OBJECTIVES: To investigate the expression levels of ghrelin and liver-expressed antimicrobial peptide-2 (LEAP-2) in children with idiopathic short stature (ISS) to provide reference for further understanding the etiology of short stature. METHODS: A prospective study was conducted from December 2021 to October 2023, involving 46 children diagnosed with ISS (ISS group) and 46 healthy children with normal height (control group) at the First Affiliated Hospital of Shihezi University. General data and serum levels of ghrelin and LEAP-2 were compared between the two groups. The predictive value of these two indicators for ISS was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: The serum level of ghrelin in the ISS group was higher than that in the control group, while the level of LEAP-2 was lower (P<0.05). The ratio of LEAP-2 to ghrelin was lower in the ISS group compared to the control group (P<0.05). Multivariate logistic regression analysis showed that HtSDS, IGF-1, ghrelin, LEAP-2, and the ratio of LEAP-2/ghrelin were independently associated with the occurrence of ISS (P<0.05). ROC curve analysis indicated that the AUCs for ghrelin, LEAP-2, the ratio of ghrelin to LEAP-2, and their combination in predicting ISS were all >0.8. The optimal cutoff values for ghrelin, LEAP-2, and the LEAP-2/ghrelin ratio were 5 607 pg/mL, 1 155 pg/mL, and 0.212, respectively. In children with ISS, ghrelin showed a negative correlation with chronological age, LEAP-2, and the LEAP-2/ghrelin ratio (P<0.05), while it was positively correlated with growth rate and peak growth hormone levels (P<0.05). LEAP-2 was negatively correlated with growth rate, peak growth hormone levels, and ghrelin (P<0.05), but positively correlated with chronological age and the LEAP-2/ghrelin ratio (P<0.05). CONCLUSIONS Ghrelin and LEAP-2 are correlated with the occurrence of ISS, which may provide references for the diagnosis and etiological analysis of children with ISS.
Humans ; Ghrelin/blood* ; Male ; Child ; Female ; Prospective Studies ; Child, Preschool ; Growth Disorders/etiology* ; Antimicrobial Cationic Peptides/blood* ; Body Height ; Adolescent ; Insulin-Like Growth Factor I/analysis* ; Blood Proteins

OBJECTIVE: To evaluate the predictive value of plasma heparin-binding protein (HBP) combined with albumin (Alb) for predicting 28-day mortality in patients with sepsis. METHODS: The clinical data of patients with sepsis admitted to the emergency intensive care unit (EICU) of the People's Hospital of Shenzhen Baoan District from March 2020 to March 2024 were retrospectively analyzed. The study began at the time of the first diagnosis of sepsis upon EICU admission and ended upon patient death or at 28 days. The gender, age, length of stay in EICU, underlying diseases, and infection sites were recorded. Within 24 hours of sepsis diagnosis, blood culture results, white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), blood lactate acid (Lac), HBP, Alb, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), mortality in emergency department sepsis score (MEDS), modified early warning score (MEWS), number of organ failures, use of vasopressors, application of mechanical ventilation, renal replacement therapy, and 28-day prognosis were recorded, the differences in these indicators between two groups were compared. Univariate and multivariate Logistic regression analyses were used to analyze the risk factors of 28-day mortality in patients with sepsis. Receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to evaluate the early predictive value of various risk factors for 28-day mortality in patients with sepsis. RESULTS: A total of 300 patients with sepsis were included, with 16 excluded, resulting in 284 patients being analyzed. Among them, 191 survived and 93 died within 28 days. There were no statistically significant differences between the two groups in terms of gender, age, underlying diseases, infection sites, blood culture positivity rate, number of organ failures, and length of stay in EICU. Univariate analysis showed that the rate of vasopressor use, the rate of mechanical ventilation, HBP, PCT, CRP, Lac, SOFA score, APACHE II score, MEDS score, and MEWS score were significantly higher in the death group than those in the survival group, while Alb was significantly lower in the death group than that in the survival group. Multivariate Logistic regression analysis showed that HBP and Alb were independent risk factors for predicting 28-day mortality in patients with sepsis [odds ratio (OR) and 95% confidence interval (95%CI) were 1.093 (0.989-1.128) and 1.174 (1.095-1.259), both P < 0.05]. ROC curve analysis showed that both HBP and Alb had certain predictive value for 28-day mortality in patients with sepsis [AUC and 95%CI were 0.820 (0.717-0.923) and 0.786 (0.682-0.890), both P < 0.05]. When the critical value of HBP was 117.50 μg/L, the sensitivity was 85.90%, and the specificity was 70.50%. When the critical value of Alb was 28.30 g/L, the sensitivity was 69.30%, and the specificity was 81.20%. When the two indexes were combined for diagnosis, the AUC was 0.881 (95%CI was 0.817-0.945, P < 0.001), the sensitivity was 92.70%, and the specificity was 76.80%. CONCLUSIONS HBP and Alb are independent risk factors for predicting 28-day mortality in patients with sepsis. The combined prediction efficiency of HBP and Alb for 28-day mortality in patients with sepsis is superior to a single indicator.
Humans ; Sepsis/diagnosis* ; Retrospective Studies ; Predictive Value of Tests ; Intensive Care Units ; Blood Proteins/analysis* ; Prognosis ; Antimicrobial Cationic Peptides/blood* ; APACHE ; Male ; Female ; Organ Dysfunction Scores ; ROC Curve ; Middle Aged ; C-Reactive Protein/analysis* ; Emergency Service, Hospital ; Aged ; Hospital Mortality ; Serum Albumin/analysis*

