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Expression and clinical significance of plasma S100A8/A9 and sOX40L levels in children with primary immune thrombocytopenia
Author:Chen Yanyan Li Yali Liu Qingqing Chen Ling Jin Xin
keyword:Primary immune thrombocytopenia ; S100 calcium-binding protein A8/A9 ; Soluble Oxford 40 ligand ; Bleeding severity ; Prognosis ; Children
Objective To investigate the expression of plasma S100 calcium-binding protein A8/A9(S100A8/A9) and soluble OX40 ligand(sOX40L) in children with primary immune thrombocytopenia(ITP) and their relationship with bleeding severity and prognosis. Methods A total of 120 children with ITP(ITP group) and 60 healthy children(control group) admitted to Affiliated 3201 Hospital of Xi'an Jiaotong University School of Medicine from October 2021 to February 2024 were prospectively selected. Based on bleeding grade, ITP children were divided into non-bleeding subgroup(19 cases), minor bleeding subgroup(32 cases), mild bleeding subgroup(32 cases), moderate bleeding subgroup(26 cases), and severe bleeding subgroup(11 cases). According to 1-year prognosis, they were categorized into poor prognosis and good prognosis subgroups. Enzyme-linked immunosorbent assay was used to detect plasma S100A8/A9 and sOX40L levels. Multivariate Logistic regression and ROC analysis were employed to analyze the relationship between plasma S100A8/A9 and sOX40L levels and poor prognosis in children with ITP, and to evaluate predictive efficacy. Results Compared with the control group, plasma levels of S100A8/A9 and sOX40L in the ITP group were significantly increased(t/P=36.784/<0.001, 32.693/<0.001). Plasma S100A8/A9 and sOX40L levels progressively increased across the non-bleeding, minor bleeding, mild bleeding, moderate bleeding, and severe bleeding subgroups(F/P=265.204/<0.001, 344.140/<0.001). After 1 year of follow-up, the poor prognosis rate among 120 ITP children was 17.50%(21/120). Compared with the good prognosis subgroup, the poor prognosis subgroup showed higher bleeding grade, lower platelet count(PLT), lower absolute lymphocyte value, and higher S100A8/A9 and sOX40L levels(t/P=7.226/<0.001, 5.537/<0.001, 3.745/<0.001, 4.951/<0.001, 5.084/<0.001). Increased bleeding grade, high S100A8/A9, and high sOX40L were independent risk factors for poor prognosis in ITP children, while high platelet count was an independent protective factor [OR(95%CI)=3.952(1.062-14.703), 1.137(1.043-1.241), 1.557(1.158-2.093), 0.839(0.730-0.965)]. The area under the curve(AUC) of plasma S100A8/A9, sOX40L levels, and their combination for predicting poor prognosis in ITP children were 0.798, 0.817, and 0.897, respectively. The combined detection was superior to either marker alone(Z/P=2.478/0.013, 2.145/0.032). Conclusion Plasma levels of S100A8/A9 and sOX40L are elevated in children with ITP, correlating with increased bleeding severity and poorer prognosis. The combination of plasma S100A8/A9 and sOX40L levels demonstrates high predictive efficacy for prognosis.
