The influenza A virus (IAV), renowned for its high contagiousness and potential to catalyze global pandemics, poses significant challenges due to the emergence of drug-resistant strains. Given the critical role of RNA polymerase in IAV replication, it stands out as a promising target for anti-IAV therapies. In this study, we identified a novel C-3-substituted oleanolic acid benzyl amide derivative, A5, as a potent inhibitor of the PA_C-PB1_N polymerase subunit interaction, with an IC₅₀ value of 0.96 ± 0.21 μmol/L. A5 specifically targets the highly conserved PA_C domain and demonstrates remarkable efficacy against both laboratory-adapted and clinically isolated IAV strains, including multidrug-resistant strains, with EC₅₀ values ranging from 0.60 to 1.83 μmol/L. Notably, when combined with oseltamivir, A5 exhibits synergistic effects both in vitro and in vivo. In a murine model, dose-dependent administration of A5 leads to a significant reduction in IAV titers, resulting in a high survival rate among treated mice. Additionally, A5 treatment inhibits virus-induced Toll-like receptor 4 activation, attenuates cytokine responses, and protects against IAV-induced inflammatory responses in macrophages. In summary, A5 emerges as a novel inhibitor with high efficiency and broad-spectrum anti-influenza activity.

Objective:To analyze the clinical characteristics，laboratory tests，endoscopic features，treatment，and follow-up of peptic ulcers caused by eosinophilic gastrointestinal disorders（EGIDs）in children，with the aim of improving the level of understanding，diagnosis and treatment of EGIDs in children with the onset of peptic ulcers.Methods:A retrospective analysis was conducted on children admitted to the Department of Gastroenterology，Capital Center for Children's Health，Capital Medical University from January 1st，2019 to October 31st，2023，who underwent complete endoscopic examination. The first examination showed the presence of peptic ulcers（gastric or duodenal ulcers）under the endoscope，and were ultimately diagnosed with peptic ulcers caused by EGIDs through examination and follow-up. The clinical characteristics，laboratory tests，endoscopic results，and treatment follow-up were analyzed.Results:Thirty-five children were EGIDs，22 males and 13 females.Twenty-two cases（62.9%）had abdominal pain as the main symptom.Laboratory tests：17 cases（48.6%）showed a decrease in hemoglobin，15 cases（42.9%）showed an increase in eosinophil count，20 cases（57.1%）tested gastro positive for food allergen specific IgE，and 17 cases（48.6%）showed thickening of the intestinal wall on gastrointestinal ultrasound. Endoscopic features：8 cases（22.9%）showed gastric antral ulcers，including 7 cases（20.0%）with multiple gastric antral ulcers，and 25 cases（71.4%）showed duodenal bulb ulcers.There were 15 cases（42.9%）showed huge ulcers，and 14 cases（40.0%）were located in the duodenal bulb. Comparison of clinical characteristics between children with EGIDs（EGIDs group）and those with peptic ulcers caused by Helicobacter pylori infection（Hp group）：the first clinical symptom in both groups was mainly abdominal pain，but the incidence rate in the EGIDs group was lower（62.9% vs 93.5%），and the weigth for length Z score in the EGIDs group was lower［0（-1.6，0.8）vs 1.1（0，1.9）］，with statistical significance（all P<0.05）. Comparison of laboratory tests：the EGIDs group showed a statistically significant difference in hemoglobin levels［120（101，124）g/L vs 130（100，138）g/L］，eosinophil count［0.28（0.13，0.71）× 10 9/L vs 0.16（0.08，0.22）×10 9/L］，a positive rate of food allergen specific IgE detection（57.1% vs 32.3%），and a positive rate of intestinal wall thickening detected by gastrointestinal ultrasound（48.6% vs 16.1%）compared with the Hp group（all P<0.05）. Comparison of endoscopic examinations：multiple ulcers in the gastric antrum were more common in the EGIDs group than in the Hp group（20.0% vs 0），and the difference was statistically significant（ P<0.05）. Conclusion:For children with peptic ulcers with onset of abdominal pain，with anemia or malnutrition，or multiple ulcers in the gastric antrum and huge ulcers in the duodenal bulb detected by endoscopy，it is recommended to perform multi site biopsies to help diagnose EGIDs early.

