1.Composition of gut microbiota and characteristics of virulence factors genes in overweight or obese children and their relationship with liver metabolic inflammation
Jiyang JIANG ; Zhenxin FAN ; Fan YANG ; Hanmin LIU ; Meng MAO ; Ling FENG ; Fei XIONG ; Ping LI
Chinese Journal of Pediatrics 2025;63(6):642-648
Objective:To explore the composition of gut microbiome, the characteristics of virulence factor genes and their relationship with liver metabolic inflammation in overweight or obese children.Methods:A case-control design was conducted. From the children who visited the West China Second University Hospital of Sichuan University for medical or physical examinations between August 2021 and April 2022, a total of 23 obese children (obesity group), 8 overweight children (overweight group), and 22 healthy children (control group) were recruited. The body mass index of children was calculated after anthropometric measurements; metabolic inflammation indexes such as the levels of fasting blood glucose and hepatic function and renal function etc. were detected. The composition and abundance of gut microbiota in the feces of the children were detected by metagenomic sequencing technology and the Shannon index and Simpson index were calculated to assess the α diversity of virulence factor genes. The Wilcoxon rank-sum test was used for pairwise comparison between groups. The Spearman′s rank correlation test was used for correlation analysis, and the Benjamini-Hochberg method was used to correct the P-value of multiple tests. Results:The obese group included 23 children aged 8.5 (6.3, 11.8) years, of whom 9 (39%) were male. The overweight group consisted of 8 children aged 9.2 (5.5, 12.3) years, of whom 4 were male. The control group comprised 22 children aged 5.3 (5.1, 5.4) years, of whom 10 (45%) were male. The obese group exhibited higher levels of alanine aminotransferase (ALT), gamma-glutamyl transferase (γ-GT), globulin, and uric acid compared to those of the control group (all P<0.05), with ALT also higher than that of the overweight group ( P<0.05). The levels of fasting blood glucose, γ-GT, globulin, and uric acid in the overweight group were all higher than those in the control group (all P<0.05). The abundance of Coprococcus A (0.76 (0.00, 3.11) vs. 0.00 (0.00, 0.00), false discovery rate ( FDR)<0.05) and Parasutterella (0.89 (0.08, 1.79) vs. 0.00 (0.00, 0.08), FDR<0.05) in the gut of children in the obese group were both higher than those of the control group. The number of virulence factor genes in the obese group was higher than those of the control group (941 (886, 977) vs. 890 (807, 920), P<0.05). The Simpson index and Shannon index of gut microbial virulence factor genes in the obese group were both higher than those of the control group (0.993 (0.992, 0.993) vs. 0.991(0.990, 0.991), (5.50 (5.46, 5.56) vs. 5.37 (5.30, 5.43), both P<0.01). The abundance of gut microbiota virulence factors genes all showed positive correlations with fasting blood glucose, ALT, γ-GT, and uric acid levels in children (all r>0.3, all FDR<0.05). The abundance of 17 gut microbial virulence factor genes were all positively associated with γ-GT levels (all r>0.3, all FDR<0.05). The virulence factor genes (LpxH, LpxB, LpxK) of lipopolysaccharide were all positively correlated with plasma γ-GT and globulin levels (all r>0.3, all FDR<0.05). Conclusions:Overweight or obese children exhibited elevated liver metabolic-inflammatory markers compared to their normal-weight counterparts. Notably, obese children demonstrated gut microbiota dysbiosis accompanied by enrichment of virulence factor genes, which may promote liver metabolic inflammation through pathways such as lipopolysaccharide biosynthesis.
2.Transplacental digoxin treatment for fetal supraventricular arrhythmias: Insights from Chinese fetuses.
