2016 and December 2020 were consecutively enrolled and screened by trained primary physicians via the “twelve-section ultrasonic screening and diagnosis method” (referred to as the “twelve-section method”). Specialized staff from the CHD Screening and Diagnosis Center of Hebei Children’s Hospital regularly visited the local area for definite diagnosis of CHD in newborns who screened positive. Newborns with CHD were managed according to the hierarchical management system. Results The centre confirmed that, except for 2 newborns with patent ductus arteriosus missed in the diagnosis of ventricular septal defect combined with severe pulmonary hypertension, newborns with other isolated or concomitant simple CHDs were identified at the grassroots level. The sensitivity, specificity and diagnostic coincidence rate of the twelve-section method for screening complex CHD were 92%, 99.6% and 84%, respectively. A total of 301 children with CHD were identified. The overall CHD prevalence was 12.4‰. According to the hierarchical management system, 113 patients with simple CHD recovered spontaneously during local follow-up, 48 patients continued local follow-up, 106 patients were referred to the centre for surgery (including 17 patients with severe CHD and 89 patients with progressive CHD), 1 patient died without surgery, and 8 patients were lost to follow-up. Eighteen patients with complex CHD were directly referred to the centre for surgery, 3 patients died without surgery, and 4 patients were lost to follow-up. Most patients who received early intervention achieved satisfactory results. The mortality rate of CHD was approximately 28.86 per 100,000 children. Conclusions The “twelve-section method” is suitable for screening neonatal CHD at the grassroots level. The establishment of a hierarchical management system for CHD screening and treatment is conducive to the scientific management of CHD, which has important clinical and social significance for early detection, early intervention, reduction in mortality and improvement of the prognosis of complex and severe CHDs.

Abstract Background RNA pseudouridylation is a critical post‐transcriptional modification that influences gene expression and impacts various biological functions. Despite its significance, the role of mRNA pseudouridylation in cancer remains poorly understood. This study investigates the impact of pseudouridine synthase 7 (PUS7)‐mediated pseudouridylation of Alpha‐ketoglutarate‐dependent Dioxygenase alkB Homolog 3 (ALKBH3) mRNA in gastric cancer. Methods Immunohistochemistry and Western blotting were used to assess PUS7 protein levels in human gastric cancer tissues. The relationship between PUS7 and gastric cancer progression was examined using 3D colony formation assays and subcutaneous xenograft models. Real‐time quantitative PCR (RT‐qPCR), Western blotting, and polysome profiling assays were conducted to investigate how PUS7 regulates ALKBH3. A locus‐specific pseudouridine (Ψ) detection assay was used to identify Ψ sites on ALKBH3 mRNA. Results Our findings indicate a significant reduction of PUS7 in gastric cancer tissues compared to adjacent non‐tumour tissues. Functional analyses reveal that PUS7 inhibits gastric cancer cell proliferation and tumour growth via its catalytic activity. Additionally, PUS7 enhances the translation efficiency of ALKBH3 mRNA by modifying the U696 site with pseudouridine, thereby attenuating tumour growth. Importantly, ALKBH3 functions as a tumour suppressor in gastric cancer, with its expression closely correlated with PUS7 levels in tumour tissues. Conclusions PUS7‐dependent pseudouridylation of ALKBH3 mRNA enhances its translation, thereby suppressing gastric cancer progression. These findings highlight the potential significance of mRNA pseudouridylation in cancer biology and suggest a therapeutic target for gastric cancer. Highlights PUS7 enhances the translation efficiency of ALKBH3 through its pseudouridylation activity on ALKBH3 mRNA, thereby inhibiting gastric tumourigenesis. The expression levels of PUS7 and ALKBH3 are significantly correlated in gastric tumours, which may be potential prognostic predictors and therapeutic targets for patients with gastric cancer.

Abstract. Background. Controlling Nutritional Status (CONUT) score was used for screening the preoperative nutritional status. The correlation between the CONUT score and the prognosis of patients with prostate cancer (PCa) has yet to be elucidated. Herein, we analyzed the prognostic value of CONUT scores in patients with PCa who underwent laparoscopic radical prostatectomy. Materials and methods. Data of 244 patients were retrospectively evaluated. Perioperative variables and follow-up data were analyzed. The patients were categorized into 2 groups according to their preoperative CONUT scores. Postoperative complication and incontinence rates were also compared. The Kaplan-Meier method was used to estimate the median biochemical recurrence-free survival (BCRFS) between the 2 groups. Univariate and multivariate Cox regression analyses were performed to identify the potential prognostic factors for BCRFS. Results. Patients were categorized into the low-CONUT group (CONUT score

An isotope dilution ultra-performance liquid chromatography–triple quadrupole mass spectrometry method was developed to simultaneously detect two typical kinds of α,β-unsaturated aldehydes, namely 4-hydroxy-2-hexenal (4-HHE) and 4-hydroxy-2-nonenal (4-HNE), in foods. The proposed method exhibited a linear range of 10–1000 ng/mL with a limit of detection of 0.1–2.0 ng/g and a limit of quantification of 0.3–5.0 ng/g. The recovery rates of these typical toxic aldehydes (i.e., 4-HHE, 4-HNE) and their d3-labeled analogues were 91.54%–105.12% with a low matrix effect. Furthermore, this proposed method was successfully applied to a real frying system and a simulated digestion system, wherein the contents of 4-HHE and 4-HNE were determined for both. Overall, the obtained results provide strong support for further research into the production of 4-HHE and 4-HNE resulting from foods during oil digestion and frying.

Abstract. Background:. Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC). Methods:. We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed ApcMin/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays. Results:. The abundance of fecal Veillonella parvula (V. parvula) decreased significantly after BBR administration (P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect. Conclusion:. BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula, thereby blocking the development of colorectal tumors. Trial Registraion:. ClinicalTrials.gov, No. NCT02226185.

BackgroundWith a variety of active ingredients, Hedyotis Diffusa (H. diffusa) can treat a variety of tumors. The purpose of our study is based on real-world data and experimental level, to double demonstrate the efficacy and possible molecular mechanism of H. diffusa in the treatment of lung adenocarcinom (LUAD).MethodsPhenotype-genotype and herbal-target associations were extracted from the SymMap database. Disease-gene associations were extracted from the MalaCards database. A molecular network-based correlation analysis was further conducted on the collection of genes associated with TCM and the collection of genes associated with diseases and symptoms. Then, the network separation SAB metrics were applied to evaluate the network proximity relationship between TCM and symptoms. Finally, cell apoptosis experiment, Western blot, and Real-time PCR were used for biological experimental level validation analysis.ResultsIncluded in the study were 85,437 electronic medical records (318 patients with LUAD). The proportion of prescriptions containing H. diffusa in the LUAD group was much higher than that in the non-LUAD group (p < 0.005). We counted the symptom relief of patients in the group and the group without the use of H. diffusa: except for symptoms such as fatigue, palpitations, and dizziness, the improvement rate of symptoms in the user group was higher than that in the non-use group. We selected the five most frequently occurring symptoms in the use group, namely, cough, expectoration, fatigue, chest tightness and wheezing. We combined the above five symptom genes into one group. The overlapping genes obtained were CTNNB1, STAT3, CASP8, and APC. The selection of CTNNB1 target for biological experiments showed that the proliferation rate of LUAD A549 cells in the drug intervention group was significantly lower than that in the control group, and it was concentration-dependent. H. diffusa can promote the apoptosis of A549 cells, and the apoptosis rate of the high-concentration drug group is significantly higher than that of the low-concentration drug group. The transcription and expression level of CTNNB1 gene in the drug intervention group were significantly decreased.ConclusionH. diffusa inhibits the proliferation and promotes apoptosis of LUAD A549 cells, which may be related to the fact that H. diffusa can regulate the expression of CTNNB1.

