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 protective effect of Naoluoxintong(NLXT)on mouse hippocampal neuronal HT22 cells in the oxygen-glucose deprivation/reoxygenation(OGD/R)model,focusing on its impact on mitochondrial function and the role of the cal-cium/calmodulin-dependent protein kinase kinase β(CaMKKβ)in it.Methods HT22 cell were cultured to establish OGD/R model,and the cell were divided into normal group(Control),model group(OGD/R),NLXT group(OGD/R+10％NLXT),positive drug dl-3-n-butylphthalide(NBP)group(OGD/R+NBP 50μmol/L)after the screening of the optimal concentrations of different con-centrations of NLXT-containing serum(0-20％)in interfering with the HT22 cells by the CCK-8 assay.Then,using CCK-8 assay to detect the cell survival rate of each group,inverted fluorescence microscope to observe the morphology of each group,flow cytometry to detect the apoptosis rate of each group,and the kit to detect the activity or content of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)in each group.Nest,the CaMKKβ inhibitor(STO-609,5μmol/L)was introduced,HT22 cells were di-vided into Control group,OGD/R group,OGD/R+10％NLXT group,OGD/R+NBP group,OGD/R+STO-609group,OGD/R+STO-609+NLXT group.The mitochondrial membrane potential in each group was observed by using JC-1 fluorescent probe,and the end products Na+-K+-ATP,Ca+-Mg+-ATPase activity were detected by the kit.The expression changes of CaMKKβ protein in cells of each group were detected by Western blot,the changes of mitochondrial DNA copy number and CaMKKβ mRNA expression in cells of each group were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results The optimal concentration of NLXT-containing serum was 10％,which resulted in the most significant effects.Compared with the OGD/R group,NLXT intervention significantly increased cell viability(P＜0.05)and restored cellular morphological characteristics.Compared with the Control group,the OGD/R group showed significantly increased apoptosis(P＜0.05),elevated MDA levels,and decreased activities of SOD and GSH,alongside a reduction in mitochondrial membrane potential,ATP activity,and mitochondrial DNA copy number.Further-more,CaMKKβ protein and mRNA expression were downregulated(P＜0.05).Compared with the OGD/R group,the NLXT and NBP groups antagonized these effects and upregulated CaMKKβ protein and mRNA expression(P＜0.05).Additionally,the application of the CaMKKβ inhibitor STO-609 significantly attenuated the protective effects of NLXT on mitochondrial function and neurons(P＜0.05).Conclusion NLXT exerts neuroprotective effects by activating the CaMKKβ to enhance mitochondrial function after OGD/R in HT22 cells.

Objective To investigate the protective effect of Naoluoxintong(NLXT)on mouse hippocampal neuronal HT22 cells in the oxygen-glucose deprivation/reoxygenation(OGD/R)model,focusing on its impact on mitochondrial function and the role of the cal-cium/calmodulin-dependent protein kinase kinase β(CaMKKβ)in it.Methods HT22 cell were cultured to establish OGD/R model,and the cell were divided into normal group(Control),model group(OGD/R),NLXT group(OGD/R+10％NLXT),positive drug dl-3-n-butylphthalide(NBP)group(OGD/R+NBP 50μmol/L)after the screening of the optimal concentrations of different con-centrations of NLXT-containing serum(0-20％)in interfering with the HT22 cells by the CCK-8 assay.Then,using CCK-8 assay to detect the cell survival rate of each group,inverted fluorescence microscope to observe the morphology of each group,flow cytometry to detect the apoptosis rate of each group,and the kit to detect the activity or content of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)in each group.Nest,the CaMKKβ inhibitor(STO-609,5μmol/L)was introduced,HT22 cells were di-vided into Control group,OGD/R group,OGD/R+10％NLXT group,OGD/R+NBP group,OGD/R+STO-609group,OGD/R+STO-609+NLXT group.The mitochondrial membrane potential in each group was observed by using JC-1 fluorescent probe,and the end products Na+-K+-ATP,Ca+-Mg+-ATPase activity were detected by the kit.The expression changes of CaMKKβ protein in cells of each group were detected by Western blot,the changes of mitochondrial DNA copy number and CaMKKβ mRNA expression in cells of each group were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results The optimal concentration of NLXT-containing serum was 10％,which resulted in the most significant effects.Compared with the OGD/R group,NLXT intervention significantly increased cell viability(P＜0.05)and restored cellular morphological characteristics.Compared with the Control group,the OGD/R group showed significantly increased apoptosis(P＜0.05),elevated MDA levels,and decreased activities of SOD and GSH,alongside a reduction in mitochondrial membrane potential,ATP activity,and mitochondrial DNA copy number.Further-more,CaMKKβ protein and mRNA expression were downregulated(P＜0.05).Compared with the OGD/R group,the NLXT and NBP groups antagonized these effects and upregulated CaMKKβ protein and mRNA expression(P＜0.05).Additionally,the application of the CaMKKβ inhibitor STO-609 significantly attenuated the protective effects of NLXT on mitochondrial function and neurons(P＜0.05).Conclusion NLXT exerts neuroprotective effects by activating the CaMKKβ to enhance mitochondrial function after OGD/R in HT22 cells.