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Lipid metabolite pathways in idiopathic pulmonary fibrosis: A Mendelian randomization and regulatory network analysis
Author:Wan Naihui Zhuang Yi Zhong Guanning Dai Jinghong
keyword:Idiopathic pulmonary fibrosis ; Lipid metabolites ; Regulatory proteins ; Mendelian randomization
Objective This study aimed to identify lipid metabolites associated with the risk of idiopathic pulmonary fibrosis(IPF) and investigate their upstream regulatory proteins. Methods Lipid metabolites were selected as candidates based on two published genome-wide association studies(GWAS) on metabolites along with the Lipid Maps, HMDB, and SwissLipids databases. The FinnGen cohort and UK Biobank cohort were used as the discovery cohort and replication cohort for IPF, respectively. Two-sample Mendelian randomization(MR) was utilized to assess the causal associations between lipid metabolites and IPF. Cochran's Q, MR-Egger, and colocalization analyses were performed to evaluate the robustness of the results. Overlapping proteins were screened by integrating IPF lung tissue proteomics data with transcriptomics data from the GEO dataset GSE70866. Subsequent MR was conducted to verify causal associations between candidate proteins and lipid metabolites. Results MR analysis identified two lipid metabolites significantly associated with IPF in the discovery cohort: 1-oleoyl-2-linoleoyl-sn-glycerol(18:1/18:2)(OR=0.659, P=0.041) and isobutyrylcarnitine(C4)(OR=1.165, P=0.025). Cochran's Q and MR-Egger excluded heterogeneity and pleiotropy(P>0.05), and the posterior probability of Bayesian colocalization PPH4 = 92.2%. Multi-omics analysis screened a total of 132 candidate regulatory proteins with GWAS data, including NT5E(OR=1.000, P=0.004), RNASET2(OR=1.000, P=0.013), MYL3(OR=0.998, P=0.003), SERPIND1(OR=0.999, P=0.035), PLG(OR=1.000, P=0.002), and CKAP4(OR=1.000, P=0.002). Conclusion A decreased level of 1-oleoyl-2-linoleoyl-sn-glycerol is associated with an elevated risk of IPF, and its level may be regulated by the following proteins: NT5E, RNASET2, MYL3, SERPIND1, PLG, CKAP4, and ITIH1.
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The ameliorative effects of interleukin-33 on repetitive stereotyped behaviors and social deficits in autism and its mechanisms
Author:Hu Limin Yang Jiahan Duan Lian Gao Yuan Li Lili
keyword:Autistic spectrum disorder ; Autophagy ; Interleukin-33 ; Repetitive stereotyped behaviors ; Social deficits ; Mechanism ; Mice
Objective To investigate the effects of IL-33 on social deficits and repetitive stereotyped behaviors in the BTBR T+Itpr3tf/J(BTBR) mouse model of autism. Methods The experiment will be conducted at the Children's Hospital Affiliated to Soochow University from January 2025 to June 2025. Ten 6-week-old male BTBR mice were selected and randomly divided into the BTBR+Vehicle group(n=5) and the BTBR+IL-33 group(n=5) according to the random number table method. Five C57BL/6(B6) mice were selected as the B6+Vehicle group. The BTBR+IL-33 group received daily intraperitoneal injections of IL-33(300 ng/mouse) for 7 consecutive days, while the B6+Vehicle and BTBR+Vehicle groups were administered an equivalent volume of saline. Following treatment, behavioral tests were conducted, including self-grooming, social interaction, three-chamber social test, and novel object recognition. After the behavioral experiments, brain tissue samples were collected. Dendrites were detected by Golgi staining, the pathological morphology of brain tissue was observed by transmission electron microscopy, and protein expression was detected by Western blot. Results The interaction time of mice in the B6+Vehicle group and the BTBR+IL-33 group was longer than that in the BTBR+Vehicle group(t=10.523,7.201, all P<0.001), and the self-grooming time was shorter than that in the BTBR+Vehicle group(t=4.750,14.114, all P<0.001). The TS1 of mice in the B6+Vehicle group and the BTBR+IL-33 group was greater than that of TOb(t=14.992,14.521, all P<0.001). The social preference index of mice in the B6+Vehicle group and the BTBR+IL-33 group was greater than that of mice in the BTBR+Vehicle group(t=10.570,10.48, all P<0.001). The social novelty preference index of mice in the B6+Vehicle group and the BTBR+IL-33 group was greater than that of mice in the BTBR+Vehicle group(t=16.768,14.162, all P<0.001). There was no statistically significant difference in the novel object recognition index between the B6+Vehicle group mice and the BTBR+Vehicle group mice, or between the BTBR+Vehicle group mice and the BTBR+IL-33 group mice(t=0.485,0.527, P=0.640,0.612). The dendritic spine density and dendrite complexity of mice in the BTBR+Vehicle group were both higher than those in the B6+Vehicle group and the BTBR+IL-33 group(t=2.944,2.734,P=0.021,0.032). The expression level of ULK1 in the brains of mice in the B6+Vehicle group and the BTBR+IL-33 group was higher than that in the BTBR+Vehicle group(t=3.324,3.687,P=0.011,0.007). The expression level of ATG12 in the B6+Vehicle group and the BTBR+IL-33 group was higher than that in the BTBR+Vehicle group(t=3.792,3.174,P=0.005,0.013). There was no difference in the expression levels of Beclin1, ATG5, and ATG16L1 between the BTBR+Vehicle group and the BTBR+IL-33 group(t=1.083,0.300,1.857,P=0.312,0.771,0.101).Conclusion IL-33 ameliorates repetitive stereotyped behaviors and social deficits in BTBR mice by upregulating ULK1 and ATG12 expression, thereby improving neuronal structure and function.