Advancements in D-allulose production have seen significant strides in recent years, focusing on enzymatic conversion methods. Key developments include traditional immobilization techniques, the discovery of novel enzymes, directed evolution studies, and biosynthesis through metabolic pathway modification. Enzymatic conversion, particularly utilizing D-allulose 3-epimerase, remains fundamental for industrial-scale production. Innovative immobilization strategies, such as functionalized nano-beads and magnetic MOF nanoparticles, have significantly enhanced enzyme stability and reusability. Directed evolution has led to improved enzyme thermostability and catalytic efficiency, while synthetic biology methods, including phosphorylation-driven and thermodynamics-driven pathways, have optimized production processes. High-throughput screening methods have been crucial in identifying and refining enzyme variants for industrial applications. Collectively, these advancements not only enhance production efficiency and cost-effectiveness but also adhere to sustainable and economically viable manufacturing practices. The past five years have witnessed critical developments with significant potential impact on the commercial viability and global demand for allulose.

Abstract Purpose Reactive lymphocytes are substantial components of germinoma, which are believed to be related to the favorable prognosis of this intracranial tumor and better response to immunotherapy. However, the mechanisms managing the recruitment of lymphocytes are poorly understood. High endothelial venules (HEVs) are specialized blood vessels that play key roles in lymphocyte trafficking in Lymph nodes. These vessels are associated with lymphocyte infiltration in chronic inflammatory diseases and various malignant tumors, but their distribution and implications in germinoma are unknown. This study aimed to investigate the distribution and implications of HEVs in intracranial germinomas. Methods We investigated the presence and distribution of HEVs in 42 germinomas by immunohistochemical staining of peripheral node addressin (PNAd) and transmission electron microscopic examination. The correlation of the densities of HEVs with the extent of T and B lymphocyte infiltration and several clinicopathological characteristics were also analyzed to determine whether HEVs are responsible for lymphocyte recruitment and their roles in anti‐tumor immunity in germinoma. Results PNAd‐positive HEVs were detected in 31% (13/42) of germinomas, and their presence correlated with abundant infiltrating CD3+ T cells, CD20 + B cells and CD8+ cytotoxic T lymphocytes (p = 0.0410, 0.0023, and 0.0061, respectively). Higher HEVs density was also correlated with several clinicopathological parameters, which are recognized indicators for favorable prognosis in germinomas, including typical tumor location (p = 0.0093), lower tumor cell content (p = 0.0428), and younger age at diagnosis (p = 0.0121). Furthermore, bioinformatics analysis showed HEVs‐associated genes mainly enriched in immune‐related Gene Ontology terms, including innate immune response, inflammatory response, and B cell receptor signaling pathway. The xCell analysis revealed that germinomas with higher HEVs enrichment scores had increased levels of the immune score, microenvironment score, dendritic cells, CD8+ central memory T‐cells, CD4+ memory T‐cells, and B‐cells. Conclusions Our findings indicate that HEVs could contribute to lymphocyte recruitment in germinomas, thus may serve as a predictor of favorable prognosis and better response to immunotherapy in this intracranial tumor.

Gastric cancer: Gene shutdown helps spread to the liver Reduced activity of a key cell control gene mediates an interaction between gastric cancer cells and immune system cells called macrophages that allows the cancer to spread to the liver. Cancer cells migrating to the liver is a major cause of death for gastric cancer patients, but the mechanisms driving this process have been unclear. Researchers in China led by Tianhua Zhou and Wei Zhuo at Zhejiang University School of Medicine, Hangzhou, studied the activity of genes and their corresponding proteins in patients’ cancer cells, and analyzed gene activity in mouse models of gastric cancer. They found that the gene that generates a protein called MAPK4 is significantly reduced in the cancer cells. This allows the cells to interact with macrophages, promoting their spread to the liver.

Abstract Background Advanced glycation end product receptor (RAGE) acts as a receptor of pro-inflammatory ligands and is highly expressed in alveolar epithelial cells (AECs). Autophagy in AECs has received much attention recently. However, the roles of autophagy and RAGE in the pathogenesis of acute lung injury remain unclear. Therefore, this study aimed to explore whether RAGE activation signals take part in the dysfunction of alveolar epithelial barrier through autophagic death. Methods Acute lung injury animal models were established using C57BL/6 and Ager gene knockout (Ager −/− mice) mice in this study. A549 cells and primary type II alveolar epithelial (ATII) cells were treated with siRNA to reduce Ager gene expression. Autophagy was inhibited by 3-methyladenine (3-MA). Lung injury was assessed by histopathological examination. Cell viability was estimated by cell counting kit-8 (CCK-8) assay. The serum and bronchoalveolar lavage fluid (BALF) levels of interleukin (IL)-6, IL-8 and soluble RAGE (sRAGE) were evaluated by Enzyme-linked immunosorbent assay (ELISA). The involvement of RAGE signals, autophagy and apoptosis was assessed using western blots, immunohistochemistry, immunofluorescence, transmission electron microscopy and TUNEL test. Results The expression of RAGE was promoted by lipopolysaccharide (LPS), which was associated with activation of autophagy both in mice lung tissues and A549 cells as well as primary ATII cells. sRAGE in BALF was positively correlated with IL-6 and IL-8 levels. Compared with the wild-type mice, inflammation and apoptosis in lung tissues were alleviated in Ager −/− mice. Persistently activated autophagy contributed to cell apoptosis, whereas the inhibition of autophagy by 3-MA protected lungs from damage. In addition, Ager knockdown inhibited LPS-induced autophagy activation and attenuated lung injury. In vitro, knockdown of RAGE significantly suppressed the activation of LPS-induced autophagy and apoptosis of A549 and primary ATII cells. Furthermore, RAGE activated the downstream STAT3 signaling pathway. Conclusion RAGE plays an essential role in the pathogenesis of ATII cells injury. Our results suggested that RAGE inhibition alleviated LPS-induced lung injury by directly suppressing autophagic apoptosis of alveolar epithelial cells.

Abstract Background Skull is a relatively rare metastasis site for prostate cancer (PCa). There is no evidence regarding the prognostic indication of skull metastasis (SM) in PCa patients. In this study, we analyzed the prognostic value of SM for metastatic PCa patients receiving androgen deprivation therapy (ADT). Methods 107 consecutive patients were included from September 2008 to August 2021. All patients were administered with standard ADT. Abiraterone plus glucocorticoid and/or docetaxel chemotherapy were given after failure to castration-resistant prostate cancer. Clinical parameters and follow-up prognostic data were retrospectively analyzed. The association of clinical and pathological parameters with SM were analyzed. The progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan–Meier analysis and Cox regression analyses. Results Patients with SM (n = 26) had significantly higher biopsy Gleason scores, higher clinical T stage, higher prostate-specific antigen level at diagnosis, and were more likely to have high-burden metastasis and lymph node metastasis, compared with those without SM (n = 81). They also showed significantly lower level of hemoglobin, albumin and serum calcium, along with higher level of alkaline phosphatase. SM was significantly associated with shorter medium PFS (9.4 vs. 18.3 months, p

ABSTRACTIn this study, we evaluated the association between the PPAT volume and the prognosis of PCa patients after LRP. We retrospectively analysed data of 189 PCa patients who underwent LRP in Beijing Chaoyang Hospital. Volumes of PPAT and prostate were measured by magnetic resonance imaging (MRI), and normalized PPAT volume was computed (PPAT volume divided by prostate volume). Patients were then stratified into the high-PPAT group (n = 95) and low-PPAT group (n = 94) by the median of normalized PPAT volume (73%). The high-PPAT group had significantly higher Gleason score (total score 8 or more, 39.0% vs. 4.3%, p 73%) (hazard ratio 1.787 [1.075–3.156], p = 0.002) were independent risk factors for BCR post-operatively. In conclusion, MRI-measured PPAT volume is of significant prognostic value for PCa patients undergoing LRP.

