Hyperactive lateral habenula mediates the comorbidity between rheumatoid arthritis and depression-like behaviors.

Rheumatoid arthritis (RA) patients have a high prevalence for depression. On the other hand, comorbid with depression is associated with worse prognosis for RA. However, little is known about the underlying mechanisms for the comorbidity between RA and depression. It remains to be elucidated which brain region is critically involved in the development of depression in RA, and whether alterations in the brain may affect pathological development of RA symptoms. Here, by combining clinical and animal model studies, we show that in RA patients, the level of depression is significantly correlated with the severity of RA disease activity and affects patients' quality of life. The collagen antibody-induced arthritis (CAIA) mouse model of RA also develops depression-like behaviors, accompanied by hyperactivity and alterations in gene expression reflecting cerebrovascular disruption in the lateral habenula (LHb), a brain region critical for processing negative valence. Importantly, inhibition of the LHb not only alleviates depression-like behaviors, but also results in rapid remission of RA symptoms and amelioration of RA-related pathological changes. Together, our study highlights a critical but previously overlooked contribution of hyperactive LHb to the comorbidity between RA and depression, suggesting that targeting LHb in conjunction with RA treatments may be a promising strategy for RA patients comorbid with depression.

Exploring watershed ecological risk bundles based on ecosystem services: A case study of Shanxi Province, China.

Humans are having an increasingly profound impact on the environment along with the advent of the Anthropocene. Ecological risk assessment (ERA) as a method to quantify ecological problems can provide support for decision-makers, and it is one of key issues to integrate ecosystem services into ERA. In this study, an ERA framework was proposed under the loss-probability paradigm from the perspective of ecosystem services risk bundles. The results showed that initiatives aimed at ecological protection in Shanxi Province had been effective, the number of watersheds with low-risk bundles increased significantly (from 16.09% to 34.49%) and the watersheds basically overlapped with key forestation areas. However, the effects of forestation activities may no longer be as significant as they once were, as the relationship between forestation and water supply was becoming increasingly contradictory. Meanwhile, the conflict between urban expansion and natural ecosystem protection was intensifying, habitat degradation risks were gradually polarized, and the risk bundles dominated by high carbon emission and habitat degradation were increasing significantly (from 15.88% to 33.54%). Strengthening the construction of urban green space and controlling the expansion of human activities may be the next focus of ecological conservation in Shanxi Province. This study enriched the ERA framework with an ecosystem services risk bundle approach.

Identification and validation of necroptosis-related gene signatures to predict clinical outcomes and therapeutic responses in acute myeloid leukemia.

BACKGROUND: Necroptosis is a tightly regulated form of necrotic cell death that promotes inflammation and contributes to disease development. However, the potential roles of necroptosis-related genes (NRGs) in acute myeloid leukemia (AML) have not been elucidated fully. METHODS: We conducted a study to identify a robust biomarker signature for predicting the prognosis and immunotherapy efficacy based on NRGs in AML. We analyzed the genetic and transcriptional alterations of NRGs in 151 patients with AML. Then, we identified three necroptosis clusters. Moreover, a necroptosis score was constructed and assessed based on the differentially expressed genes (DEGs) between the three necroptosis clusters. RESULTS: Three necroptosis clusters were correlated with clinical characteristics, prognosis, the tumor microenvironment, and infiltration of immune cells. A high necroptosis score was positively associated with a poor prognosis, immune-cell infiltration, expression of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1), immune score, stromal score, interferon-gamma (IFNG), merck18, T-cell dysfunction-score signatures, and cluster of differentiation-86, but negatively correlated with tumor immune dysfunction and exclusion score, myeloid-derived suppressor cells, and M2-type tumor-associated macrophages. Our observations indicated that a high necroptosis score might contribute to immune evasion. More interestingly, AML patients with a high necroptosis score may benefit from treatment based on immune checkpoint blockade. CONCLUSIONS: Consequently, our findings may contribute to deeper understanding of NRGs in AML, and facilitate assessment of the prognosis and treatment strategies.

