Two cases of infantile-onset primary generalized glucocorticoid hypersensitivity and the effect of mifepristone.

BACKGROUND: Primary generalized glucocorticoid hypersensitivity (PGGH) is a very rare disease caused by terminal organ hypersensitivity to glucocorticoids for which the aetiology is unknown. The incidence of PGGH is extremely rare, especially in children. To date, the literatures about the etiology, prognosis and treatment of PGGH are scarce. Aim of the study is describing the cases of two Chinese children with infantile-onset PGGH in one family, one of whom died and one who was treated with mifepristone. They are the two youngest children with PGGH reported in the literature. CASE PRESENTATION: Two siblings with infantile-onset PGGH were affected in this family. The main manifestations of patient 1 were typical Cushing's syndrome-like manifestations, significantly aggravated symptoms after physiological doses of glucocorticoids and very low levels of serum cortisol and adrenocorticotropin hormone (ACTH) during attacks. After being diagnosed with PGGH, he was given guidance to avoid glucocorticoids and took mifepristone therapy for 5 months, and his symptoms improved. Patient 2 was the younger brother of patient 1, with similar manifestations to his brother at the age of 4 months. Patient 2 ultimately died at the age of 9 months. CONCLUSION: PGGH is a very rare disease that can lead to death if not diagnosed and treated in a timely manner. This article describes the cases of the two youngest children with PGGH reported in the literature, one of whom improved after mifepristone treatment, and increases the knowledge of the clinical manifestations of and the treatment experience in PGGH.

Short term outcomes of extremely low birth weight infants from a multicenter cohort study in Guangdong of China.

With the increase in extremely low birth weight (ELBW) infants, their outcome attracted worldwide attention. However, in China, the related studies are rare. The hospitalized records of ELBW infants discharged from twenty-six neonatal intensive care units in Guangdong Province of China during 2008-2017 were analyzed. A total of 2575 ELBW infants were enrolled and the overall survival rate was 55.11%. From 2008 to 2017, the number of ELBW infants increased rapidly from 91 to 466, and the survival rate improved steadily from 41.76% to 62.02%. Increased survival is closely related to birth weight (BW), regional economic development, and specialized hospital. The incidence of complications was neonatal respiratory distress syndrome (85.2%), oxygen dependency at 28 days (63.7%), retinopathy of prematurity (39.3%), intraventricular hemorrhage (29.4%), necrotizing enterocolitis (12.0%), and periventricular leukomalacia (8.0%). Among the 1156 nonsurvivors, 90.0% of infants died during the neonatal period (≤ 28 days). A total of 768 ELBW infants died after treatment withdrawal, for reasons of economic and/or poor outcome. The number of ELBW infants is increasing in Guangdong Province of China, and the overall survival rate is improving steadily.

STAT3-mediated ferroptosis is involved in ulcerative colitis.

Ferroptosis is a form of iron-dependent lipid peroxidation cell death that plays an important role in inflammation. However, the mechanism of ferroptosis in ulcerative colitis (UC) remains to be further investigated. In the present study, we merged the differentially expressed genes (DEGs) of UC in GEO database with the ferroptosis-related genes of FerrDb for bioinformatics analysis and successfully screened out the ferroptosis-related hub gene STAT3 (signal transducer and activator of transcription 3). Then we further validated the role of STAT3-mediated ferroptosis in vitro and in vivo models of colitis. The results showed that ferroptosis was increased in DSS-induced colitis, salmonella typhimurium (S. Tm) colitis and H2O2-induced IEC-6 cells. And the phosphorylation level of the hub gene STAT3 was down-regulated in IEC-6 cells treated with H2O2, while Fer-1, an ferroptosis inhibitor, reactivated the phosphorylation level of STAT3. In addition, co-treatment of cells with H2O2 and STAT3 inhibitor (stattic) showed an additive effect on the extent of ferroptosis. Taken together, these findings suggest that ferroptosis is closely associated with the development of colitis and ferroptosis-related gene STAT3 could serve as a potential biomarker for diagnosis and treatment of ulcerative colitis.