Granular computing (GrC) is a methodology for reducing the complexity of problem solving and includes two basic aspects: granulation and granular-based computing. Strongly connected components (SCCs) are a significant subgraph structure in digraphs. In this paper, two new granulation strategies were devised to improve the efficiency of computing SCCs. Firstly, four SCC correlations between the vertices were found, which can be divided into two classes. Secondly, two granulation strategies were designed based on correlations between two classes of SCCs. Thirdly, according to the characteristics of the granulation results, the parallelization of computing SCCs was realized. Finally, a parallel algorithm based on granulation strategy for computing SCCs of simple digraphs named GPSCC was proposed. Experimental results show that GPSCC performs with higher computational efficiency than algorithms.

In this study, we retrospectively evaluated the data of 901 men undergoing ultrasonography-guided systematic prostate biopsy between March 2013 and May 2022. Adipose features, including periprostatic adipose tissue (PPAT) thickness and subcutaneous fat thickness, were measured using MRI before biopsy. Prediction models of all PCa and clinically significant PCa (csPCa) (Gleason score higher than 6) were established based on variables selected by multivariate logistic regression and prediction nomograms were constructed. Patients with PCa had higher PPAT thickness (4.64 [3.65–5.86] vs. 3.54 [2.49–4.51] mm, p

Abstract Background 5-α reductase inhibitors (5-ARIs) are first-line drugs for managing benign prostatic hyperplasia (BPH). Unfortunately, some patients do not respond to 5-ARI therapy and may even show worsening symptoms. The decreased expression of steroid 5-α reductase type 2(SRD5A2) in BPH tissues may explain the failure of 5-ARI therapy, however, the mechanisms underlying SRD5A2 decreased remained unelucidated. Objectives To investigate microRNA-mediated regulation of the expression of SRD5A2 resulting in 5-ARI therapy failure. Materials and methods The expression of SRD5A2 and microRNAs in BPH tissues and prostate cells were detected by immunohistochemistry, western blotting, and quantitative real-time PCR. Dual-luciferase reporter assay was performed to confirm that microRNA directly combine to SRD5A2 mRNA. The apoptosis of prostatic cells was detected by flow cytometry. Results SRD5A2 expression was variable; it was negative, weak, and strong in 13.6%, 28.8%, and 57.6% of BPH tissues respectively. The normal human prostatic epithelial cell line RWPE-1 strongly expressed SRD5A2, whereas the immortalized human prostatic epithelial cell line BPH-1 weakly expressed SRD5A2. miR-1199-5p expression was remarkably higher in BPH-1 than in RWPE-1 cells(P

Abstract Background Isolated distal deep vein thrombosis (IDDVT), a disease frequently detected in hospitalized patients, can progress to proximal deep vein thrombosis (PDVT) and pulmonary embolism (PE). Here, we evaluated the effects of anticoagulation in hospitalized IDDVT patients. Methods We conducted a retrospective study in our hospital and enrolled hospitalized IDDVT patients diagnosed by compression ultrasonography (CUS) from January to December 2020. Participants were divided into anticoagulation (AC) and non-anticoagulation (non-AC) groups. After propensity score matching (PSM), multivariate Cox regression analyses were performed to assess whether anticoagulation was associated with PDVT/PE, and all-cause mortality. Results A total of 426 IDDVT inpatients with CUS follow-up were screened from 1502 distal DVT patients and finally enrolled. The median age was 67 years with 51.4% males and 15.5% cancer patients. The median follow-up was 11.6 months. There were 288 and 138 patients treated with or without anticoagulants, respectively. Patients in the non-AC group had less body mass index and more comorbidities. Patients in the AC group were treated with rivaroxaban or dabigatran (52.1%), low molecular weight heparin (42.7%), and warfarin (5.2%). The PSM generated 111 pairs of well-matched IDDVT patients with or without anticoagulation. The Kaplan–Meier analysis demonstrated that neither the incidence of PDVT/PE (5.4% vs. 2.7%, log-rank p = 0.313) nor all-cause mortality (27.9% vs. 18.9%, log-rank p = 0.098) was significant different between groups. Anticoagulation was not associated with PDVT/PE and all-cause mortality in the multivariable Cox regression analyses using the matched cohorts. The main risk factors for all-cause mortality were age, malignancy history, BMI, sepsis, heart failure, and white blood cell (WBC) count. Conclusions In hospitalized IDDVT patients, the thrombosis extension rate to PDVT/PE was low. Anticoagulation did not reduce the incidence of thrombosis extension of IDDVT and was not associated with all-cause mortality.

Objectives: Vascular hyperpermeability by loss of endothelial barrier integrity is a hallmark of sepsis. Vimentin is involved in the regulation of the endothelial function and inflammatory response. However, the serum level of vimentin and its clinical relevance in pediatric severe sepsis (PSS) remain unknown. Methods: We conducted a prospective study of PSS cases who were admitted to the pediatric intensive care unit (PICU) from January 2018 to December 2020. Results: A total of 108 patients with PSS with a median age of 19.5 month were enrolled. The hospital mortality rate was 19.44% (21/108). Comparing with healthy controls, serum vimentin levels on PICU admission were significantly higher in patients with PSS (P < 0.001). The area under the ROC curve for vimentin to predict the hospital mortality was 0.712 (95% CI: 0.578–846) with a sensitivity of 71.43% and a specificity of 70.11%. Moreover, hospital mortality was significantly higher in patients with vimentin level over the cutoff value of 24.53 ng/ml than in patients with vimentin level below 24.53 ng/ml (P < 0.001). Conclusions: Serum vimentin level as an indicator of endothelial injury is associated with the prognosis of PSS, and serum vimentin level ≥24.53 ng/ml on PICU admission predicts high risk for hospital mortality in PSS.

Abstract Benign prostatic hyperplasia (BPH) is the most common and progressive urological disease in elderly men worldwide. Epidemiological studies have suggested that the speed of disease progression varies among individuals, while the pathophysiological mechanisms of accelerated clinical progression in some BPH patients remain to be elucidated. In this study, we defined patients with BPH as belonging to the accelerated progressive group (transurethral resection of the prostate [TURP] surgery at ≤50 years old), normal-speed progressive group (TURP surgery at ≥70 years old), or non-progressive group (age ≤50 years old without BPH-related surgery). We enrolled prostate specimens from the three groups of patients and compared these tissues to determine the histopathological characteristics and molecular mechanisms underlying BPH patients with accelerated progression. We found that the main histopathological characteristics of accelerated progressive BPH tissues were increased stromal components and prostatic fibrosis, which were accompanied by higher myofibroblast accumulation and collagen deposition. Mechanism dissection demonstrated that these accelerated progressive BPH tissues have higher expression of the CYP19 and G protein-coupled estrogen receptor (GPER) with higher estrogen biosynthesis. Estrogen functions via GPER/Gαi signaling to modulate the EGFR/ERK and HIF-1α/TGF-β1 signaling to increase prostatic stromal cell proliferation and prostatic stromal fibrosis. The increased stromal components and prostatic fibrosis may accelerate the clinical progression of BPH. Targeting this newly identified CYP19/estrogen/GPER/Gαi signaling axis may facilitate the development of novel personalized therapeutics to better suppress the progression of BPH.

Fusobacterium nucleatum contributes to host epitranscriptomic modifications and colorectal cancer (CRC) development. Here, the authors show that Fusobacterium nucleatum reduces global m6A modifications to promote CRC metastasis through a YAP/FOXD3/METTL3/KIF26B axis.