Detection of NPM1 Mutations in Acute Myeloid Leukemia by using Drop-Off Droplet Digital PCR and its Clinical Application.

BACKGROUND: Nucleophosmin 1 (NPM1) mutations, which occur in 25 - 30% of acute myeloid leukemia (AML) and 50 - 60% of AML with normal karyotype, have been identified as an important marker for stratification of prog-nosis in AML. This study aimed to establish a new quantitative polymerase chain reaction (PCR) technique, the drop-off droplet digital PCR (ddPCR), for rapid and sensitive detection of NPM1 mutations in AML. METHODS: We established the drop-off ddPCR system and verified its performance. NPM1 mutations were screened in 130 AML patients by drop-off ddPCR and were validated by Sanger sequencing and next-generation sequencing (NGS). Then, the NPM1 mutation burden was dynamically monitored in five patients. RESULTS: The limit of blank (LOB) of drop-off ddPCR established for NPM1 mutation was 3.36 copies/µL, and the limit of detection (LOD) was 5.00 - 5.37 copies/µL in 50 ng DNA, and the sensitivity was about 0.05%, which had good linearity. Drop-off ddPCR identified 33/130 (25.4%) NPM1 mutated cases, consistent with Sanger sequencing. In 18 NPM1 positive cases selected randomly, NGS identified fourteen with type A mutation, two with type D mutation, and two with rare type mutations. The mutation burden of NPM1 mutation analyzed by NGS was consistent with the drop-off ddPCR. The sequential samples were detected for measurable residual disease (MRD) monitoring in 5 patients showed that the NPM1 mutation burden was consistent with clinical remission and recurrence. Compared with traditional ddPCR, drop-off ddPCR was also suitable for MRD monitoring. CONCLUSIONS: In this study, we established a drop-off ddPCR method for detecting three common mutations in AML with good sensitivity and repeatability, which can be used to screen mutations in newly diagnosed AML patients and for MRD monitoring after remission to guide treatment.

A wavelet coherence approach to zoning supply-demand matching of carbon sequestration service.

Carbon sequestration (CS) is an important regulating service provided by natural ecosystem which plays an important role in mitigating global climate change. However, there is often spatial mismatch between the carbon sequestration supply and demand (CSSD), which makes it difficult to reduce carbon emissions and increase carbon sinks to achieve local carbon balance. Therefore, it is important to clarify the optimal scale to explore spatial matches and mismatches between CSSD and delimit spatial units for implementing effective carbon-focused management policies. Taking Hunan Province, China as an example, we evaluated CSSD in 2001 and 2017, and identified the optimal scale of spatial matching based on wavelet coherence analysis. The results showed that from 2001 to 2017, CS supply in Hunan Province increased by 6.45 %, while CS demand increased by 261.11 %. 8.40 km was identified as the optimal scale of CSSD spatial matches and mismatches, and Hunan Province could be divided into 3231 spatial units including four types according to the combination of CSSD, i.e. High supply-High demand, Low supply-Low demand, High supply-Low demand and Low supply-High demand. Based on the type changes of spatial units from 2001 to 2017, it was found that the key areas in need of ecological restoration were located in the east side of Xuefeng Mountains and the west side of Luoxiao Mountains, which could support accurate ecosystem monitoring and management under the background of improving the 'one map' of territorial space in Hunan Province. Based on wavelet coherence analysis, this study provided a spatial zoning approach for sustainable land use management, with a special focus on carbon sequestration supply and demand.

A Review of Aspects of Synaptic Plasticity in Hippocampus via mT Extremely Low-Frequency Magnetic Fields.

