OBJECTIVE To identify the quality markers （Q-Markers） of Hyssopus cuspidatus against airway remodeling in bronchial asthma （referred to as “asthma”）， an d to provide a reference for the quality control research of H. cuspidatus based on pharmacodynamic activity. METHODS Potential active components and action targets of H. cuspidatus were screened by network pharmacology method. Using human airway smooth muscle cells （HASMCs） as objects， airway remodeling cell model was induced by platelet-derived growth factor-BB （PDGF-BB）； validation test was then performed for anti-asthmatic effects of H. cuspidatus and the potential active components. HPLC method was employed to establish the fingerprints of 14 batches of H. cuspidatus samples， and chemometric analysis was also conducted. Combined with the results of pharmacodynamic experiments and fingerprint analysis， the Q-Markers of H. cuspidatus against airway remodeling in asthma were determined. RESULTS&CONCLUSIONS Network pharmacology analysis showed that the potential active components of H. cuspidatus against asthma might be flavonoids and phenolic acids such as luteolin， quercetin and rosmarinic acid， and the core anti-asthmatic targets were interleukin-6， mitogen-activated protein kinase， etc. In vitro experimental results confirmed that 25， 50， 100 μg/mL of H. cuspidatus ， as well as neochlorogenic acid （80 μmol/L）， acacetin （80 μmol/L）， salvianolic acid B （40 μmol/L） and quercetin-3- O - β -D-glucuronide （80 μmol/L）， significantly reduced the cell viability induced by PDGF-BB， inhibited cell proliferation， migration， and the phosphorylation level of extracellular signal-regulated protein kinase 1/2， decreased the levels of interleukin-6， tumor necrosis factor-α and reactive oxygen species， and generally arrested cells in the G 0 /G 1 phase （ P ＜0.05）. Fingerprint analysis showed that there were 27 common peaks in the fingerprints of the 14 batches of H. cuspidatus samples， with 15 compounds （including luteolin） identified， and the similarities of fingerprints were all greater than 0.8. The 14 batches of samples could be divided into three categories： S1-S7 as one category， S8-S13 as one category， and S14 as one category. The variable importance in the projection values of rosmarinic acid， chlorogenic acid， caffeic acid， salvigenin， luteolin， ferulic acid， quercetin-3- O - β -D-glucuronide， and the components corresponding to peaks 5 and 8 were greater than 1， indicating they were potential differential markers affecting quality. Integrating network pharmacology， in vitro experimental validation， and chemometric analysis， rosmarinic acid， neochlorogenic acid， caffeic acid， salvigenin， luteolin， ferulic acid， quercetin-3- O - β -D-glucuronide， acacetin， salvianolic acid B and chlorogenic acid may be the Q-Markers of H. cuspidatus against asthma.

OBJECTIVE To explore the improvement effect and potential mechanism of modified Yanghe decoction on bone destruction in rats with breast cancer bone metastasis based on the receptor-interacting serine/threonine-protein kinase 1 （RIPK1）/RIPK3 pathway. METHODS The rat model of breast cancer bone metastasis was established by injecting a suspension of breast cancer cells into the bone marrow cavity. The rats with successful modeling were randomly divided into a model group （intragastric administration of equal volume of normal saline）， modified Yanghe decoction low-， medium-， and high-dose groups （intragastric administration of corresponding decoction at 1.30， 2.60 and 5.20 g/kg， calculated by the dosage of crude drug）， high-dose modified Yanghe decoction+si-RIPK1 group （intragastric administration of corresponding decoction at 5.20 g/kg， calculated by the dosage of crude drug； simultaneous injection of small interfering RNA for RIPK1 via the tail vein）， and high-dose modified Yanghe decoction+si-NC group （intragastric administration of corresponding decoction at 5.20 g/kg， calculated by the dosage of crude drug； simultaneous injection of small interfering RNA for negative control via the tail vein）， with 12 rats in each group. Another 12 healthy rats were selected as the control group and were given the same volume of normal saline intragastrically， once a day， for 14 consecutive days. Body weight was measured before administration and at the end of the last administration. The mechanical pain threshold and thermal pain threshold were measured， and the bone destruction， pathological changes and osteoclast formation of the tibia were observed. The positive expression of receptor activator of nuclear factor-κB （RANK） and receptor activator of nuclear factor-κB ligand （RANKL） in the tibial tissue， as well as the phosphorylation levels of RIPK1， RIPK3 and mixed lineage kinase domain-like protein （MLKL） were detected. RESULTS Compared with the control group， the tumor cells of tibia tissues in rats of the model group showed significant proliferation and diffuse infiltration into the bone marrow cavity. Extensive areas of tumor necrosis of cells， severe bone destruction， thinning of the bone cortex， and damage to the bone trabeculae were observed. The body weight （before administration and at the end of the last administration）， mechanical pain threshold， thermal pain threshold， and the phosphorylation levels of RIPK1， RIPK3 and MLKL were decreased significantly； the tumor volume， the proportion of bone destruction area， the number of osteoclasts， and the positive expressions of RANK and RANKL were increased/up-regulated significantly （P＜0.05）. Compared with the model group， the above pathological changes in the tibial tissues of rats in modified Yanghe decoction low-， medium- and high-dose groups were all alleviated， and all quantitative indicators showed dose-dependent improvement （P＜0.05）. After silencing RIPK1， the aforementioned beneficial effects of high-dose modified Yanghe decoction were significantly weakened （P＜0.05）.CONCLUSIONSModified Yanghe decoction can alleviate bone destruction in rats with breast cancer bone metastasis. The above effect is related to the activation of the RIPK1/RIPK3 pathway.

