As a mercury-containing elixir， Hongshengdan has been known as a sacred medicine for surgery by ancient medical practitioners because of its precise curative effects. It originated from Yizong Shuoyue in the Qing dynasty， Qing dynasty and modern medical practitioners have adapted and modified its formula for clinical application. Employing bibliometric methods， the authors systematically organized relevant ancient literature of the Qing dynasty and modern literature， and analyzed the composition and dosage， preparation method， and clinical application. Among the 25 ancient books concerning Hongshengdan， a total of 12 medicinal formulas， 15 refining methods and 9 clinical applications were obtained. Research confirms that Hongshengdan consisted of mercury， saltpeter， alum， soap alum， cinnabar and realgar. Using measurement conversion standards of Qing dynasty， the modern single-batch formulation comprised 37.30 g of mercury， 149.20 g of saltpeter， 37.30 g of alum， 22.38 g of soap alum， 18.65 g of cinnabar， and 18.65 g of realgar. In modern refining of Hongshengdan， most medical practitioners take the core medicines， with dosages approximately 30 g of mercury， 30 g of saltpeter， and 30 g of alum. Refining method involves pretreatment stewing the materials during preparation， and alum， soap alum， and saltpeter are first ground together， then combined with mercury， cinnabar， and realgar for grinding until mercury and other drugs grind to the degree of no star points. The mixture is then placed in a pot or vessel by cold-forming method. After covering， the opening is sealed using either raw gypsum salt mud or honey-dipped cotton paper strips. Sand is packed around the vessel and then pressurized. During the calcination process， begin with a low flame（30 min）， then increase to a medium flame（30 min）， followed by a high flame（30 min）， after removing fire toxins， collect the final product. Hongshengdan has the efficacy of lifting the poison， removing the corrosion， producing muscle and dispersing， and is often used in the treatment of surgical sore and carbuncle type of diseases. Modern research indicates that Hongshengdan is commonly used to treat skin system diseases such as ulcers and herpes. The aforementioned findings provide a reference basis for the subsequent refining method and clinical application of Hongshengdan.

Hongsheng Dan, historically referred to as the "surgical sacred medicine", is at risk of losing its refining technology in contemporary times. This study aimed to preserve and innovate this traditional non-heritage refining technology. By utilizing the analytic hierarchy process(AHP) combined with the entropy weight method, this study established the hierarchical structure model of refining process of Hongsheng Dan and conducted a single factor experiment and an L_9(3~4) orthogonal experiment to optimize the refining method of Hongsheng Dan. Additionally, the study employed infrared thermal imaging to monitor temperature variations of Hongsheng Dan during the refining process. The optimized refining parameters for Hongsheng Dan were established as follows: a slow fire temperature of 175 ℃ with a duration of 30 minutes, a strong fire temperature of 270 ℃ with a duration of 60 minutes, and a tail fire temperature of 180 ℃ with a duration of 15 minutes. The stability and feasibility of this optimized process were confirmed through validation tests. The research focused on the material transformation of Hongsheng Dan, starting from the material changes during the refining process of Hongsheng Dan and the synthesis of mercuric oxide from nitric acid. The study investigated elemental transformations, physical phase changes, and alterations in thermal properties. 78.98% of the mercury in Hongsheng Dan and 80.21% of the mercury in mercuric oxide from nitric acid were retained. The diffraction peak intensity of the(011) crystal plane of Hongsheng Dan was highest at approximately 30.07°, indicating that the(011) crystal plane had a preferred crystalline orientation. Furthermore, the temperature range for the alteration in thermal properties during the refining process of Hongsheng Dan was found to be between 80 ℃ and 130 ℃. This research not only optimized the refining technology of Hongsheng Dan but also pioneered the application of infrared thermal imaging to study temperature changes throughout the refining process. By exploring the material transformation patterns of Hongsheng Dan and the synthesis of mercuric oxide from nitric acid, the study provided technical support for the preservation and innovation of Hongsheng Dan.
Drugs, Chinese Herbal/standards* ; Temperature

