To develop and validate a model for predicting intensive care unit (ICU) mortality risk in patients with malignant tumors complicated by acute respiratory failure (ARF) based on an explainable machine learning framework.

Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces. Here we have developed a deep learning algorithm, GPT2 Ion Channel Classifier (GPT2-ICC), which effectively distinguishing ion channels from a test set containing approximately 239 times more non-ion-channel proteins. GPT2-ICC integrates representation learning with a large language model (LLM)-based classifier, enabling highly accurate identification of potential ion channels. Several potential ion channels were predicated from the unannotated human proteome, further demonstrating GPT2-ICC's generalization ability. This study marks a significant advancement in artificial-intelligence-driven ion channel research, highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data. Moreover, it provides a valuable computational tool for uncovering previously uncharacterized ion channels.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

OBJECTIVE To explore the characteristics and influential factors of pharmaceutical clinic service demands， providing evidence for optimizing pharmaceutical service models and facilitating pharmaceutical service models of pharmacist role transformation. METHODS A cross-sectional survey design was adopted， and 410 outpatient participants were selected from Fudan University Shanghai Cancer Center through convenience sampling for questionnaire administration from February to May 2025. Kano model was applied to analyze the demand attributes of 25 pharmaceutical services， while questionnaires were used to assess patients’ awareness and demand status. Subgroup analyses were conducted based on key demographic variables such as gender， age， educational attainment， and economic burdens， to SACA- systematically examine the differences in Kano attribute classification among patients in each subgroup. RESULTS The awareness rate of pharmaceutical outpatient services among patients was only 14.63%， yet those who were aware demonstrated a significantly higher demand rate for such services compared to those who were unaware （P＜0.001）. The demand for pharmaceutical clinic services exhibited a hierarchical characteristic： twelve items were identified as attractive attributes （e. g.， providing suggestions for more affordable treatment options， offering online consultation services， etc.）， five items as expected attributes （e.g.， having a good attitude and being able to patiently answer your questions， etc.）， three items as must-have attributes （e.g.， providing guidance on medication dosage and usage， providing guidance on medication precautions， etc.）， five items as indifferent attributes （e.g.， providing treatment plan recommendations based on the patient’s condition）. There were zero items classified as reverse attribute. Subgroup analysis revealed that female patients showed greater concern for “neat and clean attire of medical staff” than male patients （P＜0.001）； patients under 60 years of age demonstrated stronger demand for “providing treatment plan recommendations based on patients’ conditions” compared to patients aged 60 or above （P＝0.016）； those with below high school education placed greater emphasis on “providing guidance on medication precautions” compared to those with a high school education or above （P＝0.011）； patients with lower economic burdens exhibited stronger preferences for “neat and clean attire of medical staff ” （P＝0.002）. CONCLUSIONS The public awareness rate of pharmaceutical clinic services is considerably low； however， those who are aware of such services demonstrate significantly higher demand. The medication safety-related services and convenience-oriented demands should be prioritized in the development of pharmaceutical clinics. Moreover， the study also revealed that factors such as gender， age， educational level， and economic burdens exert significant influences on patients’ service demands.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Knee osteoarthritis(KOA)is a common musculoskeletal disease,and ferroptosis is a new type of programmed cell death involving iron ions.This paper summarized the relationship between the pathological changes of ferroptosis and the onset of KOA,and reviewed the progress of traditional Chinese medicine(TCM)intervention in KOA based on the pathological changes of ferroptosis.The pathological changes of ferroptosis are mainly related to the imbalance of amino acid antioxidant system,iron metabolism disorder and lipid peroxide accumulation.The cystine/glutamate antiporter(System XC-),glutathione(GSH)and glutathione peroxidase 4(GPX4)are the core targets for regulating ferroptosis,involving the main signaling pathways for studying the TCM intervention of KOA via ferroptosis.Single herbs such as Drynariae Rhizoma,Scutellariae Barbatae Herba,Epimedii Folium,Astragali Radix,Ligustri Lucidi Fructus,and Achyranthis Bidentatae Radix,and multi-herb formulae such as Duhuo Jisheng Decoction and Yougui Pills,can inhibit the ferroptosis of chondrocytes through multiple targets and multiple pathways,thus treating KOA.The research of the TCM intervention on the ferroptosis of chondrocytes and its associated signaling pathways can provides a novel approach for expanding the TCM therapy of KOA.

ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action， so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group， model group， carbamazepine group （0.06 g·kg^-1·d^-1）， high-dose Lutongning group （2.70 g·kg^-1·d^-1）， and low-dose Lutongning group （1.35 g·kg^-1·d^-1） according to the stratified basic mechanical pain thresholds， with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg^-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin （HE） staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors interleukin （IL）-1， IL-6， IL-8， tumor necrosis factor （TNF）-α， neuropeptide substance P， and β-endorphins （β-EP） in the serum of rats， and Western blot was used to detect the protein expression levels of IL-1β， purinergic receptor P2X7 （P2X7R）， and phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）. ResultCompared with that in the normal group， the pain threshold of rats in the model group was significantly lower （P<0.01）. The absolute value of neutrophils （NEUT#） and the percentage of neutrophils （NEUT） were significantly improved， and the percentage of lymphocytes （LYMPH） was significantly reduced （P<0.01）. The serum levels of IL-1， IL-6， IL-8， and TNF-α were significantly increased （P<0.01）. SP content in brain tissue was significantly increased， and β-EP content was significantly decreased （P<0.01）. The relative protein expression of IL-1β， P2X7R， and p-p38 MAPK was significantly increased （P<0.05）. HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration， mild proliferation of microglial cells， reduction in the number of myelinated nerves， and obvious demyelination. The trigeminal nerve fibers of rats were disarranged， and some nerve fibers showed vacuolization. Axons were swollen， and Schwann cells proliferated. Demyelination was observed. Compared with the model group， each administration group significantly increased the pain threshold of rats （P<0.05， P<0.01）， reduced NEUT# and NEUT， and elevated LYMPH （P<0.05， P<0.01）. The administration group significantly decreased the levels of IL-1， IL-6， IL-8， and TNF-α in serum and SP in brain tissue （P<0.01） and increased the level of β-EP （P<0.01）. They significantly down-regulated the protein expression of IL-1β， P2X7R， and p-p38 MAPK（P<0.05， P<0.01） and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats， and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca²⁺-interfering therapeutic effect. Based on these characteristics, amorphous calcium carbonate (ACC), as a brunch of calcium-based biomaterials, has the potential to become a widely used biomaterial. Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However, the standalone presence of ACC is unstable in vivo. Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination. ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo, such as Ca²⁺ with an immune-regulating ability and CO₂ with an imaging-enhancing ability. Owing to these characteristics, ACC has been studied for self-sacrificing templates of carrier construction, targeted delivery of oncology drugs, immunomodulation, tumor imaging, tissue engineering, and calcium supplementation. Emphasis in this paper has been placed on the origin, structural features, and multiple applications of ACC. Meanwhile, ACC faces many challenges in clinical translation, and long-term basic research is required to overcome these challenges. We hope that this study will contribute to future innovative research on ACC.

Objective:To investigate the predictive value of systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), and CT perfusion imaging (CTP) parameters for early neurological deterioration (END) in patients with mild stroke duo to anterior circulation large vessel occlusion.Methods:Patients with minor stroke duo to anterior circulation large vessel occlusion admitted to the First People's Hospital of Suqian from November 2021 to December 2023 were included. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score ≤ 5, and END was defined as an increase of ≥ 4 in NIHSS score within 24 hours of admission compared to the baseline. SIRI and SII were calculated based on the findings of blood routine examination. According to CTP at admission, the cerebral blood volume (CBV) index, infarct core volume, and early infarct growth rate (EIGR) were obtained. Multivariate logistic regression analysis was used to determine the independent risk factors for END. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of each predictor on END. Results:A total of 132 patients were included, with 85 males (64.4%) and a median age of 68 years (interquartile range, 58-77 years). Thirty-nine patients (29.5%) experienced END. The baseline NIHSS score, fasting blood glucose, neutrophil count, lymphocyte count, SIRI, SII, infarct core volume, and EIGR in the END group were significantly higher than those in the non-END group, while the CBV index was significantly lower than that in the non-END group (all P<0.05). Multivariate logistic regression analysis showed that SIRI (odds ratio [ OR] 3.672, 95% confidence interval[ CI] 1.838-6.326; P<0.001), SII ( OR 4.824, 95% CI 2.057-7.135; P<0.001), CBV index ( OR 0.968, 95% CI 0.947-0.986; P<0.001), and EIGR ( OR 2.527, 95% CI 1.918-3.589; P<0.001) were the independent predictive factors of END. ROC curve analysis showed that the area under the curves of SIRI, SII, CBV index, and EIGR for predicting END were 0.780 (95% CI 0.692-0.863), 0.798 (95% CI 0.709-0.888), 0.775 (95% CI 0.697-0.853), and 0.772 (95% CI 0.732-0.829), respectively. Conclusion:SIRI, SII, CBV index, and EIGR are the independent predictive factors of END in patients with minor stroke duo to anterior circulation large vessel occlusion, and have certain predictive value for END.