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 construct a predictive model for patients with ischemic stroke(IS)based on the clinical features of carotid plaques.Methods A total of 189 patients with suspected acute IS who were admitted to the Depart-ment of Neurology at the First Affiliated Hospital of Soochow University for the first time were included in the study.Ac-cording to the results of diffusion-weighted imaging(DWI)of cranial magnetic resonance imaging,these patients were di-vided into IS group and non-ischemic stroke(NIS)group.According to the features of carotid atherosclerotic plaque as-sessed by ultrasound,the lesions were divided into vulnerable plaques and stable plaques.Logistic regression was used to analyze the nature of carotid plaques and clinical features in patients with IS,and the area under the ROC curve was calcu-lated.Results There were significant differences in the number of patients with vulnerable plaques,degree of carotid ste-nosis,hypertension,diabetes,and neutrophil-lymphocyte ratio(NLR)between the IS group and the NIS group(P<0.05).Multivariate logistic regression analysis revealed that the presence of vulnerable carotid plaques,poor control of hypertension and diabetes,and elevated NLR were the main influencing factors for IS events(P<0.05).The area under the ROC curve of vulnerable carotid plaques combined with clinical features(poor control of hypertension and diabetes and elevated NLR)to predict the occurrence of IS events in patients was 0.776(95%confidence interval:0.709?0.842),with a sensitivity of 0.748 and a specificity of 0.758.Conclusion The predictive model based on vulnerable carotid plaques combined with clinical features shows promise.

Objective:To explore the interaction needs between depressed adolescents with non-suicidal self-injury behavior and their parents.Methods:From June to November 2023, purposive sampling was used to select depression adolescents with non-suicidal self-injury behavior and their parents admitted to Huai'an Third People's Hospital as respondents. The semi-structured interview was used to collect data. The paired interview and Colaizzi 7-step analysis methods were used to analyze and summarize interview data.Results:Fifteen pairs of adolescents and their parents were interviewed. The needs of depressed adolescents with non-suicidal self-injury behavior for parental attention were summarized as controlling emotions, empathetic perception, reducing stress, mental dependence, autonomous decision-making, and mutual respect. The needs of parents for depressed adolescents with non-suicidal self-injury behavior were summarized as overcoming depression, restoring education, emotional response, actively seeking help, deep communication, and easing relationships.Conclusions:There are various interactive needs between depressed adolescents with non-suicidal self-injury behavior and their parents, which are closely related but contradictory in coping with the illness. It is recommended that medical and nursing staff conduct research on patients and their parents as a whole and provide personalized and targeted two-way guidance and emotional support through in-depth understanding and careful consideration of the multi-level interaction needs of both parties.

Objective To explore the dynamic changes in cerebral hemodynamics in patients with unilateral middle cerebral artery(MCA)occlusion after superficial temporal artery(STA)-MCA bypass surgery.Methods One hundred and nine patients diagnosed with unilateral MCA occlusion by DSA who underwent STA-MCA bypass surgery were retrospectively included in the Department of Neurosurgery of the First Affiliated Hospital of Soochow University.Clinical data of patients were collected within 24 hours after admission,including age,sex,body mass index,stroke risk factors including hypertension,hyperlipidemia,diabetes,smoking,drinking history and atrial fibrillation,clinical manifestations(within the last 6 months;nonspecific symptoms[dizziness,memory loss,unresponsiveness,etc.],transient ischemic attack,and stroke),blood biochemical markers(low density lipoprotein cholesterol,high density lipoprotein cholesterol,triglyceride,total cholesterol,fasting blood glucose,and hypersensitive C-reactive protein),and National Institutes of Health stroke scale(NIHSS)score at admission.Color Doppler ultrasound(CDU)and transcranial color coded Doppler(TCCD)ultrasound were used to evaluate the hemodynamic parameters of STA before and at different periods after surgery(4-7 days and 1,3,6,12 months after surgery)to analyze the patency of bypass arteries and intracranial hemodynamic changes,and to check the consistency of the results of the bridge artery patency at 12 months postoperatively by CDU and DSA,consistency test was performed.According to the results of the DSA examination 12months after surgery,the patients were divided into the bypass artery patency group and the non-patency