Post-stroke aphasia is associated with a significantly elevated risk of depression, yet the underlying mechanisms remain unclear. This study recorded 64-channel electroencephalogram data and depression scale scores from 12 aphasic patients with depression, 8 aphasic patients without depression, and 12 healthy controls during resting state and an emotional Stroop task. Spectral and microstate analyses were conducted to examine brain activity patterns across conditions. Results showed that depression scores significantly negatively explained the occurrence of microstate class C and positively explained the transition probability from microstate class A to B. Furthermore, aphasic patients with depression exhibited increased alpha-band activation in the frontal region. These findings suggest distinct neural features in aphasic patients with depression and offer new insights into the mechanisms contributing to their heightened vulnerability to depression.
Humans ; Electroencephalography ; Aphasia/etiology* ; Stroop Test ; Emotions/physiology* ; Depression/etiology* ; Male ; Female ; Middle Aged ; Stroke/complications* ; Brain/physiopathology* ; Aged ; Adult ; Rest/physiology*

Zishen Huoxue decoction (ZSHX) enhances cardiomyocyte viability following hypoxic stress; however, its upstream therapeutic targets remain unclear. Network pharmacology and RNA sequencing analyses revealed that ZSHX target genes were closely associated with mitophagy and apoptosis in the mitochondrial pathway. In vitro, ZSHX inhibited pathological mitochondrial fission following hypoxic stress, regulated FUN14 domain-containing protein 1 (FUNDC1)-related mitophagy, and increased the levels of mitophagy lysosomes and microtubule-associated protein 1 light chain 3 beta II (LC3II)/translocase of outer mitochondrial membrane 20 (TOM20) expression while inhibiting the over-activated mitochondrial unfolded protein response. Additionally, ZSHX regulated the stability of beta-tubulin through Sirtuin 5 (SIRT5) and could modulate FUNDC1-related synergistic mechanisms of mitophagy and unfolded protein response in the mitochondria (UPR^mt) via the SIRT5 and -β-tubulin axis. This targeting pathway may be crucial for cardiomyocytes to resist hypoxia. Collectively, these findings suggest that ZSHX can protect against cardiomyocyte injury via the SIRT5-β-tubulin axis, which may be associated with the synergistic protective mechanism of SIRT5-β-tubulin axis-related mitophagy and UPR^mt on cardiomyocytes.
Mitophagy/drug effects* ; Tubulin/genetics* ; Animals ; Myocytes, Cardiac/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Sirtuins/genetics* ; Unfolded Protein Response/drug effects* ; Myocardial Ischemia/genetics* ; Rats ; Humans ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Male

Objective:To analyze the clinical characteristics, RAN-binding protein 2 ( RANBP2) gene variations, and prognosis in Chinese acute necrotizing encephalopathy (ANE) patients. Methods:A retrospective analysis of ANE cases registered in the Peking Union Medical College Hospital Encephalitis Registry System from 2022 to 2024, involving patients from Peking Union Medical College Hospital and other hospitals, was conducted. A descriptive study was performed on the clinical characteristics, treatments and prognosis, cerebrospinal fluid examination results, and imaging findings of these patients based on adjusted ANE diagnostic criteria. Whole-exome sequencing technology was used to detect gene mutations in these patients.Results:A total of 18 ANE cases were included, ranged in age from 2 to 72 [20(5, 43)] years. The male-to-female ratio was 4∶5. All patients were found with precipitating infections including COVID-19, influenza A virus and Mycoplasma pneumoniae infections. All patients presented with fever, with varying degrees of consciousness disturbance observed in 16 cases, and seizures in 10 cases. All patients underwent lumbar puncture, with normal or mildly elevated white cell counts [3(2, 13)×10 6/L] and mildly to moderately elevated protein levels [1.90(0.92, 4.65) g/L]. A total of 6 patients were found with extremely elevated interleukin-6 level [950(164, 2 000) pg/ml] in cerebrospinal fluid. Bilateral symmetric thalamic lesions were typical imaging features of ANE, while involvement of other areas such as cortical and subcortical white matter, brainstem, and cerebellum was also observed. A total of 14 patients performed genetic tests while 4 patients were identified with RANBP2 gene mutations (c.1754C>T in 3 cases, c.1966A>G in 1 case). All patients received immunotherapy, and 7 patients died at discharge while other patients presented with neurological sequelae of varying degrees. Conclusions:ANE is a rare and severe parainfectious encephalopathy that can occur in both children and adults. Clinically, it is characterized by rapidly progressing encephalopathy following systematic infection, with bilateral symmetric thalamic lesions. The detection of RANBP2 gene mutations could help make the diagnosis.

