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 investigate the expression characteristics of granzyme B(GZMB)and C-X-C motif chemokine ligand 9(CXCL9)in gastric cancer(GC)tissues,explore their association with the tumor immune microenvironment(TME),and evaluate their clinical prognostic significance.Methods Bioinformatic analyses were conducted using public databases(TIMER,GEPIA,UALCAN)to validate the expression levels of GZMB and CXCL9 across various cancer types,with a focus on GC.Paired tumor and adjacent normal tissue samples were collected from 89 GC patients who underwent radical gastrectomy at Nanyang First People's Hospital between 2018 and 2019.The mRNA expression levels of GZMB and CXCL9 were measured using quantitative real-time PCR(qRT-PCR),and their associations with clinicopathological characteristics were statistically analyzed.Immune cell infiltration levels were estimated using the TIMER and GSCA databases.Diagnostic performance was evaluated through receiver operating characteristic(ROC)curve analysis,while survival outcomes were assessed using data from the Kaplan-Meier Plotter database and patient follow-up records.Results Both database analysis and qRT-PCR results demonstrated that GZMB and CXCL9 expression levels were significantly elevated in GC tissues compared to adjacent non-tumor tissues(P<0.05).Clinical correlation analysis revealed no significant associations between mRNA expression levels of GZMB and CXCL9 and clinicopathological parameters,including gender,age,pathological type,tumor differentiation,TNM stage,tumor size,or lymph node metastasis(P>0.05).Immune infiltration analysis indicated that both genes were significantly positively correlated with CD8+T cell and dendritic cell infiltration(P<0.05),while showing a negative correlation with B cell infiltration(P<0.05).ROC curve analysis showed that the combined detection of GZMB and CXCL9 yielded an AUC of 0.890(95%CI:0.843～0.936),which was higher than that of GZMB alone(AUC=0.832,95%CI:0.772～0.891)or CXCL9 alone(AUC=0.782,95%CI:0.715～0.850).Survival analysis further revealed that patients with high expression of GZMB and CXCL9 had significantly improved overall survival compared to those with low expression(P<0.05).Conclusion GZMB and CXCL9 are highly expressed in GC and are strongly associated with the infiltration of anti-tumor immune cells.These molecules represent promising diagnostic biomarkers for GC,and their elevated expression is correlated with a more favorable prognosis in patients.

Objective To investigate the expression characteristics of granzyme B(GZMB)and C-X-C motif chemokine ligand 9(CXCL9)in gastric cancer(GC)tissues,explore their association with the tumor immune microenvironment(TME),and evaluate their clinical prognostic significance.Methods Bioinformatic analyses were conducted using public databases(TIMER,GEPIA,UALCAN)to validate the expression levels of GZMB and CXCL9 across various cancer types,with a focus on GC.Paired tumor and adjacent normal tissue samples were collected from 89 GC patients who underwent radical gastrectomy at Nanyang First People's Hospital between 2018 and 2019.The mRNA expression levels of GZMB and CXCL9 were measured using quantitative real-time PCR(qRT-PCR),and their associations with clinicopathological characteristics were statistically analyzed.Immune cell infiltration levels were estimated using the TIMER and GSCA databases.Diagnostic performance was evaluated through receiver operating characteristic(ROC)curve analysis,while survival outcomes were assessed using data from the Kaplan-Meier Plotter database and patient follow-up records.Results Both database analysis and qRT-PCR results demonstrated that GZMB and CXCL9 expression levels were significantly elevated in GC tissues compared to adjacent non-tumor tissues(P<0.05).Clinical correlation analysis revealed no significant associations between mRNA expression levels of GZMB and CXCL9 and clinicopathological parameters,including gender,age,pathological type,tumor differentiation,TNM stage,tumor size,or lymph node metastasis(P>0.05).Immune infiltration analysis indicated that both genes were significantly positively correlated with CD8+T cell and dendritic cell infiltration(P<0.05),while showing a negative correlation with B cell infiltration(P<0.05).ROC curve analysis showed that the combined detection of GZMB and CXCL9 yielded an AUC of 0.890(95%CI:0.843～0.936),which was higher than that of GZMB alone(AUC=0.832,95%CI:0.772～0.891)or CXCL9 alone(AUC=0.782,95%CI:0.715～0.850).Survival analysis further revealed that patients with high expression of GZMB and CXCL9 had significantly improved overall survival compared to those with low expression(P<0.05).Conclusion GZMB and CXCL9 are highly expressed in GC and are strongly associated with the infiltration of anti-tumor immune cells.These molecules represent promising diagnostic biomarkers for GC,and their elevated expression is correlated with a more favorable prognosis in patients.