group(stenosis or occlusion).The hemodynamic parameters at the trunk of STA,namely the extracranial segment,transcranial,and intracranial part of the bypass arteries,were compared between the two groups.It included inner diameter(D),peak systolic velocity(PSV),end-diastolic velocity(EDV),resistance index(RI),pulsation index(PI),time-averaged mean velocity(TAMV),time-averaged peak velocity(TAPV),and calculated flow of the STA trunk including TAMV flow and TAPV flow.Head CT,CT angiography(CTA)above the aortic arch,and CT perfusion(CTP)of the whole brain were performed 1 to 3 days before surgery and 12 and 18 months after surgery to observe the changes in cerebral perfusion.Head CT was performed 1 to 2 days after the operation to observe whether there were new hemorrhagic and ischemic lesions in the operative area.the CTP parameters of the two groups were compared including 12 and 18 months after the operation with 1 to 3 days before the surgery,and the differences in CTP parameters between the two groups were compared.The modified Rankin scale(mRS)was used to evaluate the neurological function prognosis of the patients at 12 and 18 months after surgery.The mRS score 2 was divided into a good prognosis and mRS score≥3 was a poor prognosis.NIHSS score of the patients was recorded 7 days,12,and 18 months after surgery.Results(1)Consistency analysis of CDU and DSA:the consistency of the assessment of bypass artery patency was excellent at 12 months after surgery,and the Kappa value was 0.94(95％CI 0.81-1.00,P＜0.01).According to DSA,101 cases(92.7％)were in bypass artery patency group,while 8 cases(7.3％)in the non-patency group(no case of occluded bridge vessel was found),and the sites of stenosis in the bypass arteries were all located in the transcranial segment.(2)Hemodynamic parameters:compared with the preoperative results,the D of the extracranial segment increased on 4-7 days and 1,3,6,and 12 months after the operation(Wald x2=30.438).Hemodynamic parameters included increased blood velocity such as PSV,EDV,TAMV,and TAPV(Waldx2 was 12.117,29.310,31.075 and 17.525,respectively)and blood flow including TAMV flow and TAPV flow(Wald x2 was 54.503 and 34.986,respectively)increased,while RI and PI values were decreased(Waldx2 was 112.568 and 103.629,respectively),and the differences were statistically significant(all P＜0.05).However,there was no significant difference in hemodynamic parameters in the non-patency group at 12 months after operation(all P＞0.05).Compared with 4-7 days after surgery,PSV(252.0[206.8,315.3]cm/s vs.102.5[84.0,119.0]cm/s)and EDV(119.5[106.3,159.8]cm/s vs.43.5[36.8,52.0]cm/s)in the non-patency group were significantly higher at the cranial entrance 12 months after surgery(both P＜0.05),but there was no significant difference in RI and PI values(both P＞0.05).Compared with 4-7 days after surgery,the blood flow parameters of STA intracranial segment,including PSV(29.4[24.8,41.4]cm/s vs.111.5[63.3,120.0]cm/s),EDV(19.7[15.2,22.2]cm/s vs.58.5[28.3,70.0]cm/s)and PI(0.55[0.42,0.63]vs.0.83[0.61,0.90])values in the non-patency group at 12 months after surgery were significantly decreased(all P＜0.05).(3)CTP parameters:the relative cerebral blood flow(rCBF)of the patency group increased at 12 and 18 months after surgery compared to preoperative levels,while relative cerebral blood volume(rCBV),relative peak time(rTTP)and relative mean transit time(rMTT)decreased,with statistical significance(all P＜0.05).At 12 and 18 months after operation,rCBF increased,while rMTT decreased in the non-patency group(both P＜0.05),but there was no significant difference as for rCBV and rTTP.The rTTP of the patency group at 12 and 1 8 months was lower than that of the non-patency group(12 months after surgery:1.14[1.06,1.15]vs.1.20[1.14,1.28],P=0.024;1 8 months after surgery:1.14[1.06,1.15]vs.1.20[1.14,1.28],P=0.023),but there was no statistical significance for other parameters between the two groups(all P＞0.05).(4)NIHSS score and prognosis:clinical follow-up results 18 months after the operation showed that no new stroke occurred during the follow-up period.The NIHSS scores in the patency group and the non-patency group were remarkably lower at 7 days,12,and 18 months after surgery than at admission(patency group:2[0,4],1[0,2],0[0,2]vs.3[0,6],respectively;the non-patency group:3[1,5],3[1,6],2[1,6]vs.4[1,7],respectively),with significant differences(all P＜0.05);However,the NIHSS scores in the patency group were significantly lower than that in the non-patency group at 12 and 18 months after surgery,and the proportion of patients with good prognosis in the patency group was substantially higher than that in the non-patency group(12months:87.1％[88/101]vs.4/8,P=0.039;18 months:90.1％[91/101]vs.4/8,P=0.025).Conclusion CDU can quantitatively evaluate the hemodynamic changes of bypass arteries after the STA-MCA bypass procedure,which can be applied to the long-term dynamic follow-up after the surgery.

