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 observe the effect of butylphthalide sequential therapy combined with injection of alteplase(injection with recombinant human collagenous tissue plasminogen activator) in the treatment of acute cerebral infarction (ACI).Methods 61 patients with ACI and within 4.5 hours of onset were selected,and they were divided into treatment group(butylphthalide combined with alteplase group,31 cases) and the control group (alteplase only group,30 cases) by random number table.The two groups were given glucose-lowering,statins for maintaining the blood pressure,as well as aspirin enteric tablets or clopidogrel for those without bleeding on the 24 hour review head CT in the acute phase.The treatment group was given alteplase for injection with sequential butylphthalide therapy (butylphthalide injection for 2 weeks followed by an oral administration of butylphthalide soft capsules for 3 months),and the control group was given only alteplase for injection.The National Institute of Health stroke scale (NIHSS) and Barthel index (BI) were used for evaluating the final clinical efficacy.Results The NIHSS scores of the treatment group compared with the control group at 24 hour,14 days and 3.5 months after the treatment had statistically significant differences (t =-0.102,-1.964,-2.444,P =0.037,0.018 and 0.012).The NIHSS scores of the treatment group had decreased 2％,27％ and 41％ compared with the control group at 24 hour,14 days and 3.5 months after the treatment,respectively.The BI score of the treatment group and control group at 3.5 months after treatment had statistically significant difference (t =-1.956,P =0.029).Conclusion The sequential butylphthalide therapy combined with injection of alteplase has good synergistic effect for the patients with onset of ACI less than 4.5 hours,and it is a safe and effective treatment method for ACI within 4.5 h and it is worthy of clinical promotion.

Objective To study curative efficacy of Pramipexole in treatment of Parkinson's Disease and its effects on Serum C-reactionprotein (CRP), cystatin C, brain derived neurotrophic factor(BDNF) and oxidative stress.Methods 100 patients of Parkinson's Disease who received therapy from February 2014 to April 2016 in our hospital were selected as research objects were randomLy divided into control group and observation group, 50 patients in each group.The control group was treated with Dobasidate tablets;The observation group was given pramipexole tablets on the basis of the control group.Then the clinical effects and adverse reactions were compared.CRP, Cystatin C, BDNF and oxidative stress were measured. Results After treatment, the total effective rate of the observation group [(90.00% (45/50)] was significantly higher than the control group[74.00%(37/50)] (P<0.05);The symptoms of palpitation, depression, nausea, anorexia, diarrhea and vomiting were lower in observation group than in observation group, and the differences of depression, anorexia and vomiting were statistically significant(P<0.05);The BDNF index of the observation group (13.38 ±1.93)ng/L was higher than that of the control group (12.03 ±1.83) ng/L(P<0.05);CRP (3.53 ±0.97) mg/L and Cystatin C index (0.98 ±0.12) mg/L were lower than the control group(4.62 ±1.15)、(1.06 ±0.14) mg/L (P<0.05).After treatment, the glutathione peroxidate (GPX),superroxide dismutase(SOD),glutathione(GSH)and catalase(CAT) of oxidative stress in observation group were higher than those in control group,the difference was statistically significant (P<0.05).Conclusion Pramipexole in the treatment of Parkinson's disease is obvious, can effectively improve the serum CRP, Cystatin C and BDNF index, high security, it is worth promoting the application.

Objective To observe the change of comprehensive agitating coefficient in the intracerebral hem -orrhage( ICH) patients monitoring by non-invasive cerebral edema and dynamical method ,and to find out dynamical change of cerebral edema in patients with ICH ,and to evaluate the specificity and sensitivity of non-invasive dynami-cal brain edema monitor in ICH treatment .Methods The change of comprehensive agitating coefficient in 130 patients was detected by non-invasive dynamical brain edema monitor at day 1,3,5 and 7 from ICH onset.Results The comprehensive agitating coefficient in focus side was lower than the unaffected side in both groups at the first day .The coefficient in the focus side was higher than the unaffected side at the third day ,and then became approximately equal at day 5 and basically normal at day 7.The comprehensive agitating coefficients in focus side were significantly differ-ent to unaffected side at day 3,5(P<0.01),and quite different at day 1,7(P<0.05).Conclusion The compre-hensive disturbance coefficient takes on dynamical changes in the ICH and reflects the course of edema formation . Cerebral edema monitoring by non-invasive and dynamical method can evaluate the course of cerebral edema ,and has a guiding role to the therapy of the ICH .