Objective To optimize the water extraction process of modified Wendan Formula.Methods The comprehensive scores of the content of naringin and neohesperidin as well as the extraction yields of solids were used as the evaluation indexes,the number of decoctions,the decoction time and the solid-liquid ratio as three factors were take into consideration,L9(34)orthogonal experiment was designed to optimize the water extraction process of modified Wendan Formula.Results Combining the orthogonal experiment with the principle of energy conservation and emission reduction in actual production,this study suggests that the optimized process was under the conditions of 1∶8 for the solid-liquid ratio,decoction were performed twice,the first time was 1.5 hours,and the second time was 1 hour.The average composite score of validation of three batches of modified Wendan Formula was 99.00％.Conclusion Such optimized process was stable,feasible and realizable,and it can be applied in water extraction process of modified Wendan Formula.

Objectives: . Hypoxia-inducible factor 1α (HIF1α) and Tet methylcytosine dioxygenase 2 (TET2) have been reported to mediate nasal polypogenesis through the epithelial-to-mesenchymal transition (EMT). Additionally, HIF1α can regulate the expression and function of TET2. However, the precise mechanism of how TET2 regulates the EMT through HIF1α mediation in nasal epithelial cells is still poorly understood. Methods: . Nasal tissue samples were collected from patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls. The expression of HIF1α and TET2 was detected using Western blotting and immunohistochemistry. EMT markers (E-cadherin and vimentin) were also evaluated by immunohistochemistry. Primary human nasal epithelial cells (hNECs) were stimulated with CoCl2 to mimic hypoxia. Vitamin C (VC), a TET2 non-specific activator, and small interfering RNA (siRNA) transfection of TET2 were used to further determine the role of TET2 in hypoxia-induced EMT. Finally, reactive oxygen species (ROS) and Nrf2 were measured to explore the downstream consequences of TET2 in hypoxic hNECs. Results: . TET2 levels were lower in the nasal epithelium of CRSwNP patients and were positively correlated with E-cadherin but negatively correlated with vimentin in CRS. However, HIF1α exhibited the opposite pattern and was negatively correlated with TET2 expression. CoCl2-simulated hypoxia led to EMT and increased HIF1α in hNECs in vitro, with simultaneous downregulation of TET2 expression. Addition of VC activated TET2 expression in hNECs, but inhibited EMT and HIF1α expression. Furthermore, siRNA knockdown of TET2 contributed to the EMT in CoCl2-simulated hNECs despite the addition of VC. Finally, TET2 regulated the EMT in hypoxic hNECs through Nrf2 expression and ROS generation. Conclusion . TET2 was negatively correlated with HIF1α and EMT in vivo. TET2 was downregulated by HIF1α, resulting in the EMT in CoCl2-hypoxic hNECs via regulation of oxidative stress in vitro. Hence, TET2 might provide a new therapeutic approach for CRSwNP

Intestinal microbiota is the most complex and important microecosystem in the human body， and gut microbiota dysbiosis is closely associated with the development and progression of acute pancreatitis. Targeted regulation of intestinal microecology in assisting the treatment of acute pancreatitis has attracted more attention in recent years. This article describes the changes in intestinal microbiota and related mechanisms in patients with acute pancreatitis， summarizes the current research status of the use of probiotics， points out the research direction of probiotics as the adjuvant treatment regime， and proposes a new method for predicting the dominant flora in patients with acute pancreatitis， in order to bring new ideas for the treatment of acute pancreatitis.

We report a family of glucocorticoid-remediable aldosteronism (GRA). A 20-year-old man presented with early-onset hypertension accompanied by hypokalemia was admitted to our hospital. Clinical data and family history were collected. Following genetic analyses with PCR and Sanger sequencing to document the chimeric gene and crossover site, respectively, we identified CYP11B1/CYP11B2 and determined the breakpoint of unequal crossover to be located in 264-380 nucletide, which was considered as GRA. There were 4 cases of GRA in the family, the average age of onset was 28 years, and all had different degrees of hypertension. Among them, the proband′s uncle suffered from moyamoya disease and died 6 months later due to sudden cerebral hemorrhage. In order to improve the understanding of this rare disease, the pathogenesis, biochemical profiles, diagnosis and treatment of GRA were summarized and analyzed.