Data-independent acquisition (DIA) is a high-throughput, unbiased mass spectrometry data acquisition method which has good quantitative reproducibility and is friendly to low-abundance proteins. It becomes the preferred choice for clinical proteomic studies especially for large cohort studies in recent years. The mass-spectrometry (MS)/MS spectra generated by DIA is usually heavily mixed with fragment ion information of multiple peptides, which makes the protein identification and quantification more difficult. Currently, DIA data analysis methods fall into two main categories, namely peptide-centric and spectrum-centric. The peptide-centric strategy is more sensitive for identification and more accurate for quantification. Thus, it has become the mainstream strategy for DIA data analysis, which includes four key steps: building a spectral library, extracting ion chromatogram, feature scoring and statistical quality control. This work reviews the peptide-centric DIA data analysis procedure, introduces the corresponding algorithms and software tools, and summarizes the improvements for the existing algorithms. Finally, the future development directions are discussed.
Humans ; Proteomics/methods* ; Reproducibility of Results ; Peptides/chemistry* ; Software ; Algorithms ; Tandem Mass Spectrometry/methods* ; Proteome/analysis*

OBJECTIVES: To study the value of heparin-binding protein (HBP) in the diagnosis of severe infection in children. METHODS: This study was a prospective observational study. The medical data of children who were admitted to the pediatric intensive care unit due to infection from January 2019 to January 2020 were collected. According to the diagnostic criteria for severe sepsis and sepsis, the children were divided into a severe sepsis group with 49 children, a sepsis group with 82 children, and a non-severe infection group with 33 children. The three groups were compared in terms of related biomarkers such as plasma HBP, serum C-reactive protein, serum procalcitonin, and platelet count. The receiver operating characteristic (ROC) curve was plotted to investigate the value of plasma HBP level in the diagnosis of severe infection (including severe sepsis and sepsis). RESULTS: The severe sepsis and sepsis groups had a significantly higher plasma HBP level on admission than the non-severe infection group (P<0.05). Compared with the sepsis and non-severe groups, the severe sepsis group had significantly higher serum levels of C-reactive protein and procalcitonin and a significantly lower platelet count (P<0.05). Plasma HBP level had an area under the ROC curve of 0.590 in determining severe infection, with a sensitivity of 38.0% and a specificity of 82.4% (P<0.05). CONCLUSIONS There is an increase in plasma HBP level in children with severe infection, and plasma HBP level has a lower sensitivity but a higher specificity in the diagnosis of severe infection and can thus be used as one of the markers for the judgment of severe infection in children.
Antimicrobial Cationic Peptides ; Biomarkers ; Blood Proteins ; C-Reactive Protein/analysis* ; Child ; Humans ; Procalcitonin ; Prospective Studies ; ROC Curve ; Sepsis/diagnosis*

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/β-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.
Adult ; Aged ; Animals ; Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition/genetics* ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism* ; Kinesins/metabolism* ; Liver Neoplasms/pathology* ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Neoplasm Staging ; Prognosis ; Protein Binding ; RNA, Small Interfering/metabolism* ; Survival Analysis ; Tumor Burden ; Wnt Signaling Pathway ; Xenograft Model Antitumor Assays ; beta Catenin/metabolism*

