An Inductive Reasoning Model based on Interpretable Logical Rules over temporal knowledge graph.

Extrapolating future events based on historical information in temporal knowledge graphs (TKGs) holds significant research value and practical applications. In this field, the methods currently utilized can be classified as either embedding-based or logical rule-based. Embedding-based methods depend on learned entity and relation embeddings for prediction, but they suffer from the lack of interpretability due to the opaque reasoning process. On the other hand, logical rule-based methods face scalability challenges as they heavily rely on predefined logical rules. To overcome these limitations, we propose a hybrid model that combines embedding-based and logical rule-based methods to capture deep causal logic. Our model, called the Inductive Reasoning Model based on Interpretable Logical Rule (ILR-IR), aims to provide interpretable insights while effectively predicting future events in TKGs. ILR-IR delves into historical information, extracting valuable insights from logical rules embedded within relations and interaction preferences between entities. By considering both logical rules and interaction preferences, ILR-IR offers a comprehensive perspective for predicting future events. In addition, we propose the incorporation of a one-class augmented matching loss during optimization, which serves to enhance performance of the model during training. We evaluate ILR-IR on multiple datasets, including ICEWS14, ICEWS0515, and ICEWS18. Experimental results demonstrate that ILR-IR outperforms state-of-the-art baselines, showcasing its superior performance in TKG extrapolation reasoning. Moreover, ILR-IR demonstrates remarkable generalization capabilities, even when applied to related datasets that share a common relation vocabulary. This suggests that our proposed model exhibits robust zero-shot reasoning abilities. For interested parties, we have made our code publicly available at https://github.com/mxadorable/ILR-IR.

Learning to Summarize Chinese Radiology Findings With a Pre-Trained Encoder.

Automatic radiology report summarization has been an attractive research problem towards computer-aided diagnosis to alleviate physicians' workload in recent years. However, existing methods for English radiology report summarization using deep learning techniques cannot be directly applied to Chinese radiology reports due to limitations of the related corpus. In response to this, we propose an abstractive summarization approach for Chinese chest radiology report. Our approach involves the construction of a pre-training corpus using a Chinese medical-related pre-training dataset, and the collection of Chinese chest radiology reports from Department of Radiology at the Second Xiangya Hospital as the fine-tuning corpus. To improve the initialization of the encoder, we introduce a new task-oriented pre-training objective called Pseudo Summary Objective on the pre-training corpus. We then develop a Chinese pre-trained language model called Chinese medical BERT (CMBERT), which is used to initialize the encoder and fine-tuned on the abstractive summarization task. In testing our approach on a real large-scale hospital dataset, we observe that the performance of our proposed approach achieves outstanding improvement compared with other abstractive summarization models. This highlights the effectiveness of our approach in addressing the limitations of previous methods for Chinese radiology report summarization. Overall, our proposed approach demonstrates a promising direction for the automatic summarization of Chinese chest radiology reports, offering a viable solution to alleviate physicians' workload in the field of computer-aided diagnosis.

BPTF activates the MAPK pathway through coexpression with Raf1 to promote proliferation of T-cell lymphoma.

The aim of the present study was to explore the role and biological function of bromodomain PHD finger transcription factor (BPTF) in T-cell lymphoma. Reverse transcription-quantitative PCR (RT-qPCR), western blotting, immunohistochemistry and bioinformatics analysis were used to determine the expression levels of BPTF and Raf1 in T-cell lymphoma tissues and matched adjacent normal tissues. RT-qPCR and western blot analyses were used to examine the role of BPTF in the activation of MAPK signaling. The function of BPTF and Raf1 in T-cell lymphoma was investigated through in vitro and in vivo assays (MTT assay, colony formation assay, flow cytometry, western blotting, tumor xenograft model and TUNEL assay) following silencing and overexpression experiments in Hut-102 cells. The results demonstrated that BPTF and Raf1 were overexpressed in T-cell lymphoma tissues compared with normal tissues, and high expression of BPTF or Raf1 was associated with advanced clinical stage. BPTF promoted the activation of the MAPK pathway and was coexpressed with Raf1 in T-cell lymphoma tissues. Functional assays demonstrated that silencing of BPTF or Raf1 in Hut-102 cells suppressed cell proliferation and induced apoptosis. Furthermore, the carcinogenic effect of BPTF was confirmed by xenograft experiments in nude mice. The present findings suggested that BPTF may function as a crucial oncogenic factor and may serve as a novel therapeutic target in T-cell lymphoma.