ObjectiveTo establish an educational intervention framework of electronic picture books for children with autism spectrum disorder (ASD) based on Creative Problem Solving (CPS) model, and observe the effect on social function. MethodsElectronic picture books were designed using CPS model, including the program of reading, interactive animation design and associated artistic activities. From March to June, 2023, 24 children with mild to moderate ASD were recruited from Maanshan Institute of Special Education, and randomly assigned into experimental group 1 (CPS-based cognitive picture book interventions, n = 8), experimental group 2 (CPS-based social picture book interventions, n = 8) and control group (Bloom's Taxonomy-based picture book interventions, n = 8), and received the interventions for four weeks, with a total of twelve times. They were assessed with speech, social, perceptual and health behavior using Autism Treatment Evaluation Checklist (ATEC) before and after treatment, and the differences were calculated. ResultsThere was a significant difference among the groups in the social and perceptual scores differences (F > 4.344, P < 0.05) and a near-significant difference in the health behaviour score difference (F = 2.921, P = 0.076). Post Hoc test showed that the differences in social scores were higher in both experimental groups than in the control group (P < 0.05); the difference in perceptual scores was significantly higher in experimental group 1 than in experimental group 2 (P < 0.01), but there was no significant difference with the control group (P > 0.05); the difference in health behavior scores was higher in experimental group 2 than in the control (P < 0.05), and the difference in experimental group 1 was slightly higher than in the control group (P = 0.072). ConclusionElectronic picture book interventions based on the CPS model may be more effective in enhancing social, perceptual and health behavior in children with ASD, but there may be differences among models.

Objective To systematically search the research literature related to the application of machine learning models in hospice care,with a view to providing references for clinical practice.Methods A systematic search of Wanfang database,CNKI,VIP database,China Biomedical Literature Database,PubMed,Embase,Scopus,Cochrane Library,Web of Science,and CINAHL was conducted in accordance with the methodology of the scoping review as a guideline,with the timeframe of searching from the establishment of the database to August 30,2024,and the included literature was screened,summarized,extracted,and analyzed.Results Totally 17 studies were included.Analysis revealed that supervised machine learning algorithms(including random forest,decision tree,and neural networks)predominated in palliative care applications.Data sources and collection methods varied widely,with models applied across diverse scenarios.Model functions include assessing hospice needs,predicting a patient's risk of death,assisting with symptom management,analyzing hospice communication content,and more.Conclusion Machine learning models in palliative care demonstrate considerable utility and broad applicability.Future research should enhance data quality,optimize model development workflows,and improve model performance.

