Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult

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*

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*

OBJECTIVE: To screen potential plasma protein biomarkers for the progression of cervical precancerous lesions into cervical carcinoma and analyze their functions. METHODS: Plasma samples obtained from healthy control subjects, patients with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC), and patients with CC after treatment were enriched for low-abundance proteins for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS data of the samples were analyzed using Discoverer 2.2 software, and the differential proteins (peptide coverage ≥20%, unique peptides≥2) were screened by comparison of LSIL, HSIL and CC groups against the control group followed by verification using target proteomics technology. Protein function enrichment and coexpression analyses were carried out to explore the role of the differentially expressed proteins as potential biomarkers and their pathological mechanisms. RESULTS: Compared with the control group, both LSIL group and HSIL group showed 9 differential proteins; 5 differentially expressed proteins were identified in CC group. The proteins ORM2 and HPR showed obvious differential expressions in LSIL and HSIL groups compared with the control group, and could serve as potential biomarkers for the progression of cervical carcinoma. The expression of F9 increased consistently with the lesion progression from LSIL to HSIL and CC, suggesting its value as a potential biomarker for the progression of cervical cancer. CFI and AFM protein levels were obviously decreased in treated patients with CC compared with the patients before treatment, indicating their predictive value for the therapeutic efficacy. Protein function enrichment analysis showed that all these differentially expressed proteins were associated with the complement system and the coagulation cascades pathway. CONCLUSIONS We identified 5 new protein biomarkers (F9, CFI, AFM, HPR, and ORM2) for cervical precancerous lesions and for prognostic evaluation of CC, and combined detection of these biomarkers may help in the evaluation of the development and progression of CC and also in improving the diagnostic sensitivity and specificity of cervical lesions.
Antigens, Neoplasm ; blood ; Biomarkers, Tumor ; blood ; Carrier Proteins ; blood ; Case-Control Studies ; Cervical Intraepithelial Neoplasia ; blood ; diagnosis ; Chromatography, Liquid ; Complement Factor I ; analysis ; Early Detection of Cancer ; Female ; Glycoproteins ; blood ; Haptoglobins ; Humans ; Neoplasm Proteins ; blood ; Orosomucoid ; analysis ; Precancerous Conditions ; blood ; diagnosis ; Serum Albumin, Human ; Tandem Mass Spectrometry ; Uterine Cervical Neoplasms ; blood ; diagnosis

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*

BACKGROUND: Carotid artery intima medial thickness (IMT), brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI) are commonly used surrogate markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The cardio-ankle vascular index (CAVI) is a complement to the baPWV, which is affected by blood pressure. However, it is unclear which marker is the most sensitive predictor of atherosclerotic cardiovascular disease (ASCVD). METHODS: This was a retrospective non-interventional study that enrolled 219 patients with T2DM. The correlations among IMT, ABI, and CAVI as well as the relationship of these tests to the 10-year ASCVD risk were also analyzed. RESULTS: Among the 219 patients, 39 (17.8%) had ASCVD. In the non-ASCVD group, CAVI correlated significantly with IMT after adjusting for confounding variables, but ABI was not associated with CAVI or IMT. The analyses after dividing the non-ASCVD group into three subgroups according to the CAVI score ( < 8, ≥8 and < 9, and ≥9) demonstrated the significant increase in the mean IMT, 10-year ASCVD risk and number of metabolic syndrome risk factors, and decrease in the mean ABI in the high-CAVI group. A high CAVI was an independent risk factor in the non-ASCVD group for both a high 10-year ASCVD risk (≥7.5%; odds ratio [OR], 2.42; P < 0.001) and atherosclerosis (mean IMT ≥1 mm; OR, 1.53; P=0.007). CONCLUSION: In Korean patients with T2DM without ASCVD, CAVI was the most sensitive of several surrogate markers for the detection of subclinical atherosclerosis.
Ankle Brachial Index ; Atherosclerosis ; Biomarkers* ; Blood Pressure ; Cardiovascular Diseases* ; Carotid Arteries ; Complement System Proteins ; Confounding Factors (Epidemiology) ; Diabetes Mellitus, Type 2* ; Humans ; Korea ; Odds Ratio ; Pulse Wave Analysis ; Retrospective Studies ; Risk Factors

