OBJECTIVE: To identify and validate novel biomarkers for the early diagnosis of sepsis-associated acute kidney injury (SA-AKI) and precise continuous renal replacement therapy (CRRT) using proteomics. METHODS: A prospective multicenter cohort study was conducted. Patients with sepsis admitted to five hospitals in Taizhou City of Zhejiang Province from April 2019 to December 2021 were continuously enrolled, based on the occurrence of acute kidney injury (AKI). Sepsis patients were divided into SA-AKI group and non-SA-AKI group, and healthy individuals who underwent physical examinations during the same period were used as control (NC group). Peripheral blood samples from participants were collected for protein mass spectrometry analysis. Differentially expressed proteins were identified, and functional enrichment analysis was conducted on these proteins. The levels of target proteins were detected by enzyme linked immunosorbent assay (ELISA), and the predictive value of target protein for SA-AKI were evaluated by receiver operator characteristic curve (ROC curve). Additionally, sepsis patients and healthy individuals were selected from one hospital to externally verify the expression level of the target protein and its predictive value for SA-AKI, as well as the accuracy of CRRT treatment. RESULTS: A total of 37 patients with sepsis (including 19 with AKI and 18 without AKI) and 31 healthy individuals were enrolled for proteomic analysis. Seven proteins were identified with significantly differential expression between the SA-AKI group and non-SA-AKI group: namely cystatin C (CST3), β ₂-microglobulin (β ₂M), insulin-like growth factor-binding protein 4 (IGFBP4), complement factor I (CFI), complement factor D (CFD), CD59, and glycoprotein prostaglandin D2 synthase (PTGDS). Functional enrichment analysis revealed that these proteins were involved in immune response, complement activation, coagulation cascade, and neutrophil degranulation. ELISA results demonstrated specific expression of each target protein in the SA-AKI group. Additionally, 65 patients with sepsis (38 with AKI and 27 without AKI) and 20 healthy individuals were selected for external validation of the 7 target proteins. ELISA results showed that there were statistically significant differences in the expression levels of CST3, β ₂M, IGFBP4, CFD, and CD59 between the SA-AKI group and non-SA-AKI group. ROC curve analysis indicated that the area under the curve (AUC) values of CST3, β ₂M, IGFBP4, CFD, and CD59 for predicting SA-AKI were 0.788, 0.723, 0.723, 0.795, and 0.836, respectively, all exceeding 0.7. Further analysis of patients who underwent CRRT or not revealed that IGFBP4 had a good predictive value, with an AUC of 0.84. CONCLUSIONS Based on proteomic analysis, CST3, β ₂M, IGFBP4, CFD, and CD59 may serve as potential biomarkers for the diagnosis of SA-AKI, among which IGFBP4 might be a potential biomarker for predicting the need for CRRT in SA-AKI patients. However, further clinical validation is required.
Humans ; Sepsis/complications* ; Acute Kidney Injury/blood* ; Proteomics ; Prospective Studies ; Biomarkers/blood* ; Male ; Female ; beta 2-Microglobulin/blood* ; Middle Aged ; Cystatin C/blood* ; Aged

OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:Based on bioinformatics analysis, this study aimed to identify the complement component 5a receptor 1(C5aR1)and chemokine C-C motif ligand-2(CCL2)genes in vascular dementia(VaD)and to explore the expression and clinical significance of serum C5aR1 and CCL2 levels in VaD patients.Methods:The GSE122063 dataset was selected from the Gene Expression Omnibus(GEO)database to screen for consistently differentially expressed genes in the frontal and temporal lobes of VaD patients and non-dementia patients.The Matascape database was used to analyze the functions and pathways of differentially expressed genes, and the STRING network and Cytoscape software were used to identify key genes.In this case-control study, 53 VaD patients seeking care at the Department of Neurology of the Affiliated Hospital of Jiangsu University between January 2022 and December 2022 were included in the VaD group, and 50 non-dementia individuals were included in the control group.General information, Montreal Cognitive Assessment(MoCA)scores, Mini-Mental State Examination(MMSE)scores, and scores of the total cerebral small vessel disease(CSVD)burden were collected for both groups, and serum C5aR1 and CCL2 expression was detected.The correlation of serum C5aR1 and CCL2 levels with MoCA scores, MMSE scores, and scores of the total CSVD burden in the VaD group was analyzed.Receiver operating characteristic(ROC)curve analysis was used to assess the diagnostic value of serum C5aR1 and CCL2 levels in VaD.Results:In the GSE122063 dataset, compared with non-dementia patients, there were 43 upregulated genes and 63 downregulated genes simultaneously in the frontal and temporal lobes in the VaD group.After importing 106 genes into the Cytoscape software and using the Stress and Betweenness algorithms in the cytoHubba plugin, two key genes, C5aR1 and CCL2, were identified.Serum levels of C5aR1[(57.25±10.34)μg/L vs.(43.26±8.24)μg/L, t=7.607, P<0.001]and CCL2[(210.42±42.19)ng/L vs.(151.73±36.04)ng/L, t=7.570, P<0.001]in the VaD group were higher than those in the control group.Serum levels of C5aR1 and CCL2 were negatively correlated with MoCA scores( r=-0.691, -0.668, P<0.001)and MMSE scores( r=-0.736, -0.729, P<0.001), and positively correlated with scores of the total CSVD burden( r=0.598, 0.582, P<0.001).The areas under the ROC curve for serum C5aR1 and CCL2 levels in diagnosing VaD was 0.838 and 0.845, respectively.The area under the ROC curve with the combination of C5aR1 and CCL2 for the diagnosis of VaD was 0.896. Conclusions:Serum levels of C5aR1 and CCL2 are elevated in VaD patients and closely related to their cognitive function and the total CSVD burden, and may be used as an auxiliary diagnostic tool for VaD patients.

