Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS). Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes. Furthermore, glutamate activated Ca2+ release, thereby inducing endoplasmic reticulum (ER) stress in astrocytes, while morphine attenuated this deleterious effect. Using siRNA to reduce the expression of κ-opioid receptor, morphine could not effectively inhibit glutamate-stimulated Ca2+ release in astrocytes, the protective effect of morphine on glutamate-injured astrocytes was also suppressed. These results suggested that morphine could protect astrocytes from glutamate-induced apoptosis via reducing Ca2+ overload and ER stress pathways. In conclusion, this study indicated that excitotoxicity participated in the glutamate mediated apoptosis in astrocytes, while morphine attenuated this deleterious effect via regulating Ca2+ release and ER stress.

ObjectiveTo investigate the efficacy of rituximab in the treatment of idiopathic membranous nephropathy (IMN).MethodsA total of 77 patients with IMN diagnosed in both our hospital and other hospitals were included in this study; the patients were divided into two groups: a treatment-naïve group (n = 19) and a refractory/relapsed group (n = 58). The clinical data of the patients, including urine examination, blood test, safety evaluation and efficacy evaluation results, were analysed retrospectively. The changes in clinical biochemical indexes and adverse reactions were compared between the two groups before and after treatment, and the clinical efficacy of rituximab (RTX) in the treatment of primary IMN and refractory recurrent membranous nephropathy was evaluated.ResultsOf the 77 patients included in this study, the average age was 48 years, and there was a male-to-female ratio of 61:16. There were 19 cases in the initial treatment group and 58 cases in the refractory/relapse group. The 24-hour urine protein quantification, cholesterol, B cell count and M-type phospholipase A2 receptor (PLA2R) results in the 77 patients with IMN after treatment were all lower than those before treatment, and the differences were statistically significant (P < 0.05). Serum albumin was higher than before treatment, and the difference was statistically significant (P < 0.05). The total remission rate in the initial and refractory/relapsed treatment groups was 84.21% and 82.76%, respectively. There was no statistical difference in the total remission rate between the two groups (P > 0.05). During treatment, nine patients (11.69%) experienced infusion-related adverse reactions, which were relieved rapidly after symptomatic treatment. The anti-PLA2R antibody titre of the refractory/relapsed group was significantly negatively correlated with serum creatinine (r = −0.187, P = 0.045) and significantly correlated with 24-hour urine protein (r = −0.490, P < 0.001). There was a positive correlation and a significant negative correlation with serum albumin (r = −0.558, P < 0.001).ConclusionsRegardless of whether RTX is used as an initial therapy or refractory/relapsed membranous nephropathy, most patients with IMN have complete or partial remission after RTX treatment, with mild adverse reactions.

Objective In this study, we used network pharmacology to explore the possible therapeutic mechanism underlying the treatment of diabetic nephropathy with Yishen capsules. Methods The active chemical constituents of Yishen capsules were acquired using the Traditional Chinese Medicine Systems Pharmacology platform and the Encyclopedia of Traditional Chinese Medicine. Component target proteins were then searched and screened in the BATMAN database. Target proteins were cross-validated using the Comparative Toxicogenomics Database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the target proteins were performed. Then, protein–protein interaction (PPI) analysis was performed using the STRING database. Finally, a pharmacological network was constructed to show the component-target-pathway relationships. Molecular docking was used to analyse the interaction between drug components and target proteins. Results In total, 285 active chemical components were found, including 85 intersection targets against DN. In the pharmacological network, 5 key herbs (A. membranaceus, A. sinensis, E. ferox, A. orientale, and R. rosea) and their corresponding 12 key components (beta-sitosterol, beta-carotene, stigmasterol, alisol B, mairin, quercetin, caffeic acid, 1-monolinolein, kaempferol, jaranol, formononetin, and calycosin) were screened. Furthermore, the 12 key components were related to 24 target protein nodes (e.g., AGT, AKT1, AKT2, BCL2, NFKB1, and SIRT1) and enriched in 24 pathway nodes (such as the NF-kappa B, AGE-RAGE, toll-like receptor, and relaxin signaling pathways). Molecular docking revealed that hydrogen bond was formed between drug components and target proteins. Conclusion In conclusion, the active constituents of Yishen capsules modulate targets or signaling pathways in DN pathogenesis.

Refractory peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) caused by Burkholderia cepacia is very rare. Herein, we describe a case of B. cepacia-related refractory peritonitis and present a literature review of similar cases. A 62-year-old male patient presented with diffuse abdominal pain, bloating, and turbid peritoneal effluent. Initial dialysis effluent culture was negative for any microorganism. The patient initially underwent treatment with piperacillinsulbactam. The second dialysis effluent culture was positive for gram stain and later tested positive for B. cepacia. Peritoneal dialysis (PD) catheter removal was recommended, and the patient agreed to undergo regular hemodialysis. To the best of our knowledge, this is the first case of B. cepacia-related refractory peritonitis in a patient undergoing CAPD with no history of a recent hospitalization. B. cepacia infections can result in death in some areas. Therefore, timely catheter removal and switching treatment to hemodialysis is recommended for patients with B. cepacia-related refractory peritonitis. | INTRODUCTIONPeritonitis is a common and serious infection-related complication in patients undergoing peritoneal dialysis (PD) and a cause of mortality in about 16% of all patients receiving PD. 1 Previous studies have shown that gram-positive bacteria (mainly coagulase-negative staphylococcus, enterococcus species, and streptococcal species) are the most common bacteria causing peritonitis. Gram-negative bacteria (mainly Corynebacterium and Pseudomonas) account for 15%-35%. 2Burkholderia cepacia is a gram-negative bacteria that has become increasingly recognized as an important nosocomial pathogen responsible for hospital outbreaks. However, B. cepacia-related peritonitis in CAPD is a very rare occurrence in clinical practice. One possible reason is that B. cepacia is often misdiagnosed as non-lactose-fermenting bacillus, especially of Pseudomonas spp. in most developing countries. 3 To the best of our knowledge, this is the first report of a patient undergoing CAPD who developed refractory peritonitis due to B. cepacia infection with no history of recent hospitalization.