OBJECTIVE To systematically evaluate the effects of oral non-peptidic thrombopoietin receptor agonists （TPO-RAs） on hepatic enzyme in adult patients with immune thrombocytopenia. METHODS A comprehensive literature search was conducted in PubMed， Web of Science， CNKI， Wanfang database and the Chinese Medical Association Journal Full-Text Database to collect randomized controlled trials （RCTs） comparing oral non-peptidic TPO-RAs （intervention group） with placebo or conventional therapy （control group）. All databases were searched from their inception to June 2025. After literature screening， data extraction and quality assessment of the included studies， meta-analysis was conducted using RevMan 5.4.1 software. RESULTS Twelve RCTs comprising 1 388 patients were included， with 971 in the intervention group and 417 in the control group. Meta-analysis results showed that there were no significant differences between the two groups in terms of the incidence of hepatic enzyme elevation[OR＝1.24， 95%CI （0.77， 1.99）， P ＝0.37 ] ， the incidence of hepatic enzyme elevation in patients treated for ≥6 weeks[OR＝1.21， 95%CI （0.73， 1.99）， P ＝0.46 ] ， and the incidence of severe hepatic enzyme elevation[OR＝1.39， 95%CI（0.46， 4.20）， P ＝0.55 ] . Subgroup analysis showed that there were no significant differences in the incidence of hepatic enzyme elevation between the intervention group and control group among patients using eltrombopag[OR＝1.57，95%CI（0.85，2.87）， P ＝0.15 ] ， avatrombopag[OR＝0.88，95%CI （0.09，8.46）， P ＝0.91 ] ， and hetrombopag[OR＝1.04，95%CI（0.30，3.65）， P ＝0.95 ] ， respectively. CONCLUSIONS Oral non-peptidic TPO-RAs do not significantly increase the risk of hepatic enzyme elevation in adult patients with immune thrombocytopenia， and show an overall favorable hepatic safety profile.

Objective:To investigate the longitudinal relationship between self-esteem and hope of adolescents and to explore gender differences.Methods:A total of 1 982 adolescents,aged 11 to 24,participated in a l-year lon-gitudinal study with 3 waves of assessments(T1,baseline time;T2,6 months later;T3,1 year later).The Self-Es-teem Scale(SES)and the Children's Hope Scale(CHS)were used to measure levels of self-esteem and hope.The data were analyzed using a cross-lagged panel model and multi-group structural equation modeling.Results:Across the three measurement waves,the self-esteem scores were positively correlated with the hope scores(r=0.40-0.67).Results from the cross-lagged analysis indicated a bidirectional predictive relationship between the self-es-teem scores and hope scores over the year(β=0.09-0.22).The results of multi-group analysis showed significant gender differences in the autoregressive path of self-esteem in the three measures(Waldx2=3.78-3.84).Conclu-sion:Adolescents' self-esteem and hope exhibit a bidirectional predictive relationship,with no significant gender differences in the cross-lagged paths.

Objective:To investigate the longitudinal relationship between self-esteem and hope of adolescents and to explore gender differences.Methods:A total of 1 982 adolescents,aged 11 to 24,participated in a l-year lon-gitudinal study with 3 waves of assessments(T1,baseline time;T2,6 months later;T3,1 year later).The Self-Es-teem Scale(SES)and the Children's Hope Scale(CHS)were used to measure levels of self-esteem and hope.The data were analyzed using a cross-lagged panel model and multi-group structural equation modeling.Results:Across the three measurement waves,the self-esteem scores were positively correlated with the hope scores(r=0.40-0.67).Results from the cross-lagged analysis indicated a bidirectional predictive relationship between the self-es-teem scores and hope scores over the year(β=0.09-0.22).The results of multi-group analysis showed significant gender differences in the autoregressive path of self-esteem in the three measures(Waldx2=3.78-3.84).Conclu-sion:Adolescents' self-esteem and hope exhibit a bidirectional predictive relationship,with no significant gender differences in the cross-lagged paths.

Objective:To diagnose and explore the genetic etiology of a neonate with Hereditary epidermolysis bullosa.Methods:A neonate who was admitted to Suqian Hospital Affiliated to Xuzhou Medical University on July 10, 2021 was selected as the study subject. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. And target gene capture and next-generation sequencing were carried out. Candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:The child was found to harbor compound heterozygous variants of the COL17A1 gene, namely c. 997C>T (p.Q333X) and c. 3481dupT (p.Y1161fs*2), which were respectively inherited from his father and mother. Both variants were predicted to be pathogenic. Conclusion:The child was diagnosed with Generalized atrophic benign epidermolysis bullosa due to the compound heterozygous variants of the COL17A1 gene.

Blood brain barrier (BBB) injury is the main pathological manifestation of many neurological diseases. Glycocalyx is the gel layer covering the lumen side of vascular endothelial cells, which plays an important role in regulating BBB function. However, glycocalyx is very fragile and easily damaged in various neurological diseases, leading to BBB destruction. This article focuses on the potential role of glycocalyx in cerebrovascular disease, the possible mechanisms related to glycocalyx and BBB injury, and explores the potential therapeutic strategies for protecting and restoring endothelial glycocalyx.