Emerging Roles of Non-Coding RNAs in Childhood Asthma.

Asthma is a chronic airway inflammatory disease in children characterized by airway inflammation, airway hyperresponsiveness and airway remodeling. Childhood asthma is usually associated with allergy and atopy, unlike adult asthma, which is commonly associated with obesity, smoking, etc. The pathogenesis and diagnosis of childhood asthma also remains more challenging than adult asthma, such as many diseases showing similar symptoms may coexist and be confused with asthma. In terms of the treatment, although most childhood asthma can potentially be self-managed and controlled with drugs, approximately 5-10% of children suffer from severe uncontrolled asthma, which carries significant health and socioeconomic burdens. Therefore, it is necessary to explore the pathogenesis of childhood asthma from a new perspective. Studies have revealed that non-coding RNAs (ncRNAs) are involved in the regulation of respiratory diseases. In addition, altered expression of ncRNAs in blood, and in condensate of sputum or exhalation affects the progression of asthma via regulating immune response. In this review, we outline the regulation and pathogenesis of asthma and summarize the role of ncRNAs in childhood asthma. We also hold promise that ncRNAs may be used for the development of biomarkers and support a new therapeutic strategy for childhood asthma.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China. / è¶ æœªæˆç†ŸåŒèƒŽå„¿ä¸´åºŠæ•‘æ²»ç»“å±€åŠå˜åŒ–åˆ†æžï¼šä¸€é¡¹å¹¿ä¸œçœå¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS: There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Risk Factors for Severe Hand-Foot-Mouth Disease in China: A Systematic Review and Meta-Analysis.

Background: This study aimed to identify potential risk factors for severe hand-foot-mouth disease (HFMD). Methods: The PubMed, Embase, the Cochrane Library, Sinomed, WanFang, CNKI, and VIP databases were searched (up to August 2021). Results: Twenty-nine studies (9,241 and 927,355 patients with severe HFMD and controls, respectively; all from China) were included. EV71 was associated with higher odds of severe HFMD compared with other agents (OR = 4.44, 95%CI: 3.12-6.33, p < 0.001). Being home-raised (OR = 1.99, 95%CI: 1.59-2.50, p < 0.001), higher number of children in the family (OR = 2.09, 95%CI: 1.93-2.27, p < 0.001), poor hand hygiene (OR = 2.74, 95%CI: 1.78-4.23, p < 0.001), and no breastfeeding (OR = 2.01, 95%CI: 1.45-2.79, p < 0.001) were risk factors for severe HFMD. First consulting to a district-level or above hospital (OR = 0.34, 95%CI: 0.25-0.45, p < 0.001) and diagnosis of HFMD at baseline (OR = 0.17, 95%CI: 0.13-0.24, p < 0.001) were protective factors against severe HFMD. Fever, long fever duration, vomiting, lethargy, leukocytosis, tic, and convulsions were each associated with severe HFMD (all p < 0.05), while rash was not. Conclusions: EV71, lifestyle habits, frequent hospital visits, and symptoms are risk factors for severe HFMD in children in China, while early diagnosis and admission to higher-level hospitals are protective factors.

Drug repurposing against coronavirus disease 2019 (COVID-19): A review.

Since December 2019, severe acute respiratory syndrome coronavirus 2 has been found to be the culprit in the coronavirus disease 2019 (COVID-19), causing a global pandemic. Despite the existence of many vaccine programs, the number of confirmed cases and fatalities due to COVID-19 is still increasing. Furthermore, a number of variants have been reported. Because of the absence of approved anti-coronavirus drugs, the treatment and management of COVID-19 has become a global challenge. Under these circumstances, drug repurposing is an effective method to identify candidate drugs with a shorter cycle of clinical trials. Here, we summarize the current status of the application of drug repurposing in COVID-19, including drug repurposing based on virtual computer screening, network pharmacology, and bioactivity, which may be a beneficial COVID-19 treatment.