Objective To investigate the effects of calcitriol intervention on PI3K/AKT signaling pathway and wound healing in rats with diabetic foot ulcer(DFU).Methods Thirty-two male SD rats were divided into normal control(Con)group,DFU group,calcitriol low dose(L)group and calcitriol high dose(H)group.A circular wound of 5 mm in diameter and deep to the fascia was made on the dorsum of the left foot of rats in each group.HE staining was used to evaluate the histopathological changes of the wounds.Immunohistochemical method was selected to compare the distribution of CD34-positive cells and the expression of p-PI3K and p-AKT in traumatic tissues of each group.ELISA was adopted in the detection of serum IL-6,IFN-γ,TNF-α and IL-7.RT-PCR was used to detect the mRNA expression of PI3K and AKT in each group,and western blot was used to detect the protein expression of PI3K,p-PI3K,AKT,p-AKT and VEGF.Results Compared with Con group,the expressions of IL-6,IFN-γ,TNF-α,IL-7,CD34,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K,p-AKT/AKT increased,while PI3K protein expression decreased in DFU,L and H groups(P<0.05),VEGF and AKT protein expression decreased in DFV and L groups(P<0.05).Compared with DFU group,the expressions of VEGF,AKT and PI3K protein increased(P<0.05),while the expressions of p-PI3K/PI3K,p-AKT/AKT decreased in L and H groups(P<0.05),IL-6 decreased in L group(P<0.05),and CD34 expression increased in H group(P<0.05),while IL-6,IFN-γ,TNF-α and IL-7,PI3K mRNA,AKT mRNA,p-AKT protein and p-PI3K protein expression decreased(P<0.05).Compared with L group,the expressions of CD34,VEGF,AKT and PI3K protein increased(P<0.05),while IL-6,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K and p-AKT/AKT decreased in H group(P<0.05).Conclusions Calcitriol intervention may reduce the activity of the PI3K/AKT signaling pathway,inhibit inflammation,promote neovascularization,and facilitate wound healing in rats with DFU.

Objective To understand the status of intra-abdominal hypertension(IAH)in children after liver transplantation,and to analyze the risk factors,to provide references for clinical medical staff to identify high-risk early,and formulate the prevention and intervention program of IAH after liver transplantation.Methods A prospective cohort study was conducted,and the clinical data of 208 children who received liver transplantation from October 2021 to June 2023 in a tertiary hospital in Zhejiang Province were enrolled.The status of IAH after liver transplantation was described,and participants were divided into 2 groups according to transbladder monitoring intra-abdominal pressure levels.Children with ≥10 mmHg(1 mmHg=0.133 kPa)was classified as an intra-abdominal hypertension group,while those with＜10 mmHg was classified as a non-intra-abdominal hypertension group.Results There were 51 cases(24.52％)which had IAH,including 12 cases(23.53％)of grade I to Ⅱ and 39 cases(76.47％)of grade Ⅲ to Ⅳ in 208 intra-abdominal hypertension in children after liver transplantation.Binary Logistic regression analysis showed that the graft to recipient weight ratio(OR=1.391),duration of postoperative mechanical ventilation(OR=1.006),and postoperative central venous pressure(OR=1.375)were independent risk factors for IAH(P＜0.05).Conclusion The incidence of IAH in children after liver transplantation were high.Greater graft to recipient weight ratio,longer mechanical ventilation time,higher central venous pressure could increase the risk of IAH.During clinical practice,more emphasis should be strengthened on the abdominal pressure dynamic monitoring and providing timely intervention to reduce the occurrence of IAH,and improving the prognosis of children after liver transplantation.