Abstract Background To assess the outcome of extracorporeal membrane oxygenation (ECMO) for severe adenovirus (Adv) pneumonia with refractory hypoxic respiratory failure (RHRF) in paediatric patients. Methods A retrospective observational study was performed in a tertiary paediatric intensive care unit (PICU) in China. Patients with RHRF caused by Adv pneumonia who received ECMO support after mechanical ventilation failed to achieve adequate oxygenation between 2017 and 2020 were included. The outcome variables were the in-hospital survival rate and the effects of ECMO on the survival rate. Results In total, 18 children with RHRF received ECMO. The median age was 19 (9.5, 39.8) months, and the median ECMO duration was 196 (152, 309) h. The in-hospital survival rate was 72.2% (13/18). Thirteen patients (72.2%) required continuous renal replacement therapy (CRRT) due to fluid imbalance or acute kidney injury (AKI). At ECMO initiation, compared with survivors, nonsurvivors had a lower PaO2/FiO2 ratio [49 (34.5, 62) vs. 63 (56, 71); p = 0.04], higher oxygen index (OI) [41 (34.5, 62) vs. 30 (26.5, 35); p = 0.03], higher vasoactive inotropic score (VIS) [30 (16.3, 80) vs. 100 (60, 142.5); p = 0.04], longer duration from mechanical ventilation to ECMO support [8 (4, 14) vs. 4 (3, 5.5) h, p=0.02], and longer time from confirmed RHRF to ECMO initiation [9 (4.8, 13) vs. 5 (1.3, 5.5) h; p = 0.004]. Patients with PaO2/FiO2 43 and hypoxic respiratory failure for more than 9 days before the initiation of ECMO had worse outcomes. Conclusions ECMO seemed to be effective, as severe paediatric Adv pneumonia patients with RHRF had a cumulative survival rate of 72.2% in our study. Our study provides insight into ECMO rescue in children with severe Adv pneumonia.

To predict the maturity of bananas, the present study used non-destructive methods to analyze changes in the sweetness and color of the stalks, middles, and tips of bananas during ripening. The results indicated that the respective maturation of these three segments did not occur simultaneously, as indicated by the differential enzyme activity and gene expression levels recorded in these segments. A principal component analysis and cluster plots were used to review the classification of banana maturity, highlighting that banana maturation can be divided into six stages. Two distinct maturity prediction algorithms were established using random forest, artificial neural network, and support vector machines, and they also indicated that dividing the maturity of bananas into six stages was adequate. These findings contribute to the development of quality evaluation and of a rapid grading system for processing, which improves the quality and sale of banana fruits and the related processed products.

PurposeTo identify immune-related biomarkers in coronary artery disease (CAD), investigate their possible function in the immunological milieu of tumors, and initially investigate the mechanisms and therapeutic targets shared by CAD and cancer.MethodsDownload the CAD-related dataset GSE60681 from the GEO database. GSVA and WGCNA analyses were performed based on the GSE60681 dataset to identify the modules most pertinent to CAD, identify candidate hub genes and finally intersect the genes associated with immunity downloaded from the import database to find the hub genes. The GTEx, CCLE, and TCGA database were used to examine the expression of the hub gene in normal tissues, tumor cell lines, tumor tissues, and different tumor STAGES. One-factor cox and Kaplan-Meier analyses were performed to explore the prognosis of hub genes. Hub gene methylation levels in CAD and cancer were analyzed in the diseaseMeth 3.0 and ualcan databases, respectively. R package CiberSort processed the GSE60681 dataset to assess immune infiltration in CAD. TIMER2.0 evaluated hub genes with pan-cancer immune infiltration. The hub genes were analyzed for drug sensitivity and correlation with TMB, MSI, MMR, cancer-related functional status, and immune checkpoints in different tumors. Finally, GSEA was carried out on the crucial genes.ResultsWGCNA were used to pinpoint the green modules that were most closely related to CAD and intersections with immune-related genes were taken to remember the pivotal gene RBP1. RBP1 is hypermethylated in CAD and multiple cancers. Its expression levels in different cancers were associated with poor prognosis of cancer, with significant expression levels at higher stages of cancer staging. The immune infiltration results showed that RBP1 was closely associated with CAD and tumor-associated immune infiltration. The results indicated that RBP1 was strongly correlated with TMB, MSI, MMR, cancer-associated functional status, and immune checkpoints in various cancers. RBP1 was related to the sensitivity of six anticancer drugs. GSEA showed RBP1 was associated with immune cell activation, immune response, and cancer development.ConclusionRBP1 is a pivotal gene associated with immunity in CAD and pan-cancer and may mediate the development of CAD and cancer through immunity, making it a common therapeutic target for both.

As a representative of flexible electronics, epidermal electronic devices (EEDs) are extremely suitable for integration with biological tissues, such as human epidermis benefiting from the advantages of ultrathin, stretchability, and perfectly conformal attachment. Considering the low thermal conductivity of the EEDs polymer material, a large amount of undesired heat accumulation is prone to occur at the EEDs/skin interface, which brings challenges to the thermal management of the EEDs/skin system. The sharp temperature increment caused by ungratified heat dissipation will lead to thermal comfort issues, such as damage to biological tissues and also device failure, which will limit the application and promotion of EEDs to a large extent. A growing quantity of interesting and fruitful literature are addressing this conundrum. In this review, we comb and review the research of EEDs active thermal management, which mainly summarizes the strategies of heat flow regulation, phase change energy storage, and heating mode design. This review aims to provide the overall advances and reference source for future innovative research directions.

Protein phosphorylation and glycosylation coordinately regulate numerous complex biological processes. However, the main methods to simultaneously enrich them are based on the coordination interactions or Lewis acid-base interactions, which suffer from low coverage of target molecules due to strong intermolecular interactions. Here, we constructed a poly-histidine modified silica (SiO2@Poly-His) microspheres-based method for the simultaneous enrichment, sequential elution and analysis of phosphopeptides and glycopeptides. The SiO2@Poly-His microspheres driven by hydrophilic interactions and multiple hydrogen bonding interactions exhibited high selectivity and coverage for simultaneous enrichment of phosphopeptides and glycopeptides from 1,000 molar folds of bovine serum albumin interference. Furthermore, “on-line deglycosylation” strategy allows sequential elution of phosphopeptides and glycopeptides, protecting phosphopeptides from hydrolysis during deglycosylation and improving the coverage of phosphopeptides. The application of our established method to HT29 cell lysates resulted in a total of 1,601 identified glycopeptides and 694 identified phosphopeptides, which were 1.2-fold and 1.5-fold higher than those obtained from the co-elution strategy, respectively. The SiO2@Poly-His based simultaneous enrichment and sequential separation strategy might have great potential in co-analysis of PTMs-proteomics of biological and clinic samples.

BackgroundMyeloid-derived suppressor cells (MDSCs) expansion is an important mechanism underlying immunosuppression during sepsis. Though continuous renal replacement therapy (CRRT) may attenuate hyperinflammatory response in sepsis, its role in regulating MDSCs is unknown. The aim of this study was to assess the potential role of CRRT involved in sepsis-induced MDSCs expansion in pediatric sepsis.MethodThe proportion of polymorphonuclear MDSCs (PMN-MDSCs) was detected before CRRT (pre-CRRT), at 24 hours after CRRT (CRRT 1st day) and on the 7th day after CRRT (CRRT 7th day). The correlation analyses were performed to elucidate the relationship of MDSCs with clinical indexes in sepsis.ResultsTotally 22 pediatric patients with sepsis were enrolled [median age 44 (IQR15, 83) months]. PMN-MDSCs were expanded in pediatric sepsis compared with healthy controls (4.30% vs. 0.37%, P=0.04). The proportion of PMN-MDSCs showed a decreased tendency on the CRRT 7th day compared with that on the CRRT 1st day in survivors (2.29% vs.5.32%, P = 0.088). There was no significant difference in the proportion of PMN-MDSCs between survivors and non-survivors before CRRT (4.51% vs. 3.33%, P=0.745). The levels of interleukin 6 (IL-6) was decreased on the CRRT 7th day compared with CRRT 1st day in survivors. In the subgroups of patients with significantly decreased IL-6 levels after CRRT, the proportion of PMN-MDSCs on the CRRT 7th day were also significantly decreased compared with that on the CRRT 1st day (2.21% vs. 6.67%, P = 0.033).ConclusionThe proportion of PMN-MDSCs was down-regulated on the CRRT 7th day in survivors with sepsis. The reduced PMN-MDSCs expansion may relate to decreased IL-6 level.