In the ICU,nutritional status is intimately related to the prognosis of critically ill patients and cannot be neglected;nonetheless,between 38%～78%of critically ill patients are malnourished.Individualized nutritional monitoring and therapy is recommended for critically ill patients to improve prognosis.Nutritional treatment includes enteral and parenteral nutrition.Enteral nutrition can be provided by prepyloric feeding through a nasogastric tube,which is simple and generally applicable,or by retropyloric feeding through a nasojejunal tube,which can reduce the risk of reflux aspiration.Parenteral feeding can be administered by creating peripheral venous access for convenient administration or central venous access for the delivery of nutritional solutions with high osmotic pressure.In addition to the patient's condition,the choice of nutrition route should take into account the initiation time,ability to meet nutritional needs,and potential feeding related complications.Current guidelines are not united,and previ-ous research has not fully addressed existing conflicts.In this paper,problems associated with each nutrition pathway are reviewed to provide a clinical reference.

Objective Based on HPLC fingerprinting and chemometrics,to evaluate the quality of Schefflera kwangsiensis Merr.from Guangxi.Methods HPLC was used to establish fingerprints of Schefflera kwangsiensis Merr.from ten different origins,and gradient elution was carried out with methanol-0.1％phosphoric acid aqueous solution as mobile phase.Cluster analysis(CA),principal component analysis(PCA)and orthogonal partial least squares-discriminant analysis(OPLS-DA)were applied to evaluate quality.Results The fingerprints of Schefflera kwangsiensis Merr.from ten different origins were established by HPLC,a total of 22 common peaks were calibrated,with a similarity range of 0.922-0.999.Four chromatographic peaks were identified as rhodopsin,4,5-bis-O-caffeoylquinic acid,caffeic acid,and naringin.The samples were classified into four types according to the CA and OPLS-DA.PCA identified four principal components with a cumulative contribution rare of 95.39％.Conclusion The quality of Schefflera kwangsiensis Merr.can be comprehensively evaluated by fingerprinting combined with CA,PCA and OPLS-DA analysis.The Study can provide a reference for improving the quality control and assessment of Schefflera kwangsiensis Merr.

Objective:To investigate the current status of research on the construction of leadership indicator system in the medical field at home and abroad, and to analyze the characteristics of the indicator system therein.Methods:This was a bibliometric study. The group applied subject keywords to search relevant literature on the construction of leadership indicator system in the medical field at home and abroad on English websites PubMed, Web of Science, Google Scholar, CINAHL, Scopus and Chinese websites Baidu Academic, CNKI, CQVIP, Wanfang Data Knowledge Service Platform, with a time frame of 2016-2023. The basic characteristics of the literature, the theoretical framework of the research application and the research theme were extracted, and the content of the indicator system in the literature was reviewed and summarized.Results:A total of 21 literatures were included, including 7 Chinese literatures and 14 English literatures. Of these literatures, 10 focused on physician leadership, 5 on medical manager leadership, and 2 on general practitioner leadership. Among 16 research literatures, 9 informed the theoretical basis of leadership, and 4 literatures were applied research. Five main themes were identified: leadership studies of individual healthcare administrators, leadership development in healthcare, interest and attitudes of healthcare workers towards leadership learning, applications of leadership in healthcare, and the impact of leadership in healthcare on patients and healthcare organizations.Conclusions:At present, research on the construction of the leadership indicator system in the medical field presents is diverse, with differences in theoretical basis and content. The original and empirical research is still insufficient.

Background: Gout is the most prevalent form of inflammatory arthritis in the world. Total hip arthroplasty (THA) has emerged as a widely sought-after and highly effective surgical procedure for advanced hip diseases. However, there is a lack of research on the impact of gout on primary THA outcomes in large cohorts. This study aimed to address this gap by primarily investigating complications following THA in patients with or without gout. Methods: Patients with records of gout in the 2 years leading up to their primary THA and who also have at least 2 years of follow-up were identified using a national insurance database and compared to a 5:1 matched control. A total of 32,466 patients with gout and 161,514 patients without gout undergoing THA were identified. Multivariable logistic regression analyses were done for medical complications up to 90 days and surgical complications up to 2 years. In addition, 90-day emergency department (ED) visits and inpatient readmission were also documented. Results: Patients with gout demonstrated higher rates of medical complications including deep vein thrombosis, transfusion, acute kidney injury, and urinary tract infection than non-gout patients (p < 0.001). Gout patients also showed higher rates of pulmonary embolism (p = 0.017). Increased incidences of surgical complications were identified in gout patients, specifically wound complications and periprosthetic joint infection (p < 0.001). There was an increased risk of revision for gout patients up to 90 days (p = 0.003), 1 year (p = 0.027), and 2 years (p = 0.039). There was also an increased risk of dislocation for gout patients up to 90 days (p = 0.022) and 1 year (p = 0.047), but not at 2 years. No significant difference was observed in aseptic loosening or periprosthetic fracture. Additionally, gout patients also demonstrated a higher likelihood of 90-day ED visits and readmission (p < 0.001). Conclusions Primary THA in gout patients is associated with increased risks of multiple medical and surgical complications. Our findings provide insights into the planning and expectation of THA for patients with gout. These insights have the potential to benefit the decision-making process for gout patients considering THA.