Simvastatin potentiates the cell-killing activity of imatinib in imatinib-resistant chronic myeloid leukemia cells mainly through PI3K/AKT pathway attenuation and Myc downregulation.

Constitutively activated BCR-ABL kinase is considered the driver event responsible in the initiation and development of chronic myeloid leukemia (CML). The advent of the first BCR-ABL inhibitor imatinib has significantly improved the clinical outcome of CML cases. However, resistance to imatinib occurs in 25-30% of CML patients. Due to the lack of effective therapeutic strategies, novel treatment approaches are urgently required for imatinib-resistant CML. Simvastatin, a well-known HMG-CoA reductase inhibitor that confers tremendous clinical benefits in cardiovascular diseases, has attracted mounting attentions for its potent antitumor effects on multiple tumor types. In this study, we demonstrated that simvastatin monotherapy was effective in diminishing cell viability in both imatinib-sensitive and imatinib-resistant CML cells, including T351I mutated cells, with the latter being less vulnerable to the simvastatin than the former. Notably, we found that simvastatin acted as a robust cytotoxic sensitizer of imatinib to kill imatinib-resistant and T315I mutated CML cells in vitro and in vivo. Mechanistically, the cooperative interaction of simvastatin and imatinib was associated with the inactivation of the PI3K/Akt signaling pathway, which was a classical downstream pro-survival cascade of the BCR-ABL kinase. In addition, this drug combination obviously decreased Myc expression through attenuation of canonical Wnt/ß-catenin signaling and increased H3K27 trimethylation. Taken together, we provide attractive preclinical results for the combinatorial regimen of simvastatin and imatinib against imatinib-resistant and T315I mutated CML cells. This combined regimens warrants further clinical investigations in patients with imatinib-resistant CML.

The efficacy and safety of multiple versus single doses dexamethasone in unicompartmental knee arthroplasty: A protocol of randomized controlled trial.

BACKGROUND: Concerns exist regarding the analgesia effect and safety of multiple versus single doses dexamethasone in unicompartmental knee arthroplasty. There is an urgent need of studies that efficiently control for confounding, conduct comprehensive and consecutive observation of potential risks of the dexamethasone administration, and investigate its clinical applicability. We thus further designed a randomized controlled study to assess the different dose of dexamethasone on postoperative pain and complications in patients undergoing unicompartmental knee arthroplasty. METHODS: This randomized, prospective, controlled study was carried out between January 2018 and August 2019. It was approved by the institutional review board in our hospital (HBRM2020013). A total of 80 patients were randomly assigned to each group: the study group (n = 40) and the control group (n = 40). All surgical procedures were performed by a similar orthopedic surgeon. In the study group, patients received intravenously 20 mg dexamethasone (4 mL, Tianjin Kingyork group Co., Ltd., China) just after the anesthesia, and repeated at 24 hours after the surgery. Patients in the control group received intravenously 10 mg dexamethasone solution (2 mL) just after the anesthesia, and repeated at 24 hours after the surgery. CRP, IL-6, VAS pain scores at rest and walking, the VAS scores of nausea, and the incidence of postoperative vomiting and nausea (POVN) were recorded at 24, 48, and 72 hours postoperatively. CONCLUSION: We hypothesized that patients receiving multiple doses of dexamethasone was associated with better outcomes compared with patients receiving single dose of dexamethasone. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5770).