Objective:To observe the proteomic changes in vitreous fluid samples from patients with rhegmatogenous retinal detachment combined with choroidal detachment (RRDCD).Methods:A prospective cross-sectional clinical study. Vitreous fluid samples were collected from 35 patients with RRDCD (RRDCD group) and 40 patients with rhegmatogenous retinal detachment (RRD group) who were diagnosed at Wuhan Aier Eye Hospital between November 2021 and December 2023. Prior to vitrectomy, 0.3-0.5 ml of vitreous fluid was collected from the affected eyes. Differentially expressed proteins were analyzed using Data-Independent Acquisition (DIA). Three of these proteins were randomly selected for validation using enzyme-linked immunosorbent assay (ELISA). Bioinformatics analyses, including gene ontology functional enrichment and kyoto encyclopedia of genes and genomes pathway enrichment, were performed to explore the functions of the differentially expressed proteins.Results:Significant differences were observed between the RRDCD and RRD groups in intraocular pressure ( t=-12.795), the number of retinal tears ( t=4.601), the extent of retinal detachment ( χ2=39.642), axial length ( t=0.840), postoperative proliferative vitreoretinopathy incidence ( χ2=4.730), single-surgery reattachment rate ( χ2=7.717), and best-corrected visual acuity ( t=7.033) at 6 months postoperatively ( P<0.05). A total of 237 differentially expressed proteins were identified between the RRDCD and RRD groups, with 63 upregulated and 174 downregulated. These proteins were involved in pathways such as extracellular matrix-receptor interaction, complement activation, coagulation, and lysosomal pathways. ELISA validation results showed that the expression trends of the three selected proteins in the RRDCD and RRD groups were consistent with the DIA proteomic analysis. Compared to the RRD group, proteins such as fibrin, coagulation factors, cathepsins, and trypsin inhibitors were significantly upregulated in the RRDCD group. Conclusions:The protein expression profile in vitreous fluid samples from RRDCD patients show significant alterations compared to the RRD group. These differential changes suggest that RRDCD is closely associated with complement and coagulation cascade activation, lysosomal pathways, and extracellular matrix remodeling.

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 understand the current situation of college students'sleep quality and the effect of rumination and psychological resilience on sleep quality.Methods:A total of 406 college students from two universities in Wuhu city were randomly selected and investigated by the general information questionnaire,Pittsburgh sleep quality index scale,rumination scale and psychological resilience scale.Pearson correlation analysis was used to analyze the correlation between rumination,psychological resilience and sleep quality.Multiple linear stepwise regression was used to analyze the influence of college students'self-improvement and symptom rumination on sleep quality.Finally,Bootstrap mediating effect was used to test the mediating effect of symptom rumination between self-improvement and sleep quality.Results:There were 107(26.4%)college students with sleep problems.The overall level of rumination and its dimensions were positively correlated with the total score of sleep quality(P＜0.05),and the self-improvement factor of psychological resilience was negatively correlated with the total score of sleep quality(P＜0.05).Self-improvement and symptom rumination had certain predictive power for sleep quality.Symptomatic rumination was a mediating variable between self-improvement and sleep quality,and the mediating effect value was-0.025.Conclusions:The sleep situation of college students is not optimistic.Reducing college students'rumination and improving their psychological resilience can effectively improve their sleep quality and promote the development of physical and mental health.

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.

Osteoporosis can be induced by various factors including prolonged glucocorticoid usage, diminished estrogen levels, secondary hyperparathyroidism, and alterations in the microenvironment of bone tissue. The bone metabolism imbalance(osteogenic-lipogenic imbalance) plays a crucial role in the development of osteoporosis. This imbalance is primarily driven by an increase in the differentiation of bone marrow mesenchymal stem cells into adipocytes and a decrease in their differentiation into osteoblasts, thus forming the core of the osteogenic-lipogenic imbalance observed in osteoporosis. The bone morphogenesis protein(BMP) plays a crucial role in the regulation of the osteogenic-lipid balance in osteoporosis. This regulatory function is accomplished through both the Smad-dependent and Smad-independent pathways. This review centers on the Smad-dependent and Smad-independent pathways facilitated by BMP, offering a comprehensive overview of the potential mechanisms through which BMP-2, 4, 6, 7, and 9 contribute to the regulation of osteogenesis and lipid metabolism in osteoporosis via these pathways. In order to present novel insights for the identification of efficacious targets for clinical anti-osteoporosis medications.

Objective To analyze the characteristics of platelet changes and their influencing factors during postoperative hospitalization in patients who underwent transcatheter aortic valve implantation (TAVI). Methods The patients who underwent TAVI at Beijing Anzhen Hospital Valve Surgery Center between March 2017 and October 2021 were retrospectively selected. The patients were divided into a self-limiting group and a non-self-limiting group according to the characteristics of postoperative platelet decline. In addition, the general preoperative data, preoperative and postoperative ultrasound data, intraoperative data, and the use of anticoagulant drugs during the postoperative stay in the hospital were compared between the two groups. Results A total of 249 patients were enrolled in this study. There were 175 (70.3%) patients in the self-limiting group, including 100 males and 75 females, and there were 74 (29.7%) patients in the non-self-limiting group, including 43 males and 31 females, with no statistical difference between the two groups (P=0.863). The mean age of patients was 73.11±8.88 years in the self-limiting group and 71.54±10.39 years in the non-self-limiting group (P=0.231). The decline of platelets in the self-limiting group generally occurred on the postoperative day 2 and reached the lowest count on the postoperative day 4, and returned to the baseline level on the postoperative day 5-7, while the platelets in the non-self-limiting group changed by simple rise, fall or irregular fluctuation. Patients in the self-limiting group had severer preoperative aortic stenosis (P<0.001) and used more extracorporeal circulation assistance during surgery (P<0.001). Postoperatively, patients in the self-limiting group were more likely to have periaortic valve leakage than those in the non-self-limiting group (P=0.013). Conclusion Platelet changes in most patients after TAVI show a self-limiting decline, which may be related to the severity of patients’ preoperative aortic stenosis, intraoperative extracorporeal circulation device use, and postoperative perivalvular leakage.