ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 （GluR2）/Parkin signal-mediated mitophagy in rats with diabetes-related depression （DD）. MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin （STZ） tail intravenous injection + 28 days of chronic unpredictable mild stress （CUMS） combined with isolation. The rats were randomly divided into a normal group， a model group， a GluR2 blocker group （5 μg·kg^-1）， a GluR2 agonist group （10 μg·kg^-1）， a metformin + fluoxetine group （0.18 g·kg^-1 metformin + 1.8 mg·kg^-1 fluoxetine）， and high- and low-dose Zuogui Jiangtang Jieyu prescription groups （20.52 and 10.26 g·kg^-1， respectively）. The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling， respectively， while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate （ATP） in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine （5-HT） and dopamine （DA） in hippocampus were detected by enzyme-linked immunosorbent assay （ELISA）. The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2， Parkin， regulating synaptic membrane exocytosis protein 3 （RIMS3）， and postsynaptic density protein 95 （PSD95） in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group， the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming （P<0.01）， lowered levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.01）， increased autophagosomes of hippocampal neurons， significantly damaged morphology and structure of dendrites and spines of hippocampal neurons， decreased expression levels of GluR2， RIMS3， and PSD95 in hippocampus， and an increased Parkin expression level （P<0.05， P<0.01）. Compared with the model group， the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes， respectively （P<0.05， P<0.01）. The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically， the two groups saw elevated levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.05， P<0.01）， restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons， up-regulated protein expression levels of GluR2， RIMS3， and PSD95， and down-regulated Parkin expression level （P<0.05， P<0.01）. ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats， the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.

In September 2023， the Measures for Scientific and Technological Ethics Review （Trial Implementation） was issued， revising the provisions related to the simplified procedure for ethical review in Chapter 3， Section 3. This revision of these provisions provides systematic guarantees for further optimizing ethical review work， ensuring that ethical review procedure is well-regulated， and improving scientific research efficiency. The “simplified procedure” does not mean reducing the quality and requirements of the review. Instead， based on always following internationally recognized ethical standards and emphasizing not violating national laws and regulations， improving the efficiency of ethical review and subsequent research work， and promoting the development of life sciences and medical research involving humans. In practical work， it introduces numerous new opportunities and challenges for the improvement of ethics review ability， such as new tests on the judgment and decision-making power of ethics committees， how to ensure the reliability and controllability of the conditions related to the simplified review procedure， and how to determine the basic conditions for adopting the simplified review procedure for review. Therefore， to actively respond to the challenges and possible risks brought by the simplified procedure review， efforts should be made to achieve three “unifications”， including the unification of researchers’ moral autonomy and the heteronomy of supervision implemented by relevant departments； the unification of the standard formulation of the simplified procedure review and the review work in practice； and the unification of ethical responsibility and legal responsibility.

Objective: To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

Objective:To retrieve, evaluate, and integrate the best evidence for the management of neurogenic bowel dysfunction (NBD) in spinal cord injury patients both domestically and internationally, providing a basis for relevant evidence-based practices.Methods:The guidelines, expert consensus, clinical decision-making, and systematic review of NBD management for spinal cord injury patients were electronically searched in various databases and professional association websites at home and abroad. The search period was from database establishment to March 31, 2023.Results:A total of 13 articles were included, including five guidelines, five evidence summaries, two expert consensus, and one clinical decision-making. A total of 33 recommendations for NBD management in spinal cord injury patients were summarized from five aspects of medical history assessment, medication management, physical therapy, diet and exercise, and health education.Conclusions:The best evidence for NBD management in spinal cord injury patients summarized is scientific and practical. Medical and nursing staff should selectively apply the best evidence based on clinical practice.

