Up-regulation on cytochromes P450 in rat mediated by total alkaloid extract from Corydalis yanhusuo

BACKGROUND: Yanhusuo (Corydalis yanhusuo W.T. Wang; YHS), is a well-known traditional Chinese herbal medicine, has been used in China for treating pain including chest pain, epigastric pain, and dysmenorrhea. Its alkaloid ingredients including tetrahydropalmatine are reported to inhibit cytochromes P450 (CYPs) activity in vitro. The present study is aimed to assess the potential of total alkaloid extract (TAE) from YHS to effect the activity and mRNA levels of five cytochromes P450 (CYPs) in rat. METHODS: Rats were administered TAE from YHS (0, 6, 30, and 150 mg/kg, daily) for 14 days, alanine aminotransferase (ALT) levels in serum were assayed, and hematoxylin and eosin-stained sections of the liver were prepared for light microscopy. The effects of TAE on five CYPs activity and mRNA levels were quantitated by cocktail probe drugs using a rapid chromatography/tandem mass spectrometry (LC-MS/MS) method and reverse transcription-polymerase chain reaction (RT-PCR), respectively. RESULTS: In general, serum ALT levels showed no significant changes, and the histopathology appeared largely normal compared with that in the control rats. At 30 and 150 mg/kg TAE dosages, an increase in liver CYP2E1 and CYP3A1 enzyme activity were observed. Moreover, the mRNA levels of CYP2E1 and CYP3A1 in the rat liver, lung, and intestine were significantly up-regulated with TAE from 6 and 30 mg/kg, respectively. Furthermore, treatment with TAE (150 mg/kg) enhanced the activities and the mRNA levels of CYP1A2 and CYP2C11 in rats. However, the activity or mRNA level of CYP2D1 remained unchanged. CONCLUSIONS: These results suggest that TAE-induced CYPs activity in the rat liver results from the elevated mRNA levels of CYPs. Co-administration of prescriptions containing YHS should consider a potential herb (drug)–drug interaction mediated by the induction of CYP2E1 and CYP3A1 enzymes

Clinical analysis of 21 cases of primary Ewing sarcoma of the thoracic wall

Background and Purpose: Primary Ewing sarcoma of the thoracic wall (PEST) is a rare extraosseous Ewing sarcoma that occurs in the chest wall or thoracic cavity with a short survival, poor prognosis and a high rate of recurrence. Early diagnosis and treatment are the best way to prolong survival time since the cause of PEST is not clear. This study aimed to explore the clinicopathologic characteristics, diagnosis and treatment of PEST to improve clinical understanding of this disease. Methods: A total of 21 cases with PEST were treated at The First Affiliated Hospital of Soochow University, and reviews were published from 2018 to 2023. Clinical data, pathological features, treatment and follow-up of the patients were analyzed respectively. The survival was from the start of treatment to the death of the patient or the end of the follow-up. Cumulative survival was estimated by Kaplan-Meier method. Results: A total of 21 cases with PEST (male/female ratio, 13:8; sites of left/right chest ratio, 6:15; median age, 20 years; mean age, 28 years; median diameter of the tumor, 8.0 cm; mean diameter of the tumor, 18.1 cm) met the inclusion criteria. 65.2% of the patients presented with the pain in the ipsilateral thoracic and abdominal area. In 47.1% of cases, the ipsilateral ribs were invaded with pleural effusion. Pathological morphology microscopy showed most tumor cells were tightly packed or lobular distribution of small blue round cells. In immunohistochemistry, CD99 and vimentin were positive in 100% and 80% cases respectively while neurogenic markers were expressed to varying degrees. EWSR1 separated signal was found by fluorescence in situ hybridization (FISH), and the EWSR1-FLI1 fusion was detected by next-generation sequencing (NGS) in two cases at our hospital. Two cases received neoadjuvant chemotherapy, 10 patients received chemotherapy and radiotherapy after operation, 5 cases were treated with radiotherapy only, 1 case received surgery only, and 3 cases had no surgical data. A total of 14 cases were followed up for 3-38 month while 7 cases were lost to visit. Cumulative survival correlates with age at disease. The mean survival time was 19.98 months, and the median survival time was 13.00 months. Conclusion: Young males, right chest and the mass larger than 8 cm are more often found. Most cases can be initially diagnosed using histopathology and immunohistochemical markers. FISH or NGS of the EWSR1 gene test are a highly accurate method for diagnosis. The prognosis of PEST is extremely poor, and the cumulative survival rate is negatively correlated with the age of onset. Surgery, radiotherapy and chemotherapy are the main treatments for this disease

Entanglement control in one-dimensional s=1/2s=1/2 random XY spin chain

The entanglement in one-dimensional random XY spin systems where the impurities of exchange couplings and the external magnetic fields are considered as random variables is investigated by solving the different spin-spin correlation functions and the average magnetization per spin. The entanglement dynamics near particular locations of the system is also studied when the exchange couplings (or the external magnetic fields) satisfy three different distributions(the Gaussian distribution, double-Gaussian distribution, and bimodal distribution). We find that the entanglement can be controlled by varying the strength of external magnetic field and the different distributions of impurities. Moreover, the entanglement of some nearest-neighboring qubits can be increased for certain parameter values of the three different distributions.Comment: 13 pages, 4 figure

DSRM: Boost Textual Adversarial Training with Distribution Shift Risk Minimization

Adversarial training is one of the best-performing methods in improving the robustness of deep language models. However, robust models come at the cost of high time consumption, as they require multi-step gradient ascents or word substitutions to obtain adversarial samples. In addition, these generated samples are deficient in grammatical quality and semantic consistency, which impairs the effectiveness of adversarial training. To address these problems, we introduce a novel, effective procedure for instead adversarial training with only clean data. Our procedure, distribution shift risk minimization (DSRM), estimates the adversarial loss by perturbing the input data's probability distribution rather than their embeddings. This formulation results in a robust model that minimizes the expected global loss under adversarial attacks. Our approach requires zero adversarial samples for training and reduces time consumption by up to 70\% compared to current best-performing adversarial training methods. Experiments demonstrate that DSRM considerably improves BERT's resistance to textual adversarial attacks and achieves state-of-the-art robust accuracy on various benchmarks.Comment: Accepted by ACL202