Objective The alkaloids contained in the Chinese herb Sophora flavescens have good anti-inflammatory activity. To investigate the structure-activity relationship between the novel matrine and the anti-inflammatory activity by modifying the structure of matrine. Methods Fourteen novel matrine derivatives were obtained by chemical modification using matrine as the lead compound with matrine and M19 as positive controls. The cytotoxicity of matrine derivatives against RAW264.7 cells was detected by the cell counting kit 8 （CCK8） assay, and the relative amount of NO produced by matrine derivatives against lipopolysaccharide （LPS）-induced inflammation model of RAW264.7 cells was detected using an NO assay kit. The enzyme-linked immunosorbent assay （Elisa） was used to detect the secretion of interleukin-6 （IL-6） and tumor necrosis factor alpha （TNF-α） by matrine derivatives in LPS-induced inflammation model of RAW264.7 cells. Results The novel matrine derivatives all exhibited lower cytotoxicity compared with M19. The NO inhibition rates of the novel matrine derivatives were all higher than that of matrine, and some were higher than that of M19, with compound A12 having the highest NO inhibition rate. Compounds A11 and A12 showed higher IL-6 inhibition than the control M19. Additionally, compound A12 had higher TNF-α inhibition than M19. Conclusion Compound A12 inhibited the strongest inhibition of NO, IL-6 and TNF-α release and had the best anti-inflammatory activity, which provided an important lead compound for this subsequent in-depth study.

Depressive disorder is a mental illness characterized by poor mood and cognitive dysfunction caused by a range of complicated factors. Antidepressants have strong short-term efficacy in clinical application, yet with significant adverse effects and resistance in long-term use. Essential oils are small molecular compounds mainly composed of monoterpenes and sesquiterpenes, most of which are characterized by aromatic odors, easy permeability through the blood-brain barrier, and low toxic side effects. Volatile oil from traditional Chinese medicine can regulate neurotransmitter monoamine, hypothalamic-pituitary-adrenal axis, brain-derived neurotrophic factor, neuroinflammation and oxidative stress, and intestinal microbiota-gut-brain axis to exert an antidepressant effect through multiple pathways and targets. This review summarizes the main antidepressant chemical components of essential oil of traditional Chinese medicine, their pharmacological mechanisms and clinical application, aiming to provide some reference for further development and clinical application of essential oil of traditional Chinese medicine.

Objective To evaluate the current radiation doses in pediatric non-cardiac interventional procedures, and analyze the associated clinical factors, and to provide data references for reducing pediatric radiation exposure. Methods We conducted a retrospective analysis of the radiation doses of children who had undergone non-cardiac interventional procedures at the interventional department of a tertiary pediatric hospital in Jinan from January 2022 to October 2024. The collected data included basic demographic information, surgical date, anatomical site, disease type, and radiation dose parameters (cumulative fluoroscopy time, cumulative dose area product in cine mode, cumulative air kerma, and the number of images acquired). The Kruskal-Wallis H test was used for comparative analysis between groups (P < 0.05 was considered statistically significant). Results Among the 475 included children, 99 cases (20.8%) had infantile hemangioma (median P_ka, 0.136 Gy·cm²; median K_a,r, 0.38 mGy), 235 cases (49.5%) had venous malformation (median P_ka, 9.82 Gy·cm²; median K_a,r, 40.99 mGy), 75 cases (15.8%) had lymphatic malformation (median P_ka, 0.06 Gy·cm²; median K_a,r, 0.18 mGy), 32 cases (6.7%) had retinoblastoma (median P_ka, 6.58 Gy·cm²; median K_a,r, 52.34 mGy), 12 cases (2.5%) had arteriovenous malformation (median P_ka, 42.3 Gy·cm²; median K_a,r, 162.87 mGy), and 22 cases (4.6%) had other vascular malformations (median P_ka, 21.7 Gy·cm²; median K_a,r, 89.1 mGy). There were significant differences between children with different disease types in the cumulative fluoroscopy time, cumulative dose area product in cine mode, cumulative air kerma at the patient entrance reference point, and the number of images acquired during non-cardiac interventional procedures (all P < 0.01). Conclusion This study presented the types and proportions of pediatric non-cardiac interventional procedures, evaluated the radiation dose levels of different surgical types, and analyzed the effects of weight and anatomical site on radiation exposure, which can be useful for preliminary assessment of radiation doses in pediatric non-cardiac interventional procedures.

