Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Objective:To analyze the multimodal ultrasound characteristics of primary breast cancer and sentinel lymph node (SLN) and to establish a nomogram model for predicting SLN metastasis in invasive breast cancer, thereby providing reference for precise clinical diagnosis and treatment.Methods:A total of 329 patients diagnosed with invasive breast cancer and admitted to the Affiliated Hospital of Nanjing University of Chinese Medicine from June 2018 to October 2023 were retrospectively enrolled. They were randomly divided into a training cohort ( n=230) and a validation cohort ( n=99) in a ratio of 7 to 3. In the training cohort, ultrasound findings and clinical parameters were analyzed, univariate and multivariate Logistic regression analyses were used to identify independent predictive factors for SLN metastasis, and a nomogram model was constructed based on these factors. The ROC curve, calibration curve, and decision curve analysis (DCA) were plotted between the training and validation cohorts to assess the discrimination, calibration, and clinical applicability of the nomogram model. Results:Regression analysis identified 3 independent risk factors for establishing the nomogram prediction model: ratio of the long diameter to the short diameter of SLN ( P=0.020), lymphatic contrast-enhanced ultrasound (LCEUS) enhancement pattern ( P<0.001) and intravenous contrast-enhanced ultrasound (ICEUS) enhancement mode ( P=0.002). The area under the curve (AUC) of the training cohort was 0.888, the accuracy was 0.865; the AUC of the validation cohort was 0.870, the accuracy was 0.859, demonstrating good predictive performance of the model in both cohorts. The calibration curve demonstrated that the nomogram has a strong concordance between predicted and actual probability. DCA demonstrated that the nomogram could increase net benefit within a certain probability threshold range. Conclusions:The nomogram based on ratio of the long diameter to the short diameter of SLN, LCEUS enhancement pattern and ICEUS enhancement mode can effectively predict SLN status in patients with invasive breast cancer, facilitating precise diagnosis and treatment.

OBJECTIVE: To carry out genetic and metabolite analysis for an infant with cerebral creatine deficiency syndrome type 2 (CCDS2). METHODS: Clinical data of the child was collected. Whole-exome sequencing was carried out to identify potential variants by next generation sequencing. Candidate variants were confirmed by Sanger sequencing. Metabolites were determined by tandem mass spectrometry and magnetic resonance spectroscopy. Treatment was carried out following the diagnosis and genetic counseling for the affected family. RESULTS: Two novel heterozygous variants (c.289delC and c.392-1G>C) of the GAMT gene were identified in the proband, which were respectively inherited from her father and mother. In silico analysis suggested both variants to be pathogenic. Creatine (Cr) level of the child was very low, and cerebral guanidinoacetate (GAA) level was slightly increased. But both had recovered to normal in two weeks, and cerebral Cr level was significantly improved after two months. Intellectual and motor development of the child were significantly improved. CONCLUSION The child was diagnosed with CCDS type 2, for which pathogenic variants of the GAMT gene may be accountable. Treatment has attained a satisfactory effect for the patient.