Objective: To analyze the clinical manifestations of a patient with branchiootic syndrome(BOS) and her families and to carry out genetic testing in order to specify the biological pathogenesis. Methods: Clinical data of the patient and her families were collected. Genomic DNA in the peripheral blood of the proband and her family members was extracted. All exons of 406 deafness-related susceptible genes as well as their flanking regions were sequenced by high-throughput sequencing, and the mutation sites of the proband and her parents were validated by Sanger sequencing. Results: There were nine members in three generations, of whom four presented with hearing loss, preauricular fistula and branchial fistula which met the diagnostic criteria of BOS. Proband and her mother presented with auricle malformation and inner ear malformation. And no one had abnormalities in the kidneys of all the patients. Pedigree analysis revealed that the mode of inheritance in the family was consistent with the autosomal dominant pattern. Mutational analysis showed that all the affected patients detected a heterozygous frameshift variation c.1255delT in the EYA1 gene, which had not been reported. Genotype and phenotype were co-isolated in this family. Such a frameshift variation produced a premature termination codon, thereby causing premature termination of translation (p.C419VFS*12). ACMG identified that the mutation was pathogenic. This mutation was novel and not detected in controls. A heterozygous missense variation mutation c.403G>A(p.G135S) in EYA1 gene was also detected in three members of this family. ACMG identified that the mutation clinical significance was uncertain. However, two of whom were normal, which seemed the disease was not caused by this mutation in this family. Conclusions: A novel frameshift mutation in EYA1(c.1255delT) is the main molecular etiology of BOS in the Chinese family. This study expands the mutational spectrum of EYA1 gene. The clinical manifestations are heterogeneous among patients in this family. The diagnosis of BOS should combine gene tests with clinical phenotypes analysis.
Branchio-Oto-Renal Syndrome/genetics* ; DNA Mutational Analysis ; Female ; Genetic Testing ; Humans ; Intracellular Signaling Peptides and Proteins/genetics* ; Mutation ; Nuclear Proteins ; Pedigree ; Protein Tyrosine Phosphatases/genetics*

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia characterized by progressive accumulation of fibroblastic foci and destruction of the alveolar structure. Due to an incomplete understanding of the mechanism of the occurrence and progression of IPF, currently no effective means have been available for its early screening or treatment. With a poor overall prognosis, the patients with IPF have a median survival of only 2-4 years. In recent years, several studies have confirmed that dozens of molecules are involved in the development of IPF and can be used as potential biomarkers. These biomarkers play important roles in early diagnosis (such as SP-D, MMP-7, and osteopontin), prognostic evaluation (such as telomerase length, KL-6, mtDNA, HSP-70, LOXL2, CXCL13, miRNA, ICAM-1, and CCL18), and guiding treatment of IPF (such as TOLLIP rs3750920 genotype, SAMS score, and SP-D), and also provide potential therapeutic targets (such as TERT, TERR, RTEC, and PARN).
Amino Acid Oxidoreductases ; metabolism ; Biomarkers ; analysis ; Disease Progression ; Humans ; Idiopathic Pulmonary Fibrosis ; diagnosis ; therapy ; Intracellular Signaling Peptides and Proteins ; metabolism ; Prognosis

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in cancer development and progression. However, the mechanism by which they enhance the chemoresistance of ovarian cancer is unknown. METHODS: Conditioned media of BM-MSCs (BM-MSC-CM) were analyzed using a technique based on microRNA arrays. The most highly expressed microRNAs were selected for testing their effects on glycolysis and chemoresistance in SKOV3 and COC1 ovarian cancer cells. The targeted gene and related signaling pathway were investigated using in silico analysis and in vitro cancer cell models. Kaplan-Merier survival analysis was performed on a population of 59 patients enrolled to analyze the clinical significance of microRNA findings in the prognosis of ovarian cancer. RESULTS: MiR-1180 was the most abundant microRNA detected in BM-MSC-CM, which simultaneously induces glycolysis and chemoresistance (against cisplatin) in ovarian cancer cells. The secreted frizzled-related protein 1 (SFRP1) gene was identified as a major target of miR-1180. The overexpression of miR-1180 led to the activation of Wnt signaling and its downstream components, namely Wnt5a, β-catenin, c-Myc, and CyclinD1, which are responsible for glycolysis-induced chemoresistance. The miR-1180 level was inversely correlated with SFRP1 mRNA expression in ovarian cancer tissue. The overexpressed miR-1180 was associated with a poor prognosis for the long-term (96-month) survival of ovarian cancer patients. CONCLUSIONS BM-MSCs enhance the chemoresistance of ovarian cancer by releasing miR-1180. The released miR-1180 activates the Wnt signaling pathway in cancer cells by targeting SFRP1. The enhanced Wnt signaling upregulates the glycolytic level (i.e. Warburg effect), which reinforces the chemoresistance property of ovarian cancer cells.
Adenosine Triphosphate/chemistry* ; Adult ; Aged ; Bone Marrow Cells/cytology* ; Cell Line, Tumor ; Cell Proliferation ; Cells, Cultured ; Drug Resistance, Neoplasm/genetics* ; Female ; Flow Cytometry ; Follow-Up Studies ; Glycolysis ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism* ; Membrane Proteins/metabolism* ; Mesenchymal Stem Cells/cytology* ; MicroRNAs/genetics* ; Middle Aged ; Multivariate Analysis ; Ovarian Neoplasms/genetics* ; Up-Regulation ; Wnt Signaling Pathway