Analysis of 4 imaging features in patients with COVID-19.

BACKGROUND: The aim of this was to analyze 4 chest CT imaging features of patients with coronavirus disease 2019 (COVID-19) in Shenzhen, China so as to improve the diagnosis of COVID-19. METHODS: Chest CT of 34 patients with COVID-19 confirmed by the nucleic acid test (NAT) were retrospectively analyzed. Analyses were performed to investigate the pathological basis of four imaging features("feather sign","dandelion sign","pomegranate sign", and "rime sign") and to summarize the follow-up results. RESULTS: There were 22 patients (65.2%) with typical "feather sign"and 18 (52.9%) with "dandelion sign", while few patients had "pomegranate sign" and "rime sign". The "feather sign" and "dandelion sign" were composed of stripe or round ground-glass opacity (GGO), thickened blood vessels, and small-thickened interlobular septa. The "pomegranate sign" was characterized as follows: the increased range of GGO, the significant thickening of the interlobular septum, complicated with a small amount of punctate alveolar hemorrhage. The "rime sign" was characterized by numerous alveolar edemas. Microscopically, the wall thickening, small vascular proliferation, luminal stenosis, and occlusion, accompanied by interstitial infiltration of inflammatory cells, as well as numerous pulmonary interstitial fibrosis and partial hyaline degeneration were observed. Repeated chest CT revealed the mediastinal lymphadenectasis in one patient. Re-examination of the NAT showed another positive anal swab in two patients. CONCLUSION: "Feather sign" and "dandelion sign" were typical chest CT features in patients withCOVID-19; "pomegranate sign" was an atypical feature, and "rime sign" was a severe feature. In clinical work, accurate identification of various chest CT signs can help to improve the diagnostic accuracy of COVID-19 and reduce the misdiagnosis or missed diagnosis rate.

Isobavachalcone attenuates Sephadex-induced lung injury via activation of A20 and NRF2/HO-1 in rats.

The aim of this study is to investigate the protective effect and underlying molecular mechanisms of isobavachalcone on Sephadex-induced lung injury in rats. The result showed isobavachalcone inhibited massive granulomas, decreased inflammatory cells infiltration and oxidative stress markers level, but it can increase antioxidant enzymes level. The ELISA assay exhibited isobavachalcone decreased TNF-α production in BALF and lung tissue. Western blotting analysis showed isobavachalcone can inhibit NF-κB pathway that may be mediated by upregulation of A20. Furthermore, we also found isobavachalcone can activate NRF2/HO-1 pathway and inhibit adhesion molecule expression. Taken together, the present results suggested that isobavachalcone can attenuate Sephadex-induced lung injury that may be related to inhibition of NF-κB mediated by upregulation of A20 and activation of NRF2/HO-1 signaling pathway.

Altered Gray Matter Volume in Stable Chronic Obstructive Pulmonary Disease with Subclinical Cognitive Impairment: an Exploratory Study.

Gray matter volume deficits have been identified in cognitively impaired patients with chronic obstructive pulmonary disease (COPD). However, it remains unknown whether the gray matter volume is altered in COPD patients with subclinical cognitive impairment. To determine whether any gray matter abnormalities are present in these patients, neuropsychological tests and structural MRI data were analyzed from 60 patients with COPD and 60 age-, gender-, education-, and handedness-matched normal controls (NCs). The COPD patients had similar Mini-Mental State Examination (MMSE) scores compared with the NCs. However, they had reduced Montreal Cognitive Assessment (MoCA) scores for visuospatial and executive and naming and memory functions (P < 0.001). Voxel-based morphometry (VBM) analysis revealed that the COPD patients had significantly lowered gray matter volumes in several brain regions, including the left precuneus (PrCU), bilateral calcarine (CAL), right superior temporal gyrus/middle temporal gyrus (STG/MTG), bilateral fusiform gyrus (FG), and right inferior parietal lobule (IPL) (P < 0.01, corrected). Importantly, the forced vital capacity (FVC) was found to be associated with the gray matter volume in the calcarine. The present study confirmed that brain structural changes were present in stable COPD patients with subclinical cognitive impairment. These findings may provide new insights into the pathogenesis of COPD.