The subthreshold magnetic modulation technique stimulates cells with mT extremely low-frequency magnetic fields (ELF-MFs), which are insufficient to induce neuronal action potentials. Although they cannot directly induce resting neurons to discharge, mT magnetic stimulation can regulate the excitability of the nervous system, which regulates learning and memory by some unknown mechanisms. Herein, we describe the regulation of mT ELF-MFs with different parameters on synaptic plasticity in hippocampal neurons. Additionally, we summarize the latest research on the possible mechanism of the effect of ELF-MFs on synaptic plasticity. Some studies have shown that ELF-MFs are able to inhibit long-term potentiation (LTP) by increasing concentration of intracellular Ca2+ concentration ([Ca2+ ]i ), as well as concentration of reactive oxygen species. The research in this paper has significance for the comprehensive understanding of relevant neurological mechanisms of learning and memory by mT ELF-MFs stimulation. However, more high-quality research is necessary to determine the regulatory mechanism of mT ELF-MFs on synaptic plasticity in order to optimize this technique as a treatment for neurological diseases. © 2023 Bioelectromagnetics Society.

Pan-cancer analysis identifies CD300 molecules as potential immune regulators and promising therapeutic targets in acute myeloid leukemia.

BACKGROUND: CD300s are a group of proteins playing vital roles in immune responses. However, much is yet to be elucidated regarding the expression patterns and clinical significances of CD300s in cancers. METHODS: In this study, we comprehensively investigated CD300s in a pan-cancer manner using multi-omic data from The Cancer Genome Atlas. We also studied the relationship between CD300s and the immune landscape of AML. RESULTS: We found that CD300A-CD300LF were generally overexpressed in tumors (especially AML), whereas CD300LG was more often downregulated. In AML, transactivation of CD300A was not mediated by genetic alterations but by histone modification. Survival analyses revealed that high CD300A-CD300LF expression predicted poor outcome in AML patients; the prognostic value of CD300A was validated in seven independent datasets and a meta dataset including 1115 AML patients. Furthermore, we demonstrated that CD300A expression could add prognostic value in refining existing risk models in AML. Importantly, CD300A-CD300LF expression was closely associated with T-cell dysfunction score and could predict response to AML immunotherapy. Also, CD300A was found to be positively associated with HLA genes and critical immune checkpoints in AML, such as VISTA, CD86, CD200R1, Tim-3, and the LILRB family genes. CONCLUSIONS: Our study demonstrated CD300s as potential prognostic biomarker and an ideal immunotherapy target in AML, which warrants future functional and clinical studies.

Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9 / 中西医结合学报

OBJECTIVE@#To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation.@*METHODS@#Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9.@*RESULTS@#EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.@*CONCLUSION@#Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.

Acupuncture-Neuroimaging Research Trends over Past Two Decades: A Bibliometric Analysis / 中国结合医学杂志

OBJECTIVE@#To identify topics attracting growing research attention as well as frontier trends of acupuncture-neuroimaging research over the past two decades.@*METHODS@#This paper reviewed data in the published literature on acupuncture neuroimaging from 2000 to 2020, which was retrieved from the Web of Science database. CiteSpace was used to analyze the publication years, countries, institutions, authors, keywords, co-citation of authors, journals, and references.@*RESULTS@#A total of 981 publications were included in the final review. The number of publications has increased in the recent 20 years accompanied by some fluctuations. Notably, the most productive country was China, while Harvard University ranked first among institutions in this field. The most productive author was Tian J with the highest number of articles (50), whereas the most co-cited author was Hui KKS (325). Evidence-Based Complementary and Alternative Medicine (92) was the most prolific journal, while Neuroimage was the most co-cited journal (538). An article written by Hui KKS (2005) exhibited the highest co-citation number (112). The keywords "acupuncture" (475) and "electroacupuncture" (0.10) had the highest frequency and centrality, respectively. Functional magnetic resonance imaging (fMRI) ranked first with the highest citation burst (6.76).@*CONCLUSION@#The most active research topics in the field of acupuncture-neuroimaging over the past two decades included research type, acupoint specificity, neuroimaging methods, brain regions, acupuncture modality, acupoint specificity, diseases and symptoms treated, and research type. Whilst research frontier topics were "nerve regeneration", "functional connectivity", "neural regeneration", "brain network", "fMRI" and "manual acupuncture".