Chuan WANG ; Li ZHAO ; Shuran SHAO ; Haiyan YU ; Shu ZHOU ; Yifei LI ; Qi ZHU ; Xiaoliang LIU ; Hongyu DUAN ; Hanmin LIU ; Yimin HUA ; Kaiyu ZHOU
Chinese Medical Journal 2025;138(12):1499-1501
3.Differential Characteristics of Human Airway Organoids at Different Stages of Differentiation After Respiratory Syncytial Virus Infection
Jiaxin LUO ; Wenhao YANG ; Yanan HU ; Danli LU ; Lina CHEN ; Hanmin LIU
Journal of Sichuan University (Medical Sciences) 2025;56(2):411-418
Objective To investigate the differences in pathological changes and immune responses of human airway organoids at different stages of differentiation following respiratory syncytial virus(RSV)infection.Methods Models of human fetal lung organoids(FLO)and induced airway organoids(iAO)were established to simulate immature and mature airway epithelium.Immunofluorescence staining,electron microscopy,and quantitative polymerase chain reaction(Q-PCR)were used to confirm the successful construction of the lung organoid models.Human lung organoids were infected with RSV,and samples were collected at 6 and 48 hours post-infection.The immune characteristics of immature and mature RSV-infected organoids were assessed using immunofluorescence staining,droplet digital PCR(DDPCR),and Q-PCR.Results We successfully generated FLO expressing both the progenitor markers sex determining region Y-box transcription factor 2(SOX2)and sex determining region Y-box transcription factor 9(SOX9),as well as iAO containing basal cells,ciliated cells,club cells,and goblet cells.In addition,organoid models of RSV infection were established.DDPCR results showed that,at the initial stage of RSV infection,the viral load in iAO was significantly higher than that in FLO(P<0.001).However,at 48 hours post-infection,the viral load in iAO was lower than that in FLO(P<0.05).Q-PCR results indicated that the expression of RSV infection receptor genes,including epidermal growth factor receptor(EGFR),insulin-like growth factor 1 receptor(IGF1R),and nucleolin(NCL),was significantly higher in iAO compared to that in FLO(P<0.001).RSV infection led to an increase in the expression levels of immune factors,including interleukin 6(ILL-6),interleukin 8(CXCL8),interferon α(IFN-α),granulocyte colony-stimulating factor(G-CSF),granulocyte-macrophage colony-stimulating factor(GM-CSF),and tumor necrosis factor α (TNF-α),in iAO compared to those in FLO,and the differences were statistically significant(P<0.05).Conclusion The expression of RSV infection receptor proteins increases with airway maturation,and mature airway epithelial cells exhibit a stronger immune response than immature ones do,effectively inhibiting RSV replication.
4.Composition of gut microbiota and characteristics of virulence factors genes in overweight or obese children and their relationship with liver metabolic inflammation
Jiyang JIANG ; Zhenxin FAN ; Fan YANG ; Hanmin LIU ; Meng MAO ; Ling FENG ; Fei XIONG ; Ping LI
Chinese Journal of Pediatrics 2025;63(6):642-648
Objective:To explore the composition of gut microbiome, the characteristics of virulence factor genes and their relationship with liver metabolic inflammation in overweight or obese children.Methods:A case-control design was conducted. From the children who visited the West China Second University Hospital of Sichuan University for medical or physical examinations between August 2021 and April 2022, a total of 23 obese children (obesity group), 8 overweight children (overweight group), and 22 healthy children (control group) were recruited. The body mass index of children was calculated after anthropometric measurements; metabolic inflammation indexes such as the levels of fasting blood glucose and hepatic function and renal function etc. were detected. The composition and abundance of gut microbiota in the feces of the children were detected by metagenomic sequencing technology and the Shannon index and Simpson index