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 explore the clinical efficacy of super-selective ophthalmic artery thrombolysis in the treatment of central retinal artery occlusion (CRAO).Methods:This is a retrospective case series study,based on the analysis of clinical data of 50 non-arteritic CRAO patients. The patients were advised to be treated with super-selective intra-ocular arterial thrombolysis at the Neurosurgery Department, Shenyang No. 4 People′s Hospital from May to December 2024, and treated with intra-arterial thrombolysis and postoperative management guidance by the Department of Neurosurgery, General Hospital of the Northern Theater Command. There were 36 males and 14 females, aged (59.5±10.2)years (range: 41 to 75 years). There were 5 cases of complete obstruction of the central retinal artery and 45 cases of subtotal obstruction.Before the operation, all patients underwent optical coherence tomography angiography (OCTA)+ocular vascular ultrasonography, and their visual acuity was measured using a standard visual acuity logarithmic scale, visual field was measured using the contrast visual field examination method;One week after the operation, all patients were rechecked for OCTA, visual acuity and visual field. The patients′ preoperative and postoperative visual field recovery status were compared. Significant effect was defined as an improvement of more than 3 lines of visual acuity or a complete improvement of visual field defects after treatment compared with pretreatment visual acuity; effectiveness was defined as an improvement of 1 to 2 lines of visual acuity or an improvement of visual field defects after treatment compared with pretreatment visual acuity.Results:The overall effective rate of 50 patients with CRAO treated with super-selective ophthalmic artery urokinase thrombolysis was 94.0% (47/50), with 29 very effective, 18 effective and 3 ineffective. The time from onset to surgery was 0 to 6 hours in 5 patients, with an effective rate of 5/5; >6 to 24 hours in 11 patients, with an effective rate of 10/11; >1 to 7 days in 21 patients, with an effective rate of 90.5%(19/21); >7 to 14 days in 9 patients, with an effective rate of 9/9; and >14 to 21 days in 4 patients, with an effective rate of 4/4, and the difference in effective rate between the different time windows of thrombolytic therapy was not statistically significant ( P=0.961). There were 3 cases of intraoperative and postoperative complications, including 1 case of ophthalmic artery entrapment, 1 case of femoral artery pseudoaneurysm and 1 case of fundus hemorrhage, but all of them were cured after symptomatic treatment. Conclusions:Intra-arterial thrombolysis for CRAO patients has a high effective rate and a low complication rate. The surgical time window can be extended to 21 days after the onset, which is of positive significance for the recovery and improvement of the patient′s final visual acuity.

Through a comprehensive analysis of four cases involving repeated forensic clinical identification on the degree of human injury,disability grade,causal relationship of injury and disease,medical damage liability dispute,the reasons for the emergence of different appraisal opinions are explored.According to the reasons for the disputed conclusion,the deviation or error of the appraisal opinion can be classified in a variety of ways.Among them,the inherent limitations of theories and methods used as appraisal bases,the lack of operational skills or cognitive ability of appraisers,the unclear provisions of appraisal standards and the lack of adequacy and validity in the process of analysis and reasoning are the key reasons for the deviation or error of appraisal opinions.In light of these findings,it is necessary to strengthen the review of expert opinions in judicial practice and form a powerful error correction mechanism.