SLC22A3 methylation-mediated gene silencing predicts adverse prognosis in acute myeloid leukemia.

BACKGROUND: We screened out several hypermethylated solute carrier (SLC) family genes in acute myeloid leukemia by reduced representation bisulfite sequencing. SLC22A3 encodes an organic cation transport protein, which is critical for drug transportation and cellular detoxification. SLC22A3 is significantly downregulated and associated with tumor progression and worse prognosis in a variety of solid tumors. However, there are no data available regarding the role of SLC22 in AML. This study aimed to explore the regulatory mechanism of DNA methylation on SLC22A3 expression, as well as its clinical significance in AML prognosis. RESULTS: SLC22A3 was identified as the sole prognosis-associated gene among SLCs based on TCGA and Beat AML databases. Bone marrow mononuclear cells (BMMNCs) from AML, MDS patients, and healthy donors were enrolled in this study. SLC22A3 methylation was significantly increased in AML compared with controls and MDS patients; meanwhile, the expression level of SLC22A3 was decreased. SLC22A3 hypermethylation presented an obvious association with some specific clinical characteristics and affected the survival time of AML patients as an independent risk indicator. SLC22A3 expression changed regularly as the disease complete remissions and relapses. Demethylation drug 5-aza-2'-deoxycytidine (DAC) activated transcription and increased mRNA expression of SLC22A3 in leukemia cell lines and AML fresh BMMNCs. Knockdown of SLC22A3 in leukemia cells enhanced cell proliferation and suppressed cell apoptosis. Data from public programs were used for auxiliary screening of probable molecular mechanisms of SLC22A3 in the antileukemia effect. CONCLUSIONS: Our results showed that increased methylation and decreased expression of SLC22A3 may be indicators of poor prognosis in AML. Methylation-silenced SLC22A3 expression may have potential guiding significance on antileukemia effect of DAC.

A functional role of meningeal lymphatics in sex difference of stress susceptibility in mice.

Major depressive disorder is one of the most common mental health conditions. Meningeal lymphatics are essential for drainage of molecules in the cerebrospinal fluid to the peripheral immune system. Their potential role in depression-like behaviour has not been investigated. Here, we show in mice, sub-chronic variable stress as a model of depression-like behaviour impairs meningeal lymphatics in females but not in males. Manipulations of meningeal lymphatics regulate the sex difference in the susceptibility to stress-induced depression- and anxiety-like behaviors in mice, as well as alterations of the medial prefrontal cortex and the ventral tegmental area, brain regions critical for emotional regulation. Together, our findings suggest meningeal lymphatic impairment contributes to susceptibility to stress in mice, and that restoration of the meningeal lymphatics might have potential for modulation of depression-like behaviour.

m6A regulator-based methylation modification patterns and characterization of tumor microenvironment in acute myeloid leukemia.

RNA N6-methyladenosine (m6A) is the most common and intensively studied RNA modification that critically regulates RNA metabolism, cell signaling, cell survival, and differentiation. However, the overall role of multiple m6A regulators in the tumor microenvironment (TME) has not yet been fully elucidated in acute myeloid leukemia (AML). In our study, we explored the genetic and transcriptional alterations of 23 m6A regulators in AML patients. Three distinct molecular subtypes were identified and associated with prognosis, patient clinicopathological features, as well as TME characteristics. The TME characterization revealed that m6A patterns were highly connected with metabolic pathways such as biosynthesis of unsaturated fatty acids, cysteine and methionine metabolism, and citrate cycle TCA cycle. Then, based on the differentially expressed genes (DEGs) related to m6A molecular subtypes, our study categorized the entire cohort into three m6A gene clusters. Furthermore, we constructed the m6Ascore for quantification of the m6A modification pattern of individual AML patients. It was found that the tumor-infiltrating lymphocyte cells (TILs) closely correlated with the three m6A clusters, three m6A gene clusters, and m6Ascore. And many biological processes were involved, including glycogen degradation, drug metabolism by cytochrome P450, pyruvate metabolism, and so on. Our comprehensive analysis of m6A regulators in AML demonstrated their potential roles in the clinicopathological features, prognosis, tumor microenvironment, and particularly metabolic pathways. These findings may improve our understanding of m6A regulators in AML and offer new perspectives on the assessment of prognosis and the development of anticancer strategy.