Objective To analyze the characteristics of influenza incidence and the changes of innate immune cells among children who visited the pediatric outpatient or emergency department of a hospital in Shanghai from Jan.2019 to Dec.2023,so as to provide references for the prevention of influenza in children.Methods Influenza-like illness(ILI)children who first visited the pediatric outpatient or emergency department of The First Affiliated Hospital of Naval Medical University from Jan.2019 to Dec.2023,and underwent influenza virus antigen or nucleic acid testing were enrolled.Their clinical and laboratory data were collected for retrospective analysis.With a month as the basic monitoring unit,a line chart was used to describe the changes in the number of influenza cases and the positive rate.Then,these cases were assigned to pre-coronavirus disease 2019(COVID-19)group(Jan.2019 to Dec.2019),mid-COVID-19 group(Jan.2020 to Dec.2022),or post-COVID-19 group(Jan.2023 to Dec.2023),and the influenza positive rates among these groups were compared.To further observe the changes of the innate immune cells of children with influenza A after non-pharmacological intervention(NPI)measures,considering the development characteristics of children's white blood cells,children with influenza A were assigned to 2 subgroups according to age:0-6 years or 7-16 years.Within each subgroup,they were assigned to pre-NPI group or post-NPI group according to time.A ratio of 1∶1 matching was carried out according to gender and age using propensity score matching,and the blood routine parameters were compared between the 2 groups.Results A total of 41 028 ILI children were enrolled.During the COVID-19 period from Jan.2020 to Dec.2022,the influenza positive rates decreased significantly(P＜0.001),and almost no influenza virus was detected.The peak of influenza reappeared in Mar.2023,with a lag in the peak period,but higher than previous years'peak,and the speed of reaching the peak was faster.In each subgroup,the white blood cell count and lymphocyte ratio of children with influenza A in the post-NPI group were lower than those in the pre-NPI group(all P＜0.001),and the monocyte ratio was higher than that in the pre-NPI group(both P＜0.001).Conclusion The implementation of NPI measures during COVID-19 leads to disruption of influenza transmission route and changes in the epidemic trend of influenza.The influenza virus causes serious public health problems after COVID-19 period,and children with influenza A experience more serious immune response.It is recommended to strengthen the vaccination of influenza vaccine before the flu season.

Objective:To analyze the epidemiological characteristics of cases involving monkey injuries at medical institutions surrounding Qianlingshan Park in Guiyang City, and to provide a reference basis for preventive measures to reduce monkey injuries and standardized post-exposure treatment.Methods:A retrospective cross-sectional study was conducted, collecting 1 900 cases of monkey-induced injuries in Qianlingshan Park treated at the outpatient clinic of Guizhou Provincial Center for Disease Control and Prevention and the Department of Surgery at Qianling Hospital, Guiyang City, from 2021 to 2024. Statistical analysis was performed using Pearson′s chi-square test.Results:Total of 1 900 cases of monkey-related injuries in Qianlingshan Park were collected from 2021 to 2024. The exposure time distribution exhibited significant seasonality, with 48.58% of cases occurring during July and August, totaling 923 cases, indicating a peak in the summer. There were 774 male patients and 1 126 female patients, with a ratio of 1∶1.45.and significant differences were observed between different age groups and genders (χ2=195.00, P<0.001), with the highest number of cases occurring in the 0-9 and 20-29 age groups, accounting for 22.05%(419 cases) and 21.79%(414 cases), respectively. The upper limbs were the most common injury site, accounting for 50.84% of the total cases(966 cases in total), with significant differences between gender and injury location (χ2=22.00, P<0.001), Among females, the proportion of injuries to the upper and lower limbs (30.11% and 16.47%, respectively) was higher than that among males (20.74% and 8.63%, respectively). The majority of injuries were classified as Grade Ⅲ, making up 57.38% of cases(1 069 cases in total). Self-treatment after exposure was the most common approach(60.44%), with significant differences observed between wound severity and treatment method (χ2=6.90, P=0.032), Patients with Grade Ⅱ and Grade Ⅲ wounds were more likely to choose self-management (26.84% and 33.23%, respectively) than outpatient management (15.14% and 24.15%). Approximately 98.05% (1 863 cases) of monkey-injured patients had received rabies vaccinations. Conclusions:This study analyzes monkey-related injuries in Qianlingshan Park from 2021 to 2024, clarifying the temporal distribution of injuries, demographic characteristics, injury sites, and treatment methods. The findings provide references for optimizing human-monkey conflict management and the prevention and control of zoonotic diseases in urban ecological parks.

Pyroptosis is a form of programmed cell death characterized by prominent inflammatory responses.As a classic chronic inflammatory disease,atherosclerosis(As)has been demonstrated to exhibit specific expression of multiple pyroptosis-related proteins within plaques.Accumulating evidence indicates that pyroptosis plays a crucial regulatory role in the initiation and progression of As.This review primarily focuses on three key cell types involved in As—endothelial cell,macrophage,and vascular smooth muscle cell(VSMC),and systematically summarizes their pyroptotic mechanisms and contributions to atherosclerotic development.Furthermore,we comprehensively summarize current advances in anti-atherosclerotic drugs and bioactive compounds targeting pyroptosis,aiming to provide theoretical foundations and research perspectives for developing novel strategies for the prevention and treatment of As.

