Objective:To explore the effects and mechanisms of Shen-su-yin (SSY) on acute lung injury (ALI) in rats based on untargeted Metabolomics, network pharmacology, and experimental verification.Methods:Untargeted Metabolomics was performed to detect the ingredients of SSY by using ultra-high performance liquid chromatography-Q-exactive orbitrap mass spectrum, and the active ingredients were screened from the detected ingredients. Common targets of the active ingredient targets and ALI targets were utilized to screen hub targets to perform gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Then, key hub targets were selected from the hub targets, and the active ingredients-hub targets network was built to screen core ingredients. Subsequently, molecular docking was performed between the key hub targets and the core ingredients. 48 rats were randomly and equally divided into 4 groups by using a random number table: normal control group, lipopolysaccharide-induced ALI group, ALI+SSY group, and ALI+dexamethasone group. 24 hours after lipopolysaccharide induction, the levels of respiratory rate, blood lactate, lung wet/dry weight ratio, ALI score, inflammatory factors of bronchoalveolar lavage fluid, and oxidative stress mediators of lung tissue in each group were evaluated, and the expression of phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-glycogen synthase kinase (GSK) 3β-nuclear factor erythroid 2-related factor 2 (Nrf2)/nuclear factor (NF)-κB signaling pathway was also detected by using Western blot. Finally, one-way analysis of variance, Welch test, or Kruskal-Wallis H test was used to compare data differences among groups. Results:A total of 415 ingredients were detected from the SSY. 66 of the detected ingredients were identified as active ingredients, and 10 of them were selected as core ingredients. The number of common targets, hub targets, and key hub targets was 337, 50, and 10, respectively. Total of 285 biological processes, 32 cellular components, and 51 molecular functions were enriched though GO analysis, and 148 cell signaling pathways such as pathways in cancer and PI3K-AKT signaling pathway were enriched though KEGG analysis. Molecular docking studies revealed that all binding energies between the 10 key hub targets and the 10 core ingredients were less than -5 kcal/mol. Compared with the ALI group, the levels of the respiratory rate, blood lactate, and lung wet/dry weight ratio in ALI+SSY group were significantly decreased (all P<0.01), and the level of ALI score showed a downward trend, but the difference was not statistically significant ( P>0.05). In addition, the levels of interleukin-6, interleukin-1β, and tumor necrosis factor-α in bronchoalveolar lavage fluid and the levels of malondialdehyde, protein carbonyl, and 8-hydroxy-2-deoxyguanosine in lung tissue of rats in ALI+SSY group were significantly decreased in comparison with those in ALI group (all P<0.01). Moreover, compared with the ALI group, the phosphorylation levels of PI3K p85α, AKT1, and GSK3β and the expression level of Nrf2 in lung tissue of ALI+SSY group were significantly up-regulated (PI3K p85α phosphorylation and AKT1 phosphorylation, P<0.01; GSK3β phosphorylation and Nrf2, P<0.05), while the phosphorylation level of NF-κB p65 was significantly down-regulated ( P<0.01). Conclusions:Active ingredients detected from SSY via untargeted Metabolomics can inhibit oxidative stress and inflammation in ALI rats by regulating the PI3K-AKT-GSK3β-Nrf2/NF-κB signaling pathway, thereby alleviating lung lesions.

