ObjectiveThis study aims to explore the neurotoxicity mechanism of Dictamni Cortex by integrating network toxicology and metabolomics techniques. MethodsThe neurotoxicity targets induced by Dictamni Cortex were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCM-ID）， and Comparative Toxicogenomics Database （CTD）. The target predictions of the components were performed by the Swiss Target Prediction tool. Neurotoxicity-related targets were collected from the Pharmacophore Mapping and Potential Target Identification Platform （PharmMapper）， GeneCards Human Gene Database （GeneCards）， DisGeNET Disease Gene Network （DisGeNET）， and Online Mendelian Inheritance in Man （OMIM）， and the intersection targets were identified. Protein-protein interaction （PPI） analysis， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis， and Gene Ontology （GO） enrichment analysis were conducted. A "drug-compound-toxicity target-pathway" network was constructed via Cytoscape software to display the core regulatory network. Based on the prediction results， the neurotoxicity mechanism of Dictamni Cortex in mice was verified by using hematoxylin-eosin （HE） staining， Nissl staining， enzyme-linked immunosorbent assay （ELISA）， quantitative real-time fluorescence polymerase chain reaction （Real-time PCR）， and Western blot. The effects of Dictamni Cortex on the metabolic profile of mouse brain tissue were further explored by non-targeted metabolomics. ResultsNetwork toxicology screening identified 13 compounds and 175 targets in Dictamni Cortex that were related to neurotoxicity. PPI network analysis revealed that serine/threonine-protein kinase （Akt1） and tumor protein 53 （TP53） were the core targets. Additionally， GO/KEGG enrichment analysis indicated that Dictamni Cortex may regulate the phosphatidylinositol 3-kinase （PI3K）/Akt pathway and affect oxidative stress and cell apoptosis， thereby inducing neural damage. The "Dictamni Cortex-compound-toxicity target-pathway-neural damage" network showed that dictamnine， phellodendrine， and fraxinellone may be the toxic compounds. Animal experiments showed that compared with those in the blank group， the hippocampal neurons in the brain tissue of mice treated with Dictamni Cortex were damaged. The level of superoxide dismutase （SOD） and acetylcholine （ACh） in the brain tissue was significantly reduced， while the content of malondialdehyde （MDA） was significantly increased. The level of Akt1 and p-Akt1 mRNAs and proteins in the brain tissue was significantly decreased， while the level of TP53 was significantly increased. Non-targeted metabolomics results showed that Dictamni Cortex could disrupt the level of 40 metabolites in mouse brain tissue， thereby regulating the homeostasis of 13 metabolism pathways， including phenylalanine， glycerophospholipid， and retinol. Combined analysis revealed that Akt1， p-Akt1， and TP53 were significantly correlated with phenylalanine， glycerophospholipid， and retinol metabolites. This suggested that Dictamni Cortex induced neurotoxicity in mice by regulating Akt1， p-Akt1， and TP53 and further modulating the phenylalanine， glycerophospholipid， and retinol metabolism pathways. ConclusionDictamni Cortex can induce neurotoxicity in mice， and its potential mechanism may be closely related to the activation of oxidative stress， inhibition of the PI3K/Akt signaling pathway， and regulation of phenylalanine， glycerophospholipid， and retinol metabolism pathways.