OBJECTIVE: To investigate the role of telomerase reverse transcriptase (TERT) in alleviating doxorubicin (DOX)-induced cardiotoxicity. METHODS: (1) Cell experiments: rat H9c2 cardiomyocytes were divided into control group (CON group), null adenovirus transfection group (NC group), TERT overexpression adenovirus transfection group (TERT group), DOX group (treated with 1 μmol/L DOX for 12 hours), DOX+NC group, and DOX+TERT group (null adenovirus or TERT overexpression adenovirus were transfected for 24 hours and then treated with 1 μmol/L DOX for 12 hours). The mRNA expression of TERT in cardiomyocytes was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The level of mitochondrial membrane potential was detected by immunofluorescence. The expression levels of intracellular Bax, Bcl-2, microtubule-associated protein 1 light chain 3 (LC3) and p62 were detected by Western blotting. (2) Animal experiments: male C57BL/6 mice were randomly divided into a sham operation group (Sham group), DOX group (acute cardiotoxicity model was constructed by intraperitoneal injection of DOX 15 mg/kg), DOX+NC group and DOX+TERT group (modeled after transfection with airborne adenovirus or TERT overexpression adenovirus for 7 days). After 7 days of modeling, the area of myocardial fibrosis was detected by Sirius scarlet staining, and cardiac function was detected by echocardiography. RESULTS: (1) Cellular experiments: the mRNA expression level of TERT was significantly higher in the TERT group compared with the CON and NC groups. Compared with the CON group, the TERT mRNA expression level of cardiomyocytes in the DOX group and the DOX+NC group were significantly lower, the level of mitochondrial membrane potential was significantly lower, the protein expressions of Bax and LC3 were significantly increased, and the protein expressions of Bcl-2 and p62 were significantly decreased. No significant differences were found between the DOX group and DOX+NC group. Compared with the DOX group and DOX+NC group, the TERT mRNA expression level was increased in the DOX+TERT group (relative expression: 1.02±0.10 vs. 0.61±0.05, 0.54±0.03, both P < 0.05), the level of mitochondrial membrane potential was significantly increased (1.14±0.05 vs. 0.96±0.01, 0.96±0.01, both P < 0.05), the protein expressions of Bax and LC3 were significantly decreased, and the protein expressions of Bcl-2 and p62 were significantly increased (Bax/β-actin: 0.88±0.01 vs. 1.31±0.02, 1.26±0.01; LC3-II/I: 2.16±0.05 vs. 2.64±0.06, 2.58±0.02; Bcl-2/β-actin: 0.65±0.01 vs. 0.40±0.01, 0.41±0.01; p62/β-actin: 0.45±0.01 vs. 0.23±0.02, 0.29±0.01; all P < 0.05). (2) Animal experiments: compared with the Sham group, the percentage of myocardial fibrosis area was significantly increased and left ventricular ejection fraction (LVEF) and fractional shortening (FS) were significantly decreased in the DOX group and DOX+NC group. Compared with the DOX group and DOX+NC group, the percentage of myocardial fibrotic area was significantly decreased in the DOX+TERT group (%: 2.33±0.06 vs. 3.76±0.07, 3.87±0.06, both P < 0.05), and the LVEF and FS were significantly increased [LVEF (%): 67.00±1.14 vs. 54.60±1.57, 53.40±2.18; FS (%): 38.60±0.51 vs. 30.60±1.10, 30.00±0.71; all P < 0.05]. CONCLUSION Up-regulation of TERT expression can inhibit DOX-induced cardiomyocyte autophagy and apoptosis, attenuate DOX-induced myocardial fibrosis in mice, improve cardiac function, and thus alleviate DOX-induced cardiotoxicity.
Animals ; Doxorubicin/toxicity* ; Telomerase/metabolism* ; Myocytes, Cardiac/metabolism* ; Rats ; Male ; Cardiotoxicity ; Mice, Inbred C57BL ; Mice ; Membrane Potential, Mitochondrial ; Adenoviridae ; bcl-2-Associated X Protein/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Transfection ; Apoptosis