ObjectiveTo investigate the mechanism of liver injury induced by tripterygium glycosides tablets （TG） and the molecular mechanism of compound glycyrrhizin tablets （CG） in alleviating the abnormalities of cholesterol metabolism caused by TG via cholesterol metabolism. MethodsAccording to the body weights， male Sprague-Dawley （SD） rats were randomly grouped as follows： control （pure water）， low-dose TG （TG-L， 189.0 mg·kg^-1·d^-1）， high-dose TG （TG-H， 472.5 mg·kg^-1·d^-1）， TG-L+CG （189.0 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， and TG-H+CG （472.5 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， with 6 rats in each group. Rats were administrated with corresponding drugs once daily for 3 weeks. At the end of the last administration， the mRNA and protein levels of liver X receptor-alpha （LXR-α）， low-density lipoprotein receptor （LDLR）， adenosine triphosphate-binding cassette transporter A1 （ABCA1）， adenosine triphosphate-binding cassette transporter G1 （ABCG1）， 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， cholesterol 12α-hydroxylase （CYP8B1）， and sterol 27-hydroxylase （CYP27A1） in the liver tissue were determined by Real-time PCR and Western blotting， respectively. The level of 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMG-CoAR）， a regulatory enzyme of cholesterol synthesis， was measured by enzyme-linked immunosorbent assay （ELISA）. HepG2 cells were used to observe the effect of TG on the cell proliferation in vitro. Specifically， HepG2 cells were grouped as follows： Low-dose TG （TG-l， 15 mg·L^-1）， medium-dose TG （TG-m， 45 mg·L^-1）， high-dose TG （TG-h， 135 mg·L^-1）， fenofibrate （FB， 10 μmol·L^-1）， CG extract， TG-h+FB （135 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-m+FB （45 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-l+FB （15 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-h+CG （135 mg·L^-1 TG + 60 μmol·L^-1 CG）， TG-m+CG （45 mg·L^-1 TG + 60 μmol·L^-1 CG）， and TG-l+CG （15 mg·L^-1 TG + 60 μmol·L^-1 CG）. The mRNA and protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells were determined by Real-time PCR and Western blotting， respectively. ResultsThe rat experiment showed that compared with the control group， the TG-H group showed down-regulated mRNA levels of CYP7A1， CYP8B1， and CYP27A1 in the liver tissue （P<0.05， P<0.01）， which were up-regulated by the application of CG （P<0.05， P<0.01）， and the TG-H+CG group showed up-regulated mRNA level of LDLR （P<0.01）. Compared with the control group， the TG-L and TG-H groups showed down-regulated protein levels of LDLR， CYP7A1， and CYP8B1 in the liver tissue （P<0.05， P<0.01）. In addition， the protein levels of ABCG1 and LXR-α were down-regulated in the TG-H and TG-L groups， respectively （P<0.05）. Compared with TG alone， TG+CG up-regulated the protein levels of ABCG1 and LDLR （P<0.05， P<0.01）， and the protein levels of CYP7A1 and CYP8B1 in the TG-H+CG group were up-regulated （P<0.05， P<0.01）. The cell experiment showed that compared with the control group， the TG-h group presented up-regulated mRNA level of LXR-α （P<0.01）， and the TG-m and TG-h groups showcased down-regulated mRNA levels of LDLR and CYP7A1 （P<0.01） and up-regulated mRNA level of CYP27A1 （P<0.01） in HepG2 cells. The combination of CG with TG restored the above changes （P<0.01）. Western blotting results showed that compared with the control group， the TG-m and TG-h groups showed down-regulated protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells （P<0.01）. Compared with the TG-h group， the TG-h+CG group showed up-regulated protein level of LDLR （P<0.05）. Compared with the TG-m group， the TG-m+CG group showcased up-regulated protein levels of LDLR， ABCG1， CYP7A1， and CYP27A1 （P<0.05， P<0.01）. ConclusionThe administration of TG at 189.0， 472.5 mg·kg^-1 for 3 weeks could modulate the signaling pathways associated with cholesterol efflux， endocytosis， and cholesterol biotransformation in hepatocytes， leading to the accumulation of cholesterol and subsequent liver injury in rats. CG could ameliorate the liver injury induced by lipid metabolism disorders caused by TG by up-regulating the expression of LXR-α， LDLR， ABCG1， CYP7A1， CYP8B1， and CYP27A1 to promote cholesterol biotransformation.