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

A method was developed for determination of dilauryl thiodipropionate(DLTDP)in fried foods by coupling solid-phase extraction(SPE)pretreatment with reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS/MS)detection.Samples were extracted with n-hexane as the solvent,purified using a neutral alumina SPE cartridge,and finally analyzed by RPLC-MS/MS.Quantitative analysis was performed using matrix-matched calibration curves combined with an external standard method under optimal experimental conditions.The results showed that DLTDP exhibited good linearity in the range of 2.0-50.0 μg/L,with a correlation coefficient(R2)≥0.999.The limit of detection(LOD)and the limit of quantification(LOQ)of the method were 0.15 mg/kg and 0.5 mg/kg,respectively.The mean recoveries at three fortification levels(0.5,1.0,and 200 mg/kg)in different samples ranged from 84.8%to 96.8%,with the relative standard deviations(RSDs)all less than 8.0%.The developed method was highly sensitive,accurate and reliable,and easy to operate,making it well suited for the routine quantitative analysis of DLTDP in fried foods.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of vericiguat in the treatment of heart failure （HF） by rapid health technology evaluation method， and provide reference for the selection and decision-making of clinical treatment plans. METHODS Chinese and foreign databases such as CNKI， PubMed and related health technology evaluation websites were searched by computer. Relevant researchers independently screened literature， extracted data， and comprehensively analyzed the results of the included literature based on literature quality evaluation. RESULTS A total of 17 pieces of literature were included， involving 12 systematic reviews/meta-analyses and 5 pharmacoeconomic studies. The effectiveness analysis showed： for HF patients， compared with placebo， vericiguat （10 mg/d） significantly improved the EuroQol five dimensions questionnaire （EQ-5D） index and decreased the rate of hospitalization due to HF （P＜0.05）. For heart failure with reduced ejection fraction （HFrEF） patients， vericiguat reduced the incidence of hospitalization due to HF compared with sodium-glucose cotransporter 2 inhibitor （SGLT2i）（P＜0.05）； compared with angiotensin-converting enzyme inhibitor， vericiguat significantly reduced the occurrence risk of composite endpoints of cardiovascular death or hospitalization due to HF（P＜0.05）. For HFrEF patients with chronic kidney disease， vericiguat had a tendency to reduce the occurrence risk of composite endpoints of cardiovascular death or hospitalization due to HF compared with neurohormone inhibitors. Safety analysis showed： vericiguat did not increase drug-related adverse reactions compared to placebo （P＞0.05）. Economic analysis showed： domestic studies indicated that vericiguat had a higher incremental cost-effectiveness ratio. CONCLUSIONS Vericiguat has good safety and efficacy in the treatment of HF but does not possess an economic advantage in the Chinese population.

Purpose::Under-foot impact loadings can cause serious lower limb injuries in many activities, such as automobile collisions and underbody explosions to military vehicles. The present study aims to compare the biomechanical responses of the mainstream vehicle occupant dummies with the human body lower limb model and analyze their robustness and applicability for assessing lower limb injury risk in underfoot impact loading environments.Methods::The Hybrid III model, the test device for human occupant restraint (THOR) model, and a hybrid human body model with the human active lower limb model were adopted for under-foot impact analysis regarding different impact velocities and initial lower limb postures.Results::The results show that the 2 dummy models have larger peak tibial axial force and higher sensitivity to the impact velocities and initial postures than the human lower limb model. In particular, the Hybrid III dummy model presented extremely larger peak tibial axial forces than the human lower limb model. In the case of minimal difference in tibial axial force, Hybrid III's tibial axial force (7.5 KN) is still 312.5% that of human active lower limb's (2.4 KN). Even with closer peak tibial axial force values, the biomechanical response curve shapes of the THOR model show significant differences from the human lower limb model.Conclusion::Based on the present results, the Hybrid III dummy cannot be used to evaluate the lower limb injury risk in under-foot loading environments. In contrast, potential improvement in ankle biofidelity and related soft tissues of the THOR dummy can be implemented in the future for better applicability.

