Abstract: Objective To explore the clinical data of children with Talaromyces marneffei (TM) infection admitted to the pediatric intensive care unit (PICU) to improve the diagnosis and treatment of TM infection in children. Methods The clinical data of 23 children with TM infection treated in four PICUs in southern China from January 2013 to December 2022 were retrospectively analyzed, including clinical characteristics, laboratory tests, treatment regimens, and outcomes. Results Among the 23 children, there were 14 boys and 9 girls, with a median age of 24 months. The time from onset to admission was 15 (range 10-30) days, and one patient had immunodeficiency disease. Common symptoms included fever (91.3%, 21 cases), cough (78.3%, 18 cases), and hepatosplenomegaly (78.3%, 18 cases). Severe clinical complications included multiorgan dysfunction (69.6%, 16 cases), septic shock (65.2%, 15 cases), and acute respiratory distress syndrome (65.2%, 15 cases). All patients elevated CRP levels, and 69.2% (9/13) had a positive G test. Elevated IgE levels were observed in 53.3% (8/15) cases, CD4/CD8 inversion in 17.6% (3/17) cases, and reduced NK cells in 84.2% (16/19) cases. HIV tests were negative in all cases. TM was most frequently detected by blood and bone marrow cultures. Seven cases were diagnosed with immunodeficiency by genetic testing. With monotherapy or combination of amphotericin B or/and voriconazole, followed by oral medication, 13 (56.5%) children died. Conclusions TM infection is clinically atypical in HIV-negative children, and patients admitted to PICU have rapidly deteriorated, with severe complications and a high mortality rate. Early use of multiple samples, and multiple methods to detect TM, combined with immune function and genetic test, is helpful to early diagnosis. The antifungal treatment strategies still need further study.

Objective:To explore the immunological characteristics of peripheral blood and genetic variations of 11 immunodeficiency virus(HIV)-negative children with Talaromyces marneffei(TM) infection, thus enhancing the diagnostic and therapeutic levels of TM infection in children. Methods:Clinical data of 11 HIV-negative children with TM infection who presented to Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from January 2010 to December 2022 were retrospectively analyzed, including clinical characteristics, peripheral immune profile and genetic test results.Results:A total of 11 HIV-negative children with TM infections were recruited, involving 9 males and 2 females with a median age of 19 months.The main clinical manifestations were fever (10/11, 90.91%), cough (10/11, 90.91%) and hepatomegaly (7/11, 63.64%). Common severe complications included acute respiratory distress syndrome (7/11, 63.64%) and septic shock (5/11, 45.45%). Finally, 2 children died.Transient neutropenia occurred in 6 cases (6/11, 54.55%), and lymphocytopenia combined with serum immunoglobulin (Ig) G decrease was observed in 4 cases (4/11, 36.36%). IgA decrease, IgM decrease, IgE decrease, IgM increase and IgE increase were observed in 6 cases, 3 cases, 5 cases, 3 cases, and 2 cases, respectively.Both T-lymphocyte and B-lymphocyte counts decreases was observed in 1 case.Genetic testing was performed in all recruited children, and genetic variations were detected in all of them.Inborn errors of immunity (IEIs) were diagnosed in 8 cases, including 4 diagnosed as CD 40 ligand deficiency with CD40LG variation, 1 of severe combined immunodeficiency with IL2RG variation, 1 of Signal transduction and activator of transcription 3(STAT3)-hyper-IgE syndrome with STAT3 variation and 1 of familial candidiasis type 2 with CARD9 compound heterozygous mutations.In the other 3 cases, 2 carried genetic variations that were likely pathogenic, and 1 case was considered uncertain. Conclusions:The clinical manifestations of HIV-negative children with TM infection are atypical, which is characterized as serious complications and high mortality.Early identification and gene testing to detect potential IEIs can improve the prognosis of TM infection.