Clinical characterization of NTCP deficiency in paediatric patients : A case-control study based on SLC10A1 genotyping analysis.

Na+ -taurocholate cotransporting polypeptide deficiency (NTCPD) is a newly described disorder arising from biallelic mutations of the SLC10A1 gene. As a result of a lack of compelling evidence from case-control studies, its genotypic and phenotypic features remain open for in-depth investigation. This study aimed to explore the genotypic and clinical phenotypic characteristics of paediatric patients with NTCPD. The SLC10A1 genotypes of all NTCPD patients were confirmed by screening for the prevalent variant c.800C>T and Sanger sequencing when necessary. The clinical presentations and laboratory changes were collected, reviewed and analysed, and then qualitatively and quantitatively compared with the relevant controls. A total of 113 paediatric NTCPD patients were diagnosed while c.374dupG and c.682_683delCT were detected as two novel pathogenic mutations. Hypercholanemia was observed in 99.12% of the patients. Indirect hyperbilirubinemia in affected neonates exhibited higher positive rates in comparison to controls. Moreover, transient cholestatic jaundice, elevated liver enzymes and 25-hydroxyvitamin D (Vit D) deficiency during early infancy were more commonly observed in patients than in controls. All NTCPD patients exhibited favourable clinical outcomes as a result of symptomatic and supportive treatment. The findings enriched the SLC10A1 mutation spectrum and provided comprehensive insights into the phenotypic characteristics of NTCPD. NTCPD should be considered and SLC10A1 gene should be analysed in patients with above age-dependent clinical features. Furthermore, over investigation and intervention should be avoided in the management of NTCPD patients.

Chemical composition and pharmacological mechanism of ephedra-glycyrrhiza drug pair against coronavirus disease 2019 (COVID-19).

Traditional Chinese medicine (TCM) had demonstrated effectiveness in the prevention and control of COVID-19. Statistics showed that Ephedra and Glycyrrhiza were frequently used in the treatment of COVID-19. We hypothesized that the Ephedra-Glycyrrhiza drug pair is a potential choice for the treatment of COVID-19. Here, 112 active compounds were identified from Ephedra-Glycyrrhiza via network pharmacology approach. Ephedra-Glycyrrhiza pair enrichment analysis demonstrated that these compounds might participate in the cAMP, PI3K-Akt, JAK-STAT and chemokine signaling pathways, which had a high correlation with respiratory, nervous, blood circulation and digestive system-related diseases. Pathway analysis between Ephedra-Glycyrrhiza and COVID-19 showed that the key targets were TNF-α, IL2, FOS, ALB, and PTGS2. They might control PI3K-Akt signaling pathway to exert immune regulation, organ protection and antiviral effects. Molecular docking results showed that the active compounds from the Ephedra-Glycyrrhiza pair bound well to COVID-19 related targets, including the main protease (Mpro, also called 3CLpro), the spike protein (S protein), and the angiotensin-converting enzyme 2 (ACE2). The Molecular dynamics simulation was analyzed for the stability and flexibility of the complex. In conclusion, our study elucidated the potential pharmacological mechanism of Ephedra-Glycyrrhiza in the treatment of COVID-19 through multiple targets and pathways.

Selective autophagy of intracellular organelles: recent research advances.

Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs, etc. In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, etc. Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.

Potential Therapeutic Effect of Traditional Chinese Medicine on Coronavirus Disease 2019: A Review.

The Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has been rapidly spreading globally and has caused worldwide social and economic disruption. Currently, no specific antiviral drugs or clinically effective vaccines are available to prevent and treat COVID-19. Traditional Chinese medicine (TCM) can facilitate syndrome differentiation and treatment according to the clinical manifestations of patients and has demonstrated effectiveness in epidemic prevention and control. In China, TCM intervention has helped to control the epidemic; however, TCM has not been fully recognized worldwide. In this review, we summarize the epidemiology and etiological characteristics of severe acute respiratory syndrome coronavirus 2 and the prevention and treatment measures of COVID-19. Additionally, we describe the application of TCM in the treatment of COVID-19 and the identification of small molecules of TCM that demonstrate anti-coronavirus activity. We also analyze the current problems associated with the recognition of TCM. We hope that, through the contribution of TCM, combined with modern technological research and the support of our international counterparts, COVID-19 can be effectively controlled and treated.

Day-1 PELOD-2 and day-1 quick PELOD-2 scores in children with sepsis in the PICU / Desempenhos dos escores PELOD-2 no dia 1 e quick PELOD-2 no dia 1 em crianças com sepse na UTIP

Abstract Objectives: This study aimed to evaluate the predictive validity of the day-1 PELOD-2 and day-1 "quick" PELOD-2 (qPELOD-2) scores for in-hospital mortality in children with sepsis in a pediatric intensive care unit (PICU) of a developing country. Methods: The data of 516 children diagnosed as sepsis were retrospectively analyzed. The children were divided into survival group and non-survival group, according to the clinical outcome 28 days after admission. Day-1 PELOD-2, day-1 qPELOD-2, pediatric SOFA (pSOFA), and P-MODS were collected and scored. Receiver operating characteristic (ROC) curves were plotted, and the efficiency of the day-1 PELOD-2, day-1 qPELOD-2 score, pSOFA, and P-MODS for predicting death were evaluated by the area under the ROC curve (AUC). Results: The day-1 PELOD-2 score, day-1 qPELOD-2 score, pSOFA, and P-MODS in the non-survivor group were significantly higher than those in the survivor group. ROC curve analysis showed that the AUCs of the day-1 PELOD-2 score, day-1 qPELOD-2 score, pSOFA, and P-MODS for predicting the prognosis of children with sepsis in the PICU were 0.916, 0.802, 0.937, and 0.761, respectively (all p < 0.05). Conclusions: Both the day-1 PELOD-2 score and day-1 qPELOD-2 score were effective and able to assess the prognosis of children with sepsis in a PICU of a developing country. Additionally, the day-1 PELOD-2 score was superior to the day-1 qPELOD-2 score. Further studies are needed to verify the usefulness of the day-1 qPELOD-2 score, particularly outside of the PICU.

Resumo Objetivos: A finalidade de nosso estudo foi avaliar a validade preditiva dos escores PELOD-2 no dia 1 e "quick" PELOD-2 no dia 1 com relação à mortalidade hospitalar em crianças com sepse em uma UTIP de um país em desenvolvimento. Métodos: Foram analisados retrospectivamente os dados de 516 crianças diagnosticadas com sepse. As crianças foram divididas em grupo sobrevida e grupo não sobrevida de acordo com o desfecho clínico de 28 dias após internação. Foram coletadas e pontuadas as variáveis PELOD-2 no dia 1, qPELOD-2 no dia 1, pediatric Sequential Organ Failure Assessment (pSOFA) e Pediatric Multiple Organ Dysfunction Score (P-MODS). A curva da característica de operação do receptor (ROC) foi plotada e a eficiência preditiva do PELOD-2 no dia 1, o escore qPELOD-2 no dia 1, pSOFA, P-MODS com relação a óbito foram avaliados pela área abaixo da curva (AUC) da curva ROC. Resultados: O escore PELOD-2 no dia 1, escore qPELOD-2 no dia 1, pSOFA e P-MODS no grupo não sobrevida foram significativamente maiores do que os no grupo sobrevida. A análise preditiva da curva ROC mostrou que as AUCs do escore PELOD-2 no dia 1, escore qPELOD-2 no dia 1, pSOFA e P-MODS com relação ao prognóstico de crianças com sepse na UTIP foi 0,916, 0,802, 0,937 e 0,761, respectivamente (todas p < 0,05). Conclusões: Tanto o escore PELOD-2 no dia 1 e o escore qPELOD-2 no dia 1 foram válidos e conseguiram avaliar o prognóstico de crianças com sepse em uma UTIP de um país em desenvolvimento. Além disso, o escore PELOD-2 no dia 1 foi superior ao escore qPELOD-2 no dia 1. São necessários estudos adicionais para verificar a utilidade do escore qPELOD-2 no dia 1, principalmente fora da UTIP.