Objective:To investigate T cell epitope spectrum of alpha fetoprotein (AFP) restricted by 13 dominant human leukocyte antigen A (HLA-A) molecules in Chinese population.Methods:AFP T cell epitope candidates presented by 13 HLA-A molecules were in silico predicted using multiple epitope prediction algorithms. Then, the candidate epitope peptides were co-cultured in vitro with fresh peripheral blood mononuclear cells (PBMCs) from hepatocellular carcinoma (HCC) patients, followed by intracellular cytokine staining (ICS) and flow cytometry to verify the immunogenicity of the candidate epitope peptides. Peptide competition binding assay of HLA-A molecules were performed using 12 HMy2.CIR cell lines expressing the indicated HLA-A molecules to analyze the affinity and cross-restriction of candidate epitope peptides with HLA-A molecules. Results:PBMCs from 67 AFP + HCC patients were co-cultured in vitro with 42 candidate T cell epitope peptides, and the result showed that 20 epitope peptides stimulated CD8 + T cell responses (named as positive epitope peptides). Peptide competitive binding assay revealed 22 candidate epitope peptides with high affinity, 13 with inter affinity, six with low affinity, and 10 without affinity with indicated HLA-A molecules, respectively. The 20 positive epitope peptides presented high or inter affinity with corresponding HLA-A molecules and most of them displayed cross-binding properties with several HLA-A molecules. Conclusions:Twenty AFP-specific CD8 + T cell epitope peptides restricted by the predominant HLA-A molecules in Chinese population are obtained by the HCC patients-derived T-cell functional experiments, and the cross-binding ability of these epitope peptides to the corresponding HLA-A molecules is preliminary identified. These results provide systematic and fundamental data for the design of AFP-specific T cell detection systems and T cell epitope-based vaccines universal for the Chinese population.

OBJECTIVE: To explore the genetic basis for a neonate affected with Glutaric aciduria type I (GA-I). METHODS: Targeted capture and high-throughput sequencing was carried out for the proband and her parents. Candidate variants were verified by Sanger sequencing. RESULTS: The proband was found to harbor compound heterozygous variants of the GCDH gene, namely c.523G>A and c.1190T>C, which was derived from her father and mother, respectively. CONCLUSION The compound heterozygous variants of the GCDH gene probably underlay the GA-I in the patient.
Amino Acid Metabolism, Inborn Errors/genetics* ; Brain Diseases, Metabolic/genetics* ; Child ; Female ; Glutaryl-CoA Dehydrogenase/genetics* ; High-Throughput Nucleotide Sequencing ; Humans ; Infant, Newborn ; Mutation

O'Sullivan-Mcleod syndrome is a very rare variant of MND with a good prognosis. Its clinical feature is distal lower motor neuron syndrome of both upper limbs, and there is no effective treatment at present. We reported a case of O'Sullivan-Mcleod syndrome in this paper.The patient exhibited with middle-aged progressive distal muscle weakness and atrophy of both upper limbs, without sensory, cognitive or behavioral impairment and without pyramidal tract sign. Laboratory examination, imaging and genetic tests showed no obvious abnormalities. EMG revealed neurogenic damage to the small muscles of both hands. Now we retrospectively analyzed the clinical features of a patient with O'Sullivan-McLeod syndrome, and data from 18 cases for comparative analysis, in order to improve its understanding by clinicians.

Objective To investigate the expression of S100A16 in pancreatic cancer and its clinical significance. Methods Immunohistochemical experiment was used to detect the expression of S100A16 protein in pancreatic cancer tissues and adjacent tissues, and we analyzed the relation between S100A16 positive expression and clinicopathological parameters, prognosis of pancreatic cancer patients. PPI was used to predict a protein relationship network that directly interacted with S100A16. Results The positive rate of S100A16 expression in cancer tissues was significantly higher than that in adjacent tissues (P=0.001). S100A16 expression was higher in patients with vascular infiltration and lymph node metastasis. The overall survival time of patients with pancreatic cancer was related to tumor size, TNM stage and S100A16 expression level. Multivariate analysis showed that the expression level of S100A16 was an independent risk factor for the prognosis of pancreatic cancer patients, and the risk of death in patients with high S100A16 expression increased by 1.5 times. PPI predicted that S100A16 and S100A14, IL36G, PITX1, PERP played an important role in the interaction network. Conclusion Pancreatic cancer patients with high S100A16 expression have poor prognosis. The positive expression of S100A16 is an independent prognostic indicator.

Objective:To investigate the effect of virtual-simulation laparoscopic training system in the training of basic skills of endoscopic surgery in trainees with different clinical experience.Method:s Eight refresher physicians, eight residents who received standardized residency training, and eight undergraduate interns in five-year clinical medicine were selected. All of them received the training of endoscopic operations with the laparoscopic training box and the virtual-simulation laparoscopic training system for 30 minutes every day for 4 weeks. Data analyses were performed using SPSS 19.0 and t-test was adopted to compare the scores before and after training among the three groups.Result:s Before training, there were significant differences in endoscopic operations between the undergraduate intern group and the other two groups ( P<0.05); after 4 weeks of training, all three groups had significant increases in the scores and spent less time on training items ( P<0.05). There was no significant difference in simple operations among the three groups ( P>0.05), and the undergraduate intern group had a significantly higher score of complex operations than did the standardized residency training group and the refresher physician group ( P<0.05). Conclusion:The virtual-simulation laparoscopic training system can improve the laparoscopic skills of clinical trainees at different levels, therefore, it is worth being promoted in the teaching of clinical skills.