were calculated to assess the α diversity of virulence factor genes. The Wilcoxon rank-sum test was used for pairwise comparison between groups. The Spearman′s rank correlation test was used for correlation analysis, and the Benjamini-Hochberg method was used to correct the P-value of multiple tests. Results:The obese group included 23 children aged 8.5 (6.3, 11.8) years, of whom 9 (39%) were male. The overweight group consisted of 8 children aged 9.2 (5.5, 12.3) years, of whom 4 were male. The control group comprised 22 children aged 5.3 (5.1, 5.4) years, of whom 10 (45%) were male. The obese group exhibited higher levels of alanine aminotransferase (ALT), gamma-glutamyl transferase (γ-GT), globulin, and uric acid compared to those of the control group (all P<0.05), with ALT also higher than that of the overweight group ( P<0.05). The levels of fasting blood glucose, γ-GT, globulin, and uric acid in the overweight group were all higher than those in the control group (all P<0.05). The abundance of Coprococcus A (0.76 (0.00, 3.11) vs. 0.00 (0.00, 0.00), false discovery rate ( FDR)<0.05) and Parasutterella (0.89 (0.08, 1.79) vs. 0.00 (0.00, 0.08), FDR<0.05) in the gut of children in the obese group were both higher than those of the control group. The number of virulence factor genes in the obese group was higher than those of the control group (941 (886, 977) vs. 890 (807, 920), P<0.05). The Simpson index and Shannon index of gut microbial virulence factor genes in the obese group were both higher than those of the control group (0.993 (0.992, 0.993) vs. 0.991(0.990, 0.991), (5.50 (5.46, 5.56) vs. 5.37 (5.30, 5.43), both P<0.01). The abundance of gut microbiota virulence factors genes all showed positive correlations with fasting blood glucose, ALT, γ-GT, and uric acid levels in children (all r>0.3, all FDR<0.05). The abundance of 17 gut microbial virulence factor genes were all positively associated with γ-GT levels (all r>0.3, all FDR<0.05). The virulence factor genes (LpxH, LpxB, LpxK) of lipopolysaccharide were all positively correlated with plasma γ-GT and globulin levels (all r>0.3, all FDR<0.05). Conclusions:Overweight or obese children exhibited elevated liver metabolic-inflammatory markers compared to their normal-weight counterparts. Notably, obese children demonstrated gut microbiota dysbiosis accompanied by enrichment of virulence factor genes, which may promote liver metabolic inflammation through pathways such as lipopolysaccharide biosynthesis.
5.Construction and operation of the multi-level medical security system of the West China Women and Children Alliance
Jia LIU ; Tianyu JIANG ; Hanmin LIU ; Ying SHAN ; Shihao ZHANG ; Lianrui XIANG ; Yuanjie LIU
Chinese Journal of Hospital Administration 2024;40(1):12-16
Medical mutual aid is an important component of multi-level medical security system. West China Second University Hospital of Sichuan University led the establishment of the pediatric specialty alliance " West China Women and Children Alliance". Based on customized and inclusive mutual insurance product " Family Doctor Mutual Aid Plan", the alliance implemented key links such as mutual aid product forms, patient risk protection, institutional financing and hematopoiesis, and distribution of benefits to all parties, explored innovative mutual aid funding, payment, and incentive mechanisms, forming a closed-loop pediatric tiered diagnosis and treatment service system with the Mutual Aid Plan as the core. This system operated continuously under the " Four-in-One" framework, stimulating the integration of medical insurance and service supply systems while enhancing the synergistic effect between mutual insurance and social security. It has formed a distinctive health-centered multi-level medical security system within the alliance, and could provide reference for the construction and exploration of hierarchical diagnosis and treatment system.