NBAS disease: 14 new patients, a recurrent mutation, and genotype-phenotype correlation among 24 Chinese patients.

AIM: Neuroblastoma amplified sequence (NBAS)-associated disease has a wide phenotypic spectrum, including infantile liver failure syndrome type 2 (ILFS2, OMIM #616483), short stature with optic nerve atrophy and Pelger-Huët anomaly (SOPH) syndrome (OMIM #614800), and a combined phenotype overlapping ILFS2 and SOPH syndrome. The mutation spectra of NBAS and its genotype-phenotype correlation among Chinese were not clear. METHODS: Clinical and genetic data were retrospectively collected from the medical charts of patients with biallelic NBAS mutations, as well as from Chinese patients in previously published reports. RESULTS: Fourteen new patients were identified, including 10 novel mutations: c.648-1G>A, c.2563_c.2577+5del/p.His855_Gln859del, c.3115C>T/p.Gln1039Ter, c.3284G>A/p.Trp1095Ter, c.2570C>T/p.Ala857Val, c.6859G>T/p.Asp2287Tyr, c.1028G>A/p.Ser343Asn, c.1177_1182delinsAGATAGA/p.Val393ArgfsTer2, c.3432_3435dupCAGT/p.Ala1146GlnfsTer14, and c.680_690dupACTGTTTCAGC/p.Phe231ThrfsTer35. All 14 patients presented as fever-triggered liver injury, including nine patients that satisfied the criteria of acute liver failure (ALF) in whom c.3596G>A/p.Cys1199Tyr occurred five times. Nine patients had extrahepatic manifestations including short stature, skeletal abnormalities, intellectual disability, ophthalmic abnormalities, low levels of serum immunoglobulins, facial dysmorphism, and cardiac abnormalities. Ten other Chinese patients were collected through a review of published works. Genotype-phenotype analysis in 24 Chinese patients revealed that the percentage of ALF patients with variants in the Sec39 domain was significantly higher than that in the C-terminal (100% vs. 12.5%, P = 0.000), and the percentage of multi-organ/system involvement in patients with variants in the Sec39 domain was significantly lower than that in the C-terminal (40% vs. 100%, P = 0.0128). CONCLUSIONS: We reported 14 new patients, 10 novel mutations, and a unique recurrent mutation. Correlation analysis indicated that the domain of missense and non-frameshift insertion/deletion mutations in NBAS protein is related to phenotype among Chinese patients.

Divergent Roles of miR-3162-3p in Pulmonary Inflammation in Normal and Asthmatic Mice as well as Antagonism of miR-3162-3p in Asthma Treatment.