BackgroundThe functional changes of the default mode network （DMN） are closely related to the onset of major depressive disorders. However， the relationship between the DMN subsystem （core subsystem， dorsomedial prefrontal cortex subsystem， medial temporal lobe subsystem） and symptoms of first-episode major depressive disorder remains unclear. ObjectiveTo investigate abnormal functional connectivity between DMN subsystems and the whole brain in first-episode major depressive disorder patients during the resting-state， and to analyse the correlations between these functional connectivity patterns and clinical symptoms， so as to reveal the potential neural mechanisms from the perspective of DMN subsystem. MethodsFrom September 2020 to September 2023， a total of 64 first-episode outpatients and inpatients meeting the diagnostic criteria for major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were enrolled at the Inner Mongolia Autonomous Region Mental Health Center as the study group. During the same period， 54 healthy volunteers matched for age， gender， and years of education were recruited from the community as the control group. Both groups were assessed using the Hamilton Depression Scale-24 item （HAMD-24）. Resting-state functional magnetic resonance images （rs-fMRI） of the two groups were acquired using a Siemens 3.0 T scanner， and differences in functional connectivity between DMN subsystems （core subsystem， dorsomedial prefrontal cortex subsystem， medial temporal lobe subsystem） and the whole brain were compared. The functional connectivity values of brain regions with statistically significant differences between the two groups were extracted. Spearman's rank correlation coefficient analysis was used to investigate the correlation between these functional connectivity values and HAMD-24 scores of the study group. ResultsUltimately， 46 patients and 43 controls completed the study. Compared with the control group， the study group exhibited significantly stronger functional connectivity in the following pathways： between the right superior parietal lobule （core subsystem） and right cerebellar lobule VIII （t=3.954， P<0.05， GRF-corrected）， between the right lateral temporal cortex （dorsomedial prefrontal cortex subsystem） and right cerebellar lobule VIII， right and left hippocampi， right medial， and paracingulate gyrus （t=4.595， 4.208， 5.200， 4.038， P<0.05， GRF-corrected）， and between the temporoparietal junction （dorsomedial prefrontal cortex subsystem） and left lingual gyrus and right cerebellar lobule VIII （t=3.557， 4.274， P<0.05， GRF-corrected）. Conversely， weaker functional connectivity was observed between the right inferior frontal gyrus and left gyrus rectus （t=-3.824， P<0.05， GRF-corrected）. Furthermore， within the study group， the functional connectivity values between the right lateral temporal cortex and right hippocampus， as well as between the temporoparietal junction and right cerebellar lobule VIII， were both negatively correlated with the HAMD-24 cognitive impairment factor score （r=-0.306， -0.318， P<0.05）. ConclusionIncreased functional connectivity between the DMN （specifically its core and dorsomedial prefrontal cortex subsystems） and cerebellum， partial limbic system， and lingual gyrus may be associated with the neuropathology of first-episode major depressive disorder. Furthermore， alterations in functional connectivity between the dorsomedial prefrontal cortex subsystem and both the cerebellum and hippocampus in these patients may be related to cognitive function. ［Funded by 2019 Annual Inner Mongolia Autonomous Region Natural Science Foundation Project （number， 2019MS03038）； 2023 Annual Inner Mongolia Autonomous Region Natural Science Foundation Project （number， 2023MS08028）］

Objective:To investigate the efficacy and treatment adherence of digital cognitive behavioral therapy for insomnia (dCBT-I) in patients with insomnia disorder accompanied by anxiety and depressive symptoms, and to provide empirical evidence for its clinical application.Methods:From December 2023 to December 2024, 102 patients with insomnia disorder accompanied by anxiety and depressive symptoms were recruited from the outpatient department of Inner Mongolia Brain Hospital and randomly assigned to either the dCBT-I group ( n=56) or the digital sleep hygiene education (dSHE) group ( n=46). The dCBT-I group received a 4-week intervention comprising 5 core modules, while the dSHE group received 4 weeks of digital sleep hygiene education. Both groups received weekly guidance from clinical psychologists. Subjective sleep quality (Insomnia Severity Index, ISI), anxiety (Hamilton Anxiety Scale, HAMA), and depressive symptoms (17-item Hamilton Depression Scale, HAMD 17) were assessed at baseline, week 4, week 8, and week 12. Objective sleep parameters (polysomnography, PSG) and cognitive function (Repeatable Battery for the Assessment of Neuropsychological Status, RBANS) were evaluated at baseline and week 4. Linear mixed-effects model was used to analyze the effects of group, timepoint, and their interaction on outcome measures, after controlling medication history, age, sex, education level, ethnicity, and marital status as covariates. Results:A total of 76 patients (dCBT-I: n=42; dSHE: n=34) completed the 4-week intervention, yielding a treatment adherence rate of 74.5%(76/102). At weeks 4, 8, and 12, the dCBT-I group demonstrated significantly lower scores on the ISI, HAMA, and HAMD 17 scales compared to the dSHE group (β=-1.70--0.66, t=-15.38--6.21, all P<0.05), along with higher rates of medication reduction (χ 2=16.40, 9.22, 6.66, all P<0.05). No significant differences were observed in PSG parameters between the two groups. However, the dCBT-I group demonstrated significant improvements in RBANS subdomains, including immediate memory, language function, and delayed memory (β=0.45, 0.86, 1.43, t=3.09, 2.67, 4.36, all P<0.05). Conclusion:dCBT-I is an effective and well-adhered intervention for patients with insomnia disorder accompanied by anxiety and depressive symptoms, warranting broader clinical implementation.