OBJECTIVES: To investigate the role of autophagy inhibitor chloroquine (CQ) in acute ethanol-induced liver injury and its mechenism. METHODS: Twenty-one C57BL/6 male mice were randomly divided into three groups:control group, ethanol group, CQ + ethanol group (=7). Mice in ethanol group were administered 33% (v/v) ethanol at a dose of 4.5 g/kg body weight. Ethanol-induced liver steatosis in each group was detected by hematoxylin and eosin staining. Hepatic lipid accumulation was detected by staining with Oil red O. Hepatic tissue triglyceride (TG) levels, serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) were determined by biochemical assays. Protein expression of microtubule-associated protein 1 light chain 3(LC3) and nuclear factorκB p65(NF-κB p65) were measured by Western blot and immunofluorescence. Pro-inflammatory factors tumor necrosis factor-α(TNF-α)、interleukin 6(IL-6) were detected by ELISA. RESULTS: Compared with control group, ethanol induced liver injury proved by accumulation of hepatic lipids, TG levels, AST and ALT activities were significantly increased by ethanol, protein expression of LC3-Ⅱ was also markedly increased by ethanol. Compared with ethanol group, addition of CQ increased furtherthe level of LC3-Ⅱexpression, and TG amount, serum AST and ALT activities, and the expression of NF-κB p65, TNF-αand IL-6. CONCLUSIONS Acute ethanol-intake could induce liver steatosis and inflammation, and autophagy inhibitor CQ exacerbatedethanol-induced liver injury, suggested that autophagy might be protective effect in acute ethanol-induced liver disease.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Autophagy ; drug effects ; Chloroquine ; pharmacology ; Interleukin-6 ; analysis ; Liver ; drug effects ; Liver Diseases, Alcoholic ; drug therapy ; Male ; Mice ; Mice, Inbred C57BL ; Microtubule-Associated Proteins ; metabolism ; Random Allocation ; Transcription Factor RelA ; metabolism ; Triglycerides ; analysis ; Tumor Necrosis Factor-alpha ; analysis

OBJECTIVE: To investigate the effect of Health Qigong Baduanjin on the related indexes of obese middle aged women with diabetes and to provide new ideas for the intervention treatment of diabetes. METHODS: A total of 40 middle-aged female obese diabetic patients were randomly divided into the control group and the exercise group(=20), the age was(57.2±5.4) years old. Fitness training group performed eight new Baduanjin exercises for 24 weeks of intervention, the control group did not exercise, body weight, waist circumference, body mass index (BMI), waist hip ratio (WHR), fasting blood glucose (FPG), glycosylated hemoglobin (HbAlc), triglyceride(TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) levels and serum retinol binding protein 4(RBP4) index were observed in the two groups. RESULTS: After exercise, the waist, WHR, FPG, TG, HbAlc, HDL and RBP4 levels of the the patients in the experimental group were decreased significantly compared with those of before exercise and those of the patients in the experimental control group before and after exercise (<0.05). CONCLUSIONS Health Qigong Baduanjin can reduce the blood sugar of obese female patients with diabetes, and has some improvement effect on the body part of obesity and blood lipid indicators.
Blood Glucose ; analysis ; Body Mass Index ; Diabetes Mellitus ; therapy ; Female ; Hemoglobins ; analysis ; Humans ; Lipids ; blood ; Middle Aged ; Obesity ; complications ; therapy ; Qigong ; Retinol-Binding Proteins, Plasma ; analysis ; Waist Circumference ; Waist-Hip Ratio

Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catalpol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.
Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; genetics ; metabolism ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; Gene Expression ; drug effects ; Glucosephosphate Dehydrogenase ; genetics ; metabolism ; Humans ; Hypoglycemic Agents ; administration & dosage ; Insulin ; metabolism ; Insulin Receptor Substrate Proteins ; genetics ; metabolism ; Iridoid Glucosides ; administration & dosage ; analysis ; Isocitrate Dehydrogenase ; genetics ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Rehmannia ; chemistry ; Suppressor of Cytokine Signaling 3 Protein ; genetics ; metabolism