Objective:To explore the characteristic categories of kinesiophobia in postoperative cardiac surgery patients and analyze the influencing factors.Methods:Using the convenient sampling method, a total of 225 inpatients from Cardiothoracic and Vascular Surgery Department of Affiliated Nanjing Hospital, Nanjing Medical University (Nanjing First Hospital) were selected as the research objects from June 2022 to April 2023. The inpatients were investigated by general information questionnaire, Numerical Rating Scale (NRS), Brief Illness Perception Questionnaire (BIPQ) and the Tampa Scale for Kinesiophobia Heart (TSK-SV Heart). The latent profile analysis was used to classify the types of kinesiophobia in postoperative cardiac surgery patients, and the Logistic regression was used to analyze the influencing factors of different categories of kinesiophobia in postoperative cardiac surgery patients.Results:A total of 225 questionnaires were distributed in this study, and 212 valid questionnaires were collected, with an effective response rate of 94.22% (212/225). There are three potential categories of kinesiophobia in postoperative cardiac surgery patients, with the low kinesiophobia group accounting for 30.66% (65/212), the low risk perception high exercise fear group accounting for 48.58% (103/212), and the severe kinesiophobia group accounting for 20.75% (44/212). There were statistically significant differences in cognitive dimension scores, fatigue, sleep quality, postoperative presence of high-risk pipelines, history of cardiovascular surgery, and duration of illness among patients of different potential categories ( P<0.05) . Conclusions:There are three different categories of kinesiophobia in postoperative cardiac surgery patients. Medical staff should develop targeted intervention measures for different categories of patients to assist in reducing exercise fear and promoting cardiac recovery.

Objective To investigate the relationship between serum L-carnitine and its related metabolites[trimethylamine(TMA)and trimethylamine N-oxide(TMAO)]levels and gestational diabetes mellitus(GDM)in the second trimester of pregnant women in Shanghai.Methods A case-control study was conducted in 280 pregnant women between 18 and 23 weeks of gestation from January 2018 to January 2021.Among them,134 cases of GDM were the case group(GDM),and 146 cases with normal blood glucose(BG)were the control group(Con).Serum L-carnitine,TMA and TMAO levels were quantified by ultra high performance liquid chromatography-mass spectrometry.Logistic regression analysis,stratified analysis and linear regression were used to explore the relationship between L-carnitine,TMA and TMAO levels and GDM and glucolipid metabolism.Results Serum L-carnitinelevelwas significantly lower in GDM group than that in Con group(P<0.01).After adjusting for confounders,logistic regression showed a 70%reduction in the risk of GDM in the group with highest tertile of L-carnitine compared with the group with lowest tertile(OR 0.30,95%CI 0.15～0.63).The risk of GDM decreased by 14%for each 1 μmol/L increase in serum L-carnitine(OR 0.86,95%CI 0.80～0.93).Serum L-carnitine was negatively correlated with 1 hPG(r=-0.21,P<0.01)and 2 hPG(r=-0.15,P<0.05),respectively,TMA was negatively correlated with 2 hPG(r=-0.21,P<0.01).Conclusions Higher serum L-carnitine level may be negatively associated with GDM.Serum L-carnitine and TMA levels were negatively correlated with blood glucose levels.

Sepsis is a prevalent form of acute and critical illness encountered in intensive care unit (ICU), characterized by a high mortality and cognitive impairments among survivors. The pathogenesis of sepsis primarily involves immune dysfunction and excessive oxidative stress. Consequently, immune modulation, along with anti-inflammatory and antioxidant strategies, has emerged as a focal point in the treatment of sepsis. Recent studies have highlighted the potential of B vitamins to modulate immune cell activity while exhibiting anti-inflammatory and antioxidant properties, thereby garnering significant interest regarding their therapeutic efficacy in sepsis management. Notably, vitamin B2 and vitamin B9 are recognized for their roles in regulating immune cells and facilitating immune modulation. Vitamins B1, B2, B6, and B12 demonstrate notable anti-inflammatory and antioxidant effects. Specifically, vitamin B1 exerts its antioxidant influence through the regulation of the tricarboxylic acid cycle while mitigating inflammation by modulating inflammatory factor levels in septic patients—an application that has been integrated into clinical practice. The anti-inflammatory action of vitamin B2 is achieved through the regulation of inflammatory mediators in septic patients alongside reducing inflammasome activation within macrophages. Vitamin B6 contributes to both anti-inflammatory responses and antioxidative defense by scavenging free radicals and enhancing the production of antioxidant enzymes. Furthermore, vitamins B1, B6, B9, and B14 have shown promise in improving neurocognitive function among individuals suffering from sepsis. This article reviews the immunomodulatory functions as well as the anti-inflammatory and antioxidative effects associated with various B vitamins while exploring their applications within sepsis treatment to propose novel therapeutic avenues.