Objective:To investigate the efficacy and treatment adherence of digital cognitive behavioral therapy for insomnia (dCBT-I) in patients with insomnia disorder accompanied by anxiety and depressive symptoms, and to provide empirical evidence for its clinical application.Methods:From December 2023 to December 2024, 102 patients with insomnia disorder accompanied by anxiety and depressive symptoms were recruited from the outpatient department of Inner Mongolia Brain Hospital and randomly assigned to either the dCBT-I group ( n=56) or the digital sleep hygiene education (dSHE) group ( n=46). The dCBT-I group received a 4-week intervention comprising 5 core modules, while the dSHE group received 4 weeks of digital sleep hygiene education. Both groups received weekly guidance from clinical psychologists. Subjective sleep quality (Insomnia Severity Index, ISI), anxiety (Hamilton Anxiety Scale, HAMA), and depressive symptoms (17-item Hamilton Depression Scale, HAMD 17) were assessed at baseline, week 4, week 8, and week 12. Objective sleep parameters (polysomnography, PSG) and cognitive function (Repeatable Battery for the Assessment of Neuropsychological Status, RBANS) were evaluated at baseline and week 4. Linear mixed-effects model was used to analyze the effects of group, timepoint, and their interaction on outcome measures, after controlling medication history, age, sex, education level, ethnicity, and marital status as covariates. Results:A total of 76 patients (dCBT-I: n=42; dSHE: n=34) completed the 4-week intervention, yielding a treatment adherence rate of 74.5%(76/102). At weeks 4, 8, and 12, the dCBT-I group demonstrated significantly lower scores on the ISI, HAMA, and HAMD 17 scales compared to the dSHE group (β=-1.70--0.66, t=-15.38--6.21, all P<0.05), along with higher rates of medication reduction (χ 2=16.40, 9.22, 6.66, all P<0.05). No significant differences were observed in PSG parameters between the two groups. However, the dCBT-I group demonstrated significant improvements in RBANS subdomains, including immediate memory, language function, and delayed memory (β=0.45, 0.86, 1.43, t=3.09, 2.67, 4.36, all P<0.05). Conclusion:dCBT-I is an effective and well-adhered intervention for patients with insomnia disorder accompanied by anxiety and depressive symptoms, warranting broader clinical implementation.

Objective:The present study aims to investigate whether there is a shared alteration of the resting-state functional connectivity and amplitude of low frequency fluctuation (ALFF) within the limbic network across all three clinical phases of bipolar disorder.Methods:From July 2019 to December 2021, 107 patients diagnosed with bipolar disorder (bipolar disorder group) were recruited from the Institute of Mental Health at Xiangya Second Hospital, Central South University. Additionally, 46 healthy controls matched for age, gender, and education level were enrolled as the control group. According to the total scores of the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HAMD 17), individuals with bipolar disorder can be categorized into three groups: bipolar manic group, bipolar depressive group, and bipolar euthymic group. Resting state functional magnetic resonance imaging data were collected from all the participants, and seed-based functional connectivity and ALFF in the limbic network were conducted to compare differences among three mood states and controls using One-way ANOVA and post hoc analysis. Finally, correlation analyses using Pearson or Spearman coefficients were performed between statistically significant intergroup differences in functional connectivity/ALFF values and total scores as well as factor scores on clinical rating scales. Results:In comparison to the healthy controls, there was a significant decrease in functional connectivity between the anterior cingulate gyrus and hippocampus across all three clinical phases of bipolar disorder after Bonferroni correction ( t=-2.60--2.07, P<0.05). Furthermore, the ALFF in the anterior cingulate gyrus during three phases showed a significantl reduction following false discovery rate correction ( t=-4.41--3.51, P<0.05). Moreover, a decreased functional connectivity between the left anterior cingulate gyrus and left hippocampus during the depressive phase demonstrated a significant negative correlation with work interest subscores of the HAMD 17 ( r=-0.406, P=0.021). Conclusions:Dysconnectivity and reduced activity within the anterior cingulate of the limbic network may represent common alterations of mood regulation disorder throughout all three clinical phases of bipolar disorder.