ObjectiveThis study aims to investigate the effect of Dictamni Cortex on intestinal barrier damage in rats and its mechanism by untargeted metabolomics and targeted metabolomics for short-chain fatty acids （SCFAs）. MethodsRats were randomly divided into a control group， a high-dose group of Dictamni Cortex （8.1 g·kg^-1）， a medium-dose group （2.7 g·kg^-1）， and a low-dose group （0.9 g·kg^-1）. Except for the control group， the other groups were administered different doses of Dictamni Cortex by gavage for eight consecutive weeks. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the ileal tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the level of cytokines， including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）， in the ileal tissue of rats. Quantitative real-time fluorescence polymerase chain reaction （Real-time PCR） technology was used to detect the expression level of tight junction proteins， including zonula occludens-1 （ZO-1）， Occludin， and Claudin-1 mRNAs， in the ileal tissue of rats to preliminarily explore the effects of Dictamni Cortex on intestinal damage. The dose with the most significant toxic phenotype was selected to further reveal the effects of Dictamni Cortex on the metabolic profile of ileal tissue in rats by non-targeted metabolomics combined with targeted metabolomics for SCFAs. ResultsCompared with the control group， all doses of Dictamni Cortex induced varying degrees of pathological damage in the ileum， increased TNF-α （P<0.01）， IL-6 （P<0.01）， and IL-1β （P<0.01） levels in the ileal tissue， and decreased the expression level of ZO-1 （P<0.05， P<0.01）， Occludin （P<0.01）， and Claudin-1 （P<0.05） in the ileal tissue， with the high-dose group showing the most significant toxic phenotypes. The damage mechanisms of the high-dose group of Dictamni Cortex on the ileal tissue were further explored by integrating non-targeted metabolomics and targeted metabolomics for SCFAs. The non-targeted metabolomics results showed that 21 differential metabolites were identified in the control group and the high-dose group. Compared with that in the control group， after Dictamni Cortex intervention， the level of 14 metabolites was significantly increased （P<0.05， P<0.01）， and the level of seven metabolites was significantly decreased （P<0.05， P<0.01） in the ileal contents. These metabolites collectively acted on 10 related metabolic pathways， including glycerophospholipids and primary bile acid biosynthesis. The quantitative data of targeted metabolomics for SCFAs showed that Dictamni Cortex intervention disrupted the level of propionic acid， butyric acid， acetic acid， caproic acid， isobutyric acid， isovaleric acid， valeric acid， and isocaproic acid in the ileal contents of rats. Compared with those in the control group， the level of isobutyric acid， isovaleric acid， and valeric acid were significantly increased， while the level of propionic acid， butyric acid， and acetic acid were significantly decreased in the ileal contents of rats after Dictamni Cortex intervention （P<0.05， P<0.01）. ConclusionDictamni Cortex can induce intestinal damage by regulating glycerophospholipid metabolism， primary bile acid biosynthesis， and metabolic pathways for SCFAs.

Objective:To understand the current status of human resources in Operating Room nursing in China, so as to provide reference for nursing management, human resource allocation, nursing education and training in Operating Rooms.Methods:Using the stratified sampling method, a self-made Operating Room nursing human resource survey questionnaire of Chinese Nursing Society was used as a research tool in July 2021 to investigate the general situation, surgical workload, human resource allocation, Operating Room management, Operating Room information construction, nursing education and training of 2 201 hospitals in 31 provinces, autonomous regions and municipalities of China.Results:Among the 2 201 hospitals, there were 1 021 tertiary hospitals (46.39%), 1 177 secondary hospitals (50.75%), and 63 primary and below hospitals (2.86%). There were 2 056 hospitals with less than 30 Operating Rooms, accounting for 93.41%. There were 1 991 hospitals with an annual number of surgical cases less than 20 000, accounting for 90.46%, the educational background of Operating Room nurses was mainly undergraduate (66.93%, 43 359/64 780), with a total of 67.99% (44 045/64 780) having a bachelor's degree or above. Nurses were the main professional titles (42.66%, 27 632/64 780). Number of Operating Rooms: the number of Operating Room nurses (median) was 1: 2.43 and 78.96% (1 738/2 201) of hospital operating theatres were managed by Nursing Departments or hospitals. A total of 1 479 hospitals (67.20%) established anesthesia recovery rooms in their Operating Rooms, which was higher than 59.34% (1 210 hospitals) surveyed in 2016, and the difference was statistically significant (χ 2=226.701, P<0.01). 74.69% (1 644/2 201) and 87.87% (1 934/2 201) of hospitals carried out post management and capacity classification management in Operating Rooms, respectively. Day surgery and robotic surgery were performed in 47.80% (1 052/201) and 7.68% (169/2 201) hospitals, respectively. 36.98% (814/2 201) of the hospitals passed the information evaluation system certification and 64.61% (1 422/2 201) of the hospitals used the Operating Room information management system. In the Operating Room information system of the hospital, 2.54% (56/2 201) had intelligent functions. And 77.24% (1 700/2 201) of hospitals participated in the qualification training of Operating Room specialist nurses. Conclusions:By July 2021, the number of Operating Rooms in most hospitals in China is less than 30, and the annual number of operating cases is less than 20 000. The educational background and professional title of Operating Room nurses are mainly undergraduate and nurse. More than 60% of hospitals have set up anesthesia recovery rooms and have information management systems for Operating Rooms. At the same time, Operating Rooms in Chinese hospitals have widely implemented diversified nursing management models such as post management and ability grading management.

