Assessing the needs of patients with breast cancer and their families across various treatment phases using a Latent Dirichlet Allocation model: a text-mining approach to online health communities.

PURPOSE: This study aimed to assess the different needs of patients with breast cancer and their families in online health communities at different treatment phases using a Latent Dirichlet Allocation (LDA) model. METHODS: Using Python, breast cancer-related posts were collected from two online health communities: patient-to-patient and patient-to-doctor. After data cleaning, eligible posts were categorized based on the treatment phase. Subsequently, an LDA model identifying the distinct need-related topics for each phase of treatment, including data preprocessing and LDA topic modeling, was established. Additionally, the demographic and interactive features of the posts were manually analyzed. RESULTS: We collected 84,043 posts, of which 9504 posts were included after data cleaning. Early diagnosis and rehabilitation treatment phases had the highest and lowest number of posts, respectively. LDA identified 11 topics: three in the initial diagnosis phase and two in each of the remaining treatment phases. The topics included disease outcomes, diagnosis analysis, treatment information, and emotional support in the initial diagnosis phase; surgical options and outcomes, postoperative care, and treatment planning in the perioperative treatment phase; treatment options and costs, side effects management, and disease prognosis assessment in the non-operative treatment phase; diagnosis and treatment options, disease prognosis, and emotional support in the relapse and metastasis treatment phase; and follow-up and recurrence concerns, physical symptoms, and lifestyle adjustments in the rehabilitation treatment phase. CONCLUSION: The needs of patients with breast cancer and their families differ across various phases of cancer therapy. Therefore, specific information or emotional assistance should be tailored to each phase of treatment based on the unique needs of patients and their families.

Activation of the TNF-α-Necroptosis Pathway in Parvalbumin-Expressing Interneurons of the Anterior Cingulate Cortex Contributes to Neuropathic Pain.

The hyperexcitability of the anterior cingulate cortex (ACC) has been implicated in the development of chronic pain. As one of the key causes of ACC hyperexcitation, disinhibition of the ACC may be closely related to the dysfunction of inhibitory parvalbumin (PV)-expressing interneurons (PV-INs). However, the molecular mechanism underlying the ACC PV-INs injury remains unclear. The present study demonstrates that spared sciatic nerve injury (SNI) induces an imbalance in the excitation and inhibition (E/I) of the ACC. To test whether tumor necrosis factor-α (TNF-α) upregulation in the ACC after SNI activates necroptosis and participates in PV-INs damage, we performed a differential analysis of transcriptome sequencing using data from neuropathic pain models and found that the expression of genes key to the TNF-α-necroptosis pathway were upregulated. TNF-α immunoreactivity (IR) signals in the ACCs of SNI rats were co-located with p-RIP3- and PV-IR, or p-MLKL- and PV-IR signals. We then systematically detected the expression and cell localization of necroptosis-related proteins, including kinase RIP1, RIP3, MLKL, and their phosphorylated states, in the ACC of SNI rats. Except for RIP1 and MLKL, the levels of these proteins were significantly elevated in the contralateral ACC and mainly expressed in PV-INs. Blocking the ACC TNF-α-necroptosis pathway by microinjecting TNF-α neutralizing antibody or using an siRNA knockdown to block expression of MLKL in the ACC alleviated SNI-induced pain hypersensitivity and inhibited the upregulation of TNF-α and p-MLKL. Targeting TNF-α-triggered necroptosis within ACC PV-INs may help to correct PV-INs injury and E/I imbalance in the ACC in neuropathic pain.

NLRP3-Mediated Piezo1 Upregulation in ACC Inhibitory Parvalbumin-Expressing Interneurons Is Involved in Pain Processing after Peripheral Nerve Injury.