Hyper-IgE syndrome (HIES) comprises a group of rare primary immunodeficiencies, which are characterized by extremely high serum IgE levels, eczema, recurrent skin and pulmonary infections.Signal transduction and activator of transcription 3( STAT3)-HIES is the most common type, which is caused by dominant-negative mutations in STAT3.STAT3-HIES confers broad innate and acquired immune defects, defects in skeletal, connective tissue, and vascular functions, causing a clinical phenotype including eczema, staphylococcal and fungal skin and pulmonary infections, scoliosis and minimal trauma fractures, vascular tortuosity and aneurysm.In this article, the advance in diverse clinical manifestations and management strategies of STAT3-HIES was summarized.

Adenovirus pneumonia is a common respiratory tract infection in children.Severe cases of adenovirus pneumonia have the characteristics of rapid onset, rapid progression and a panel of complications.Therefore, early recognition, diagnosis and treatment are particularly important.In recent years, studies on the pathogens, hosts, laboratory tests and biomarkers have provided new clinical clues for the early recognition and diagnosis of severe adenovirus pneumonia in children.There are currently no specific antiviral drugs for severe adenovirus pneumonia.Therefore, the main therapeutic strategies for adenovirus pneumonia are immune therapy and respiratory support.A large number of clinical studies have provided new ideas for standardizing therapeutic strategies and improving the prognosis of children.

BACKGROUND: Despite the progress in perinatal-neonatal medicine, complications of extremely preterm infants continue to constitute the major adverse outcomes in neonatal intensive care unit. Human umbilical cord Wharton’s Jellyderived mesenchymal stem cells (HUMSCs) may offer new hope for the treatment of intractable neonatal disorders. This study will explore the functional differences of HUMSCs between extremely preterm and term infants. METHODS: UMSCs from 5 extremely preterm infants(weeks of gestation: 22+5 w,24+4 w,25+3 w,26 w,28 w) and 2 term infants(39 w,39+2 w) were isolated, and mesenchymal markers, pluripotent genes, proliferation rate were analyzed.HUVECs were injured by treated with LPS and repaired by co-cultured with HUMSCs of different gestational ages. RESULTS: All HUMSCs showed fibroblast-like adherence to plastic and positively expressed surface marker of CD105,CD73 and CD90, but did not expressed CD45,CD34,CD14,CD79a and HLA-DR; HUMSCs in extremely preterm exhibited significant increase in proliferation as evidenced by CCK8, pluripotency markers OCT-4 tested by RT-PCR also showed increase. Above all, in LPS induced co-cultured inflame systerm, HUMSCs in extremely preterm were more capable to promote wound healing and tube formation in HUVEC cultures, they promoted TGFb1 expression and inhibited IL6 expression. CONCLUSIONS Our results suggest that HUMSCs from extremely preterm infants may be more suitable as candidates in cell therapy for the preterm infants.

Migraine is one of the most prevalent and disabling neurological disease, but the current pharmacotherapies show limited efficacy and often accompanied by adverse effects. Acupuncture is a promising complementary therapy, but further clinical evidence is needed. The influence of acupuncture on migraine is not an immediate effect, and its mechanism remains unclear. This study aims to provide further clinical evidence for the anti-migraine effects of acupuncture and explore the mechanism involved. A randomized controlled trial was performed among 10 normal controls and 38 migraineurs. The migraineurs were divided into blank control, sham acupuncture, and acupuncture groups. Patients were subjected to two courses of treatment, and each treatment lasted for 5 days, with an interval of 1 day between the two courses. The effectiveness of treatment was evaluated using pain questionnaire. The functional magnetic resonance imaging (fMRI) data were analyzed for investigating brain changes induced by treatments. Blood plasma was collected for metabolomics and proteomics studies. Correlation and mediation analyses were performed to investigate the interaction between clinical, fMRI and omics changes. Results showed that acupuncture effectively relieved migraine symptoms in a way different from sham acupuncture in terms of curative effect, affected brain regions, and signaling pathways. The anti-migraine mechanism involves a complex network related to the regulation of the response to hypoxic stress, reversal of brain energy imbalance, and regulation of inflammation. The brain regions of migraineurs affected by acupuncture include the lingual gyrus, default mode network, and cerebellum. The effect of acupuncture on patients' metabolites/proteins may precede that of the brain.
Humans ; Migraine Disorders/etiology* ; Brain/diagnostic imaging* ; Acupuncture Therapy/methods* ; Magnetic Resonance Imaging