Abstract Introduction ATP citrate lyase (ACLY) is involved in lipid metabolism and inflammatory response in immune cells. However, the serum level of ACLY and its clinical relevance in sepsis is totally unknown. Methods We conducted a prospective pilot study in patients with sepsis admitted to pediatric intensive care unit (PICU) from January 2018 to December 2018. Results Higher levels of ACLY were detected in sera of pediatric patients with sepsis than that of healthy children. The area under the receiver operating characteristic curve (AUC) of ACLY for diagnosis of sepsis was 0.855 (95% confidence interval [CI]: 0757–0.952), and an AUC of ACLY for predicting PICU mortality was 0.770 (95% CI: 0.626–0.915). ACLY levels ≤21 ng/ml on PICU admission predicted an unfavorable prognosis among patients with sepsis with a sensitivity of 87.5% and a specificity of 67.6%. Moreover, serum ACLY levels were correlated to platelet count, IL‐18 levels, and monocyte counts in pediatric patients with sepsis, implying the potential roles of ACLY in immunometabolic regulation in sepsis. Conclusions ACLY is firstly identified in sera of patients with sepsis. Serum ACLY level is an additional diagnostic and prognostic biomarker in pediatric patients with sepsis.

ObjectiveThe cancer patients with severe acute respiratory distress syndrome (ARDS) benefit from extracorporeal membrane oxygenation (ECMO) remains unanswered. We analyzed clinical characteristics and outcomes of pediatric patients with leukemia/lymphoma who developed ARDS and treated with ECMO.MethodsPediatric leukemia or lymphoma patients with ARDS who underwent ECMO between August 2017 and December 2021 were retrospectively analyzed in a tertiary pediatric intensive care unit (PICU).ResultsSeven patients with median age 53 (IQR 42–117) months and 4 males were included. Six cases of leukemia [5 of acute lymphocytic leukemia (ALL) and 1 of acute myelogenous leukemia (AML, M5)] and 1 of non-Hodgkin lymphoma with severe ARDS received ECMO on chemotherapy period. The etiology of ARDS is community or chemotherapy-associated bacterial or/and fungal or viral infection. All the patients received chemotherapy in the 2 weeks prior to ECMO and five were neutropenic at initial ECMO. Six cases underwent veno-arterial ECMO (VA ECMO) and 1 for veno-venous ECMO (VV-ECMO). The median duration of ECMO support was 122 (IQR 56–166) hours. Overall, 42.9% (three of seven) survived to hospital discharge and 6 months survival rate was 28.6% (two of seven). Bleeding was the main ECMO-associated complication occurring in 7 patients, followed by nosocomial infection in 4 cases. All the patients required vasopressor support, and 6 received continuous renal replacement therapy (CRRT).ConclusionOur experiences suggest that rescue ECMO provides a selective treatment strategy in childhood hematologic malignancies with severe ARDS.

Advanced glycation endproducts (AGEs) have been confirmed to play a causative role in the development of diabetic nephropathy (DN). In this study, we revealed that AGE-induced kidney injury with characteristic patterns in different stages and moesin phosphorylation plays a role in these processes. In WT mice treated with AGE-modified bovine serum albumin (AGE-BSA), distinct abnormal angiogenesis in Bowman’s capsule of the kidney emerged early after 1 m under AGE-BSA stimulation, while these neovessels became rare after 6 m. AGE-BSA also induced glomerular hypertrophy and mesangial expansion at 1 m but glomerular atrophy and fibrosis at 6 m. Electron microscopy imaging demonstrated the damage of foot process integrity in podocytes and the uneven thickening of the glomerular basement membrane in the AGE-BSA-treated group, which was more significant after 6 m of AGE-BSA treatment than 1 m. The kidney dysfunction appeared along with these AGE-induced morphological changes. However, these AGE-BSA-induced pathological changes were significantly attenuated in RAGE-knockout mice. Moreover, moesin phosphorylation was accompanied by AGE-BSA-induced alterations and moesin deficiency in mice attenuated by AGE-BSA-induced fibrosis. The investigation on glomerular endothelial cells (GECs) also confirmed that the phosphorylation of moesin T558 is critical in AGE-induced tube formation. Overall, this study suggests that AGEs mediate kidney injury with characteristic patterns by binding with RAGE and inducing moesin phosphorylation.

Objective Abnormal muscle response (AMR) is widely used as an indicator of the degree and effect of surgery during microvascular decompression (MVD) for hemifacial spasm (HFS). However, the positive rate of AMR during operation is quite different because of individual differences and single recording of muscle, which can not predict surgical outcomes. We present an improved method to record from multiple muscles innervated by multiple branches of the facial nerve to enlarge the AMR positive rate. Methods A total of 96 HFS patients in our hospital from January 2017 to June 2019, underwent MVD with intraoperative AMR monitoring. Ipsilateral frontalis, orbicularis oculi, orbicularis oris and mentalis were simultaneously monitored for AMR in stimulating the affected zygomatic branch of facial nerve in all cases. The effect of MVD for facial nerve was analyzed based on the disappearance of intraoperative AMR and the postoperative result. Results The AMR positive rate of frontalis was 43.75% (42/96), of orbicularis oculi was 38.54% (37/96), of orbicularis oris was 64.58% (62/96) and of mentalis was 78.13% (75/96). Total AMR positive rate was further improved to 97.92% (94/96) when the 4 muscles were monitored simultaneously. The AMR positive rates between multiple muscles monitoring group and any single muscle monitoring groups were significantly different (P = 0.000, for all). The AMR positive rates of orbicularis oris and mentalis were higher than that of frontalis (P = 0.000, 0.006) and orbicularis oculi (P = 0.000, 0.000). The postoperative results were statistically different between AMR complete disappearance group and AMR persistence group (Fisher exact probability: P = 0.043). Conclusions The method of multibranch facial muscles monitoring can effectively increase the AMR positive rate. AMR disappearance after the operation can evaluate the effect of facial nerve decompression and judge the prognosis. DOI:10.3969/j.issn.1672⁃6731.2020.11.010

Abstract Background Describe the outcome of adenovirus pneumonia in a pediatric intensive care unit (PICU) over a 3-year period, to identify the risk factors that may be associated with worse outcome. Methods A retrospective observational study was performed in the PICU of children’s hospital in Shanghai from July 2016 to June 2019. Sixty-seven children over 29 days to 14 years old with adenovirus pneumonia who were admitted to PICU with acute hypoxemic respiratory failure were included in this study. The primary outcome was hospital mortality, and secondary outcomes were hospital and PICU length of stay (LOS), and risk factors of worse outcome. Results Of 67 children with severe adenovirus pneumonia, the hospital mortality was 16.42% (11/67) and 28-day mortality was 14.93% (10/67). Median Pediatric Risk of Mortality III (PRISM III) score at admission was 13 (interquartile range [IQR], 10–15). Median PICU LOS stay was 11 days (8-18d) and hospital LOS was 22 days (16-31d). Among children with extracorporeal membrane oxygenation (n = 9), 6 cases survived and 3 cases died. The patients who need renal replacement therapy, neuromuscular blockade, parenteral nutrition, and packed red blood cell perfusion had higher hospital mortality (p < 0.001, p = 0.041, p = < 0.001, p = 0.012, respectively). Multivariate logistic analysis indicated that liver dysfunction and nosocomial infection were associated with high risk of mortality. Conclusions The hospital mortality of adenovirus pneumonia in our PICU was 16.42%. Patients complicated liver dysfunction and co-infection & nosocomial infection were associated with poor outcome.