Objective:To investigate the role of telomere length in the causal effects of immune-mediated diseases on liver fibrosis.Methods:Genome-wide association study (GWAS) data were extracted from open GWAS (https: //gwas.mrcieu.ac.uk) for a two-sample Mendelian randomization (MR) analysis. Five immune-mediated autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, primary biliary cirrhosis, primary biliary cholangitis, and Crohn′s disease) individually and collectively were included as exposure factors, telomere length as a mediator, and liver fibrosis as the outcome. The Wald ratio and inverse variance weighted (IVW) methods were performed to assess causal effects. The MR-Egger intercept test was adopted to evaluate the level of horizontal pleiotropy. Multivariable MR was employed to quantify the proportion of the effect of immune-mediated diseases on liver fibrosis mediated by telomere length. And sensitivity analyses were performed to assess the robustness of the results.Results:The results of IVW analysis revealed that the overall category of immune-mediated diseases, rheumatoid arthritis, systemic lupus erythematosus, primary biliary cirrhosis, primary biliary cholangitis, and Crohn′s disease were causally related to the high risk of liver fibrosis, and the OR were 1.63 (95% confidence intervals (95% CI): 1.33 to 2.10), 1.28 (95% CI: 1.14 to 1.43), 1.34 (95% CI: 1.02 to 1.74), 1.36 (95% CI: 1.27 to 1.47), 1.37 (95% CI: 1.23 to 1.52), and 1.52 (95% CI: 1.15 to 2.01), respectively ( P<0.001, <0.001, =0.032, <0.001, <0.001, =0.003). Horizontal pleiotropy was detected in the association between Crohn′s disease and liver fibrosis (MR-Egger intercept test, P=0.025).The results of multivariable MR indicated that telomere length acted as a mediating factor in the causal relationship between liver fibrosis and the overall category of immune-mediated diseases, rheumatoid arthritis, systemic lupus erythematosus, primary biliary cholangitis ( OR=2.24, 95% CI: 1.41 to 3.56; OR=1.78, 95% CI: 1.03 to 3.06; OR=2.11, 95% CI: 1.31 to 3.40; OR=2.01, 95% CI: 1.06 to 3.80; P<0.001, =0.038, =0.002, =0.032, respectively ). Conclusion:The causal effects of the overall category of immune-mediated diseases, rheumatoid arthritis, systemic lupus erythematosus, and primary biliary cholangitis on liver fibrosis are mediated by telomere length.

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

Objective:To evaluate the diagnostic value of targeted next-generation sequencing (tNGS) of throat swab samples for detecting community-acquired respiratory viruses (CARV) in patients with hematological diseases.Methods:Clinical and laboratory data from 64 episodes involving patients with hematological diseases and suspected infections—who underwent both pharyngeal swab tNGS and CARV polymerase chain reaction (PCR) testing concurrently—were retrospectively analyzed. The cases were drawn from the Department of Hematology, Peking University People’s Hospital, between September 2023 and April 2024. Concordance between tNGS and CARV PCR results, as well as the diagnostic performance of tNGS in detecting CARV, were evaluated.Results:Among the 64 episodes, 29 were clinically diagnosed with respiratory tract infections, including one case of cytomegalovirus pneumonia and 28 CARV-positive cases. The remaining 35 episodes involved patients with fever or respiratory symptoms attributed to other causes, including 14 with extrapulmonary infections and 21 with noninfectious etiologies. The median follow-up duration was 215.5 days (range: 7-271 days). PCR detected 24 strains of seven CARV types, whereas tNGS detected 25 strains of eight CARV types. Using PCR results as the reference standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of tNGS were 85.0%, 88.6%, 77.3%, 92.9%, and 87.5%, respectively. The two methods showed good concordance (Kappa=0.717, P<0.001) . Conclusion:Pharyngeal swab tNGS may serve as a viable alternative to PCR for diagnosing CARV infections in patients with hematological diseases.