Rheum palmatum L. Attenuates High Fat Diet-Induced Hepatosteatosis by Activating AMP-Activated Protein Kinase.

Nonalcoholic fatty liver disease (NAFLD) is a common metabolic disorder characterized by the accumulation of excess fat in the liver. Rheum palmatumL. (RP) decoctions have been reported to ameliorate NAFLD. The aim of the present study was to investigate the effects and underlying mechanisms of RP in fatty liver disease induced by a high-fat diet (HFD) in rats. Low and high doses of aqueous RP extraction were orally administered to HFD-fed rats for six weeks. Body weight, tissue weight, glucose tolerance, insulin tolerance, hepatic morphology, and liver triglyceride (TG) content were assessed. The effects of RP on the expressions of lipogenic and lipolysis genes were measured by quantitative real-time PCR. The phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) was determined by Western blotting. Treatment with low-dose RP significantly reduced liver weight, liver TG content, and improved glucose tolerance in HFD-fed rats. Consistently, RP attenuated excess fat accumulation and downregulated the expression of lipogenic genes in the liver. Further, an increased phosphorylation of AMPK and ACC was observed. These findings suggest that low-dose RP alleviates hepatosteatosis, at least in part, by stimulating AMPK activity.

[Detection of ALK, ROS1 and RET fusion genes in non-small cell lung cancer patients and its clinicopathologic correlation].

OBJECTIVE: To study the prevalence of ALK, ROS1 and RET fusion genes in non-small cell lung cancer (NSCLC), and its correlation with clinicopathologic features. METHODS: Formalin-fixed and paraffin-embedded tissue sections from samples of 302 patients with NSCLC were screened for ALK, ROS1, RET fusions by real-time polymerase chain reaction (PCR). All of the cases were validated by Sanger DNA sequencing. The relationship between ALK, ROS1, RET fusion genes and clinicopathologic features were analyzed. RESULTS: In the cohort of 302 NSCLC samples, 3.97% (12/302) were found to contain ALK fusion genes, including 3 cases with E13; A20 gene fusion, 3 cases with E6; A20 gene fusion and 3 cases with E20; A20 gene fusion. There was no statistically significant difference in patient's gender, age, smoking history and histologic type. Moreover, in the 302 NSCLC samples studied, 3.97% (12/302) were found to contain ROS1 fusion genes, with CD74-ROS1 fusion identified in 9 cases. There was no statistically significant difference in patients' gender, age, smoking history and histologic type. One non-smoking elderly female patient with pulmonary adenocarcinoma had RET gene fusion. None of the cases studied had concurrent ALK, ROS1 and RET mutations. CONCLUSIONS: The ALK, ROS1 and RET fusion gene mutation rates in NSCLC are low, they represent some specific molecular subtypes of NSCLC. Genetic testing has significant meaning to guide clinical targeted therapy.

Puerarin suppresses high glucose-induced MCP-1 expression via modulating histone methylation in cultured endothelial cells.

AIMS: Hyperglycemia is commonly associated with microcirculation dysfunction. The purpose of the present study was to investigate the epigenetic mechanism involved in the repression of monocyte chemoattractant protein-1 (MCP-1) expression by puerarin under high glucose (25mM) condition. MAIN METHODS: MCP-1 gene expression was measured by Real-Time quantitative Polymerase Chain Reaction (RT-qPCR), the histone 3 lysine 4 methylation (H3K4me) and lysine 9 methylation (H3K9me) were evaluated using chromatin immunoprecipitation assay. KEY FINDINGS: Puerarin significantly inhibited high glucose-induced upregulation of H3K4 di- and tri-methylation (H3K4me2/3) on the MCP-1 gene promotor. Additionally, the enrichment of H3K4 histone methyltransferases including MLL, menin and SET7 on the MCP-1 promotor was increased, while the demethylase LSD1 was decreased in EA.hy926 cells following exposure to high glucose. The changes of the above enzymes were reversed by puerarin treatment. The mRNA expression of MCP-1 was increased by LSD1 blockage, while was decreased by MLL3 blockage. SIGNIFICANCE: Our findings suggested that puerarin plays a critical role in transcriptional repression of high glucose-induced MCP-1 gene expression, at least in part due to alteration of H3K4me2/3 methylation, thus possesses a therapeutic potential in diabetes-induced vascular injuries.