Objective:To find out the occurrence of anxiety and depressive symptoms, and the major risk factors, and the participation rate, as well as the experience of medical personnel who are involved in the intervention.Methods:Since January 2018, a pilot intervention had been carried out on pregnant women registered in the antenatal clinic. The Generalized Anxiety Disorder Scale and the Patient Health Questionnaires were used as screening tools for anxiety and depression symptoms, and risk factors were screened too. Interventions were carried out on the psychological moderate and high risk women by obstetric medical staff and mental health personnel. A qualitative interview was conducted on the intervention providers.Results:A total of 9 488 pregnant women were included, and the positive rate of moderate anxiety symptoms was 3.0%, the positive rate of severe anxiety symptoms was 1.4%; the positive rate of moderate depression symptoms was 18.1%, and the positive rate of severe depressive symptoms was 5.2%; the comorbidity rate of anxiety and depression symptoms was 3.4%. The first three risk factors for pregnant women with anxiety symptoms were: once had premenstrual stress symptom, excessive fear of fetal growth, previous abnormal maternal history; the first three risk factors for pregnant women with depressive symptoms: once had premenstrual stress symptom, previous abnormal maternal history, this pregnancy was cherished; the first three risk factors for pregnant women with moderate and above anxiety combined with depression were: once had premenstrual stress symptom, excessive fear of fetal growth, and fear the delivery process is not successful. Among the psychological moderate risk pregnant women, 19.1% participated in the midwife joint counselor clinic, and 1.7% participated in the obstetrician joint psychological specialist nurse clinic, 2.2% of the pregnant women with high risk participated in the psychological multidisciplinary consultation, and 1.7% referred to the psychiatric department. From the interviews, providers believed that it was necessary to further strengthen the ability of psychological intervention capacity, and the psychological screening tools needed to be improved, and the problems sought by pregnant women involved in physical, psychological and social aspects, and the influence of pregnant women's treatment compliance included multiple factors.Conclusions:The psychological health care service during pregnancy was feasible, but the screening scales needed further examination. The mental health care ability of obstetric medical staff needed to be strengthened, and the compliance of pregnant women with mental health services needed to be improved.

OBJECTIVE：To provide reference for performance evaluation of pharmaceutical care for clinical pharmacists. METHODS：Based on literature review ，weighted TOPSIS method was used to formulate a performance evaluation system of pharmaceutical care. The performance of 120 pharmaceutical care work of 5 clinical pharmacists in our hospital from Jan. 2017 to Dec. 2018 was evaluated. RESULTS ：The performance evaluation detailed rules of clinical pharmacists ’pharmaceutical care work were successfully constructed ，including pharmaceutical ward round ，medication education ，medication consultation and pharmacy consultation，with a total of 17 evaluation indicators. Among 120 cases，there were 21 cases with relative approach degree ＞0.6 （17.5％）；73 cases had relative approach degree between 0.5 and ＜0.6（60.8％）；26 cases had relative approach degree between 0.4 and ＜0.5（21.7％）. The major problem was that the participation of clinical pharmacists in muti-disciplinary treatment ，the approval of scientific research fund projects were insufficient and not much paper was written. CONCLUSIONS ：The performance evaluation system of clinical pharmacists ’pharmaceutical care work based on weighted TOPSIS method is normative and reasonable，and it can be used in the evaluation of clinical pharmacists ’pharmaceutical care work . The results suggest that there are some defects in the performance of clinical pharmacists ’pharmaceutical care work in our hospital ，which need to be improved.

Antineoplastic Agents ; chemistry ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; immunology ; pathology ; Cytokines ; immunology ; Drug Screening Assays, Antitumor ; Glypicans ; antagonists & inhibitors ; immunology ; Humans ; Ligands ; Liver Neoplasms ; drug therapy ; immunology ; pathology ; T-Lymphocytes ; drug effects ; immunology

OBJECTIVE:To provide reference for rational application of Levofloxacin hydrochloride injection in the clinic. METHODS:With reference to the package insert of Levofloxacin hydrochloride injection,the guiding principles of clinical use of antibiotics,by reviewing related literatures,based on the weighted TOPSIS methods,detailed rules for drug utilization review (DUR) of Levofloxacin hydrochloride injection were made. And then 100 archived medical records of Levofloxacin hydrochloride injection in the first half of 2014 were evaluated in respect of medication rationality based on these rules. RESULTS:Among 100 cases,relative proximity of 51 cases was more than 70%(51.0%);that of 37 was between 50%-70%(37.0%);that of 12 cases was between 30%-50%(12.0%). CONCLUSIONS:Established DUR method of Levofloxacin hydrochloride injection on the basis of weighted TOPSIS methods can be used to evaluate the rationality of drug use and promote more rational evaluation behavior. And the results indicate that unreasonable use of Levofloxacin hydrochloride injection is still common in the hospital.