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Meta-analysis of the clinical efficacy and safety of traditional Chinese medicine compound for strengthening the spleen and eliminating dampness combined with Western medicine in the treatment of obese type 2 diabetes
Author:Xiong Wei Zhang Haoling Zhang Yan
keyword:Type 2 diabetes ; Obesity ; Strengthening the spleen and eliminating dampness ; Therapeutic effects ; Meta-analysis
Objective To systematically evaluate the clinical efficacy and safety of traditional Chinese medicine compound prescriptions for strengthening the spleen and eliminating dampness combined with Western medicine in the treatment of obese type 2 diabetes, and to provide evidence-based evidence for clinical application.Methods Databases such as China National Knowledge Infrastructure(CNKI), Wanfang, VIP, CBM, and PubMed were searched to include randomized controlled trials(RCTs) comparing the combination of traditional Chinese medicine compound prescriptions for strengthening the spleen and eliminating dampness with Western medicine(experimental group) versus Western medicine alone(control group) in the treatment of obese type 2 diabetes. The Cochrane Risk of Bias tool was used to assess the quality of the literature. Meta-analysis was performed using RevMan 5.4 software. Effect sizes included odds ratio(OR), mean difference(MD), and 95% confidence interval(CI). Heterogeneity and publication bias were analyzed.Results A total of 26 Chinese-language articles(2523 patients) were included. Meta-analysis showed that the clinical efficacy of the experimental group was significantly better than that of the control group(OR=4.87, 95%CI: 3.60-6.60, P<0.001). After treatment, the experimental group showed significantly lower levels of fasting plasma glucose(MD=-0.89, 95%CI:-1.18 to-0.60, P<0.001), 2-hour postprandial glucose(MD=-0.99, 95%CI:-1.45 to-0.52, P<0.001), total cholesterol(TC)(MD=-0.57, 95%CI:-0.75 to-0.38, P<0.001), triglycerides(TG)(MD=-0.33, 95%CI:-0.59 to-0.17, P<0.001), low-density lipoprotein cholesterol(LDL-C)(MD=-0.38, 95%CI:-0.52 to-0.24, P<0.001), body mass index(BMI)(MD=-1.15, 95%CI:-1.50 to-0.81, P<0.001), waist-to-hip ratio(WHR)(MD=-0.07, 95%CI:-0.12 to-0.01, P=0.03), and homeostasis model assessment of insulin resistance(HOMA-IR)(MD=-1.38, 95%CI:-1.65 to-1.11, P<0.001). The homeostasis model assessment of β-cell function(HOMA-β) was significantly higher in the experimental group than in the control group(MD=8.53, 95%CI: 2.47-14.57, P=0.006). In terms of safety, there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion The combination of traditional Chinese medicine compound prescriptions for strengthening the spleen and eliminating dampness with Western medicine is superior to Western medicine alone in improving clinical efficacy, glycolipid metabolism, obesity-related indicators, and pancreatic β-cell function in patients with obese type 2 diabetes, with good safety. Affected by the quality and heterogeneity of the included studies, more high-quality RCTs are needed for further verification.
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Clinical observation and literature review of 5 cases of Tropheryma whipplei pneumonia
Author:You Yong Huang Huxiang Cai Rongsong
keyword:Pneumonia ; Tropheryma whipplei ; Bronchoalveolar lavage fluid ; Metagenomic next-generation sequencing ; Diagnosis ; Treatment
The clinical data of five patients with Tropheryma whipplei pneumonia were reported and a literature review was conducted.