Objective:To investigate the alterations of multilayer network and dynamic causal connectivity in patients with bilateral sudden sensorineural hearing loss.Methods:The hearing ability, neural-scale data and resting-state functional magnetic resonance imaging(fMRI)data of 60 patients with bilateral sudden sensorineural hearing loss from the Department of Otolaryngology and 60 healthy controls from Physical Examination Center, Nanjing First Hospital were collected from January 2022 to January 2024. Multilayer brain network analysis was computed to identify the nodes with abnormal switching rate. Then these abnormal nodes were used as regions of interest (ROIs) in the subsequent dynamic causal model analysis. The SPSS 26.0 software was used to analyze causal connectivity between two groups based on independent-sample Mann-Whitney U test. And Pearson correlation coefficients between fMRI results and clinical parameters were calculated. Results:Pure tone audiometry test showed that the left and right hearing thresholds of bilateral sudden sensorineural hearing loss were significantly higher than those of healthy controls( Z=-9.460, -9.462, both P<0.01). The score of depressive emotion in patients with bilateral sudden hearing loss was 6.00(2.00, 9.00).Multilayer brain network analysis showed that the switching rates in the left superior frontal gyrus (0.073(0.049, 0.102), Z=3.603, P<0.001), left anterior cingulate gyrus (0.077(0.044, 0.105), Z=3.189, P=0.001), right hippocampus (0.080(0.045, 0.116), Z=3.616, P<0.001), left para-hippocampal gyrus (0.080(0.043, 0.108), Z=3.577, P<0.001), left superior parietal gyrus (0.079(0.047, 0.103), Z=3.160, P=0.002), and right inferior parietal gyrus (0.078(0.043, 0.105), Z=3.396, P<0.001) in patients with bilateral sudden sensorineural hearing loss were lower that those in healthy controls. These six brain areas were used as ROIs to compute dynamic causal model analysis, and the results showed that the connection strength from left superior frontal gyrus to the left para-hippocampal gyrus in patients with bilateral sudden sensorineural hearing loss was significantly higher than that in healthy controls ( Z=-2.593, P<0.05). Additionally, enhanced connectivity from left superior frontal gyrus to the left para-hippocampal gyrus was positively correlated with duration of hearing loss ( r=0.376, P=0.003). Conclusions:Bilateral sudden sensorineural hearing loss patients have decreased switching rates in many brain areas, and the causal connectivity from left superior frontal gyrus to the left para-hippocampal gyrus is enhanced.

Unplanned readmission is one of the adverse outcomes of patients after left ventricular assist device implantation,which seriously affects the prognosis of patients.This article reviews the incidence,causes,influencing factors and intervention measures of unplanned readmission of patients after left ventricular assist device implantation,in order to improve the attention of nursing staff,early identify high-risk groups of unplanned readmission of patients after left ventricular assist device implantation and provide references for formulating personalized intervention measures.