Objective To investigate the key targets and pathways of Juhongtai formula granules in improving acute lung injury(ALI).Methods Juhongtai formula granules and their drug-containing serum components were analyzed by UPLC-QTOF-MS/MS,and the active ingredients were screened based on the"Lipinski Rule of Five".The action targets of the above active ingredients were obtained through the TCMSP,Swiss Target Prediction and SuperPred databases,and the ALI-related targets were obtained from the GeneCards,OMIM,PharmGKB,CTD databases and GEO chip.The target protein-protein interaction network was constructed using the String database and Cytoscape to analyze the key targets.The DAVID database was used for GO functional annotation and KEGG pathway enrichment analysis,and the CB-dock2 platform was used for molecular docking verification.After one week of adaptive feeding,the experimental SD rats were randomly divided into the blank group,the model group,the positive control group,the negative control group and the Juhongtai formula granules group,with 6 rats in each group.The rat model of ALI was replicated by tracheal infusion of lipopolysaccharide.The pathological morphology of lung tissues in each group of rats was observed by HE staining,and the mRNA expressions of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1 β(IL-1β)and nitric oxide were detected by reverse transcription quantitative polymerase chain reaction(RT-qPCR).Results In total,44 components of the Juhongtai formula granules were identified,including 26 drug-containing serum components,and 21 key compounds were screened.A total of 22 intersection targets were obtained.The pathway enrichment results indicated the action of these targets on the advanced glycation end product receptor(AGE-RAGE)and TNF signaling pathways.The docking results showed that limonin,kaempferol and naringenin could be matched with prostaglandin peroxidase 2,nitric oxide synthase 2 and TNF.Animal experiments confirmed that the Juhongtai formula granules can alleviate inflammatory infiltration in lung tissue and reduce the expressions of TNF-α,IL6,IL-1β mRNA and nitric oxide.Conclusion Juhongtai formula granules can inhibit ALI-related inflammatory targets through the synergistic effects of multiple components such as limonin and kaempferol,regulate signaling pathways such as AGE-RAGE and TNF,reduce the production of inflammatory factors and nitric oxide,and improve ALI.

Objective To investigate the key targets and pathways of Juhongtai formula granules in improving acute lung injury(ALI).Methods Juhongtai formula granules and their drug-containing serum components were analyzed by UPLC-QTOF-MS/MS,and the active ingredients were screened based on the"Lipinski Rule of Five".The action targets of the above active ingredients were obtained through the TCMSP,Swiss Target Prediction and SuperPred databases,and the ALI-related targets were obtained from the GeneCards,OMIM,PharmGKB,CTD databases and GEO chip.The target protein-protein interaction network was constructed using the String database and Cytoscape to analyze the key targets.The DAVID database was used for GO functional annotation and KEGG pathway enrichment analysis,and the CB-dock2 platform was used for molecular docking verification.After one week of adaptive feeding,the experimental SD rats were randomly divided into the blank group,the model group,the positive control group,the negative control group and the Juhongtai formula granules group,with 6 rats in each group.The rat model of ALI was replicated by tracheal infusion of lipopolysaccharide.The pathological morphology of lung tissues in each group of rats was observed by HE staining,and the mRNA expressions of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1 β(IL-1β)and nitric oxide were detected by reverse transcription quantitative polymerase chain reaction(RT-qPCR).Results In total,44 components of the Juhongtai formula granules were identified,including 26 drug-containing serum components,and 21 key compounds were screened.A total of 22 intersection targets were obtained.The pathway enrichment results indicated the action of these targets on the advanced glycation end product receptor(AGE-RAGE)and TNF signaling pathways.The docking results showed that limonin,kaempferol and naringenin could be matched with prostaglandin peroxidase 2,nitric oxide synthase 2 and TNF.Animal experiments confirmed that the Juhongtai formula granules can alleviate inflammatory infiltration in lung tissue and reduce the expressions of TNF-α,IL6,IL-1β mRNA and nitric oxide.Conclusion Juhongtai formula granules can inhibit ALI-related inflammatory targets through the synergistic effects of multiple components such as limonin and kaempferol,regulate signaling pathways such as AGE-RAGE and TNF,reduce the production of inflammatory factors and nitric oxide,and improve ALI.

Through a comprehensive analysis of four cases involving repeated forensic clinical identification on the degree of human injury,disability grade,causal relationship of injury and disease,medical damage liability dispute,the reasons for the emergence of different appraisal opinions are explored.According to the reasons for the disputed conclusion,the deviation or error of the appraisal opinion can be classified in a variety of ways.Among them,the inherent limitations of theories and methods used as appraisal bases,the lack of operational skills or cognitive ability of appraisers,the unclear provisions of appraisal standards and the lack of adequacy and validity in the process of analysis and reasoning are the key reasons for the deviation or error of appraisal opinions.In light of these findings,it is necessary to strengthen the review of expert opinions in judicial practice and form a powerful error correction mechanism.