[CT angiography features of the involved arterial branches of the spontaneous isolated superior mesenteric artery dissection].

OBJECTIVE: To explore the CT angiography features of the involved arterial branches of the spontaneous isolated superior mesentery artery dissection(SISMAD). METHODS: Clinical and CT angiogram data of 6 patients with SISMAD confirmed by dual source energy CT angiography were analyzed retrospectively. The CT angiography features and prognosis of patients were investigated. RESULTS: Average age of 6 patients was(45.83±5.60) years old. Ten branches of jejunoileal artery were involved in 4 patients. All the dissections of the superior mesenteric arteries(SMA) were extended from its proximal to its end. Intramural hematoma was found in all the involved branches, which showed eccentric target sign in the transverse section and sandwich sign in the longitudinal axial section. In 7 branches of 3 patients, the involved branches originated from the false lumina of the SMA. In one patient, the intramural hematoma of the jejunoileal arteries was found to be completely absorbed in a repeated CT angiography one year late. CONCLUSIONS: For the SISMAD, the involvement of the branches of the SMA may be associated with the extension of the dissection of the SMA. The inflation of the false lumina of the branches is worse than that of the SMA. With the improvement of the dissection of the SMA, the intramural hematoma of the branches can be absorbed. The conservative treatment may be the first choice for SISMAD without emergency.

Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles.

The high aqueous solubility, poor permeability, and absorption of berberine (BBR) result in its low plasma level after oral administration, which greatly limits its clinical application. BBR solid lipid nanoparticles (SLNs) were prepared to achieve improved bioavailability and prolonged effect. Developed SLNs showed homogeneous spherical shapes, small size (76.8 nm), zeta potential (7.87 mV), encapsulation efficiency (58%), and drug loading (4.2%). The power of X-ray diffraction combined with (1)H nuclear magnetic resonance spectroscopy was employed to analyze chemical functional groups and the microstructure of BBR-SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50 mg/kg) oral pharmacokinetic studies in rats showed significant improvement (P<0.05) in the peak plasma concentration, area under the curve, and variance of mean residence time of BBR-SLNs when compared to BBR alone (P<0.05), suggesting improved bioavailability. Furthermore, oral administration of both BBR and BBR-SLNs significantly suppressed body weight gain, fasting blood glucose levels, and homeostasis assessment of insulin resistance, and ameliorated impaired glucose tolerance and insulin tolerance in db/db diabetic mice. BBR-SLNs at high dose (100 mg/kg) showed more potent effects when compared to an equivalent dose of BBR. Morphologic analysis demonstrated that BBR-SLNs potentially promoted islet function and protected the islet from regeneration. In conclusion, our study demonstrates that by entrapping BBR into SLNs the absorption of BBR and its anti-diabetic action were effectively enhanced.

Meta-analysis of acupuncture for relieving non-organic dyspeptic symptoms suggestive of diabetic gastroparesis.