Objective:To consolidate the current evidences regarding the efficacy of vitamin D supplementation in age-related sarcopenia.Methods:In this systemic review, a comprehensive literature search of scientific research including journal articles and academic dissertations was performed in prominent databases such as PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang Database platforms, spanning from January 31, 2014 to January 31, 2024. Two search protocols integrating keywords and citation tracking were adopted to ensure comprehensiveness of the literature. Using “vitamin D” “ergocalciferols” “cholecalciferol” “sarcopenia” “muscle mass” “muscle strength” “myopenia” “muscle loss” “muscle reduction” “gait speed” “grip strength” “handgrip” as the main key words, focusing on the systematic reviews, meta-analyses of randomized controlled trials (RCT), and individual RCT, the scientific evidence of individual vitamin D intervention on age-related sarcopenia was evaluated and summarized. Research concerning particular disease conditions, children and adolescents, menopausal women, athletes and other specific populations were excluded.Results:A initial search yielded 2 448 articles in Chinese or English. A total of 8 systemic reviews/meta-analysis and 22 individual RCT literatures were included in the final analysis. Although some earlier lower-quality studies reported subtle improvements in skeletal muscle strength with vitamin D supplementation, high-quality systematic reviews/meta-analysis over the past three years had not shown significant positive effects of vitamin D intervention on sarcopenia and its breakdown parameters, such as skeletal muscle mass, muscle strength, and muscle function. Furthermore, the efficiency was influenced to some extent by the participants′ baseline status, such as muscle health and vitamin D nutritional status.Conclusions:Present evidence does not robustly support the efficacy of sole vitamin D supplement on age-related sarcopenia. High-quality clinical trials are imperative to accumulate more robust evidence in the future.

Objective:To explore the relationship between insomnia and osteoporosis.Methods:Mendelian randomization (MR) analysis were used in this study. The single nucleotide polymorphisms (SNPs) related to insomnia from genome-wide association analysis research data were selected as the instrumental variables by using inverse variance weighted (IVW), MR-Egger regression, weighted median method, maximum likelihood, penalized weighted median estimator, and Mendelian randomization robust adjusted profile score (MR-RAPS) to determine the causal relationship between insomnia and osteoporosis. Odds ratio ( OR) and 95% confidence interval ( CI) values were used to evaluate the association between insomnia and osteoporosis. Cochran′s Q-test was used to detect heterogeneity of SNPs, MR-Egger regression was used to test for level pleiotropy, and the leave-one-out method was used to test sensitivity, MR pleiotropy residual sum and outlier (MR-PRESSO) method and radial MR were used to detect erroneous outliers. Results:The screening criteria were set based on the three major assumptions of MR; finally, 31 SNPs were included in the MR analysis. The results of MR causal effect analysis using the IVW method showed that insomnia increased the risk of osteoporosis by about 0.7% ( OR=1.007, 95% CI 1.001-1.014, P=0.044); heterogeneity testing showed heterogeneity between SNPs ( Q=57.91, P<0.001); and the MR- Egger intercept test did not indicate horizontal pleiotropy in this study (intercept value=3.807×10 -5, P=0.888). Leave-one-out method showed that no single SNP had a significant impact on the overall results. No abnormal SNP was detected according to the MR-PRESSO results ( P=0.059), and radial MR did not detect any outliers. Conclusion:Mendelian randomization analysis showed that insomnia can increase the risk of osteoporosis.

Objective: This study aims to clarify the mechanical action of cyclin-dependent protein kinase 1 (CDK1) in the development of endometrial carcinoma (EMCA), which may be associated with the phosphorylation of kinesin family member C1 (KIFC1) and further activate the PI3K/AKT pathway. Methods: The protein and gene expression of CDK1 in EMCA tissues and tumor cell lines were evaluated by western blot, quantitative polymerase chain reaction, and immunohistochemistry staining. Next, Cell Counting Kit-8 and colony formation assay detected cell survival and proliferation. Cell migration and invasion were measured by Transwell assay. Cell apoptosis and cell cycle were tested by flow cytometry.Immunofluorescence staining of γH2AX was used to evaluate DNA damage, respectively.Subsequently, a co-immunoprecipitation assay was used to detect the interaction between CDK1 and KIFC1. The phosphorylated protein of KIFC1 and PI3K/AKT was detected by western blot. Finally, the effect of CDK1 on the tumor formation of EMCA was evaluated in a nude mouse xenograft model. Results: CDK1 was highly expressed in EMCA tumor cell lines and tissues, which contributed to cell survival, proliferation, invasion, and migration, inhibited cell apoptosis, and induced DNA damage of EMCA cells dependent on the phosphorylation of KIFC1. Moreover, the CDK1-KIFC1 axis further activated PI3K/AKT pathway. Finally, CDK1 knockdown repressed tumor formation of EMCA in vivo. Conclusion We report that increased CDK1 promotes tumor progression and identified it as a potential prognostic marker and therapeutic target of EMCA.

