BACKGROUND:Ca2+expression in astrocytes has been found to be closely related to cognitive function,and the Ca2+signaling pathway regulated by inositol 1,4,5-trisphosphate receptors(IP3R2)and ryanodine receptor(RYR)2 receptors has become a hot spot in the study of cognitive disorder-related diseases. OBJECTIVE:To investigate the expression of Ca2+signals mediated by IP3R2 and RYR2 in hippocampal astrocytes in animal models of delayed encephalopathy after acute carbon monoxide poisoning,and to explore the possible pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning. METHODS:C57BL mice with qualified cognitive function were selected by Morris water maze experiment and randomly divided into control group and experimental group.An animal model of delayed encephalopathy after acute carbon monoxide poisoning was established by static carbon monoxide inhalation in the experimental group,and the same amount of air was inhaled in the control group.Behavioral and neuronal changes,astrocyte specific marker glial fibrillary acidic protein,IP3R2,RYR2 receptor and Ca2+concentration in astrocytes of the two groups were detected using Morris water maze,hematoxylin-eosin staining,western blot,immunofluorescence double labeling and Ca2+fluorescence probe at 21 days after modeling. RESULTS AND CONCLUSION:In the Morris water maze,the escape latency of the experimental group was significantly longer than that of the control group(P<0.05).Hematoxylin-eosin staining results showed that in the experimental group,the number of hippocampal pyramidal cells decreased,the cell structure was disordered,and the nucleus was broken and dissolved.Immunofluorescence results showed that IP3R2 and RYR2 were co-expressed with glial fibrillary acidic protein in the hippocampus,and the expressions of IP3R2,RYR2 and glial fibrillary acidic protein were up-regulated in the hippocampus of the experimental group(P<0.05).Western blot analysis showed that the expressions of IP3R2,RYR2,and glial fibrillary acidic protein in the hippocampus of the experimental group were increased(P<0.05).Ca2+concentration in hippocampal astrocytes increased significantly in the experimental group(P<0.05).To conclude,astrocytes may affect Ca2+signals by mediating IP3R2 and RYR2 receptors,then impair the cognitive function of mice with carbon monoxide poisoning,and eventually lead to delayed encephalopathy after acute carbon monoxide poisoning.

The study aims to elucidate the existence forms(original constituents and metabolites) of Notoginseng Radix et Rhizoma in rats and reveal its metabolic pathways. After Notoginseng Radix et Rhizoma was administered orally once a day for seven consecutive days to rats, all urine and feces samples were collected for seven days, while the blood samples were obtained 6 h after the last administration. Using the ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technique, this study identified 6, 73, and 156 existence forms of Notoginseng Radix et Rhizoma in the rat plasma, urine, and feces samples, respectively. Among them, 101 compounds were identified as new existence forms, and 13 original constituents were identified by comparing with reference compounds. The metabolic reactions of constituents from Notoginseng Radix et Rhizoma were mainly deglycosylation, dehydration, hydroxylation, hydrogenation, dehydrogenation, acetylation, and amino acid conjugation. Furthermore, the possible in vivo metabolic pathways of protopanaxatriol(PPT) in rats were proposed. Through comprehensive analysis of the liquid chromatography-mass spectrometry(LC-MS) data, isomeric compounds were discriminated, and the planar chemical structures of 32 metabolites were clearly identified. According to the literature, 48 original constituents possess antitumor and cardiovascular protective bioactivities. Additionally, 32 metabolites were predicted to have similar bioactivities by SuperPred. This research lays the foundation for further exploring the in vivo effective forms of Notoginseng Radix et Rhizoma.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacokinetics* ; Rhizome/metabolism* ; Male ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid ; Panax notoginseng/chemistry* ; Tandem Mass Spectrometry ; Feces/chemistry*