Objective:To explore the clinical efficacy of super-selective ophthalmic artery thrombolysis in the treatment of central retinal artery occlusion (CRAO).Methods:This is a retrospective case series study,based on the analysis of clinical data of 50 non-arteritic CRAO patients. The patients were advised to be treated with super-selective intra-ocular arterial thrombolysis at the Neurosurgery Department, Shenyang No. 4 People′s Hospital from May to December 2024, and treated with intra-arterial thrombolysis and postoperative management guidance by the Department of Neurosurgery, General Hospital of the Northern Theater Command. There were 36 males and 14 females, aged (59.5±10.2)years (range: 41 to 75 years). There were 5 cases of complete obstruction of the central retinal artery and 45 cases of subtotal obstruction.Before the operation, all patients underwent optical coherence tomography angiography (OCTA)+ocular vascular ultrasonography, and their visual acuity was measured using a standard visual acuity logarithmic scale, visual field was measured using the contrast visual field examination method;One week after the operation, all patients were rechecked for OCTA, visual acuity and visual field. The patients′ preoperative and postoperative visual field recovery status were compared. Significant effect was defined as an improvement of more than 3 lines of visual acuity or a complete improvement of visual field defects after treatment compared with pretreatment visual acuity; effectiveness was defined as an improvement of 1 to 2 lines of visual acuity or an improvement of visual field defects after treatment compared with pretreatment visual acuity.Results:The overall effective rate of 50 patients with CRAO treated with super-selective ophthalmic artery urokinase thrombolysis was 94.0% (47/50), with 29 very effective, 18 effective and 3 ineffective. The time from onset to surgery was 0 to 6 hours in 5 patients, with an effective rate of 5/5; >6 to 24 hours in 11 patients, with an effective rate of 10/11; >1 to 7 days in 21 patients, with an effective rate of 90.5%(19/21); >7 to 14 days in 9 patients, with an effective rate of 9/9; and >14 to 21 days in 4 patients, with an effective rate of 4/4, and the difference in effective rate between the different time windows of thrombolytic therapy was not statistically significant ( P=0.961). There were 3 cases of intraoperative and postoperative complications, including 1 case of ophthalmic artery entrapment, 1 case of femoral artery pseudoaneurysm and 1 case of fundus hemorrhage, but all of them were cured after symptomatic treatment. Conclusions:Intra-arterial thrombolysis for CRAO patients has a high effective rate and a low complication rate. The surgical time window can be extended to 21 days after the onset, which is of positive significance for the recovery and improvement of the patient′s final visual acuity.

Objective To investigate the oral health status of the first-grade primary school students in Shanghai and analyze its influencing factors.Methods In 2021,Huangpu,Xuhui,Jiading,and Jing'an districts were selected in Shanghai by random sampling method.The first-grade students of 8 primary schools in these 4 districts were enrolled by random cluster sampling.Oral clinical examinations and questionnaires were conducted according to the criteria of the Fourth National Oral Health Epidemiological Survey.EpiData 3.1 software was used to create the database.SPSS 26.0 software was applied for statistical analysis.Chi-square test was used to compare the caries prevalence between groups,and two independent samples non-parametric test was used to compare the decayed,missing and filled teeth(DMFT)between groups.Multifactorial logistic regression model was used to analyzse the influencing factors of caries.Results A total of 824 informed consent forms and questionnaires were collected,of which 764 were completed,with an effective rate of 92.7％.The total caries prevalence of the participating students was 65.6％(501/764),and the mean DMFT was 3.24±3.47.A total of 2 473 carious teeth were found in the participating students,and 671 teeth were filled,with a filling rate of 27.1％.There were 7.91±2.76 permanent teeth erupted per student,and 56.3％(430/764)of the students had all 4 first permanent molars erupted.Multivariate logistic regression showed that eating sweets＞3 times a day(P=0.030),eating regularly before bedtime(P=0.001),and parents'cognition of kids'poor oral health status(P=0.025)were the influencing factors for the detection of caries in children.Conclusion The first-grade primary school students in Shanghai have high prevalence of caries.Eating sweets＞3 times a day,eating regularly before bedtime,and parents'cognition of kids'poor oral health status(P＜0.05)are the influencing factors for the detection of caries in children.