Objective:To explore the association between aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms and abnormal liver function-induced by acetaminophen (APAP) drugs.Methods:An ALDH2 gene knockout mouse model was constructed using CRISPR/Cas9 gene editing technology. The obtained heterozygous mice were mated with opposite sex of heterozygotes. Genomic DNA was extracted from the tail of the offspring mouse. The polymerase chain reaction (PCR) method was used to determine the ALDH2 genotype. APAP was further used to induce acute drug-induced liver injury models in wild-type and ALDH2 knockout mice. Blood and liver tissues of mice were collected for liver function index, HE staining, F4/80 immunohistochemistry, and other detections. The intergroup mean was compared using a one-way ANOVA. The LSD-? t test was used for pairwise comparison. Results:ALDH2 knockout mice were bred successfully. The genotyping of the offspring was segregated into the wild-type (ALDH2 +/+), heterozygous mutant (ALDH2 +/-), and homozygous mutant (ALDH2 -/-), respectively. Biochemical and histological results after APAP modeling showed that the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) was not significantly increased in the blank control group ( P ?

Objective To explore the value of the combination of serum hemoglobin A1c(HbA1c),Alarin and Ficolin-3 in predicting adverse pregnancy outcomes in patients with gestational diabetes mellitus(GDM).Methods From March 2021 to March 2023,129 GDM patients who underwent prenatal examination and hospital delivery in Yantai Yeda Hospital were collected as the GDM group,while 133 pregnant women with normal glucose tolerance test results were regarded as the control group.Fully automated glycated hemoglobin analyzer was applied to detect serum HbA1c level.Enzyme linked immunosorbent assay(ELISA)was applied to detect serum Alarin and Ficolin-3 levels.Pearson method was used to analyze the correlation between serum HbA1c,Alarin,Ficolin-3 levels and 2 hour postprandial glucose(2 h PG),fasting blood glucose(FBG)and homeostasis model assessment method for insulin resistance(HOMA-IR)in GDM patients.Logistic regression was applied to analyze the relationship between HbA1c,Alarin,Ficolin-3 levels and adverse pregnancy outcomes in GDM patients.Receiver operating characteristic(ROC)curve was plotted to analyze the value of serum HbA1c,Alarin and Ficolin-3 levels in predicting adverse pregnancy outcomes in GDM patients.Results The 2 h PG,FBG,HOMA-IR,and serum HbA1c,Alarin,and Ficolin-3 levels were significantly higher in the GDM group than those in the control group(P＜0.05).The serum levels of HbA1c,Alarin and Ficolin-3 were positively correlated with 2 h PG,FBG and HOMA-IR in GDM patients(P＜0.05).The serum HbA1c,Alarin and Ficolin-3 levels were greatly higher in GDM patients with poor blood glucose control than those in GDM patients with good blood glucose control(P＜0.05).The above levels of three indicators in GDM patients with adverse pregnancy outcomes were significantly higher than those in GDM patients without adverse pregnancy outcomes(P＜0.05).Elevated levels of HbA1c,Alarin and Ficolin-3 were independent risk factors for adverse pregnancy outcomes in GDM patients(P＜0.05).The area under the curves of HbA1c,Alarin and Ficolin-3 alone and in combination were 0.840,0.865,0.815 and 0.979,respectively in predicting adverse pregnancy outcomes in GDM patients.Conclusion The serum HbA1c,Alarin and Ficolin-3 levels are abnormally elevated in GDM patients,and the combined detection of the three can improve the value in predicting adverse pregnancy outcomes.