OBJECTIVE: To analyze the MYH9 gene sequence of a patient with hereditary thrombocytopenia and diffuse large B-cell lymphoma and his family members, and to explore the relationship between MYH9 gene and tumors. METHODS: Peripheral blood samples were collected from the patients and their family members for complete blood count analysis. The platelet morphology was observed under microscope. The MYH9 gene sequence was analyzed by Whole Exon Sequencing and Sanger Sequencing. RESULTS: The mutation site c.279C>A:p.(Asn93Lys) in exon 2 of the MYH9 gene were found in patient and his family members, both presenting as thrombocytopenia. The platelet count was significantly increased after the administration of Avatrombopag. CONCLUSION A novel mutation of MYH9 was found in this study, and the case was sensitive to Avatrombopag, by exploring the relationship between the MYH9 gene and tumors, suggesting that the MYH9 gene may be associated with the development of diffuse large B-cell lymphoma.
Humans ; Myosin Heavy Chains/genetics* ; Thrombocytopenia/genetics* ; Mutation ; Male ; Lymphoma, Non-Hodgkin/genetics* ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Molecular Motor Proteins/genetics* ; Pedigree

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

OBJECTIVE: This study investigated the antidepression mechanisms of Xiaoyaosan (XYS), a classic Chinese prescription, from the perspective of energy metabolism in the brain and intestinal tissues. METHODS: Chronic unpredictable mild stress model-a classic depression rat model-was established. Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated. Effects of XYS on energetic charge (EC), adenosine triphosphate-related enzymes, and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography, biochemical analysis, and real-time quantitative polymerase chain reaction, respectively. Spearman correlation analysis was conducted to construct a correlation network of "behavior-brain energy metabolism-intestinal energy metabolism" of depression. RESULTS: XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na⁺-K⁺-adenosine triphosphatase (ATPase) and Ca²⁺-Mg²⁺-ATPase in hippocampus and jejunum tissues of depressed rats. XYS restored the key energetic pathways that had been interrupted by depression, including glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine. CONCLUSION XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues, alleviating both core and concomitant symptoms of depression. The current findings underscore the role of energy metabolism in the antidepressive activity of XYS, providing a fresh perspective on depression, and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases. Please cite this article as: Xiao MT, Wang SY, Wu XL, Zhao ZY, Wang HM, Liu HM, Qin XM, Liu XJ. Antidepressant mechanism of Xiaoyaosan: A perspective from energy metabolism of the brain and intestine. J Integr Med. 2025; 23(6):706-720.
Animals ; Energy Metabolism/drug effects* ; Antidepressive Agents/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Brain/drug effects* ; Male ; Depression/metabolism* ; Rats ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Hippocampus/drug effects*

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To investigate the risk factors of periprosthetic femoral fracture(PFF)after total knee arthroplasty(TKA)in the elderly and to construct a predictive model for the prevention of PFF after clinical operation.Methods The clinical data of 537 elderly patients who underwent TKA in the orthopedic department of the First Affiliated Hospital of Air Medical University from October 2016 to October 2021 were retrospectively analyzed.The occurrence of PFF during the follow-up period was statistically analyzed and the clinical data were collected.Binary Logistic regression was used to analyze the risk factors of PFF after TKA in the elderly,and a predictive model of PFF after TKA in the elderly was constructed based on the risk factors.Receiver operating characteristic(ROC)curve and Hosmer-Lemeshow(H-L)were used to test the discrimination and calibration of prediction model.Results The patients were followed up for 12 to 72 months after discharge,with a median time of 47 months.During the follow-up period,31 patients(5.77%)developed PFF.Age,osteoporosis,Parkinson's disease and anterior femoral notch(AFN)were the risk factors for PFF after TKA in the elderly(P<0.05),and cross fixation of prosthesis and bone cement fixation were the protective factors(P<0.05).The results of H-L test showed that the risk prediction model of PFF after TKA in the elderly had good calibration(P>0.05).ROC curve analysis showed that the risk prediction model of PFF after TKA in the elderly has high discrimination(area under the curve was 0.858,95%CI:0.826 to 0.887),the sensitivity was 83.87%,the specificity was 88.34%.Conclusion The risk of PFF after TKA in the elderly is high,and prevention should be carried out according to the high risk factors.The prediction model constructed based on the high risk factors has good prediction efficiency.