6.Exosomal let-7a-5p derived from human umbilical cord mesenchymal stem cells alleviates coxsackievirus B3-induced cardiomyocyte ferroptosis via the SMAD2/ZFP36 signal axis
LI XIN ; HU YANAN ; WU YUETING ; YANG ZUOCHENG ; LIU YANG ; LIU HANMIN
Journal of Zhejiang University. Science. B 2024;25(5):422-437
Viral myocarditis(VMC)is one of the most common acquired heart diseases in children and teenagers.However,its pathogenesis is still unclear,and effective treatments are lacking.This study aimed to investigate the regulatory pathway by which exosomes alleviate ferroptosis in cardiomyocytes(CMCs)induced by coxsackievirus B3(CVB3).CVB3 was utilized for inducing the VMC mouse model and cellular model.Cardiac echocardiography,left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS)were implemented to assess the cardiac function.In CVB3-induced VMC mice,cardiac insufficiency was observed,as well as the altered levels of ferroptosis-related indicators(glutathione peroxidase 4(GPX4),glutathione(GSH),and malondialdehyde(MDA)).However,exosomes derived from human umbilical cord mesenchymal stem cells(hucMSCs-exo)could restore the changes caused by CVB3 stimulation.Let-7a-5p was enriched in hucMSCs-exo,and the inhibitory effect of hucMSCs-exolet-7a-5p mimic on CVB3-induced ferroptosis was higher than that of hucMSCs-exomimicNC(NC:negative control).Mothers against decapentaplegic homolog 2(SMAD2)increased in the VMC group,while the expression of zinc-finger protein 36(ZFP36)decreased.Let-7a-5p was confirmed to interact with SMAD2 messenger RNA(mRNA),and the SMAD2 protein interacted directly with the ZFP36 protein.Silencing SMAD2 and overexpressing ZFP36 inhibited the expression of ferroptosis-related indicators.Meanwhile,the levels of GPX4,solute carrier family 7,member 11(SLC7A11),and GSH were lower in the SMAD2 overexpression plasmid(oe-SMAD2)+let-7a-5p mimic group than in the oe-NC+let-7a-5p mimic group,while those of MDA,reactive oxygen species(ROS),and Fe2+increased.In conclusion,these data showed that ferroptosis could be regulated by mediating SMAD2 expression.Exo-let-7a-5p derived from hucMSCs could mediate SMAD2 to promote the expression of ZFP36,which further inhibited the ferroptosis of CMCs to alleviate CVB3-induced VMC.
7.Effect of cognitive style and temperament type on learning effect in flipped classroom of pediatrics
Yuxi DU ; Lina QIAO ; Yujiang YAN ; Xue YANG ; Hanmin LIU
Chinese Journal of Medical Education Research 2024;23(5):582-588
Objective:To investigate the performance of medical students with different cognitive styles and temperament types in the flipped classroom of pediatrics.Methods:A total of 85 medical students of the class of 2018 in eight-year program who studied the course of Pediatrics 2 in West China Medical School, Sichuan University, were selected and received the flipped classroom teaching of pediatrics. The cognitive style figure test was used to investigate the cognitive style of students, and the temperament self-test questionnaire was used to investigate the temperament type of students. The methods such as the cluster analysis, the ANOVA analysis of variance, the Pearson correlation analysis, and the chi-square test were used to describe the distribution of flipped classroom scores and related differences between the students with different cognitive styles and temperament types.Results:There were four temperament types of these students, i.e., choleric and sanguine temperament, sanguine and phlegmatic temperament, melancholic temperament, and choleric temperament, accounting for 28.24%, 23.53%, 27.06%, and 21.18%, respectively. There were two cognitive styles of field independence and field dependence, accounting for 51.76% and 48.24%, respectively. There was a significant difference in flipped classroom scores between the students with different cognitive styles ( t=3.18, P<0.05), while there was no significant difference in such scores between the students with different temperament types ( F=0.38, P>0.05). The correlation analysis showed that the score of phlegmatic temperament was significantly negatively correlated with flipped classroom scores ( r=-0.283, P<0.05), and the score of cognitive test was significantly positively correlated with flipped classroom scores ( r=0.346, P<0.05). Conclusions:In the flipped classroom teaching of pediatrics, it is necessary to flexibly apply specific interaction and evaluation methods in students with different temperament types and cognitive styles and grasp the relationship between cooperative learning and independent learning. The design of different links of flipped classroom should be further improved.
8.A multicenter study on respiratory pathogen detection with Mycoplasma pneumoniae pneumonia in children
Xiaoyan DONG ; Yingxue ZOU ; Fangfang LYU ; Wenhao YANG ; Hailin ZHANG ; Yanhua NIU ; Haojie WANG ; Run GUO ; Xu WANG ; Li LI ; Zihao LIN ; Li LUO ; Danli LU ; Quan LU ; Hanmin LIU ; Lina CHEN
Chinese Journal of Pediatrics 2024;62(4):310-316
Objective:To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods:A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15 th and December 20 th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results:A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ2=10.62, P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×10 9vs. 4.06 (2.91, 5.65)×10 9/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions:The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.
