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 To evaluate the efficacy of Anzhong-Fuyuan decoction combined with western routine therapy in the treatment of helicobacter pyiori(H.pylori)-positive chronic atrophic gastritis (CAG).Methods A total of 110 H.pylori positive CAG patients who met the inclusion criteria were divided into two groups according to random number table method,55 in each group.The control group was treated with quadruple therapy.On the basis of the control group,the study group was treated with Anzhong-Fuyuan decoction.Both groups were treated continuously for 40 days.The serum level of pepsinogen Ⅰ (Pepsinogen Ⅰ,PG Ⅰ),pepsinogen Ⅱ (PG Ⅱ),gastrin (GAS),endothelin (ET),CRP,IL-6 and TNF-α were detected by ELISA.The eradication rate of H.pylori was measured by 14C urea breath test,and the clinical efficacy was evaluated.Results The total effective rate was 92.7％ (51/55) in the study group and 78.2％ (43/55) in the control group.There were significant differences between the two groups (x2=4.681,P=0.031).The eradication rate of H.pylori was 89.1％ (49/55) in the study group and 76.4％ (42/55) in the control group.There was significant difference between the two groups (x2=3.911,P=-0.048).After treatment,the level of serum PG Ⅰ (84.87 ± 13.95 g/L vs.78.05 ± 12.69 g/L,t=3.434) and PG Ⅰ/PG Ⅱ (6.71 ± 1.26 vs.5.86 ± 1.13,t=2.861) in the study group was significantly higher than those in the control group (P＜0.05),and PG Ⅱ (12.64 ± 1.94 g/L vs.13.31 ± 2.10 g/L,t=3.725) was significantly lower than those in the control group (P＜0.01).The serum level of gastrin (10.76 ± 3.06 mmol/L vs.8.11 ± 2.84 mmol/L,t=4.707) was higher than that of control group (P＜0.01),endothelin (56.64 ± 4.42 ng/L vs.60.42 ± 5.13 ng/L,t=4.140) was significantly lower than that of control group (P＜0.01).After treatment,the level of CRP,IL-6 and TNF-α in the study group was significantly lower than those in the control group (t=11.100,9.571 and 8.687,respectively,all Ps＜ 0.001).Conclusions The Anzhong-Fuyuan decoction combined with routine therapy can significantly enhance the gastric mucosal secretion ability of H.pylori positive CAG patients,increase the ratio of PG Ⅰ/PG Ⅱ,promote the repair and regeneration of gastric mucosa,reduce the level of inflammatory cytokines.

Objective To explore the expression of Tiaml in clear cell renal cell carcinoma and analyze its correlations to pathology of disease and prognosis.Methods The expressions of Tiam1 protein in 107 specimens of human clear cell renal cell carcinoma and 20 specimens of normal renal tissues were detected by immunohistochemical staining and its clinical significance was then analyzed.Results The expression of Tiam1 protein was higher in renal cancers than in the adjacent normal tissues ( P ＜ 0.01 ).Tiam1 protein expression rates were 47.6％ and 72.7％ in Ⅰ - Ⅱ and Ⅲ - Ⅳ tumors,while 49.3％ and 76.5％ in T1 - T2 and T3 - T4 tumors,respectively ( P ＜ 0.01 ).Expression of Tiam1 protein was higher in lymph node positive renal carcinoma tissues than in lymph node negative renal carcinoma tissues ( 71.7％ versus 47.5％,P ＜ 0.05 ).The expression of Tiam1 in carcinoma tissues showed a positive relationship with tumor vascular invasion (81.3％ versus 48.0％,P ＜ 0.01 ).In patients followed-up 5 - 8 years,Kaplan-meier analysis and the log-rank test showed that the 5-year survival was significantly different between the group of lower and higher Tiaml expression groups ( 84.4％ versus 46.8％,P ＜ 0.05 ).Conclusions The expression of Tiaml protein was higher in human primary renal carcinoma than in normal renal tissues.The positive rate of Tiam1 protein expression was related to classification,TNM stage,lymph node metastasis and vascular invasion.The detection of the expression of Tiaml protein may be helpful in the diagnosis and prognosis of renal carcinoma.

Objective To evaluate endoscopic ultrasonography (EUS) for diagnosis of gastric stromal tumors (GST) by analyzing EUS features of tumors with different invasive capacities.Methods Clinical data of 34 patients with GST were analyzed retrospectively.The tumors were classified according to Fletcher′s GIST biological behavior ranking system and the corresponding EUS features were analyzed.Results The mean maximal diameter of GST in this cohort was 6.7cm.The echo heterogeneity, big tumors size, irregular shape and ulceration were more common in tumors of high risk (P<0.05).Conclusion Tumor size, shape, echo quality and ulceration detected by EUS are useful features for pretreatment evaluation of GST, and can guide the choice of following managements.