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

Objective:To explore the effect and mechanism of Andrias davidianus skin mucopolysaccharides (ASMP) on full-thickness skin defect wound healing in diabetic mice. Methods:This study was an experimental study. The ASMP with polysaccharide content of (70.0±0.3)% was prepared; the proliferation activity of human umbilical vein endothelial cells (HUVECs) was detected by cell counting kit-8, showing that the optimal concentration of ASMP was 0.05 mg/mL. The HUVECs were taken and divided into blank control group, vascular endothelial growth factor (VEGF) group, and ASMP group according to the random number table method (the same grouping method below), which were cultured with conventional medium and the media containing 50 ng/mL VEGF and 0.05 mg/mL ASMP, respectively, and then cultured under hypoxic (with volume fraction of oxygen being 5%) and normal-oxygen conditions for 12 hours, and the length of tube formation was observed. Human monocytic leukemia cells were induced with phorbol ester to differentiate into M0 macrophages. These cells were then divided into blank control group, lipopolysaccharide (LPS) group, and ASMP group, which were cultured respectively using conventional medium, LPS-containing medium followed by conventional medium, and LPS-containing medium followed by 0.05 mg/mL ASMP-containing medium. After 48 hours of culture, the expressions of CD86 and CD206 proteins (expressed as relative fluorescence intensity, the same below) were measured by immunofluorescence, and the mRNA expression levels of arginase-1 (Arg1) and CD206 were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Eighteen male C57 mice aged 8-10 weeks were used, and diabetic model was successfully established using streptozotocin combined with a high-fat and high-sugar diet. Full-thickness skin defect wounds were created on the backs of the mice, and the mice were divided into blank control group, alginate dressing group, and ASMP group (with 6 mice in each group), which were treated with physiological saline, alginate dressing, and ASMP, respectively. Wound healing was observed on post injury day (PID) 3, 7, 10, and 14, and the wound healing rates of mice were calculated. On PID 7, the expressions of CD31 and CD206 proteins in the wound tissue of mice were observed by immunofluorescence. On PID 14, the thickness of granulation tissue in wounds of mice was observed by hematoxylin-eosin staining. The sample size for all experiments was 3.Results:After 12 hours of culture in normal-oxygen condition, compared with that in blank control group, the tube formation length of HUVECs in VEGF and ASMP groups was significantly increased (with q values of 10.08 and 16.91, respectively, P<0.05). After 12 hours of culture in hypoxic condition, compared with that in blank control group, the tube formation length of HUVECs in VEGF and ASMP groups was significantly increased (with q values of 11.61 and 16.91, respectively, P<0.05); compared with that in VEGF group, the tube formation length of HUVECs in ASMP group was significantly increased ( q=5.30, P<0.05). After 48 hours of culture, the relative fluorescence intensity of CD206 protein in M0 macrophages in ASMP group was 31.90±1.76, significantly higher than 1.00±0.25 in blank control group and 2.21±0.42 in LPS group (with q values of 50.75 and 48.75, respectively, both P values <0.05); the relative fluorescence intensity of CD86 protein was 5.82±0.63, significantly lower than 53.73±4.61 in LPS group ( q=30.90, P<0.05). After 48 hours of culture, the mRNA expressions of Arg1 and CD206 in M0 macrophages in ASMP group were significantly higher than those in blank control group (with q values of 35.02 and 13.09, respectively, P<0.05) and LPS group (with q values of 32.24 and 11.24, respectively, P<0.05). On PID 3, there was no statistically significant difference in intercomparison in the wound healing rate of mice among the blank control, alginate dressing, and ASMP groups ( P>0.05). Compared with those in blank control group, the wound healing rates of mice in alginate dressing group on PID 10 and 14 were significantly increased (with q values of 11.76 and 12.50, respectively, P<0.05), and the wound healing rates of mice in ASMP group on PID 7, 10, and 14 were significantly increased (with q values of 5.84, 15.90, and 14.96, respectively, P<0.05); compared with those in alginate dressing group, the wound healing rates of mice in ASMP group on PID 7 and 10 were significantly increased (with q values of 4.77 and 4.14, respectively, P<0.05). On PID 7, the relative fluorescence intensity of CD31 protein in wound tissue of mice in alginate dressing and ASMP groups was significantly stronger than that in blank control group (with q values of 7.63 and 16.85, respectively, P<0.05); the relative fluorescence intensity of CD31 protein in wound tissue of mice in ASMP group was significantly stronger than that in alginate dressing group ( q=9.22, P<0.05). On PID 7, the relative fluorescence intensity of CD206 protein in wound tissue of mice in alginate dressing and ASMP groups was significantly stronger than that in blank control group (with q values of 8.76 and 29.36, respectively, P<0.05), and the relative fluorescence intensity of CD206 protein in wound tissue of mice in ASMP group was significantly stronger than that in alginate dressing group ( q=20.61, P<0.05). On PID 14, the wound granulation tissue of mice in ASMP group was thicker compared with that in blank control group and alginate dressing group. Conclusions:ASMP can significantly enhance the ability of new blood vessel formation and optimize the immune microenvironment by promoting HUVEC tube formation as well as inducing macrophages to polarize toward the M2 type, thereby accelerating full-thickness skin defect wound healing in diabetic mice.