[Detection of NPM1 Mutation in Acute Myeloid Leukemia by Droplet Digital PCR and Its Clinical Application Value].

OBJECTIVE: To establish the droplet digital PCR (ddPCR) assay for the detection of NPM1 type A mutation in patients with acute myeloid leukemia (AML), and to evaluate its specificity, sensitivity and its value in clinical application. METHODS: NPM1 mutant and wildtype plasmids were used to verify the performance of ddPCR. Both ddPCR and Sanger sequencing were used to detect the bone marrow samples of 87 AML patients, which were confirmed by next generation sequencing (NGS). Moreover, NPM1 mutation burden was dynamically monitored in five patients by ddPCR. RESULTS: The limit of blank (LOB) of ddPCR established for NPM1 mutation detection was 1.1 copies/µl, and the limit of detection (LOD) was 2.43 copies/µl, which had good linearity. Among the 87 newly diagnosed AML patients, ddPCR identified seventeen cases positive for NPM1 mutation (19.5%)， which was consistent with Sanger sequencing. NGS confirmed 12 positive cases, including 8 of type A mutations, 2 of type D mutations, and 2 of rare type mutations. The results of dynamic monitoring of NPM1 mutation burden in 5 patients showed that the NPM1 mutation burden decreased obviously even close to 0, when patients achieve complete remission after chemotherapy. However, the mutation burden was increased again at the time of relapse. CONCLUSION: In this study, we established a ddPCR method for detection of NPM1 mutation with good sensitivity and repeatability, which can be used for screening NPM1 mutation in newly diagnosed AML patients and for minimal residual disease monitoring after remission in positive AML patients to guide treatment.

[Clinical Significance of Low Expression of LncRNA CASC15 in Acute Myeloid Leukemia with NPM1 Mutations].

AbstractObjective: To identify the expression and methylation patterns of lncRNA CASC15 in bone marrow (BM) samples of acute myeloid leukemia (AML) patients, and further explore its clinical significance. METHODS: Eighty-two de novo AML patients and 18 healthy donors were included in the study. Meanwhile, seven public datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were included to confirm the expression and methylation data of CASC15. Receiver operating characteristic (ROC) curve analysis was applied to determine the discriminative capacity of CASC15 expression to identify AML. The patients were divided into CASC15high group and CASC15low group by X-tile method, and the prognostic value of CASC15 was identified by Kaplan-Meier method and univariate and multivariate Cox regression analysis. RESULTS: The expression level of CASC15 was significantly decreased in BM cells of AML patients compared with healthy donors (P<0.001). ROC curve analysis suggested that CASC15 expression might be a potential biomarker to discriminate AML from controls. The expression of CASC15 was high at the early stage of hematopoiesis, and reached a peak at the stage of multipotent progenitors differentiation, then decreased rapidly, and was at a range of low level fluctuations in the subsequent process. Among FAB subtypes, CASC15 expression in M0 was significantly higher than that in M1-M7. Clinically, CASC15low patients were more likely to have NPM1 mutations than CASC15high patients (P=0.048), while CASC15high patients had a significantly higher frequency of IDH1 and RUNX1 mutations (P=0.021 and 0.014, respectively). Moreover, CASC15low group had a shorter overall survival (OS) in patients with NPM1 mutations. Furthermore, multivariate analysis confirmed that CASC15 expression was a significant independent risk factor for OS in NPM1 mutated AML patients. In addition, CASC15 methylation level in BM samples of AML patients was significantly decreased compared with healthy donors. Patients with CASC15 high methylation had poor OS and disease-free survival. CONCLUSION: The expression of CASC15 is decreased in AML, and low CASC15 expression may predict adverse prognosis in AML patients with NPM1 mutations. Moreover, CASC15 methylation level in AML is significantly decreased, and high CASC15 methylation may predict poor prognosis in AML.