Objective To analyze the clinical significance of elevated CHMP2B expression in pancreatic cancer,and to explore the oncogenic mechanism of CHMP2B in pancreatic cancer.Methods A transcriptomic analysis conducted on the GEPIA website revealed CHMP2B expression in over 20 types of malignant tumors.The relation-ship between CHMP2B expression and disease-free survival and overall survival of pancreatic cancer was analyzed.The correlation between CHMP2B,MAP1LC3B and P62 expression was analyzed by TCGA database.The overex-pression plasmid of CHMP2B factor was transfected with Lipofectamine 2000 in MIA PaCa-2 cells,and the overex-pression of CHMP2B factor in MIA PaCa-2 was verified by Western blot.The effect of overexpression of CHMP2B on tumorigenic ability of MIA PaCa-2 cells was verified by clonal formation experiment.The effect of overexpression of CHMP2B on proliferation,migration and invasion of MIA PaCa-2 cells was verified by CCK-8 and Transwell ex-periments.The localization of CHMP2B factor was detected by immunofluorescence staining.The correlation be-tween CHMP2B,MAP1LC3B and P62 expression was analyzed by TCGA database.The expression of MAP1LC3B and P62 in CHMP2B overexpression was verified by qPCR.Results The expression of CHMP2B factor increased in pancreatic cancer(P＜0.01).Overexpression of CHMP2B factor was associated with overall survival and dis-ease-free survival(P＜0.01).The high expression of CHMP2B promoted the tumorigenesis of MIA PaCa-2 cells in pancreatic cancer,and also promoted the proliferation,migration and invasion of pancreatic cancer.Immunofluo-rescence staining showed that CHMP2B was distributed in both nucleus and cytoplasm and correlated with vesicle secretion.Moreover,CHMP2B was positively correlated with the expression of autophagy marker MAP1LC3B while inhibiting the expression of P62.Conclusion The high expression of CHMP2B in clinical pancreatic cancer tissue samples is consistent with the high expression in vitro pancreatic cancer cell lines.CHMP2B is localized in both nu-cleus and cytoplasm,involving in vesicle transport and lysosomal autophagy.In the pancreatic cancer cell line MIA PaCa-2,CHMP2B is positively correlated with the expression of autophagy marker MAP1LC3B and inhibits the ex-pression of P62.It is concluded that CHMP2B is related to autophagy in promoting the malignant degree of pancre-atic cancer.CHMP2B meets the high nutritional metabolic requirements of pancreatic cancer cells by regulating ve-sicular transport and autophagy,thus promoting the malignant biological behavior of pancreatic cancer.

Objective:To evaluate the prognostic value of albumin-bilirubin(ALBI)score in patients with distal cholangiocarcinoma(dCCA)after radical surgery.Methods:This retrospective study analyzed clinical data from 156 patients diagnosed with distal cholangiocarcinoma who underwent surgical treatment at the Department of Hepatobiliary Surgery,Beijing Chaoyang Hospital,affiliated with Capital Medical University,between January 2014 and December 2022.All patients gave informed consent and medical ethics guidelines were followed.The Albumin-Bilirubin(ALBI)score was calculated based on preoperative serum albumin and total bilirubin levels.Patients were then stratified into low ALBI and high ALBI groups using the optimal cut-off value.The study aimed to assess and compare the long-term prognosis of patients in these groups and to identify risk factors that influence their long-term prognosis using univariate and multivariate analyses.Results:Using the optimal ALBI cut-off value,patients were stratified into a low ALBI group(ALBI≤-1.67,92 cases)and a high ALBI group(ALBI>-1.67,64 cases).The median survival time for patients in the low ALBI group was 33 months,while the median survival time for patients in the high ALBI group was 20 months.The overall survival rates at 1 year,3 years,and 5 years postoperatively were 85.4%,43.8%,and 35.8%for the low ALBI group,and 65.5%,23.4%,and 13.6%for the high ALBI group,respectively(χ2=8.882,P=0.003).Results from both univariate and multivariate analyses indicated that high ALBI,CA19-9>37U/ml and lymph node metastasis were independent risk factors of long-term postoperative survival.Conclusion:In patients with distal cholangiocarcinoma,the preoperative ALBI score may be an effective indicator for predicting long-term survival.

The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of "eat me" signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.
Humans ; Mice ; Animals ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Lung Neoplasms/metabolism* ; Acrylamides/pharmacology* ; ErbB Receptors/metabolism* ; Cell Line, Tumor ; CD47 Antigen/therapeutic use*