Objective:To analyze the expression of heat shock protein 90α (HSP90α) in pancreatic cancer tissues and its potential diagnostic value for pancreatic cancer.Methods:A retrospective study was conducted on surgical specimens and clinical data from 99 patients with pancreatic cancer who were treated at Qingdao Municipal Hospital from January 2018 to May 2023, including 58 males and 41 females, with the age of (63.5±23.5) years. Among them, 44 patients (44.4%) were used for pathological examination and prognostic analysis, while 55 patients (55.6%) were tested for plasma HSP90α levels to evaluate its diagnostic efficacy for pancreatic cancer. Blood samples from 119 healthy individuals undergoing routine physical examinations at the same hospital during the same period were collected, including 74 males and 45 females, with the age of (50.5±25.5) years, and plasma HSP90α levels were measured. Immunohistochemistry (IHC) was performed to detect the expression of HSP90α in cancerous and adjacent non-cancerous tissues. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of HSP90α, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125) for pancreatic cancer. Survival analysis was conducted using the Kaplan-Meier method, and the log-rank test was used to compare survival rates. The correlation between HSP90α positive expression in cancer tissues and mutant p53 positive expression was analyzed using Spearman correlation analysis.Results:Immunohistochemical analysis showed that the positive expression rate of HSP90α in pancreatic cancer tissues was 81.8%(36/44), higher than that in adjacent non-cancerous tissues 13.6%(6/44)( χ2=19.82, P<0.01). HSP90α positive expression in pancreatic cancer tissues was positively correlated with mutant p53 positive expression (correlation coefficient was 0.57, P<0.001). The median plasma HSP90α level in the pancreatic cancer group ( n=55) was 83.30 (48.30, 212.00) μg/L, which was significantly higher than that in the normal control group ( n=119), with a median of 37.00 (29.20, 43.50) μg/L, showing a statistically significant difference ( Z=-7.34, P<0.001). The area under the ROC curve (AUC) for plasma HSP90α in diagnosing pancreatic cancer was 0.85 (95% CI: 0.77-0.92), with an optimal cutoff value of 53.52 μg/L, yielding a sensitivity of 69.1% (38/55) and a specificity of 98.3% (117/119). The AUC for HSP90α in diagnosing pancreatic cancer was higher than that of CEA, CA19-9, and CA125. In the immunohistochemical analysis of cancer tissues, the one-year cumulative survival rate of the HSP90α-negative group ( n=8) was 87.5%, which was significantly higher than that of the HSP90α-positive group ( n=36), which was 18.8%( χ2=12.74, P<0.001). Conclusions:HSP90α is highly expressed in pancreatic cancer tissues, which is positively correlated with mutant p53 positive expression. Patients with positive HSP90α expression have a poorer prognosis. HSP90α demonstrates good diagnostic performance for pancreatic cancer and holds potential for clinical application.

Objective:To analyze the clinical characteristics, RAN-binding protein 2 ( RANBP2) gene variations, and prognosis in Chinese acute necrotizing encephalopathy (ANE) patients. Methods:A retrospective analysis of ANE cases registered in the Peking Union Medical College Hospital Encephalitis Registry System from 2022 to 2024, involving patients from Peking Union Medical College Hospital and other hospitals, was conducted. A descriptive study was performed on the clinical characteristics, treatments and prognosis, cerebrospinal fluid examination results, and imaging findings of these patients based on adjusted ANE diagnostic criteria. Whole-exome sequencing technology was used to detect gene mutations in these patients.Results:A total of 18 ANE cases were included, ranged in age from 2 to 72 [20(5, 43)] years. The male-to-female ratio was 4∶5. All patients were found with precipitating infections including COVID-19, influenza A virus and Mycoplasma pneumoniae infections. All patients presented with fever, with varying degrees of consciousness disturbance observed in 16 cases, and seizures in 10 cases. All patients underwent lumbar puncture, with normal or mildly elevated white cell counts [3(2, 13)×10 6/L] and mildly to moderately elevated protein levels [1.90(0.92, 4.65) g/L]. A total of 6 patients were found with extremely elevated interleukin-6 level [950(164, 2 000) pg/ml] in cerebrospinal fluid. Bilateral symmetric thalamic lesions were typical imaging features of ANE, while involvement of other areas such as cortical and subcortical white matter, brainstem, and cerebellum was also observed. A total of 14 patients performed genetic tests while 4 patients were identified with RANBP2 gene mutations (c.1754C>T in 3 cases, c.1966A>G in 1 case). All patients received immunotherapy, and 7 patients died at discharge while other patients presented with neurological sequelae of varying degrees. Conclusions:ANE is a rare and severe parainfectious encephalopathy that can occur in both children and adults. Clinically, it is characterized by rapidly progressing encephalopathy following systematic infection, with bilateral symmetric thalamic lesions. The detection of RANBP2 gene mutations could help make the diagnosis.