OBJECTIVE: To explore the predictive value of heparin-binding protein (HBP) combined with sequential organ failure assessment (SOFA) score in patients with septic shock. METHODS: Seventy-eight patients with sepsis admitted to intensive care unit (ICU) of Henan Provincial People's Hospital from December 2016 to May 2017 were enrolled. Thirty healthy persons were enrolled as controls. The patient's gender, age, length of ICU stay, and blood culture results, white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), blood lactate (Lac), HBP, SOFA score, acute physiology and chronic health evaluation II (APACHE II) score, organ failure and vasoactive agents usage within 24 hours of admission were recorded. The differences in the above indicators between the groups were compared, and the receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of HBP, SOFA score and their combination in patients with septic shock. RESULTS: All patients were enrolled in the final analysis, including 64 with sepsis and 14 with septic shock. Compared with the sepsis group, the proportion of patients with septic shock who were positive for blood culture, organ failure, and vasoactive agents was higher [57.1% (8/14) vs. 7.8% (5/64), 100.0% (14/14) vs. 65.6% (42/64), 100.0% (14/14) vs. 18.8% (12/64), all P < 0.01], SOFA and APACHE II scores were also higher (SOFA: 8.93±4.16 vs. 5.89±2.68, APACHE II: 22.29±4.89 vs. 15.28±5.14, both P < 0.01); however, there was no significant difference in gender, age or length of ICU stay between the two groups. Compared with the healthy control group, HBP, PCT, CRP and Lac levels were significantly increased in the sepsis group and the septic shock group. HBP in the septic shock group was significantly higher than that in the sepsis group (μg/L: 120.33±43.49 vs. 68.95±54.15, P < 0.05), but there was no significant difference in PCT, CRP or Lac between septic shock group and sepsis group [PCT (μg/L): 1.42 (0.47, 46.00) vs. 0.71 (0.19, 4.50), CRP (mg/L): 102.90±78.12 vs. 102.07±72.15, Lac (mmol/L): 1.81 (1.14, 3.65) vs. 1.59 (1.17, 2.24), all P > 0.05]. It was shown by ROC curve analysis that the area under the ROC curve (AUC) of SOFA score for predicting septic shock was 0.715 [95% confidence interval (95%CI) = 0.540-0.890, P = 0.012], and when the optimal cut-off value was 7.5, the sensitivity was 64.3%, the specificity was 76.6%. The AUC of HBP was 0.814 (95%CI = 0.714-0.913, P < 0.001), and when the optimal cut-off value was 89.43 μg/L, the sensitivity was 78.6%, the specificity was 76.6%; when the two were combined, the AUC was 0.829 (95%CI = 0.724-0.935, P < 0.001), the sensitivity was 92.9%, and the specificity was 61.9%. CONCLUSIONS HBP can be used as a biological indicator for predicting septic shock, and the accuracy of predicting septic shock can be improved with the combination of SOFA score.
Antimicrobial Cationic Peptides/analysis* ; Blood Proteins/analysis* ; Carrier Proteins/analysis* ; Female ; Humans ; Male ; Organ Dysfunction Scores ; Predictive Value of Tests ; Shock, Septic/diagnosis*

The acquisition of somatic mutations is the most common event in cancer. Neoantigens expressed from genes with mutations acquired during carcinogenesis can be tumor-specific. Since the immune system recognizes tumor-specific peptides, they are potential targets for personalized neoantigen-based immunotherapy. However, the discovery of druggable neoantigens remains challenging, suggesting that a deeper understanding of the mechanism of neoantigen generation and better strategies to identify them will be required to realize the promise of neoantigen-based immunotherapy. Alternative splicing and RNA editing events are emerging mechanisms leading to neoantigen production. In this review, we outline recent work involving the large-scale screening of neoantigens produced by alternative splicing and RNA editing. We also describe strategies to predict and validate neoantigens from RNA sequencing data.
Alternative Splicing ; Carcinogenesis ; Humans ; Immune System ; Immunotherapy ; Mass Screening ; Peptides ; RNA Editing ; RNA ; Sequence Analysis, RNA