Abstract Background Multidrug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii presents challenges for clinical treatment and causes high mortality in children. We aimed to assess the risk factors and overall mortality for MDR/XDR Acinetobacter baumannii infected pediatric patients. Methods This retrospective study included 102 pediatric patients who developed MDR/XDR Acinetobacter baumannii infection in the pediatric intensive care unit (PICU) of Shanghai Children’s Hospital in China from December 2014 to May 2018. Acinetobacter baumannii clinical isolates were recovered from different specimens including blood, sputum, bronchoalveolar lavage fluid, cerebrospinal fluid, ascites, hydrothorax, and urine. Antibiotic susceptibility test was determined according to the Clinical and Laboratory Standards Institute interpretive criteria. Clinical and biological data were obtained from the patients’ medical records. Results 102 patients with Acinetobacter baumannii infection were enrolled. The median age was 36 (9.6, 98.8) months, and there were 63 male in the case group. The overall mortality rate was 29.4%, while the Acinetobacter baumannii-associated mortality rate was 16.7% (17/102, 12 bloodstream infections, 4 meningitis and 1 intra-abdominal infection). Bloodstream infections occurred in 28 patients (27.5%), and 10 patients (9.8%) among them had central line-associated bloodstream infections (6 central venous catheters, 2 PICCs, 1 venous infusion port and 1 arterial catheter). Cerebrospinal fluid (CSF) cultures were positive in 4(3.9%) patients. 14(13.7%) patients got positive cultures in ascites and hydrothorax. Lower respiratory isolates (56/102) accounted for 54.9% of all patients. Non-survival patients appeared to have a lower NK cell activity (6.2% ± 3.61% vs. 9.15% ± 6.21%, P = 0.029), higher CD4+ T cell ratio (39.67% ± 12.18% vs. 32.66% ± 11.44%, P = 0.039),and a higher serum level of interlukin-8 (IL-8, 15.25 (1.62, 47.22)pg/mL vs. 0.1 (0.1, 22.99)pg/mL, P = 0.01) when Acinetobacter baumannii infection developed. Multivariate logistic analysis indicated that high serum level of Cr (RR, 0.934, 95%CI, 0.890–0.981; P = 0.007) and high BUN/ALB level (RR, 107.893, 95%CI, 1.425–870.574; p = 0.005) were associated with high risk of mortality in MDR/XDR Acinetobacter baumannii infected patients. Conclusion MDR/XDR Acinetobacter baumannii infection is a serious concern in pediatric patients with high mortality. Bloodstream and central nervous system infection accounted for high risk of death. Acute kidney injury is associated with high risk of mortality.

Abstract Background Human papillomavirus (HPV) has been considered as one of the most common sexually transmitted viruses that may be linked to unexplained infertility in men. The possible mechanisms underlying correlation between HPV infection and infertility could be related to the altered sperm parameters. Current studies have investigated the effect of HPV seminal infection on sperm quality in infertile men, but have shown inconsistent results. Methods We systematically searched PubMed, Embase, Web of Science and CNKI for studies that examined the association between HPV seminal infection and sperm progressive motility. Data were pooled using a random-effects model. Outcomes were the sperm progressive motility rate. Results are expressed as standardised mean difference (SMD) with 95% confidence interval (CI). Heterogeneity was evaluated by the I-square (I 2 ) statistic. Results Ten studies were identified, including 616 infertile patients with HPV seminal infection and 2029 infertile controls without HPV seminal infection. Our meta-analysis results indicated that sperm progressive motility was significantly reduced in HPV-infected semen samples compared with non-infected groups [SMD:-0.88, 95% CI:-1.17 ~ − 0.59]. There existed statistical heterogeneity (I 2 value: 86%) and the subgroup analysis suggested that study region might be the causes of heterogeneity. Conclusions HPV semen infection could significantly reduce sperm progressive motility in infertile individuals. There were some limitations in the study such as the differences in age, sample sizes and the number of HPV genotypes detected. Further evidences are needed to better elucidate the relationship between HPV seminal infection and sperm quality.

Droplet digital PCR (ddPCR) recently has been shown to be a potential diagnostic tool for adults with bloodstream infections (BSIs); however, its application in children remains obscure. In this study, 76 blood samples of children with suspected BSIs were synchronously detected by traditional blood cultures (BCs) and ddPCRs. Our team validated the diagnostic performance of ddPCR including sensitivity, specificity, and positive and negative predictive values. The 76 pediatric patients from the hematology department (67.1%), the pediatric intensive care unit (PICU, 27.6%), and other departments (5.2%) were enrolled. The positive rate of ddPCR results was 47.9%, whereas that for BC was 6.6%. In addition, the time consumption of ddPCR was shorter, only for 4.7 ± 0.9 h, in comparison with the detection timing of BC (76.7 ± 10.4 h, p < 0.01). The levels of agreement and disagreement between BC and ddPCR were 96.1% and 4.2%, and the negative agreement reached 95.6%. The sensitivity of ddPCR was 100%, with corresponding specificities ranging from 95.3 to 100.0%. In addition, a total of nine viruses were identified by ddPCR. In China, the multiplexed ddPCR first could be a tool for the rapid and accurate diagnosis of children with suspected BSIs and can be an early indicator of the possibility of viraemia in children with immunosuppression.

BackgroundExtracorporeal membrane oxygenation (ECMO) has been increasingly used as rescue therapy for severe pediatric acute respiratory distress syndrome (PARDS) over the past decade. However, a contemporary comparison of venovenous (VV) and venoarterial (VA) ECMO in PARDS has yet to be well described. Therefore, the objective of our study was to assess the difference between VV and VA ECMO in efficacy and safety for infection-associated severe PARDS patients.MethodsThis prospective multicenter cohort study included patients with infection-associated severe PARDS who received VV or VA ECMO in pediatric intensive care units (PICUs) of eight university hospitals in China between December 2018 to June 2021. The primary outcome was in-hospital mortality. Secondary outcomes included ECMO weaning rate, duration of ECMO and mechanical ventilation (MV), ECMO-related complications, and hospitalization costs.ResultsA total of 94 patients with 26 (27.66%) VV ECMO and 68 (72.34%) VA ECMO were enrolled. Compared to the VA ECMO patients, VV ECMO patients displayed a significantly lower in-hospital mortality (50 vs. 26.92%, p = 0.044) and proportion of neurologic complications, shorter duration of ECMO and MV, but the rate of successfully weaned from ECMO, bleeding, bloodstream infection complications and pump failure were similar. By contrast, oxygenator failure was more frequent in patients receiving VV ECMO. No significant intergroup difference was observed for the hospitalization costs.ConclusionThese positive findings showed the conferred survival advantage and safety of VV ECMO compared with VA ECMO, suggesting that VV ECMO may be an effective initial treatment for patients with infection-associated severe PARDS.

Background: Polymyxin B has become the last choice for patient with carbapenem-resistant bacterial infection. However, the optimal dosing of polymyxin B in critically ill children receiving continuous renal replacement therapy (CRRT) remains unclear.Case Presentation: Two cases of critically ill pediatric patients (7 years old) with acute kidney injury requiring continuous renal replacement (CRRT) received polymyxin B treatment due to carbapenem-resistant organism bloodstream infections. Therapeutic drug monitoring (TDM) of polymyxin B was carried out by liquid chromatography tandem mass spectrometry (LC-MS/MS). The average steady-state plasma concentration (Css,avg) of 2–4 mg/L was set as the target level. Initial polymyxin B dose was 1 mg/kg every 12 h, and the Css,avg at 4–5th dosing were 1.76 and 1.06 mg/L for patient 1 and patient 2, respectively. TDM-guided polymyxin B dose was escalated to 2 mg/kg every 12 h for both patients, resulting in the Css,avg of 2.60 and 1.73 mg/L, and the infection was controlled subsequently. Css,avg of polymyxin B with the same dosing regimens and infusion length were different during CRRT and after termination of CRRT for both patients (2.60 mg/L vs. 4.94 mg/L with 2 mg/kg every 12 h in 2 h infusion for patient 1; and 1.73 mg/L vs. 3.53 mg/L with 2 mg/kg every 12 h in 2 h infusion for patient 2). The estimation of drug exposure (estimated by AUCss,12h at the same dose) during CRRT and cessation of CRRT showed that 45% and 51% of polymyxin B was cleared during CRRT.Conclusion: Our study showed high clearance of polymyxin B through CRRT, and supplanted dosing of polymyxin B is necessary in pediatric patients undergoing CRRT.