MicroRNA (miRNA) mimics or antagomirs hold great promise for asthma treatment compared with glucocorticoids as mainstay therapy for asthma. But the role of miRNA in regulating asthmatic inflammation is largely unclear. We previously reported that miR-3162-3p in the peripheral blood of children with asthma was obviously upregulated compared to that in healthy children. This study aimed to elucidate the role of miR-3162-3p in pulmonary inflammation in normal and asthmatic mice as well as preliminarily explore the potential of miR-3162-3p antagomir in asthma treatment. A noninvasive whole-body plethysmograph measured airway responsiveness. Both qRT-PCR and Western blot were used to detect the expression of miRNA, mRNA, or protein. Cells in bronchoalveolar lavage fluid were counted by platelet counting and Wright's staining. Inflammatory infiltration and mucus secretion were identified by hematoxylin and eosin and periodic acid-Schiff  staining, respectively. Cytokines in the lungs were detected by ELISA. The miR-3162-3p mimic intraperitoneally administered to normal mice decreased ß-catenin levels in the lungs without obviously altering the lung histology and cytokine levels. Antagonizing miR-3162-3p in ovalbumin-induced asthmatic mice effectively alleviated the typical features of asthma, such as airway hyper-responsiveness, airway inflammation, and Th1/Th2 cytokine imbalance, and concomitantly rescued the total and active ß-catenin expression. Collectively, we discovered divergent roles of miR-3162-3p in lung inflammation between normal and asthmatic mice. The anti-inflammatory effects of the miR-3162-3p antagomir were comparable to those of glucocorticoid treatment. Our study helped in understanding the contribution of miRNAs to the pathogenesis of asthma.

Mini-LED, Micro-LED and OLED displays: present status and future perspectives.

Presently, liquid crystal displays (LCDs) and organic light-emitting diode (OLED) displays are two dominant flat panel display technologies. Recently, inorganic mini-LEDs (mLEDs) and micro-LEDs (µLEDs) have emerged by significantly enhancing the dynamic range of LCDs or as sunlight readable emissive displays. "mLED, OLED, or µLED: who wins?" is a heated debatable question. In this review, we conduct a comprehensive analysis on the material properties, device structures, and performance of mLED/µLED/OLED emissive displays and mLED backlit LCDs. We evaluate the power consumption and ambient contrast ratio of each display in depth and systematically compare the motion picture response time, dynamic range, and adaptability to flexible/transparent displays. The pros and cons of mLED, OLED, and µLED displays are analysed, and their future perspectives are discussed.

Exploring the Emerging Role of the Gut Microbiota and Tumor Microenvironment in Cancer Immunotherapy.

The tumor microenvironment (TME) is a complex ecosystem, which includes many different types of cells, abnormal vascular systems, and immunosuppressive cytokines. TME serves an important function in tumor tolerance and escapes from immune surveillance leading to tumor progression. Indeed, there is increasing evidence that gut microbiome is associated with cancer in a variety of ways, as specific microbial signatures are known to promote cancer development and influence safety, tolerability, and efficacy of therapies. Studies over the past five years have shown that the composition of the intestinal microbiota has a significant impact on the efficacy of anticancer immunosurveillance, which contribute to the therapeutic activity of cancer immunotherapies based on targeting cytotoxic T lymphocyte protein 4 (CTLA-4) or programmed cell death protein 1 (PD-1)-programmed cell death 1 ligand 1 (PD-L1) axis. In this review, we mainly discuss the impact of TME on cancer and immunotherapy through immune-related mechanisms. We subsequently discuss the influence of gut microbiota and its metabolites on the host immune system and the formation of TME. In addition, this review also summarizes the latest research on the role of gut microbiota in cancer immunotherapy.

Infantile Rosai-Dorfman disease: an unusual case of neck swelling and a literature review.

Rosai-Dorfman disease (RDD) is a benign, rare histiocytic disorder presenting as a wide clinical spectrum, which mainly affects bilateral dilated lymph node enlargement. This study aimed to show an infantile RDD and review the clinicopathologic features, imaging, and histological features of RDD, including pitfalls in diagnosis. We report here an infant who had a 3-month history of painless bilateral cervical masses progressed to tracheal compression. Postoperative immunohistochemical results with positive characteristic staining of CD68 and S-100, negative for CD1a, which helped to determine the diagnosis. This peculiar case is the youngest case of RDD presenting with painless massive lymph node progressing to severe dyspnea due to tracheal compression. The optimal treatment still remains challenging. Future research should focus more on etiology and pathogenesis of RDD, especially relapsing cases.

Day-1 PELOD-2 and day-1 "quick" PELOD-2 scores in children with sepsis in the PICU.

