Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

Wound healing is a complex biochemical process. The use of herbal medicine in wound healing not only carries forward the wisdom of traditional medicine, with its anti-inflammatory and immune-regulating effects, but also reflects the direction of modern biopharmaceutical technology, such as its potential in developing new biomaterials like hydrogels. This article first outlines the inherent structural properties of healthy skin, along with the physiological characteristics related to chronic wounds in patients with diabetes and burns. Subsequently, the article delves into the latest advancements in clinical and experimental research on the impact of active constituents in herbal medicine on wound tissue regeneration, summarizing existing studies on the mechanisms of various herbal medicines in the healing of diabetic and burn wounds. Finally, the paper thoroughly examines the application and mechanisms of plant polysaccharide hydrogels containing active herbal compounds in chronic wound healing. The primary objective is to provide valuable resources for the clinical application and development of herbal medicine, thereby maximizing its therapeutic potential. It also represents the continuation of traditional medical wisdom, offering new possibilities for advancements in regenerative medicine and wound care.

Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.
Lung Neoplasms/genetics* ; Wnt Signaling Pathway/drug effects* ; Animals ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neoplasm Metastasis/prevention & control* ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Neutrophil Infiltration/drug effects* ; Down-Regulation/drug effects* ; Cell Movement/drug effects* ; beta Catenin/genetics* ; Apoptosis/drug effects* ; Mice, Inbred C57BL ; Male ; Neoplastic Cells, Circulating/drug effects*

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

Objective To investigate the application value of bedside ultrasound measurement of gastric antrum cross-sectional area(CSA)combined with acute gastrointestinal injury ultrasound(AGIUS)score in guiding early individualized enteral nutrition therapy for sepsis patients.Methods From January 2023 to July 2024,61 sepsis patients meeting diagnostic criteria were enrolled and divided into an observation group(n=30)and a control group(n=31).The observation group underwent bedside ultrasound monitoring of gastric antrum CSA to calculate gastric residual volume(GRV)and AGIUS score for formulating individualized en-teral nutrition strategies.The control group used gastric tube withdrawal method for GRV measurement to guide enteral nutrition.Clinical baseline characteristics,enteral nutrition-related complications,nutritional/in-fection indicators,and disease severity parameters were compared between groups.Predictive efficacy was ana-lyzed using receiver operating characteristic(ROC)curve and area under the curve(AUC).Results Both groups showed gradual increases in enteral nutrition feeding rates and total volumes over time,with the obser-vation group demonstrating significantly higher values than the control group at each time point(P＜0.05).The observation group started nasogastric feeding earlier than the control group(P＜0.05).Target calorie a-chievement rates on day 3,5,and 7 were better in the observation group(P＜0.05).The incidence of feeding intolerance progressively decreased in the observation group but increased in the control group over day 1,3,and 5,with significant intergroup differences at each time point(P＜0.05).By day 7,the observation group exhibited significantly higher prealbumin(PA),albumin(ALB),and transferrin(TF)levels compared to day 1 and the control group(P＜0.05).Both groups showed reductions in APACHE Ⅱ,SOFA,and AGI scores by day 7,with the observation group displaying significantly lower scores than the control group(P＜0.05).The observation group had shorter ICU stays[(10.83±3.26)d vs.(14.55±3.14)d,P＜0.05].The combination of gastric antrum CSA measurement and AGIUS scoring demonstrated excellent predictive value for feeding intolerance(AUC=0.920,95％CI:0.848-0.963),with 95.50％sensitivity and 82.50％specificity,achieving 87.60％predictive accuracy.Conclusion Bedside ultrasound measurement of gastric antrum cross-sectional area(CSA)combined with AGIUS scoring shows good effect as a safe and effective monitoring modality for guiding early individualized enteral nutrition therapy in sepsis patients.