Objective:To analyze the expression of heat shock protein 90α (HSP90α) in pancreatic cancer tissues and its potential diagnostic value for pancreatic cancer.Methods:A retrospective study was conducted on surgical specimens and clinical data from 99 patients with pancreatic cancer who were treated at Qingdao Municipal Hospital from January 2018 to May 2023, including 58 males and 41 females, with the age of (63.5±23.5) years. Among them, 44 patients (44.4%) were used for pathological examination and prognostic analysis, while 55 patients (55.6%) were tested for plasma HSP90α levels to evaluate its diagnostic efficacy for pancreatic cancer. Blood samples from 119 healthy individuals undergoing routine physical examinations at the same hospital during the same period were collected, including 74 males and 45 females, with the age of (50.5±25.5) years, and plasma HSP90α levels were measured. Immunohistochemistry (IHC) was performed to detect the expression of HSP90α in cancerous and adjacent non-cancerous tissues. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of HSP90α, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125) for pancreatic cancer. Survival analysis was conducted using the Kaplan-Meier method, and the log-rank test was used to compare survival rates. The correlation between HSP90α positive expression in cancer tissues and mutant p53 positive expression was analyzed using Spearman correlation analysis.Results:Immunohistochemical analysis showed that the positive expression rate of HSP90α in pancreatic cancer tissues was 81.8%(36/44), higher than that in adjacent non-cancerous tissues 13.6%(6/44)( χ2=19.82, P<0.01). HSP90α positive expression in pancreatic cancer tissues was positively correlated with mutant p53 positive expression (correlation coefficient was 0.57, P<0.001). The median plasma HSP90α level in the pancreatic cancer group ( n=55) was 83.30 (48.30, 212.00) μg/L, which was significantly higher than that in the normal control group ( n=119), with a median of 37.00 (29.20, 43.50) μg/L, showing a statistically significant difference ( Z=-7.34, P<0.001). The area under the ROC curve (AUC) for plasma HSP90α in diagnosing pancreatic cancer was 0.85 (95% CI: 0.77-0.92), with an optimal cutoff value of 53.52 μg/L, yielding a sensitivity of 69.1% (38/55) and a specificity of 98.3% (117/119). The AUC for HSP90α in diagnosing pancreatic cancer was higher than that of CEA, CA19-9, and CA125. In the immunohistochemical analysis of cancer tissues, the one-year cumulative survival rate of the HSP90α-negative group ( n=8) was 87.5%, which was significantly higher than that of the HSP90α-positive group ( n=36), which was 18.8%( χ2=12.74, P<0.001). Conclusions:HSP90α is highly expressed in pancreatic cancer tissues, which is positively correlated with mutant p53 positive expression. Patients with positive HSP90α expression have a poorer prognosis. HSP90α demonstrates good diagnostic performance for pancreatic cancer and holds potential for clinical application.

Objective:To consolidate the current evidences regarding the efficacy of vitamin D supplementation in age-related sarcopenia.Methods:In this systemic review, a comprehensive literature search of scientific research including journal articles and academic dissertations was performed in prominent databases such as PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang Database platforms, spanning from January 31, 2014 to January 31, 2024. Two search protocols integrating keywords and citation tracking were adopted to ensure comprehensiveness of the literature. Using “vitamin D” “ergocalciferols” “cholecalciferol” “sarcopenia” “muscle mass” “muscle strength” “myopenia” “muscle loss” “muscle reduction” “gait speed” “grip strength” “handgrip” as the main key words, focusing on the systematic reviews, meta-analyses of randomized controlled trials (RCT), and individual RCT, the scientific evidence of individual vitamin D intervention on age-related sarcopenia was evaluated and summarized. Research concerning particular disease conditions, children and adolescents, menopausal women, athletes and other specific populations were excluded.Results:A initial search yielded 2 448 articles in Chinese or English. A total of 8 systemic reviews/meta-analysis and 22 individual RCT literatures were included in the final analysis. Although some earlier lower-quality studies reported subtle improvements in skeletal muscle strength with vitamin D supplementation, high-quality systematic reviews/meta-analysis over the past three years had not shown significant positive effects of vitamin D intervention on sarcopenia and its breakdown parameters, such as skeletal muscle mass, muscle strength, and muscle function. Furthermore, the efficiency was influenced to some extent by the participants′ baseline status, such as muscle health and vitamin D nutritional status.Conclusions:Present evidence does not robustly support the efficacy of sole vitamin D supplement on age-related sarcopenia. High-quality clinical trials are imperative to accumulate more robust evidence in the future.