The anterior cingulate cortex (ACC) is particularly critical for pain information processing. Peripheral nerve injury triggers neuronal hyper-excitability in the ACC and mediates descending facilitation to the spinal dorsal horn. The mechanically gated ion channel Piezo1 is involved in the transmission of pain information in the peripheral nervous system. However, the pain-processing role of Piezo1 in the brain is unknown. In this work, we found that spared (sciatic) nerve injury (SNI) increased Piezo1 protein levels in inhibitory parvalbumin (PV)-expressing interneurons (PV-INs) but not in glutaminergic CaMKⅡ+ neurons, in the bilateral ACC. A reduction in the number of PV-INs but not in the number of CaMKⅡ+ neurons and a significant reduction in inhibitory synaptic terminals was observed in the SNI chronic pain model. Further, observation of morphological changes in the microglia in the ACC showed their activated amoeba-like transformation, with a reduction in process length and an increase in cell body area. Combined with the encapsulation of Piezo1-positive neurons by Iba1+ microglia, the loss of PV-INs after SNI might result from phagocytosis by the microglia. In cellular experiments, administration of recombinant rat TNF-α (rrTNF) to the BV2 cell culture or ACC neuron primary culture elevated the protein levels of Piezo1 and NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3). The administration of the NLRP3 inhibitor MCC950 in these cells blocked the rrTNF-induced expression of caspase-1 and interleukin-1ß (key downstream factors of the activated NLRP3 inflammasome) in vitro and reversed the SNI-induced Piezo1 overexpression in the ACC and alleviated SNI-induced allodynia in vivo. These results suggest that NLRP3 may be the key factor in causing Piezo1 upregulation in SNI, promoting an imbalance between ACC excitation and inhibition by inducing the microglial phagocytosis of PV-INs and, thereby, facilitating spinal pain transmission.

Neuroimmune Mechanisms Underlying Neuropathic Pain: The Potential Role of TNF-α-Necroptosis Pathway.

The neuroimmune mechanism underlying neuropathic pain has been extensively studied. Tumor necrosis factor-alpha (TNF-α), a key pro-inflammatory cytokine that drives cytokine storm and stimulates a cascade of other cytokines in pain-related pathways, induces and modulates neuropathic pain by facilitating peripheral (primary afferents) and central (spinal cord) sensitization. Functionally, TNF-α controls the balance between cell survival and death by inducing an inflammatory response and two programmed cell death mechanisms (apoptosis and necroptosis). Necroptosis, a novel form of programmed cell death, is receiving increasing attraction and may trigger neuroinflammation to promote neuropathic pain. Chronic pain is often accompanied by adverse pain-associated emotional reactions and cognitive disorders. Overproduction of TNF-α in supraspinal structures such as the anterior cingulate cortex (ACC) and hippocampus plays an important role in pain-associated emotional disorders and memory deficits and also participates in the modulation of pain transduction. At present, studies reporting on the role of the TNF-α-necroptosis pathway in pain-related disorders are lacking. This review indicates the important research prospects of this pathway in pain modulation based on its role in anxiety, depression and memory deficits associated with other neurodegenerative diseases. In addition, we have summarized studies related to the underlying mechanisms of neuropathic pain mediated by TNF-α and discussed the role of the TNF-α-necroptosis pathway in detail, which may represent an avenue for future therapeutic intervention.

Neuroinflammation in the anterior cingulate cortex: the potential supraspinal mechanism underlying the mirror-image pain following motor fiber injury.