Objective:To compare the efficacy and safety of insulin degludec and insulin glargine U100 in patients with type 2 diabetes mellitus.Methods:This study was a retrospective cohort study. The subjects were patients with type 2 diabetes mellitus who were hospitalized in 13 3A-level general hospitals in Shandong Province from September 2018 to December 2021. According to the type of basal insulin used, the patients were divided into insulin degludec group and insulin glargine U100 group. The basic information and laboratory test results in patients in the 2 groups were collected, the differences of fasting blood glucose level and incidence of hypoglycemia between the 2 groups were compared. The patients with complete blood glucose monitoring data in the 2 groups were selected and their blood glucose fluctuations were compared.Results:A total of 1 152 patients were entered in the study, including 552 patients in the insulin degludec group and 600 patients in the insulin glargine U100 group. The difference in the basic conditions in patients in the 2 groups was not statistically significant (all P>0.05). After treatment, the fasting blood glucose levels in patients in the 2 groups were lower than those before treatment, with statistically significant differences [10.2 (8.8, 12.5) mmol/L vs. 7.5 (6.6, 8.7) mmol/L, Z=-19.443, P<0.001; 10.0 (8.6, 11.7) mmol/L vs. 7.8 (6.6, 9.0) mmol/L, Z=-15.449, P<0.001], but the difference in fasting blood glucose levels between the 2 groups after treatment was not statistically significant ( Z=-1.427, P>0.05). The incidence of hypoglycemia in the insulin degludec group was lower than that in the insulin glargine U100 group [1.09% (6/552) vs. 2.83% (17/600), Z=4.481, P=0.032]. The intraday blood glucose standard deviation, maximum blood glucose fluctuation range, postprandial blood glucose fluctuation range, and average blood glucose fluctuation range in patients with complete blood glucose monitoring data in the insulin degludec group were significantly lower than those in the insulin glargine U100 group [(1.7±0.6) mmol/L vs. (2.4±1.0) mmol/L, (4.5±1.6) mmol/L vs. (6.7±2.9) mmol/L, (1.8±1.0) mmol/L vs. (3.3±1.2) mmol/L, (2.9±1.3) mmol/L vs. (4.6±2.1) mmol/L; all P<0.001]. Conclusion:The efficacy of insulin degludec in the treatment of type 2 diabetes mellitus is equivalent to that of insulin glargine U100, but the risk of hypoglycemia and blood glucose fluctuation is lower.

Objective:To compare the efficacy and safety of insulin degludec and insulin glargine U100 in patients with type 2 diabetes mellitus.Methods:This study was a retrospective cohort study. The subjects were patients with type 2 diabetes mellitus who were hospitalized in 13 3A-level general hospitals in Shandong Province from September 2018 to December 2021. According to the type of basal insulin used, the patients were divided into insulin degludec group and insulin glargine U100 group. The basic information and laboratory test results in patients in the 2 groups were collected, the differences of fasting blood glucose level and incidence of hypoglycemia between the 2 groups were compared. The patients with complete blood glucose monitoring data in the 2 groups were selected and their blood glucose fluctuations were compared.Results:A total of 1 152 patients were entered in the study, including 552 patients in the insulin degludec group and 600 patients in the insulin glargine U100 group. The difference in the basic conditions in patients in the 2 groups was not statistically significant (all P>0.05). After treatment, the fasting blood glucose levels in patients in the 2 groups were lower than those before treatment, with statistically significant differences [10.2 (8.8, 12.5) mmol/L vs. 7.5 (6.6, 8.7) mmol/L, Z=-19.443, P<0.001; 10.0 (8.6, 11.7) mmol/L vs. 7.8 (6.6, 9.0) mmol/L, Z=-15.449, P<0.001], but the difference in fasting blood glucose levels between the 2 groups after treatment was not statistically significant ( Z=-1.427, P>0.05). The incidence of hypoglycemia in the insulin degludec group was lower than that in the insulin glargine U100 group [1.09% (6/552) vs. 2.83% (17/600), Z=4.481, P=0.032]. The intraday blood glucose standard deviation, maximum blood glucose fluctuation range, postprandial blood glucose fluctuation range, and average blood glucose fluctuation range in patients with complete blood glucose monitoring data in the insulin degludec group were significantly lower than those in the insulin glargine U100 group [(1.7±0.6) mmol/L vs. (2.4±1.0) mmol/L, (4.5±1.6) mmol/L vs. (6.7±2.9) mmol/L, (1.8±1.0) mmol/L vs. (3.3±1.2) mmol/L, (2.9±1.3) mmol/L vs. (4.6±2.1) mmol/L; all P<0.001]. Conclusion:The efficacy of insulin degludec in the treatment of type 2 diabetes mellitus is equivalent to that of insulin glargine U100, but the risk of hypoglycemia and blood glucose fluctuation is lower.