Purpose/Significance To analyze the network security risk events monitored by the situational awareness platform of large hospitals,to find out the causes,and to put forward solutions and suggestions for improvement.Method/Process Taking the First Affiliated Hospital of Zhengzhou University as an example,the paper analyzes risk events on the situational awareness platform,screens the risky ter-minals on the hospital intranet,carries out rectification and reinforcement,analyzes the department distribution and causes of risky termi-nals,and puts forward suggestions for improvement.Result/Conclusion The number of risky terminals in medical and technical depart-ments is large,mainly due to the lack of management and the lack of full coverage of antivirus software.Through the rectification and rein-forcement of risky terminals,the number of network security risk events has been significantly reduced.Strengthening the hospital terminal security management,enhancing staff awareness of network security,and strengthening network security protection in different areas can ef-fectively reduce the incidence of hospital network security risk events and improve the hospital network security protection capability.

AIM:To explore the mechanism by which Chaijin-Jieyu-Anshen tablet(CJJY)-medicated serum prevents synaptic injury in rat anterior cingulate cortex(ACC)neurons using an in vitro depression model.METHODS:Cells(astrocytes,microglia and neurons)were isolated from the ACC of SD rats.The isolated cells were characterized by immunofluorescence staining.An in vitro depression model was developed using 1 mg/L lipopolysaccharide(LPS)com-bined with 200 μmol/L corticosterone(CORT).These cells were divided into control group,model group(CORT+LPS),glucocorticoid receptor(GR)blocker(GR-)group(CORT+LPS+RU486),GR agonist(GR+)group(CORT+LPS+dexa-methasone),CX3C chemokine receptor 1(CX3CR1)blocker(CX3-)group(CORT+LPS+AZD8797),CX3CR1 agonist(CX3+)group(CORT+LPS+fractalkine),CJJY group(CORT+LPS+CJJY-medicated serum),CJJY/GR+group(CORT+LPS+CJJY-medicated serum+dexamethasone),and CJJY/CX3+group(CORT+LPS+CJJY-mediated serum+fractalkine).The morphological characteristics of all ACC cells were observed by high-content analysis.The levels of neuroendocrine-related factors,adrenocorticotropic hormone(ACTH),corticotropin-releasing hormone(CRH)and CORT,and neuroin-flammatory mediators,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6 and glutamate(Glu),in the cell supernatants were quantified by ELISA.Immunofluorescence staining was used to analyze the protein expression of GR and vesicular glutamate transporter 1(VGluT1)in astrocytes,as well as CX3CR1 and adenosine A2A receptor(A2AR)in microglia.Immunofluorescence staining with Nissl and β-tubulin was performed to evaluate synaptic damage in ACC neurons.RESULTS:In an in vitro model of depression,CJJY-medicated serum prevented morphological damage to ACC neurons,microglia and astrocytes.Moreover,CJJY-medicated serum reversed abnormal increases in the levels of ACTH,CRH,CORT,TNF-α,IL-1β,IL-6 and Glu in cell supernatants(P<0.05 or P<0.01).It was also found that CJJY-medi-cated serum reduced abnormal expression of GR,VGluT1,CX3CR1 and A2AR(P<0.05 or P<0.01),alleviating damage to the neuronal dendrites and dendritic spines of ACC neurons.CONCLUSION:The CJJY-medicated serum regulates GR/CX3CR1 double signaling in glia,and attenuates rat ACC neuronal synaptic damage in an in vitro depression model,indicating that CJJY-medicated serum controls depression by affecting the GR/CX3CR1 double signaling.