BACKGROUND: Peripheral nerve inflammation or lesion can affect contralateral healthy structures, and thus result in mirror-image pain. Supraspinal structures play important roles in the occurrence of mirror pain. The anterior cingulate cortex (ACC) is a first-order cortical region that responds to painful stimuli. In the present study, we systematically investigate and compare the neuroimmune changes in the bilateral ACC region using unilateral- (spared nerve injury, SNI) and mirror-(L5 ventral root transection, L5-VRT) pain models, aiming to explore the potential supraspinal neuroimmune mechanism underlying the mirror-image pain. METHODS: The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Viral injections for the designer receptors exclusively activated by designer drugs (DREADD) were used to modulate ACC glutamatergic neurons. Immunohistochemistry, immunofluorescence, western blotting, protein microarray were used to detect the regulation of inflammatory signaling. RESULTS: Increased expressions of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and chemokine CX3CL1 in ACC induced by unilateral nerve injury were observed on the contralateral side in the SNI group but on the bilateral side in the L5-VRT group, representing a stronger immune response to L5-VRT surgery. In remote ACC, both SNI and L5-VRT induced robust bilateral increase in the protein level of Nav1.6 (SCN8A), a major voltage-gated sodium channel (VGSC) that regulates neuronal activity in the mammalian nervous system. However, the L5-VRT-induced Nav1.6 response occurred at PO 3d, earlier than the SNI-induced one, 7 days after surgery. Modulating ACC glutamatergic neurons via DREADD-Gq or DREADD-Gi greatly changed the ACC CX3CL1 levels and the mechanical paw withdrawal threshold. Neutralization of endogenous ACC CX3CL1 by contralateral anti-CX3CL1 antibody attenuated the induction and the maintenance of mechanical allodynia and eliminated the upregulation of CX3CL1, TNF-α and Nav1.6 protein levels in ACC induced by SNI. Furthermore, contralateral ACC anti-CX3CL1 also inhibited the expression of ipsilateral spinal c-Fos, Iba1, CD11b, TNF-α and IL-6. CONCLUSIONS: The descending facilitation function mediated by CX3CL1 and its downstream cascade may play a pivotal role, leading to enhanced pain sensitization and even mirror-image pain. Strategies that target chemokine-mediated ACC hyperexcitability may lead to novel therapies for the treatment of neuropathic pain.

Alfalfa's response to atrazine stress and its secreted atrazine metabolites.

Although listed as endocrine disruptor compounds, atrazine (ATZ) is still used in large quantities in agricultural production. Here, alfalfa seedling was cultivated in hydroponic media to investigate the toxic effects of ATZ on alfalfa and accumulation of ATZ in tissues of different plant parts. Alfalfa had a strong upward translocation ability to ATZ. The stress response of alfalfa under ATZ stress was studied using metabolomic and transcriptomic techniques. S-adenosylmethionine, glutathione, 3-mercaptopyruvic acid, ornithine, and aminopropylcadaverine were significantly increased by ATZ in pathways mtr00270 and mtr00480. Several genes of cysteine synthase and spermidine synthase were significantly up-regulated by ATZ induction. They may be markers and genes with potential physiological functions of alfalfa in response to ATZ stress. In addition, using high resolution mass spectrometry, a total of five ATZ metabolites secreted from alfalfa roots were detected. Among them, acetylated deisopropylated ATZ was discovered for the first time. Hydroxylated ATZ and acetylated deethylated ATZ were more readily excreted by the root system. This study not only provides potential genes for the construction of engineering plants to remediate ATZ-contaminated soil, but also provides monitoring objects for the ecological research of ATZ metabolites.

[Determination of trace elements in Mongolian medicine Susi-12 curing cholecystitis and gallstone disease by ICP-AES].

Trace elements in Mongolian medicine Susi-12 for cholecystitis and gallstones were analyzed in order to discuss the relation between Susi-12's drug action and the trace elements. The analysis was carried out using the pressure seal microwave digestion and inductive coupled plasma atomic emission spectrometry (ICP-AES). It was found that the medicine contained great amount of trace elements, especially human-body-needed trace elements, such as Ca, Al, Mg, Fe, Sr, Mn, Zn, Cu etc., whereas heavy metals are very little, e.g. the contents of Pb, Cb, As etc are below the country's limit. The recoveries of standard addition are in the range of 94.63%-106.40%. The relative standard deviation RSD< or =3.35%, and detection limit is < or =0.009 mg x L(-1). It is concluded that Mongolian medicine Susi-12 can effectively control and cure cholecystitis and gallstones, and the effective rate reaches 91.2% to 100%. So the trace elements in Susi-12 must have a close connection with the drug action.