Objective:To evaluate the efficacy of glucocorticoid sinus stents implanted 2 weeks after functional endoscopic sinus surgery（FESS） for the treatment of chronic rhinosinusitis with nasal polyps（CRSwNP）. Methods:CRSwNP patients with similar bilateral lesions were randomly divided into two groups, with a stent group of 25 patients and a control group of 24 patients. Patients in the stent group had glucocorticoid sinus stents implanted into the bilateral ethmoid sinuses 2 weeks after FESS, while the control group underwent postoperative debridement only. Follow-up assessments occurred at postoperative weeks 2, 4, 8, and 12. Patients were asked to assess their sensation of nasal symptoms using a 10-point visual analog scale. Efficacy was assessed by endoscopic evaluations. Sinus obstruction, crusting/coagulation, polyp formation, middle turbinate position, adhesions, mucosa epithelialization, and postoperative intervention were assessed as efficacy outcomes. GraphPad Prism 9 was applied for statistical analysis. Results:At 4 and 8 weeks postoperatively, the stent group showed significant improvement in VAS scores of nasal congestion and runny nose compared with the control group（P<0.05）. No significant difference was observed in the VAS scores of head and facial stuffiness, loss of smell, or nasal dryness/crusting between the two groups（P>0.05）. Compared with the control group, the stent group had a lower rate of polypoid formation at 4, 8, and 12 weeks postoperatively. At postoperative week 12, the rate of mucosal epithelialization in the ethmoid cavity was significantly higher in the stent group. During the follow-up, the frequency of postoperative intervention was significantly lower in the stent group than in the control group（P<0.05）. Besides, a lower incidence of middle turbinate lateralization was found in the stent group at 8 and 12 weeks postoperatively. At 8 weeks postoperatively, the stent group had a percentage of adhesion lower than that of the control group（all P<0.05）. Conclusion:Implantation of glucocorticoid sinus stents after FESS can maintain sinus cavity patency, improve the inflammatory status of the operative cavity, reduce postoperative interventions, and promote benign regression of the operative cavity.
Humans ; Nasal Polyps/surgery* ; Ethmoid Sinus/surgery* ; Glucocorticoids/therapeutic use* ; Rhinitis/surgery* ; Sinusitis/surgery* ; Paranasal Sinuses/surgery* ; Endoscopy ; Stents ; Chronic Disease ; Treatment Outcome

Two cases of solitary fibrous tumor (SFT) with endocrine manifestations as the first symptom were investigated through comprehensively reviewing their medical history and clinical records. One case of recurrent giant solitary fibrous tumor of the thoracic cavity had repeated dizziness, palpitation and limb weakness for one month. The patient had hypoglycemia accompanied with significantly decreased serum insulin, and the ratio of insulin-like growth factor Ⅱ(IGF-Ⅱ) and insulin-like growth factor Ⅰ (IGF-Ⅰ) was greater than 10. Non-islet cell tumor hypoglycemia (NICTH) should be considered in the patient. Another case was found to have thyroid gland SFT and developed distant metastasis. The patient presented with hypoglycemia, hypokalemia and possible consumptive hypothyroidism. Clinicians should improve our understanding of the endocrine manifestations of the disease. SFT may occur in endocrine glands (such as thyroid), and may also present as NICTH and consumptive hypothyroidism.

BACKGROUND: The mortality rate of lung cancer meningeal metastasis is extremely high. Circulating tumor DNA (ctDNA) has been confirmed to be contain the genomic alterations present in tumors and has been used to monitor tumor progression and response to treatments. Due to the presence of blood-brain barrier and other factors, peripheral blood ctDNA cannot reflect the information of brain lesions for patients with meningeal metastases. However, cerebrospinal fluid ctDNA as a test sample can better reflect the genetic status of intracranial tumors and guide clinical targeted treatment of intracranial lesions. This study explored the feasibility of cerebrospinal fluid ctNDA for evaluating non-small cell lung cancer (NSCLC) meningeal metastasis and the potential clinical value of cerebrospinal fluid ctDNA detection in NSCLC meningeal metastasis. METHODS: A total of 21 patients with NSCLC meningeal metastasis were included. Tumor genomic variation was performed on the cerebrospinal fluid and peripheral blood samples of patients by second-generation gene sequencing technology. The situation was examined, and pathological evaluation of cerebrospinal fluid cytology and head magnetic resonance imaging (MRI) enhanced examination were performed. RESULTS: ctDNA was detected in the cerebrospinal fluid of 21 patients. The sensitivity of cerebrospinal fluid ctDNA detection was superior to cytology in the diagnosis of meningeal metastasis (P<0.001). The detection rate and gene mutation abundance of cerebrospinal fluid were higher than plasma (P<0.001). Cerebro-spinal fluid had a unique genetic profile. In 6 patients with dynamic detection, changes of ctDNA allele fraction occurred at the same time or earlier than clinical disease changes, which could timely monitor drug resistance mechanism and relapse trend. CONCLUSIONS The detection rate of ctDNA in cerebrospinal fluid is higher than that in cytology and imaging. The detection of ctDNA in cerebrospinal fluid can reveal the specific mutation map of meningeal metastasis lesions. The dynamic monitoring of ctDNA in cerebrospinal fluid has hint significance for clinical response of lung cancer patients.