OBJECTIVES: This study aimed to evaluate the predictive validity of the day-1 PELOD-2 and day-1 "quick" PELOD-2 (qPELOD-2) scores for in-hospital mortality in children with sepsis in a pediatric intensive care unit (PICU) of a developing country. METHODS: The data of 516 children diagnosed as sepsis were retrospectively analyzed. The children were divided into survival group and non-survival group, according to the clinical outcome 28 days after admission. Day-1 PELOD-2, day-1 qPELOD-2, pediatric SOFA (pSOFA), and P-MODS were collected and scored. Receiver operating characteristic (ROC) curves were plotted, and the efficiency of the day-1 PELOD-2, day-1 qPELOD-2 score, pSOFA, and P-MODS for predicting death were evaluated by the area under the ROC curve (AUC). RESULTS: The day-1 PELOD-2 score, day-1 qPELOD-2 score, pSOFA, and P-MODS in the non-survivor group were significantly higher than those in the survivor group. ROC curve analysis showed that the AUCs of the day-1 PELOD-2 score, day-1 qPELOD-2 score, pSOFA, and P-MODS for predicting the prognosis of children with sepsis in the PICU were 0.916, 0.802, 0.937, and 0.761, respectively (all p < 0.05). CONCLUSIONS: Both the day-1 PELOD-2 score and day-1 qPELOD-2 score were effective and able to assess the prognosis of children with sepsis in a PICU of a developing country. Additionally, the day-1 PELOD-2 score was superior to the day-1 qPELOD-2 score. Further studies are needed to verify the usefulness of the day-1 qPELOD-2 score, particularly outside of the PICU.

Short-term outcomes of extremely preterm infants at discharge: a multicenter study from Guangdong province during 2008-2017.

BACKGROUND: An increasing number of extremely preterm (EP) infants have survived worldwide. However, few data have been reported from China. This study was designed to investigate the short-term outcomes of EP infants at discharge in Guangdong province. METHODS: A total of 2051 EP infants discharged from 26 neonatal intensive care units during 2008-2017 were enrolled. The data from 2008 to 2012 were collected retrospectively, and from 2013 to 2017 were collected prospectively. Their hospitalization records were reviewed. RESULTS: During 2008-2017, the mean gestational age (GA) was 26.68 ± 1.00 weeks and the mean birth weight (BW) was 935 ± 179 g. The overall survival rate at discharge was 52.5%. There were 321 infants (15.7%) died despite active treatment, and 654 infants (31.9%) died after medical care withdrawal. The survival rates increased with advancing GA and BW (p < 0.001). The annual survival rate improved from 36.2% in 2008 to 59.3% in 2017 (p < 0.001). EP infants discharged from hospitals in Guangzhou and Shenzhen cities had a higher survival rate than in others (p < 0.001). The survival rate of EP infants discharged from general hospitals was lower than in specialist hospitals (p < 0.001). The major complications were neonatal respiratory distress syndrome, 88.0% (1804 of 2051), bronchopulmonary dysplasia, 32.3% (374 of 1158), retinopathy of prematurity (any grade), 45.1% (504 of 1117), necrotizing enterocolitis (any stage), 10.1% (160 of 1588), intraventricular hemorrhages (any grade), 37.4% (535 of 1431), and blood culture-positive nosocomial sepsis, 15.7% (250 of 1588). The multivariate logistic regression analysis indicated that improved survival of EP infants was associated with discharged from specialist hospitals, hospitals located in high-level economic development region, increasing gestational age, increasing birth weight, antenatal steroids use and a history of premature rupture of membranes. However, twins or multiple births, Apgar ≤7 at 5 min, cervical incompetence, and decision to withdraw care were associated with decreased survival. CONCLUSIONS: Our study revealed the short-term outcomes of EP infants at discharge in China. The overall survival rate was lower than the developed countries, and medical care withdrawal was a serious problem. Nonetheless, improvements in care and outcomes have been made annually.