Objective To investigate the predictive value of combining polygenic risk score(PRS)with the National Institutes of Health Stroke Scale(NIHSS)socre for the development of deep venous thrombosis(DVT)in patients with ischemic stroke.Methods A total of 150 patients with ischemic stroke who were hos-pitalized in Jilin Provincial People's Hospital from December 2023 to May 2024 were selected as study sub-jects.After excluding patients who did not meet the criteria,139 patients were successfully followed up and di-vided into two groups based on whether DVT occurred.PRS strategy and fluorescence in situ hybridization(FISH)technology were used to detect the mutation of the gene loci associated with the risk of venous throm-boembolism(VTE).Based on these genotype data and the effect size of single nucleotide polymorphism(SNP)loci,the PRS score of patients was calculated through the model formula.The degree of neurological impairment was evaluated by NIHSS score.Receiver operating characteristics(ROC)curve was used to ana-lyze the efficacy of PRS score,NIHSS score and their combination in predicting ischemic stroke with lower limb DVT,and clinical data related to VTE formation were collected.Results There were no statistically sig-nificant differences between the two groups in terms of gender,age,body mass index(BMI),smoking,alcohol consumption,hypertension,diabetes,D-dimer(D-D),total cholesterol(TC),triglycerides(TG),and lipopro-tein(a)[(LP(a)]levels(P＞0.05).The PRS score,NIHSS score,and Barthel index in the DVT group were significantly higher than those in the non-DVT group,and the proportion of patients with bed rest exceeding 72 h and homocysteine(Hcy)levels were also relatively higher,with statistical significance(P＜0.05).Logis-tic regression analysis showed that PRS score＞2.55,NIHSS score ≥-3 and Barthel index＜60 were inde-pendent risk factors for lower limb DVT after ischemic stroke(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of PRS score,NIHSS score and combined prediction of ischemic stroke combined with lower limb DVT were 0.655,0.747 and 0.763,respectively,and the AUC of combined predic-tion was higher than that of single prediction(P＜0.05).Conclusion PRS score combined with NIHSS score has good predictive efficacy for ischemic stroke complicated with DVT.

Resistance to poly adenosine diphosphate(ADP)-ribose polymerase inhibitor(PARPi)presents a considerable obstacle in the treatment of ovarian cancer.F-box and tryptophan-aspartic(WD)repeat domain containing 11(FBXW11)modulates the ubiquitination of growth-and invasion-related factors in lung cancer,colorectal cancer,and osteosarcoma.The function of FBXW11 in PARPi therapy is still ambiguous.In this study,RNA sequencing(RNA-seq)showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi.FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer(HGSOC)tissues,and low levels of FBXW11 were associated with shorter overall survival(OS)and progression-free survival(PFS)in HGSOC patients.Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi,while knocking down FBXW11 made it less sensitive.The four-dimensional(4D)label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11(S100A11)and promoted its degradation through ubiquiti-nation.The increased degradation of S100A11 led to less efficient DNA damage repair,which in turn contributed to increased PARPi-induced DNA damage.The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models.In summary,our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S10OA11-mediated DNA damage repair.

Traditional Chinese medicine,ancient Greek medicine,Ayurvedic medicine,and Arab medicine are recognized as the four major traditional medicines in the world.It reviews the education and training systems of the four major traditional medicines and finds that traditional Chinese medicine focuses on the teacher-student relation-ship and the combination of theory and practice;Ancient Greek medicine was mainly characterized by strong theoreti-cal research and experimental observation;Ayurveda highly values cultural identity as its main characteristic;Arab medicine attaches great importance to cultural exchange and practical promotion.It suggests promoting innovative de-velopment,strengthening practical teaching,improving teaching quality,strengthening international exchanges and cooperation,and increasing public acceptance abroad.

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.
Humans ; Prions ; Neurodegenerative Diseases/pathology* ; Amyloid beta-Peptides ; Alzheimer Disease ; alpha-Synuclein ; tau Proteins ; Parkinson Disease