Objective:To analyze the trend and hot spots of research on multimorbidity.Methods:The Chinese and English literature in databases of CNKI, Wanfang data and Web of science from inception to July 2022 were retrieved using "multimorbidity" and "multiple chronic conditions" as the search terms. The scientific knowledge mapping software VOSviewer was used to analyze the co-occurrence network of scientific knowledge from the aspects of countries, Chinese and English keywords,burst terms and existing research results; and the status quo and hot trends of studies on multimorbidity at home and abroad were summarized and compared.Results:A total of 251 Chinese publications and 6 351 English publications were included. From the perspective of research trends, the overall trend of domestic and international publications showed a fluctuating upward trend in general, but the pace of development was different. The cooperation network represented by the United States, England, Canada, China, Japan, Australia and other countries was the largest regional cooperation network. Germany, the Netherlands, the United States, Australia and other countries were the first regions to carry out studies on multimorbidity. Studies on multimorbidity in China mainly focused on three topics: diagnosis, treatment and care of multimorbidity, common disease management of multimorbidity, and research methods of multimorbidity. The English literature mainly focused on the clustering of three topics: multi-disease co-diagnosis and care research, multi-disease co-management model research, and multimorbidity related research. The analysis of burst terms indicated the research focus and trend change in different time periods. The results of the outburst word analysis showed that the recent research hotspots of multimorbidity were public health, machine learning, geriatric medicine and so on.Conclusions:The number of studies on the multimorbidity is rapidly increasing both domestically and internationally, and related research in China is still in the early stages of development. In terms of research hotspots, the research of multimorbidity has gradually shifted from phenomenon description to topics such as medical services and research methods of multimorbidity.

OBJECTIVE: To explore the genetic etiology of a child featuring global developmental and mental retardation. METHODS: Chromosome G-banding karyotype analysis, copy number variation sequencing (CNV-seq) and high-resolution chromosome banding were used to screen the genomic variant in the child and his parents. RESULTS: Both the child and his father were found to have a karyotype of 46,XY,del(18)(q21.1q21.3), whilst his mother was 46,XX. CNV-seq analysis showed that the child was arr[19]18q21.2-q21.32(chr18:48 422 190-58 039 582)×1, with a 10.58 Mb deletion which encompassed the TCF4 gene. The same deletion was found in neither parent. High-resolution banding revealed that the father has a fragment of 18q21.1q21.3 inserted into 5p13.1. CONCLUSION The child was diagnosed with Pitt-Hopkins syndrome due to the 18q21.2q21.32 deletion. Chromosome karyotyping and CNV-seq can effectively identify submicroscopic chromosome anomalies.
Child ; Chromosome Banding ; Chromosome Deletion ; DNA Copy Number Variations ; Facies ; Humans ; Hyperventilation ; Intellectual Disability/genetics*

Objective:To observe any effect of electroacupuncture (EA) on the expression of phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2) and phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) in the spinal dorsal horns of diabetics experiencing neuropathic pain.Methods:Eight rats were randomly selected from 30 healthy male Sprague-Dawley rats as the normal group (N), and the remaining twenty-two rats were treated with a single high-dose intraperitoneal injection of streptozotocin (STZ) to establish a neuropathic pain model. The rats modeled successfully were randomly divided into a model group (M, n=8) and an EA group ( n=8). In the EA group, electroacupuncture was applied at the bilateral Hou san li and Kunlun acupoints starting on the 15th day after the STZ injection. The daily sessions lasted 30 minutes for 1 week. Body weight (BW), fasting blood glucose (FBG) and paw withdrawal latency (PWL) were observed before the STZ injection and on the 7th, 14th, and 21st days afterward. The expression of p-ERK1/2 and p-CREB in the dorsal horns of the rats′ spinal cords was detected using western blotting. The count of p-CREB-positive cells in the dorsal horns and their co-localization with neurons was detected using immunofluorescence. Results:In comparison with the N group, the average BW of the M group on the 7th, 14th and 21st days after the STZ injection was significantly lower, while the average FBG was significantly higher. There was no significant difference between the M and N groups in the average PWL on the 7th day after the STZ injection, but it had decreased significantly in the M group on the 14th and 21st days. Compared with the M group, the average PWL of the EA group was significantly longer on the 21st day after the injection. The expression of p-ERK1/2 and p-CREB protein in the spines of the M group was significantly higher than in the N group. p-CREB positive cells were more numerous in the M group compared with the N group, while in the EA group they were fewer. P-CREB was co-located with neurons in the spinal dorsal horn.Conclusion:EA can alleviate neuropathic pain effectively, perhaps by inhibiting the expression of p-ERK1/2 and p-CREB in the dorsal horns of the spinal cord.