Metabotropic glutamate receptor 5 (mGluR5) encephalitis is a rare type of anti-cell surface antigen antibody encephalitis mediated by autoimmune mechanisms. This article reported a case of anti-mGluR5 encephalitis. The patient was a 25-year-old young man with a history of Hodgkin′s lymphoma. Due to tumor recurrence, he developed encephalitis symptoms including fever, headache, mental and behavioral abnormalities, memory loss, consciousness disturbance, and seizures after checkpoint immunosuppressive therapy. He was finally diagnosed as anti-mGluR5 encephalitis by positive serum anti-mGluR5 antibodies. Finally, the symptoms alleviated after treatment with hormones and gamma globulin.

ObjectiveTo analyze the expression of molecular marker affecting the prognosis of acute myeloid leukemia （AML） patients from bioinformatics database， thus providing an experimental basis for further exploration of a novel molecular marker for the prognosis of AML. MethodsThe prognostic data of 179 AML patients from The Cancer Genome Atlas （TCGA） database were examined for differential gene analysis and survival analysis. The bone marrow samples of 74 healthy individuals （HI） and 542 de novo AML patients in the dataset GSE13159 downloaded from the Gene Expression Omnibus （GEO） database were analyzed to detect the difference in the expression levels of differential target genes. Peripheral blood and bone marrow samples were collected from 18 de novo AML patients and 20 age- and gender-matched healthy controls， and real-time fluorescent quantitative PCR was used to validate the expression levels of the differential genes in the AML patients. ResultsBioinformatics data analysis showed that the optimal cut-off value of Homo sapiens NK2 homeobox 3 （NKX2-3） calculated by R language was 0.051. Survival analysis revealed a statistically poorer overall survival in de novo AML patients with high NKX2-3 expression than in those with low NKX2-3 expression （P = 0.0036）. NKX2-3 was highly expressed in patients with de novo AML than in HI and the difference was statistically significant （P < 0.001）. Real-time fluorescence quantitative PCR verified the expression levels of the NKX2-3 gene in AML patients and confirmed that compared with those in HI， in the de novo AML patients， NKX2-3-1 and NKX2-3-2 were highly expressed and were significantly correlated （P = 0.000， P = 0.000）. ConclusionNKX2-3 is highly expressed in de novo AML patients， and the AML patients with high NKX2-3 expression have poor overal survival. NKX2-3 may be closely related to the clinical outcome and prognosis of AML.

Background::Pancreatic adenocarcinoma (PAAD) is an extremely lethal malignancy. Identification of the functional genes and genetic variants related to PAAD prognosis is important and challenging. Previously identified prognostic genes from several expression profile analyses were inconsistent. The regulatory genetic variants that affect PAAD prognosis were largely unknown.Methods::Firstly, a meta-analysis was performed with seven published datasets to systematically explore the candidate prognostic genes for PAAD. Next, to identify the regulatory variants for those candidate genes, expression quantitative trait loci analysis was implemented with PAAD data resources from The Cancer Genome Atlas. Then, a two-stage association study in a total of 893 PAAD patients was conducted to interrogate the regulatory variants and find the prognostic locus. Finally, a series of biochemical experiments and phenotype assays were carried out to demonstrate the biological function of variation and genes in PAAD progression process.Results::A total of 128 genes were identified associated with the PAAD prognosis in the meta-analysis. Fourteen regulatory loci in 12 of the 128 genes were discovered, among which, only rs4887783, the functional variant in the promoter of Ring Finger and WD Repeat Domain 3 ( RFWD3), presented significant association with PAAD prognosis in both stages of the population study. Dual-luciferase reporter and electrophoretic mobility shift assays demonstrated that rs4887783-G allele, which predicts the worse prognosis, enhanced the binding of transcript factor REST, thus elevating RFWD3 expression. Further phenotypic assays revealed that excess expression of RFWD3 promoted tumor cell migration without affecting their proliferation rate. RFWD3 was highly expressed in PAAD and might orchestrate the genes in the DNA repair process. Conclusions::RFWD3 and its regulatory variant are novel genetic factors for PAAD prognosis.