ObjectiveTo explore and verify the key pathway of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression by means of gene set enrichment analysis （GSEA） and short time-series expression miner （STEM）. MethodSD rats were randomly divided into six groups， including a normal group， a model group， high， medium， and low dose groups of Zuogui Jiangtang Jieyu prescription， and a positive drug group. The model of diabetes with depression was established by high-fat feeding， streptozotocin （STZ） injection， and chronic mild unpredictable stress. The high， medium， and low dose groups of Zuogui Jiangtang Jieyu prescription were orally administered at 20.52， 10.26， and 5.13 g·kg^-1 respectively. The positive drug group was orally administered 0.18 g·kg^-1 metformin and 1.8 g·kg^-1 fluoxetine. The rats in the normal group and model group were administered with an equal volume of distilled water. After 28 days， the animals were tested for depressive-like behaviors and cognitive function using the forced swimming test and Morris water maze. Fasting blood glucose was measured using blood glucose test strips. Cholesterol and triglyceride levels were measured using enzyme-linked immunosorbent assay （ELISA）. Three hippocampus samples were randomly selected from the normal group， the model group， the high dose group of Zuogui Jiangtang Jieyu prescription for high-throughput transcriptome sequencing. Differential gene analysis， GSEA analysis， and STEM analysis were used to screen the key pathways and target genes of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression. Key target genes were validated using real-time fluorescence quantitative PCR （Real-time PCR）. The expression of the signal protein mediated by the target genes was detected by Western blot. ResultCompared with the results in the normal group， the fasting blood glucose， cholesterol， and triglyceride levels in the model group were significantly increased （P<0.01）. Moreover， the immobility time in the forced swimming test was significantly increased， while the time to climb the platform was significantly prolonged， and the search distance in the target quadrant was significantly reduced in the Morris water maze test （P<0.05，P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly reduced the levels of blood glucose， cholesterol， and triglycerides in rats with diabetes with depression （P<0.05，P<0.01）， reduced the immobility time in the forced swimming test， shortened the stage time in the Morris water maze test， and increased the search distance ratio in the target area （P<0.05，P<0.01）. Transcriptome sequencing differential analysis showed that the normal group had 1 366 differentially expressed genes compared to the model group， while the model group had 1 149 differentially expressed genes compared to the high dose group of Zuogui Jiangtang Jieyu prescription， with 581 intersecting genes. The GSEA results showed that there were 9 sets of differentially expressed genes between the normal group and the model group， and 43 sets of differentially expressed genes between the model group and the high dose group of Zuogui Jiangtang Jieyu prescription， with 7 intersecting gene sets. STEM analysis showed that according to the analysis order of the normal group， model group， and high dose group of Zuogui Jiangtang Jieyu prescription， two significantly different trend clustering groups were obtained. One key gene set for axonal guidance， as well as key target signal elements Sema3c， Sema7a， Robo3， Epha8， and Epha7， were identified through synthesizing the three analysis results. Real-time PCR validated that compared with the results in the normal group， the mRNA expression of Robo3， Sema7a， and Epha7 in the hippocampus of the model rats was significantly reduced （P<0.05， P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the mRNA expression of Robo3， Sema7a， and Epha7 （P<0.05， P<0.01）. Western blot results showed that compared with the results in the normal group， the Sema7a， ITGB1， and FAK protein expression in the hippocampus of the model group was significantly reduced （P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the protein expression of Sema7a， ITGB1， and FAK in the hippocampus （P<0.05，P<0.01）. ConclusionZuogui Jiangtang Jieyu prescription may treat diabetes with depression by regulating axonal guidance based on the Sema7a/ITGB1 signaling pathway.