BACKGROUND: Acupuncture is widely used to treat diabetic patients with dyspeptic symptoms suggestive of gastroparesis in China. We conducted this systematic review of randomized controlled trials (RCTs) to evaluate the efficacy of acupuncture for diabetic gastroparesis (DGP). METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and four Chinese databases including China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database (CBM) and WanFang Data up to January 2013 without language restriction. Eligible RCTs were designed to examine the efficacy of acupuncture in improving dyspeptic symptoms and gastric emptying in DGP. Risk of bias, study design and outcomes were extracted from trials. Relative risk (RR) was calculated for dichotomous data. Mean difference (MD) and standardized mean difference (SMD) were selected for continuous data to pool the overall effect. RESULTS: We searched 744 studies, among which 14 RCTs were considered eligible. Overall, acupuncture treatment had a higher response rate than controls (RR, 1.20 [95% confidence interval (CI), 1.12 to 1.29], P < 0.00001), and significantly improved dyspeptic symptoms compared with the control group. There was no difference in solid gastric emptying between acupuncture and control. Acupuncture improved single dyspeptic symptom such as nausea and vomiting, loss of appetite and stomach fullness. However, most studies were in unclear and high risk of bias and with small sample size (median = 62). The majority of the RCTs reported positive effect of acupuncture in improving dyspeptic symptoms. CONCLUSIONS: The results suggested that acupuncture might be effective to improve dyspeptic symptoms in DGP, while a definite conclusion about whether acupuncture was effective for DGP could not be drawn due to the low quality of trials and possibility of publication bias. Further large-scale, high-quality randomized clinical trials are needed to validate this claim and translate this result to clinical practice.

An Aqueous Extract of Radix Astragali, Angelica sinensis, and Panax notoginseng Is Effective in Preventing Diabetic Retinopathy.

Diabetic retinopathy (DR), in which inflammation has been implicated playing important roles, is one of the most common diabetes complications. Dang Gui Bu Xue Tang (DBT), an aqueous extract of Radix Astragali and Radix Angelica sinensis, is a classical prescription in Traditional Chinese Medicine for treating inflammation and ischemic diseases. Here, we investigated the effects of a modified recipe of DBT, with addition of Panax notoginseng, in treating diabetic retinopathy. An aqueous extract of Radix Astragali, Radix Angelica sinensis, and Panax notoginseng (RRP) was given to Goto-Kakizaki (GK) rats and streptozotocin-induced Sprague-Dawley (SD) rats. Leukostasis, vascular leakage, and acellular capillaries in retinal vasculature of animals were determined. Expression of retinal inflammatory biomarkers was assessed. We found that RRP reduced leukostasis, acellular capillaries, and vascular leakage compared to diabetic control rats. We also found that RRP decreased the expression of inflammatory factors including IL-1 ß , IL-6, TNF- α , NF- κ B, MCP-1, ICAM-1, or VCAM-1 in the retinas of GK rats and reversed high glucose-induced inhibition of endothelial cell migration and proliferation in vitro. We conclude that RRP has a potent effect in preventing the pathogenesis and/or progression of DR and thus may serve as a promising nontoxic therapeutic approach of DR.

The molecular cloning of glial fibrillary acidic protein in Gekko japonicus and its expression changes after spinal cord transection.

The glial fibrillary acidic protein (GFAP) is an astrocyte-specific member of the class III intermediate filament proteins. It is generally used as a specific marker of astrocytes in the central nervous system (CNS). We isolated a GFAP cDNA from the brain and spinal cord cDNA library of Gekko japonicus, and prepared polyclonal antibodies against gecko GFAP to provide useful tools for further immunochemistry studies. Both the real-time quantitative PCR and western blot results revealed that the expression of GFAP in the spinal cord after transection increased, reaching its maximum level after 3 days, and then gradually decreased over the rest of the 2 weeks of the experiment. Immunohistochemical analyses demonstrated that the increase in GFAP-positive labeling was restricted to the white matter rather than the gray matter. In particular, a slight increase in the number of GFAP positive star-shaped astrocytes was detected in the ventral and lateral regions of the white matter. Our results indicate that reactive astrogliosis in the gecko spinal cord took place primarily in the white matter during a short time interval, suggesting that the specific astrogliosis evaluated by GFAP expression might be advantageous in spinal cord regeneration.