Objective:The present study aims to investigate whether there is a shared alteration of the resting-state functional connectivity and amplitude of low frequency fluctuation (ALFF) within the limbic network across all three clinical phases of bipolar disorder.Methods:From July 2019 to December 2021, 107 patients diagnosed with bipolar disorder (bipolar disorder group) were recruited from the Institute of Mental Health at Xiangya Second Hospital, Central South University. Additionally, 46 healthy controls matched for age, gender, and education level were enrolled as the control group. According to the total scores of the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HAMD 17), individuals with bipolar disorder can be categorized into three groups: bipolar manic group, bipolar depressive group, and bipolar euthymic group. Resting state functional magnetic resonance imaging data were collected from all the participants, and seed-based functional connectivity and ALFF in the limbic network were conducted to compare differences among three mood states and controls using One-way ANOVA and post hoc analysis. Finally, correlation analyses using Pearson or Spearman coefficients were performed between statistically significant intergroup differences in functional connectivity/ALFF values and total scores as well as factor scores on clinical rating scales. Results:In comparison to the healthy controls, there was a significant decrease in functional connectivity between the anterior cingulate gyrus and hippocampus across all three clinical phases of bipolar disorder after Bonferroni correction ( t=-2.60--2.07, P<0.05). Furthermore, the ALFF in the anterior cingulate gyrus during three phases showed a significantl reduction following false discovery rate correction ( t=-4.41--3.51, P<0.05). Moreover, a decreased functional connectivity between the left anterior cingulate gyrus and left hippocampus during the depressive phase demonstrated a significant negative correlation with work interest subscores of the HAMD 17 ( r=-0.406, P=0.021). Conclusions:Dysconnectivity and reduced activity within the anterior cingulate of the limbic network may represent common alterations of mood regulation disorder throughout all three clinical phases of bipolar disorder.

[ ABSTRACT] AIM:To observe the effect of high glucose on the protein expression of calreticulin ( CRT) and its association with cell apoptosis and mitochondrial dysfunction in the cardiomyocytes.METHODS: AC-16 cardiomyocytes were randomly divided into normal glucose group, high glucose group, high glucose+CRT siRNA group and isotonic con-trol group.The cell apoptotic rate, reactive oxygen species (ROS), mitochondrial membrane potential level, respiratory enzyme activity, and protein expression of CRT were observed.RESULTS: Compared with the cardiomyocytes in normal glucose group, the apoptotic rate and ROS production of cardiomyocytes increased in high glucose group, accompanying with the decreases in the mitochondrial membrane potential level and enzyme activitiy of the respiratory chain.The protein expression of CRT was significantly increased in high glucose group.However, compared with high glucose group, high glucose+CRT siRNA decreased the expression of CRT and attenuated the damage of mitochondria, but CRT siRNA did not reduce the ROS level in cardiomyocytes.CONCLUSION:High glucose brings about CRT over-expression to induce mito-chondrial injury, thus increasing myocardial apoptosis.

OBJECTIVETo observe the effect of angiotensin II (Ang II) on calreticulin (CRT) expression and its association with mitochondrial dysfunction in cardiomyocytes.

METHODSPrimary neonatal rat cardiomyocytes were randomly divided into CRT siRNA group, control siRNA group, control group, Ang II+ CRT siRNA group, Ang II+ control siRNA group and Ang II group. The cell surface area, protein synthesis rate, mitochondrial membrane potential level, enzyme activities, and CRT expression were observed.

RESULTSCompared with those in the control group, the cell surface area and protein synthesis rate were both increased and mitochondrial membrane potential level and enzyme activities decreased in Ang II groups. CRT expression was significantly down-regulated in Ang II+ CRT siRNA group with increased cell surface area, protein synthesis rate, mitochondrial membrane potential level and enzyme activities as compared with those in Ang II+ control siRNA group.

CONCLUSIONAng II up-regulates CRT expression to induce mitochondrial injury, which may be an important mechanism of myocardial hypertrophy.

Angiotensin II ; pharmacology ; Animals ; Calreticulin ; metabolism ; Cardiomegaly ; Cells, Cultured ; Membrane Potential, Mitochondrial ; Mitochondria ; pathology ; Myocytes, Cardiac ; pathology ; Protein Biosynthesis ; RNA, Small Interfering ; Rats