Objective:To analyze the clinical features of bronchiectasis in children after severe adenovirus pneumonia and to provide clinical clues for the early diagnosis of bronchiectasis in children after severe adenovirus pneumonia.Methods:A retrospective study was made to analyze the clinical data of 26 children with bronchiectasis after severe adenovirus pneumonia treated in Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from May 2016 to May 2021.Results:A total of 26 cases were reported, including 18 males and 8 females.The median onset age of severe adenovirus pneumonia was 23.0 (15.0, 48.0) months.A total of 23 cases suffered concurrent infections, and bacterial co-infection was the most common (16 cases). High resolution computed tomography (HRCT) showed multiple lobar solids in the lung with/without pleural effusion.During the acute phase, most of the cases were treated with intravenous immunoglobulin (21 cases), mechanical ventilation (20 cases), and systemic glucocorticoids (19 cases). The median age at diagnosis of bronchiectasis was 29.5 (21.0, 56.8) months, and the median time that the patients took to develop into acute adenovirus pneumonia was 6.0 (3.3, 13.0) months.Six cases suffered bronchiectasis alone, and 20 cases had bronchiectasis combined with post-infectious bronchiolitis obliterans (PIBO). Of these 20 cases, 3 cases developed bronchiectasis and PIBO simultaneously, and the remaining 17 cases developed bronchiectasis after PIBO.In the included 26 cases, diffuse bronchiectasis predominated (24 cases), most frequently involving the left lower lobes (21 cases) and right lower lobes (21 cases). Cylindrical bronchiectasis was the most common type (23 cases). All the patients had recurrent cough and wheezing during follow-up, and only 3 cases coughed up pus sputum without hemoptysis.All children had acute exacerbations, which were mostly caused by bacteria (21 cases). Nineteen cases combined with PIBO and 1 case with only bronchiectasis were rehospitalized.There was no cases of surgical resection or death.Conclusions:Bronchiectasis after severe adenovirus pneumonia mostly occurs in patients with or without PIBO.Multiple lobe involvement and co-infection may be a risk factor for PIBO patients to develop bronchiectasis.The clinical manifestations are mostly recurrent cough and wheezing, while sputum and hemoptysis are less common.Pediatricians should promptly perform chest HRCT for early diagnosis of the disease.

Penicillium marneffei (PM) is the only thermally dimorphic species as a Penicillium that causes the transmitted penicilliosis marneffei (PSM). PM infection is more common in immunodeficient children.Due to the lack of specific clinical manifestations, PSM is easily misdiagnosed as pulmonary plasmacycosis, tuberculosis or pulmonary aspergillosis.Because of the rapid progress and multiple complications of transmitted PSM, its mortality remains high without timely and effective treatment.Therefore, early diagnosis and treatment are of great significance, and the diagnosis of PSM mainly relies on the immune function examination, measurement of serum markers, pathogen detection and imaging examinations.There is no standard antifungal regimen, and Amphoterus B and Itraconazole are used as the first-line treatment.This study aims to review the progress of diagnosis and treatment of PM infection in children.