Objective To investigate the oral health status and caries related influence factors in 3-year-old children in Shanghai.Methods A total of 1 709 3-year-old children in 29 kindergartens from Huangpu,Xuhui,Jiading,and Jing'an districts were selected for the survey by random cluster sampling in 2021.Oral clinical examinations and questionnaires were conducted according to the criteria of the Fourth National Oral Health Epidemiological Survey.EpiData 3.1 software was used to build the database,analyse the prevalence of caries and the mean dmft.Multivariate logistic regression model was used to evaluate the influence factors of caries.Results A total of 1 709 questionnaires were collected in this survey,of which 1469 were complete questionnaires,with a valid rate of 86.0%.The prevalence of caries was 27.8%,and the mean dmft was 1.09±2.49.The caries filling rate was 8.2%.Frequency of eating sweet food(P<0.001),eating before bedtime(P=0.016),a history of dental discomfort(P<0.001),no history of dental visits within six months(P=0.015),a history of dental visits for therapeutic purposes(P<0.001),caries status of mothers(P<0.001),and parent's education level(P=0.012)were influence factors of caries in 3-year-old children.Conclusion The prevalence of caries in 3-year-old children in Shanghai is lower than the national level,but more improvement is needed.The frequency of eating sweet food,eating before bedtime,and parent's cognition of oral health are the influence factors of children's caries.

Objective To investigate the effect and mechanism of Liuling Jiedu Pills on acute pharyngitis caused by Staphylococcus aureus in rats.Methods The rat model of acute pharyngitis was replicated using the method of injecting 1×109 CFU·mL-1 of Staphylococcus aureus solution into the pharynx of rats.SD rats were randomly divided into a blank group,a model group,a Lanqin Oral Solution group(5 mL·kg-1),and a low-,medium-,and high-dose group of Liuling Jiedu Pills(4.375,8.750,and 17.500 mg·kg-1),with 10 rats in each group.Rats in each group were administered the drug by gavage once a day for 7 days.The general conditions of the rats were observed and recorded every day during the modeling and drug administration periods,and the local inflammation in the pharynx was scored;histopathological changes in the pharynx of the rats were observed by hematoxylin-eosin(HE)staining;serum interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor α(TNF-α),and tumor necrosis factor-α(TNF-α)were detected by ELISA.Immunohistochemistry and Western Blot were used to detect the protein expression levels of IL-1β,IL-6 and TNF-α in rat pharyngeal tissue.Results Compared with the blank group,rats in the model group had significantly increased pharyngeal erythema,significantly higher inflammation scores(P＜0.01),significantly lower body mass on days 5-7 after modeling(P＜0.05,P＜0.01),significantly higher pathological scores(P＜0.01),significantly higher levels of the serum inflammatory factors IL-1β,IL-6,and TNF-α(P＜0.01),and significantly higher pharyngeal tissues showed significantly higher levels of IL-1β,IL-6,and TNF-α proteins(P＜0.01).Compared with the model group,the pharyngeal erythema was significantly reduced in the Lanqin Oral Solution group and the low-,medium-and high-dose groups of Liuling Jiedu Pills,and the inflammation scores were significantly reduced(P＜0.01),and the serum levels of IL-1β,IL-6,and TNF-α were significantly reduced(P＜0.01);the body mass of the rats in the Lanqin Oral Solution group,and in the medium-and high-dose groups of Liuling Jiedu Pills,were significantly increased on the seventh day of the modeling(P＜0.01);the histopathological scores and the levels of IL-1β,IL-6 and TNF-α proteins in pharyngeal tissue were significantly decreased(P＜0.05,P＜0.01).Conclusion Liuling Jiedu Pills can significantly improve the symptoms and inflammatory pathological changes of pharyngeal tissues in rats with acute pharyngitis,and its mechanism may be related to the down-regulation of the expression levels of inflammatory factors such as IL-1β,IL-6,and TNF-α.