Treatment outcomes and cognitive function following electroconvulsive therapy in patients with severe depression.

BACKGROUND: Traditional treatments for major depressive disorder (MDD), including medication and therapy, often fail and have undesirable side effects. Electroconvulsive therapy (ECT) uses electrical currents to induce brief seizures in the brain, resulting in rapid and potent antidepressant effects. However, owing to misconceptions and controversies, ECT is not as widely used as it could and often faces stigmatization. AIM: To evaluate the efficacy and safety of ECT compared to those of medication and/or therapy in patients with severe MDD. METHODS: This prospective cohort study included 220 individuals with severe MDD who were divided into the ECT and non-ECT groups. The patients in the ECT group underwent bilateral ECT three times a wk until they either achieved remission or reached a maximum of 12 sessions. The non-ECT group received medication and/or therapy according to clinical guidelines for MDD. The primary outcome was the variation in the hamilton depression rating scale (HDRS) score from treatment/ECT initiation to week 12. In addition, patients' quality of life, cognitive abilities, and biomarkers were measured throughout the study. RESULTS: Although both groups showed significant improvements in their HDRS scores over time, the improvement was more pronounced in the ECT group than in the non-ECT group. Additionally, the ECT group exhibited a more substantial improvement in the quality of life and cognitive function than those of the non-ECT group. Compared with the non-ECT group, the ECT group exhibited evi-dently lower variations in the brain-derived neurotrophic factor (BDNF) and cytokine interleukin-6 (IL-6) levels. The side effects were generally mild and comparable between the two groups. ECT is safer and more potent than medication and/or therapy in mitigating depressive symptoms, enhancing well-being, and bolstering cognitive capabilities in individuals with severe MDD. ECT may also affect the levels of BDNF and IL-6, which are indicators of neuroplasticity and inflammation, respectively. CONCLUSION: ECT has emerged as a potentially advantageous therapeutic approach for patients with MDD who are unresponsive to alternative treatments.

Protection of hUC-MSCs against neuronal complement C3a receptor-mediated NLRP3 activation in CUMS-induced mice.

BACKGROUND: Hyperactivation of complement C3 and inflammation-related activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome are implicated in the etiology of stress-related disorders. Studies have shown that human umbilical cord mesenchymal stromal cells (hUC-MSCs) have immunomodulatory and anti-inflammatory effects; however, the mechanism remains unclear. METHODS: hUC-MSCs were administered to chronic unpredictable mild stress (CUMS) model mice once a week for four weeks. After the administration of hUC-MSCs, several parameters were assessed, including behavioral performance, synapse-related proteins, complement C3 receptors (C3aR) in neurons, and the NLRP3 inflammasome. Then, CUMS mice were injected with SB290157, a complement C3aR antagonist, and the behavioral index and NLRP3 inflammasome activation were tested. RESULTS: The open-field and forced swimming behavioral tests showed an improvement in depression-like behaviors in the CUMS-exposed mice after the administration of hUC-MSCs. Treatment with hUC-MSCs significantly decreased the neuronal C3aR levels and alleviated synaptic damage. Furthermore, the levels of the NLRP3 inflammasome and inflammatory factors were reduced after hUC-MSC administration. In particular, treatment with a C3aR antagonist also decreased NLRP3 inflammasome expression and inflammation, which was consistent with the observed improvements after hUC-MSC treatment. CONCLUSION: hUC-MSCs can attenuate NLRP3 activation in CUMS-induced mice, which may be correlated with C3aR in neurons.

hUC-MSCs ameliorated CUMS-induced depression by modulating complement C3 signaling-mediated microglial polarization during astrocyte-microglia crosstalk.

BACKGROUND: Major depressive disorder (MDD) has been shown to be related to immune inflammation and the complement system. Previous studies have suggested that human umbilical cord mesenchymal stem cells (hUC-MSCs) play an important role in inflammatory diseases. METHODS: hUC-MSCs were administered into chronic unpredictable mild stress model (CUMS) mice through the tail vein once a week for 4 weeks. After the administration of hUC-MSCs, the depression-like and anxiety-like phenotypes, neuronal histopathology, synaptic-related protein expression and inflammatory index of the mice were assessed. Microglial M1/M2 polarization and the expression of C3a in astrocytes and C3aR in microglia was detected by immunofluorescence co-localization. Then, CUMS mice were injected with a C3aR antagonist, and the expression of C3a and C3aR and microglial polarization were observed. RESULTS: Based on the sucrose preference and tail suspension tests, hUC-MSCs ameliorated the depression-like behaviors of CUMS mice. Additionally, the anxiety-like behaviors of CUMS mice in the open-field and plus-maze tests were improved after the administration of hUC-MSCs. hUC-MSCs altered microglia polarization by alleviating complement C3a-C3aR signaling activation, which decreased pro-inflammatory factor levels and increased anti-inflammatory factor levels, alleviating neuronal damage and synaptic deficits. CONCLUSION: hUC-MSCs have therapeutic effects on anxiety-like and depressive-like phenotypes caused by CUMS. They can alter the polarization of microglia by inhibiting C3a-C3aR signaling to reduce neuroinflammation.