9.The role of Huaiqihuang Granules in the long-term management of bronchial asthma in young children: a multicenter real-world study
Huimin WANG ; Jinghui MU ; Chuanhe LIU ; Changshan LIU ; Ying WANG ; Zhiying HAN ; Xin SUN ; Xing CHEN ; Shuhua AN ; Dolikon MUZAPAR ; Aiping LU ; Min WANG ; Yan CHENG ; Xiaomei YIN ; Hanmin LIU ; Hong WANG ; Shan HUA ; Li DONG ; Ying HUANG ; Yi JIANG ; Jianxin XIONG ; Shenggang DING ; Wei WANG ; Shunying ZHAO ; Yuzhi CHEN
Chinese Journal of Applied Clinical Pediatrics 2023;38(4):286-290
Objective:To observe the role of Huaiqihuang Granules (HQ) in the long-term management of bronchial asthma in young children, and the effective effect on concomitant rhinitis.Methods:A prospective real-world multicenter study was conducted in children aged 2-5 years with asthma diagnosed in the outpatient department (from April 2016 to March 2019)who received either inhaled corticosteroid (ICS)/leukotriene receptor antagonist (LTRA)(control group); inhaled ICS/LTRA plus HQ(combination group), or HQ alone(HQ group). All patients were followed up at week 4, 8, 12 after treatment. The number of days with asthma symptoms, the frequency of severe asthma attacks, the level of asthma control, and the days with rhinitis symptoms in the last 4 weeks were recorded. Differences before and after treatment, and those among groups after treatment were compared using Kruskal- Wallis H test or Wilcoxon rank-sum test. Results:A total of 2 234 eligible patients were recruited, and 2 147 cases completed followed-up visits, including 477, 1 374 and 296 cases in the control group, combination group, and HQ group, respectively. After the treatment, all 3 groups showed significant declines in the days with asthma symptoms, frequency of severe asthma attack and the days with rhinitis symptoms (all P<0.01), and the rate of well-controlled asthma increased significantly ( P<0.01). It lasted until the end of follow-up. Among groups, patients in the combination group showed significantly less days of asthma symptoms than those of the other 2 group at week 8 and 12[0(0, 0.9) d vs.0(0, 0.3) d, P<0.05; 0(0, 0.1) d vs. 0(0, 1.0) d, P<0.01]. Patients in the combination group and HQ group showed a significantly lower rate of severe asthma attacks than that of the control group at week 12 [0(0, 1), 0(0, 1), 0(0, 2), all P<0.05]. The well-controlled rate of asthma in the combination group was significantly higher than that of the control group and HQ group at week 8 and 12 (89.6% vs. 85.9% vs.82.1%, H=15.28; 90.9% vs. 84.1% vs. 81.8%, χ2=29.32, all P<0.01). Conclusions:HQ can significantly alleviate symptoms of asthma and rhinitis, severe attack of asthma, and increase the control rate of asthma when used as an additional treatment or used alone.
10.Expert consensus on clinical application of pulse oximetry in children
Yuejie ZHENG ; Adong SHEN ; Baoping XU ; Hanmin LIU ; Xing CHEN ; Lili ZHONG ; Guangmin NONG ; Gen LU ; Shenggang DING ; Zhiying HAN ; Yun SUN ; Qiang CHEN ; Yi JIANG ; Xiaoping ZHU ; Suping TANG ; Xiufang WANG ; Yong YIN ; Shuhua AN ; Ju YIN ; Fengxia XUE ; Xiaoli LIU ; Miao LIU ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2022;37(23):1761-1772
Hypoxemia is a common complication of pneumonia, asthma, and bronchopulmonary dysplasia in children.Rapid identification of hypoxemia is of great significance for the disposal and management of critical children.Pulse oximetry is recognized by the World Health Organization as the best way to monitor hypoxemia in children, and it can monitor pulse oxygen saturation noninvasively and continuously.Based on the related literature at home and abroad, combined with the clinical needs of pediatrics, the " Expert consensus on clinical application of pulse oximetry in children" is formulated to improve the understanding of pediatricians and nurses on the application in pediatric clinical practice, principle, operation techniques, and limitations of pulse oximetry.

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