Objective To develop a machine learning(ML)-based prediction model for assessing the therapeutic effects of resveratrol(RES)on the pathological damage of acute pancreatitis(AP),and to optimize RES administration strategies for AP through validation using an animal model.Methods AAn ML-based prediction model was constructed using published data.Interpretability analysis was applied to identify high-efficacy zones within the parameter space of administration dose and frequency,which was followed by rigorous screening to select the optimal dosing strategy that balanced therapeutic efficacy and experimental feasibility.A total of 32 C57BL/6 mice were randomly assigned to 4 groups(n=8 per group),including a control group(Ctrl),an AP model group induced by caerulein(CER)and referred to as CER-AP,a treatment group receiving RES via intraperitoneal injection(RES i.p.),and a treatment group receiving RES via intragastric gavage(RES i.g.).The Ctrl group received intraperitoneal injection of normal saline.The CER-AP and the treatment groups were induced with 10 intraperitoneal injections of CER at 50 μg/kg.RES was administered to the RES i.p.and RES i.g.groups according to the optimal dose and timing predicted by the ML model.Blood and tissue samples were collected 12 hours after the experiment started.Results The gradient boosting decision tree model,optimized via Hyperopt,yielded the best performance,predicting that the optimal dose and administration frequency were 19.992 mg/kg and 3.828 times,respectively.Accordingly,a regimen of 20 mg/kg RES,administered four times,was used in the animal experiments.Compared with the Ctrl group,the CER-AP group exhibited higher pancreatic pathology scores and elevated levels of serum amylase,lipase,pancreatic myeloperoxidase,and trypsin,with all differences reaching statistical significance(all P<0.05).The administration of 20 mg/kg RES via both intraperitoneal injection and intragastric gavage mitigated pancreatic inflammatory cell infiltration and necrosis,improved the overall pathology score,and reduced serum amylase,lipase,and pancreatic myeloperoxidase levels to varying degrees(all P<0.05).Conclusion A regimen of 20 mg/kg RES administered four times effectively alleviates the severity of CER-induced AP.The therapeutic benefits appear to arise from a multi-target regulatory network that simultaneously suppresses inflammatory cascades,mitigates oxidative stress,and reduces apoptosis,thereby reducing pancreatic tissue damage and systemic inflammatory responses.

Objective:To investigate whether sivelestat sodium (SV) mitigates paraquat (PQ)-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis in mice by suppressing the NLRP3 inflammasome signaling pathway.Methods:Male C57BL/6J mice were randomly divided into four groups ( n=8 per group): Control group, PQ group, PQ+SV group, and SV group. The PQ and PQ+SV groups received an intraperitoneal injection of PQ solution (20 mg/kg) to establish a PQ poisoning model, while the Control and SV groups received an equivalent volume of saline. One hour later, the PQ+SV and SV groups were administered SV solution (100 mg/kg) intraperitoneally, whereas the Control and PQ groups received saline. After 48 hours, the mice were euthanized, and lung tissues were collected. Pathological changes were assessed via hematoxylin-eosin (HE) and Masson staining, followed by Smith and Ashcroft scoring. Immunohistochemistry was performed to evaluate the expression of NLRP3 inflammasome, caspase-1, α-smooth muscle actin (α-SMA), and collagen I. Western blotting was used to measure NLRP3 protein levels. Intergroup comparisons were conducted using one-way ANOVA with LSD post-hoc correction. Results:The Control and SV groups exhibited normal lung morphology, whereas the PQ+SV group showed reduced hemorrhage, congestion, and edema compared to the PQ group. Both PQ and PQ+SV groups exhibited significant weight loss post-intervention compared to the Control group (both P<0.001). HE and Masson staining revealed thickened alveolar septa, congestive and edematous alveolar walls, extensive inflammatory cell infiltration, and collagen deposition in the PQ group. In contrast, the PQ+SV group demonstrated alleviated alveolar wall congestion, reduced inflammatory infiltration, and decreased collagen deposition, with significantly lower Smith and Ashcroft scores [(5.92±1.34) vs. (10.88±1.88), P<0.001; (3.42±1.35) vs. (5.75±0.79), P<0.001]. Immunohistochemistry indicated reduced expression percentages of NLRP3 and caspase-1 in the PQ+SV group compared to the PQ group [(12.79%±0.43%) vs. (16.59%±0.40%), P<0.001; (17.71%±0.92%) vs. (19.84%±0.71%), P<0.001]. Similarly, α-SMA and collagen I expression in lung interstitium was significantly lower in the PQ+SV group [(11.79%±0.58%) vs. (16.14%±0.74%), P<0.001; (16.43%±0.56%) vs. (18.86%±0.60%), P<0.001]. Western blotting confirmed decreased NLRP3 protein expression in the PQ+SV group [(0.54±0.12) vs. (0.81±0.24), P<0.05]. Conclusions:SV attenuates PQ-induced ALI/ARDS-associated pulmonary fibrosis progression by inhibiting the NLRP3 inflammasome, suggesting that NLRP3 may be a key therapeutic target for early intervention in PQ-induced pulmonary fibrosis.