Abstract Background Double-balloon enteroscopy enables performing numerous small bowel biopsies for pathologic analysis. However, most histopathological characteristics of Crohn’s disease are non-specific characteristics. We aimed to explore the small bowel mucosal histopathologic characters of Crohn’s disease and identify some disease-specific changes. Methods We included 253 patients without tumors and grouped them into Crohn’s disease, suspected Crohn’s disease, and non-Crohn’s disease groups. These patients underwent double-balloon endoscopy examination and small bowel biopsy at Renji Hospital, Shanghai. All histopathological sections were reviewed, and > 20 histopathological parameters were assessed. Immunohistochemistry was conducted when necessary. Results There were different forms of granulomatous lymphangitis on the small bowel mucosa in Crohn’s disease. They showed as various macrophages or epithelioid cells in the lumina of lymphatics or in the center of the villi with or without evident obstruction. These features were only observed in Crohn’s disease patients. Furthermore, they were correlated with granuloma and lymphangiectasia. Additionally, 15 other features showed significant differences among the three groups, and Crohn’s disease patients showed an average of almost seven histopathological characteristics. Conclusions We described the detailed morphologies of granulomatous lymphangitis on the small bowel mucosa and recommend it as a useful histopathological feature for the diagnosis of Crohn’s disease. In terms of specificity and sensitivity, it was superior to non-caseating epithelioid granuloma.

Abstract Background Accumulating evidence indicates inherited risk in the aetiology of lung cancer, although smoking exposure is the major attributing factor. Family history is a simple substitute for inherited susceptibility. Previous studies have shown some possible yet conflicting links between family history of cancer and EGFR mutation in lung cancer. As EGFR-mutated lung cancer favours female, never-smoker, adenocarcinoma and Asians, it may be argued that there may be some underlying genetic modifiers responsible for the pathogenesis of EGFR mutation. Methods We searched four databases for all original articles on family history of malignancy and EGFR mutation status in lung cancer published up to July 2018. We performed a meta-analysis by using a random-effects model and odds ratio estimates. Heterogeneity and sensitivity were also investigated. Then we conducted a second literature research to curate case reports of familial lung cancers who studied both germline cancer predisposing genes and their somatic EGFR mutation status; and explored the possible links between cancer predisposing genes and EGFR mutation. Results Eleven studies have been included in the meta-analysis. There is a significantly higher likelihood of EGFR mutation in lung cancer patients with family history of cancer than their counterparts without family history, preferentially in Asians (OR = 1.35[1.06–1.71], P = 0.01), those diagnosed with adenocarcinomas ((OR = 1.47[1.14–1.89], P = 0.003) and those with lung cancer-affected relatives (first and second-degree: OR = 1.53[1.18–1.99], P = 0.001; first-degree: OR = 1.76[1.36–2.28, P

Abstract Background Hand, foot and mouth disease (HFMD) remains a burdensome health issue in mainland China. Enterovirus71 (EV-A71) is the main pathogen of severe HFMD. Continuous hemofiltration improves fluid overload, restores kidney function and alleviates inflammatory reactions. The aim of the present study was to evaluate the effects of continuous veno-venous hemodiafiltration (CVVHDF) on severe HFMD caused by EV-A71(EV-A71-HFMD) in a pediatric intensive care unit (PICU). Methods A retrospective observational study was performed in a tertiary university PICU from January 2012 to December 2016. Children with severe EV-A71-HFMD complicated by cardiopulmonary failure were included. The patients were divided into a CVVHDF group and a conventional therapy (control) group (non-CVVHDF). The demographics, characteristics, and outcomes between the groups were collected and analyzed. Results Twenty-nine patients with severe EV-A71-HFMD were enrolled. The 28-day mortality was 17.6% (3/17) in the CVVHDF group and 33.3% (4/12) in the non-CVVHDF group, with no statistical significance between the two groups (P = 0.403). The median interval between CVVHDF initiation and PICU admission was 6 (4,8.5) hrs, and the median duration of CVVHDF was 48 (36, 64) hrs. The left ventricular ejection fraction (LVEF) and cardiac index (CI) in the CVVHDF group were improved after treatment. The plasma levels of catecholamines and renin-angiotensin-aldosterone system (RAAS) substances in the CVVHDF group were significantly decreased after treatment. The decreased catecholamines and RAAS substances included adrenalin (169.8 [145.5, 244.6] vs. 148.0 [109.0, 208.1] ng/L, P = 0.033), dopamine (152.7 [97.0, 191.1] vs. 96.0 [68.0, 160.9] ng/L, P = 0.026), angiotensin II (185.9 [125.2, 800.0] vs. 106.0 [90.8, 232.5] ng/L, P = 0.047), aldosterone (165.7 [94.0, 353.3] vs. 103.3 [84.3, 144.3] ng/L, P = 0.033), and renin (1.12 [0.74, 3.45] vs. 0.79 [0.52, 1.25] μg/L/h, P = 0.029), Conclusions CVVHDF reduced the levels of catecholamines and RAAS substances and improved cardiovascular function. Continuous hemodiafiltration may represent a potential therapy in patients with severe EV-A71-HFMD complicated with cardiopulmonary failure.

lncRNA and cellular metabolism are frequently dysregulated in cancer. In this study, the authors discover the lncGLCC1 is increased in colorectal cancer cells under glucose starvation conditions and correlates with poor prognosis in this cancer.

HKU1 is a human beta coronavirus and infects host cells via highly glycosylated spike protein (S). The N-glycosylation of HKU1 S has been reported. However, little is known about its O-glycosylation, which hinders the in-depth understanding of its biological functions. Herein, a comprehensive study of O-glycosylation of HKU1 S was carried out based on dual-functional histidine-bonded silica (HBS) materials. The enrichment method for O-glycopeptides with HBS was developed and validated using standard proteins. The application of the developed method to the HKU1 S1 subunit resulted in 46 novel O-glycosylation sites, among which 55.6% were predicted to be exposed on the outer protein surface. Moreover, the O-linked glycans and their abundance on each HKU1 S1 site were analyzed. The obtained O-glycosylation dataset will provide valuable insights into the structure of HKU1 S.