Sex-Specific Transcriptomic Signatures in Brain Regions Critical for Neuropathic Pain-Induced Depression.

Neuropathic pain is a chronic debilitating condition with a high comorbidity with depression. Clinical reports and animal studies have suggested that both the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC) are critically implicated in regulating the affective symptoms of neuropathic pain. Neuropathic pain induces differential long-term structural, functional, and biochemical changes in both regions, which are thought to be regulated by multiple waves of gene transcription. However, the differences in the transcriptomic profiles changed by neuropathic pain between these regions are largely unknown. Furthermore, women are more susceptible to pain and depression than men. The molecular mechanisms underlying this sexual dimorphism remain to be explored. Here, we performed RNA sequencing and analyzed the transcriptomic profiles of the mPFC and ACC of female and male mice at 2 weeks after spared nerve injury (SNI), an early time point when the mice began to show mild depressive symptoms. Our results showed that the SNI-induced transcriptomic changes in female and male mice were largely distinct. Interestingly, the female mice exhibited more robust transcriptomic changes in the ACC than male, whereas the opposite pattern occurred in the mPFC. Cell type enrichment analyses revealed that the differentially expressed genes involved genes enriched in neurons, various types of glia and endothelial cells. We further performed gene set enrichment analysis (GSEA), which revealed significant de-enrichment of myelin sheath development in both female and male mPFC after SNI. In the female ACC, gene sets for synaptic organization were enriched, and gene sets for extracellular matrix were de-enriched after SNI, while such signatures were absent in male ACC. Collectively, these findings revealed region-specific and sexual dimorphism at the transcriptional levels induced by neuropathic pain, and provided novel therapeutic targets for chronic pain and its associated affective disorders.

Distinguishing the impacts of land use change in intensity and type on ecosystem services trade-offs.

Changes in land use intensity and types can affect the structure and function of ecosystems, and thus ecosystem services (ESs) as well as their interactions. However, the impacts of changes in land use intensity on ESs remain poorly understood. Through four different land use scenarios, we distinguished the independent contribution of changes in agricultural land use intensity and types to grain production (GP), water purification (WP), and their trade-offs in the Dongting Lake Basin. The results showed that from 1990 to 2015, GP increased across 58.07% of the total area, but WP decreased across 64.81% of the study area. The two ESs simultaneously increased or decreased across 41.93% of the total area. Watersheds covering 48.72% of the study area where GP increased and WP decreased were mainly distributed in areas with increased land use intensity. The other regions where GP decreased and WP increased were mainly distributed in areas with decreased land use intensity. The scenario analysis of GP, WP, and their trade-offs showed that the areas where agricultural land use intensity was the dominant factor were as large as 1.95 times, 2.38 times, and 2.43 times those dominated by land use type respectively, under the same climate conditions. This study highlighted the importance of changes in agricultural land use intensity on ES, which provided further supporting to ES-based land use management.