Weighted gene co-expression network analysis reveals specific modules and biomarkers in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) ranks as the second most frequently occurring neurodegenerative disease. The precise pathogenic mechanism of this disease remains unknown. The aim of the present study was to identify the biomarkers in PD and classify the primary differentially expressed genes (DEGs). METHODS: The present study searched for and downloaded mRNA expression data from the Gene Expression Omnibus database to identify differences in mRNA expression in the substantia nigra (SN) and blood of patients with PD and healthy controls. In addition, in order to investigate the biological functions of the classified dysregulated genes, the present study utilized Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), reverse transcription-quantitative PCR (RT-qPCR), gene co-expression network analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A receiver operating characteristic (ROC) curve was applied to assay TMEM243 as a diagnostic marker. RESULTS: Between PD and controls in GSE20292, the present study identified 1862 DEGs. Using the weighted gene co-expression network analysis, the present study identified 15 modules in PD. The module preservation analysis revealed that the tan, blue and green-yellow modules were the most stable. KEGG pathway analysis revealed that five DEGs in the black module were significantly enriched in the ubiquitin-mediated proteolysis pathway, nucleotide excision repair pathway, mismatch repair pathway. The present study selected 303 genes with high connectivity in blue, green-yellow and tan modules as hub genes, where 58 were differentially expressed in both the GSE20292 and GSE54536 datasets. In the SN and blood, 11 genes exhibited the same trend of expression. Furthermore, in the blood samples of patients with PD, the results displayed a significant upregulation of TMEM243. The expression levels of CCR4, CAMK1D, ACTR1B and SPSB3 increased, while both the levels of INA and PSMD4 decreased. These findings are consistent with the bioinformatics analysis results but are not statistically significant. TMEM243 can be considered as a diagnostic biomarker (area under the curve = 0.694; sensitivity, 80 %; specificity, 56 %; P < 0.018). CONCLUSION: TMEM243 was distinctly upregulated in the blood samples of patients with PD, as validated via RT-qPCR, and was highly sensitive, revealing its potential as a biomarker for the future diagnosis of PD.

Protective effect of rhubarb combined with ulinastatin for patients with sepsis.

BACKGROUND: Sepsis is the leading cause of death in critically ill patients. Ulinastatin (UTI), a protease inhibitor, and rhubarb, used as a traditional Chinese medication, are proved to be effective in treating sepsis, but the effect of the combination therapy of these two drugs on sepsis remains unclear. This study aimed to investigate the effect of the combination treatment of UTI and rhubarb on sepsis patients. METHODS: A total of 75 septic patients were randomly divided into control group, UTI group, Rhubarb group, and UTI plus Rhubarb group. Clinical data and score of Acute Physiology and Chronic Health Evaluation II (APACHE II) were collected; lymphocyte subtypes in the peripheral blood were analyzed before and after the 5-day treatment in the Intensive Care Unit. RESULTS: All the therapeutic interventions (UTI alone, rhubarb alone, or UTI plus rhubarb) significantly reduced the levels of C-Reactive protein, white blood cell density, lactic acid, and APACH II scores, and elevated the levels of CD4/CD8, but only UTI plus rhubarb treatment obviously decreased the level of procalcitonin. CONCLUSION: This study suggested that the combination of UTI and rhubarb may be a promising therapeutic scheme to ameliorate sepsis.

The carbon footprints of home and in-center peritoneal dialysis in China.

OBJECTIVE: The provision of healthcare itself is associated with abundant greenhouse gas (GHG) emissions. This study aims to determine the carbon footprints of peritoneal dialysis (PD) with the different modalities and treatment regimes. METHODS: A total of 68 subjects performed with PD treatment were enrolled in this study. Emissions factors were applied to data that were collected for energy consumption, travel, and procurement. RESULTS: The carbon footprints generated by the provision of PD treatment for the individual patient were calculated and normalized to a 2-l PD dialysate volume. The fixed emissions were higher in patients who received PD therapy in center than at home, mostly attributing to the consumption of electricity. Conversely, PD treatment performed in center yielded less variable emissions than that of at home, which resulted from reduced constituent percentage of waste disposal and transportation. Collectively, packaging consumption mostly contributed to the total carbon footprints of PD. CONCLUSION: This study for the first time demonstrates the delivery of PD is associated with considerable GHG emissions, which is mainly attributed to packaging materials, transportation, electricity, and waste disposal. These results suggest that carbon reduction strategies focusing on packaging consumption in PD treatment are likely to yield the greatest benefits.

Effects of Rhubarb combined with ulinastatin on T-cell subsets in sepsis rats.

OBJECTIVE: The pathogenesis of sepsis, a systemic inflammatory response syndrome, is very complicated and not well understood. However, the importance of lymphocyte percentage and ratio is implicated. Rhubarb is a traditional Chinese medication and plays a role in protecting gastrointestinal mucous and controlling the SIRS damage. Ulinastatin is a protease inhibitor that prevents overproduction of inflammatory cytokines. Currently, despite numerous sepsis clinical researches, the study on the effects of combined drug therapy on sepsis is lacking. In this study, we studied Rhubarb and Ulinastatin combination treatment on T lymphocyte subsets in sepsis induced by the cecal ligation and perforation (CLP). Immunosuppression happened at the early stage of severe sepsis in the CLP rat models, as CD3(+), CD4(+), CD4(+)/CD8(+) began to decline, dropped rapidly after 24 h and continuously decreased at 36 h. CD8(+) T lymphocyte showed no significant change in all groups after CLP. The morality of CLP rats was increased with Rhubarb treatment in test dose (1.2 g/100 g). The immunosuppression state of CLP rats ameliorated with UTI treatment at early stage. The immunomodulatory properties were improved along with drug treatment, and immunities were obviously increased after 24 h, moreover, continuously increased at 36 h. The relief effect of immunosuppression after CLP showed much better in Rhubarb combined with UTI treatment than UTI monotherapy. In conclusion, the combination drug treatment facilitates the improvement of sepsis by modifying the lymphocyte percentage.