Objective To investigate the prevalence of specific IgE antibodies against Alternaria alternata and Aspergillus fumigatus in serum samples from clinical allergy patients across selected provinces in China.Methods Data on specific IgE antibodies for Alternaria A.and Aspergillus F.were collected from 20 hospital laboratories in 17 cities spanning 11 provinces.The study analyzed the levels of specific IgE and their variations across different provinces and seasons.Results A total of 27 471 cases of Alternaria A.and 32 843 cases of Aspergillus F.specific IgE data were included.The national average positive rate of Alternaria A.IgE was 10.40%,with the highest rate of 22.68%in Jiangsu and the lowest rate of 2.06%in Guangxi.For Aspergillus F.specific IgE,the average positive rate was 4.24%,with Hubei province having the highest rate(7.25%)and Hunan province the lowest(1.23%).The difference in IgE levels for both Alternaria A.and Aspergillus F.among provinces were statistically significant(H=9 955,16 993,all P<0.0001).Among patients,5.85%had Alternaria A.specific IgE levels at grade 3 or above,while only 0.57%had Aspergillus F.specific IgE levels at this level.When examining seasonal variations using data from Liaoning,Hunan and Anhui provinces,significant seasonal changes were observed for both Alternaria A.and Aspergillus F.IgE antibodies(HAlternaria A=347.6,338.0,401.3,HAspergillus F=196.6,133.7,231.7,all P<0.0001).Conclusion The sensitization to Alternaria A.and Aspergillus F.exhibits distinct geographical characteristics and vary significantly with seasons.Given the relatively high IgE levels associated with Alternaria A.,it should be given adequate clinical attention.

Objective:To analyze the changes of serum metabolites in patients with acute pancreatitis (AP) by non-targeted metabolomics method.Methods:Serum samples and clinical data of 15 AP patients hospitalized in the Affiliated Hospital of Jiangnan University from August to September 2024 were collected and included in the AP group, including 9 males and 6 females, aged (55.4±15.3) years. The serum and clinical data of 25 patients with colon polyps in the same hospital during the same period of time were collected, including 15 males and 10 females, aged (61.2±11.5) years, and were included in the control group. Serum metabolomic detection was performed using the ultra-high performance liquid chromatography tandem Fourier transform mass spectrometer. The modeling method was orthogonal partial least square discriminant analysis, and principal component analysis was performed on the data matrix to screen the differential metabolites in serum of AP patients. The Kyoto Encyclopedia database of Genes and Genomes was used to annotate differential metabolites, and the pathway of differential metabolite enrichment was analyzed by software.Results:The principal component analysis showed that the contribution ratio of the first principal component was 15.1%, the proportion of the second principal component was 10.8%, and the total proportion of the two was 25.9%. In principal component analysis, two groups of samples can be clearly distinguished and show obvious clustering characteristics. According to the analysis of OPLS-DA model, there were significant differences in serum metabolic profiles between AP group and control group. There were 683 differentially expressed metabolites between the two groups, with 367 differentially expressed metabolites up-regulated compared with the control group and 316 differentially expressed metabolites down-regulated compared with the control group. It is mainly Phosphatidic Acid (Lte4/8: 0) (+ 218%), Omeprazole Sulphone (-38%), and 2-(Propylthio) Nicotinic Acid (2-propyl thionicotinic acid) (-58%), Gein (salicyricetin) (-47%) and so on. Pathway enrichment analysis showed that the differential metabolites in AP patients were mainly concentrated in citric acid cycle, arginine biosynthesis and glycerophospholipid metabolism pathways.Conclusion:Serum metabolites in AP patients change significantly, including citric acid cycle, arginine biosynthesis, glycerophospholipid metabolism.

Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*