Application of Tiaoshen Jianpi acupuncture and moxibustion in hospice care for terminal cancer patients / 中国针灸

To analyze the application feasibility of Tiaoshen Jianpi acupuncture and moxibustion in hospice care for terminal cancer patients. Tiaoshen Jianpi acupuncture and moxibustion adjusts the spirit to regulate emotions and fortifies the spleen to supplement and boost foundation of acquired (postnatal) constitution. And it could relieve adverse reactions after radiotherapy and chemotherapy, alleviate pain and regulate emotions in hospice care for terminal cancer patients, so as to promote the progress of hospice care for terminal cancer patients.

Association Analyses of TP53 Mutation With Prognosis, Tumor Mutational Burden, and Immunological Features in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease related to a broad spectrum of molecular alterations. The successes of immunotherapies treating solid tumors and a deeper understanding of the immune systems of patients with hematologic malignancies have promoted the development of immunotherapies for the treatment of AML. And high tumor mutational burden (TMB) is an emerging predictive biomarker for response to immunotherapy. However, the association of gene mutation in AML with TMB and immunological features still has not been clearly elucidated. In our study, based on The Cancer Genome Atlas (TCGA) and BeatAML cohorts, 20 frequently mutated genes were found to be covered by both datasets in AML. And TP53 mutation was associated with a poor prognosis, and its mutation displayed exclusiveness with other common mutated genes in both datasets. Moreover, TP53 mutation correlated with TMB and the immune microenvironment. Gene Set Enrichment Analysis (GSEA) showed that TP53 mutation upregulated signaling pathways involved in the immune system. In summary, TP53 mutation is frequently mutated in AML, and its mutation is associated with dismal outcome, TMB, and immunological features, which may serve as a biomarker to predict immune response in AML.

Integrated analysis reveals distinct molecular, clinical, and immunological features of B7-H3 in acute myeloid leukemia.

The role of B7-H3 in acute myeloid leukemia (AML) is not fully understood. Two previous studies investigating its expression and significances in AML are partially different. In this study, we aimed to systematically characterize the genomic and immune landscape in AML patients with altered B7-H3 expression using multi-omics data in the public domain. We found significantly increased B7-H3 expression in AML compared to either other hematological malignancies or healthy controls. Clinically, high B7-H3 expression was associated with old age, TP53 mutations, wild-type WT1 and CEBPA, and the M3 and M5 FAB subtypes. Moreover, we observed that increased B7-H3 expression correlated significantly with a poor outcome of AML patients in four independent datasets. Gene set enrichment analysis (GSEA) revealed the enrichment of the "EMT" oncogenic gene signatures in high B7-H3 expressers. Further investigation suggested that B7-H3 was more likely to be associated with immune-suppressive cells (macrophages, neutrophils, dendritic cells, and Th17 cells). B7-H3 was also positively associated with a number of checkpoint genes, such as VISTA (B7-H5), CD80 (B7-1), CD86 (B7-2), and CD70. In summary, we uncovered distinct genomic and immunologic features associated with B7-H3 expression in AML. This may lead to a better understanding of the molecular mechanisms underlying B7-H3 dysregulation in AML and to the development of novel therapeutic strategies.

Short-Term Extremely Low-Frequency Electromagnetic Field Inhibits Synaptic Plasticity of Schaffer Collateral-CA1 Synapses in Rat Hippocampus via the Ca2+/Calcineurin Pathway.

In this study, we investigate the intrinsic mechanism by which an extremely low-frequency electromagnetic field (ELF-EMF) influences neurons in the Schaffer collateral-CA1 (SC-CA1) region of rat hippocampus using electrophysiological techniques. ELF-EMF has an interesting effect on synaptic plasticity: it weakens long-term potentiation and enhances long-term depression. Here, the magnetic field effect disappeared after a blockade of voltage-gated calcium channels and calcineurin, which are key components in the Ca2+/calcineurin pathway, with two blockers, cadmium chloride and cyclosporin A. This fully establishes that the effect of ELF-EMF on synaptic plasticity is mediated by the Ca2+/calcineurin pathway and represents a novel technique for studying the specific mechanisms of action of ELF-EMF on learning and memory.