ObjectiveUp to now, non-invasive diagnosis of laterally spreading tumor (LST) and prediction of adenoma recurrence after endoscopic resection of LSTs is inevitable. This study aimed to identify a microbial signature with clinical significance of diagnosing LSTs and predicting adenoma recurrence after LSTs colectomy.MethodsWe performed 16S rRNA sequencing in 24 mucosal samples, including 5 healthy controls (HC), 8 colorectal adenoma (CRA) patients, and 11 LST patients. The differentiating microbiota in fecal samples was quantified by qPCR in 475 cases with 113 HC, 208 CRA patients, 109 LST patients, and 45 colorectal cancer (CRC) patients. We identified differentially abundant taxa among cases and controls using linear discriminant analysis effect size analysis. ROC curve was used to evaluate diagnostic values of the bacterial candidates. Pairwise comparison of AUCs was performed by using the Delong’s test. The Mantel-Haenszel hazard models were performed to determine the effects of microbial compositions on recurrence free survival.ResultsThe microbial dysbiosis of LST was characterized by relative high abundance of the genus Lactobacillus-Streptococcus and the species enterotoxigenic Bacteroides fragilis (ETBF)–Peptostreptococcus stomatis (P. stomatis)–Parvimonas micra (P. micra). The abundance of ETBF, P. stomatis, and P. micra were steadily increasing in LST and CRC groups. P. stomatis behaved stronger value on diagnosing LST than the other two bacteria (AUC 0.887, 95% CI 0.842–0.931). The combination of P. stomatis, P. micra, and ETBF (AUC 0.922, 95% CI 0.887–0.958) revealed strongest diagnostic power with 88.7% sensitivity and 81.4% specificity. ETBF, P. stomatis, and P. micra were associated with malignant LST (PP.stomatis = 0.0015, PP.micra = 0.0255, PETBF = 0.0169) and the abundance of IL-6. The high abundance of P. stomatis was related to the adenoma recurrence after LST resection (HR = 3.88, P = 0.008).ConclusionsFecal microbiome signature (ETBF–P. stomatis–P. micra) can diagnose LSTs with high accuracy. ETBF, P. stomatis, and P. micra were related to malignant LST and P. stomatis exhibited high predictive value on the adenoma recurrence after resection of LSTs. The fecal microbiome signature of LST may provide a noninvasive alternative to early detect LST and predict the adenoma recurrence risk after resections of LSTs.

Objectives:. We aimed to describe the characteristics and outcome in children with severe Mycoplasma pneumoniae pneumonia in a Chinese PICU. Design:. A retrospective observational study from 2017 to 2019. Setting:. A 36-bed university tertiary PICU at Shanghai Children’s Hospital. Patients:. Patients admitted to a tertiary PICU 29 days to 18 years old screened for laboratory-confirmed severe M. pneumoniae pneumonia. Interventions:. None. Measurements and Main Results:. Descriptive analysis of baseline characteristics for patients included hospital mortality, organ dysfunctions, use of mechanical ventilation, continuous renal replacement therapy, and/or extracorporeal membrane oxygenation. A total of 817 children with severe pneumonia were admitted to PICU, and 203 of 817 cases (24.8%) with severe M. pneumoniae pneumonia were included in this study. The median age was 41 months (interquartile range, 20–67 mo), of which 77.3% (157/203) were younger than 6 years old. Among 163 patients with the test for macrolide resistance, 90.2% cases (147/163) were macrolide-resistant M. pneumoniae. Severe M. pneumoniae pneumonia-associated organ dysfunction included acute respiratory failure (203 cases, 100%), followed by cardiovascular disorder (79/203, 38.9%), gastrointestinal dysfunction (24/203, 11.8%). The main complications were pleural effusion (79/203, 38.9%), capillary leak syndrome (58/203, 28.6%), and plastic bronchitis (20/203, 9.9%). All patients needed respiratory support, including 64.5% patients (131/203) who received mechanical ventilation and 35.5% patients (72/203) who received high-flow nasal oxygen. Twenty-five patients (12.3%) treated with continuous renal replacement therapy and nine cases (4.4%) received extracorporeal membrane oxygenation. The case fatality rate was 3.9% (8/203). Furthermore, cardiovascular dysfunction, liver injury, or multiple organ dysfunction syndrome were associated with longer mechanical ventilation duration, delayed PICU discharge, and high hospital mortality. Coinfection was a risk factor of delayed PICU discharge. Conclusions:. Children with severe M. pneumoniae pneumonia mainly occur under the age of 6 years, showing a high proportion of extrapulmonary organ dysfunction and macrolide resistances. Extrapulmonary organ dysfunction and coinfection are associated with worse outcomes. The overall mortality is relatively low after treated with appreciate antibiotics, respiratory support, and extracorporeal life support.

Vitronectin (VTN) is a key regulator of coagulation, but clinical relevance of serum VTN in pediatric sepsis remains poorly defined. The aim of this study was to access the value of serum VTN level on pediatric intensive care unit (PICU) admission in children with sepsis. Pediatric patients with sepsis were enrolled from January 2018 to December 2018. The serum VTN levels were determined on PICU admission, and the association of serum VTN level with PICU mortality and organ dysfunction was assessed. Serum VTN levels were significantly lower in nonsurvivors compared with survivors, in patients with septic shock compared with patients with sepsis, or in patients with sepsis-associated acute liver injury (ALI) compared with patients without ALI. Serum VTN level was associated with PICU mortality (odds ratio [OR]: 0.958, 95% CI: 0.927-0.996; P = .010) or ALI (OR: 0.956, 95% CI: 0.915-0.999; P = .046), but not shock (OR: 0.996, 95% CI: 0.977-1.016; P =.716). The area under receiver operating characteristic curve for VTN in predicting the occurrence of ALI during PICU stay and PICU mortality were 0.760 (95% CI: 0.627- 0.893) and 0.737 (95% CI: 0.544-0.931), respectively. Moreover, VTN plus pediatric risk of mortality (PRISM) III had a better clinical utility according to decision curve analysis compared with VTN or PRISM III alone. These findings suggest that serum VTN level is associated with sepsis-associated ALI and PICU mortality, and VTN plus PRISM III is a powerful predictor of PICU mortality in pediatric patients with sepsis, which have a better clinical benefit compared with VTN or PRISM III alone.

Abstract Background Bordetella pertussis can cause fatal illness with severe acute respiratory distress syndrome (ARDS) and pulmonary hypertension (PHT). Case presentation A 6-month-old non-vaccinated boy with B. pertussis infection who developed ARDS was treated by extracorporeal membrane oxygenation (ECMO). During his ECMO support stage, sudden occurred decreasing of ECMO flow implied increasing intrathoracic pressure. The airway spasm followed caused sudden drop of ventilator tidal volume as well as poor lung compliance. Prone position ventilation and bundle care were conducted as lung protection ventilator strategy. After 297-h of ECMO support, the patient was weaned off ECMO, and extubated one week later. Conclusions In this patient with severe ARDS caused by Bordetella pertussis, ECMO was performed for cardiopulmonary support and rescued the infant with severe pertussis. During ECMO support period, prone position ventilation and care bundle nursing strategy contributed to the relief of continuous airway spasm.

Abstract Background Liver dysfunction is an independent risk factor for poor prognosis of patients with sepsis. The aim of this study is to evaluate the effects of continuous hemofiltration in patients with bacterial sepsis complicated by liver dysfunction. Methods We retrospectively analyzed the medical records of 27 cases of bacterial sepsis with liver dysfunction admitted to pediatric intensive care unit (PICU) of Shanghai Children’s Hospital between January 2013 and December 2016. Results 28-day mortality and length of PICU stay were significantly reduced in the continuous hemofiltration group (n = 16) compared with the conventional management group (n = 11) (31.3% vs. 72.7%, 9 [4–23] vs. 14 [4–36], respectively, both P

Abstract Background Chylopericardium effusion is characterized by the accumulation of milky effusion in the pericardium. It is often idiopathic but it can be secondary to trauma, chest radiation, tuberculosis and malignancy. If cardiac tamponade ensues, it becomes life-threatening. Herein we describe chylopericardium tamponade in a child with IgA nephropathy. To the best of our knowledge, this is the first reported case of chylopericardium tamponade in IgA nephropathy. Case presentation A 6 years old boy with IgA nephropathy presented with dyspnea, orthopnea, pretibial pitting edema, ascites and fever. Muffled heart sounds and hepatomegaly were also noted. Echocardiography and thoracic CT revealed that there was a large volume of hydropericardium. Moreover, the pericardial milky fluid by pericardiocentesis was analyzed and chylopericardium effusion was eventually confirmed. Pericardial drainage was continued and his diet was modified to low fat, rich MCT and high protein. Complete remission was achieved after 3 weeks of this combined treatment. Conclusion Chylopericardial tamponade could be a rare and life-threatening complication of IgA nephropathy. Etiological analysis is critical for determining the therapeutic approach in patients with pericardial effusion.