ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

ObjectiveTo observe the clinical efficacy of electroacupuncture in treatment of simple obesity patients and its effects on the metabolism-inflammation network. MethodsSeventy-two patients with simple obesity were randomly divided into a electroacupuncture group and a sham electroacupuncture group， with 36 patients in each group. In the electroacupuncture group， conventional acupuncture was applied at Zhongwan （CV 12）， bilateral Tianshu （ST 25）， bilateral Daheng （SP15）， Qihai （CV 6）， Guanyuan （CV 4）， bilateral Zusanli （ST 36） and Fenglong （ST 40）. The sham electroacupuncture group used placebo needle at same acupoints as the electroacupuncture group. Both groups were given sparse-dense waves with a frequency of 2/10 Hz， 30 minutes per session， 3 times a week， for a total of 8 weeks of treatment. The changes of human body parameters including body weight， body mass index （BMI）， waist circumference， and body fat percentage （BFP）， metabolic factors including serum fasting blood glucose （FBG）， triglyceride （TG）， total cholesterol （TC）， high density lipoprotein （HDL）， low density lipoprotein （LDL）， leptin， and ghrelin， and inflammatory factors including interleukin-6 （IL-6） and tumor necrosis factor α （TNF-α） were compared before and after treatment. Correlations between changes in leptin， ghrelin and inflammatory factors were further analyzed. ResultsWaist circumference was significantly reduced after treatment in both groups compared with baseline （P＜0.05）， and the post-treatment waist circumference was lower in the electroacupuncture group than in the sham electroacupuncture group （P＜0.05）； body weight， BMI and BFP decreased significantly after treatment compared to pretreatment levels in the electroacupuncture group （P＜0.05）. Serum leptin， IL-6 and TNF-α declined significantly after treatment in both groups versus baseline （P＜0.05）； the electroacupuncture group had lower post-treatment levels of leptin， IL-6 and TNF-α as well as larger pre-post changes than the sham group （P＜0.05）； ghrelin increased markedly after treatment in both groups （P＜0.05）， with higher post-treatment ghrelin and greater pre-post variation observed in the electroacupuncture group （P＜0.05）. In the electroacupuncture group， changes in ghrelin were negatively correlated with IL-6 and positively correlated with TNF-α （P＜0.01）； in the sham electroacupuncture group， ghrelin changes were negatively correlated with both IL-6 and TNF-α， whereas leptin changes were positively correlated with the two inflammatory markers （P＜0.01）. ConclusionElectroacupuncture can effectively improve clinical manifestations， as well as regulate serum metabolic and pro-inflammatory factors in patients with simple obesity， and discrepant correlation patterns of metabolism-inflammation are observed between the two groups.

Objective To explore the pathogenesis and prognostic factors of liposarcoma in the head and neck region, and simultaneously analyze the efficacy of different treatment regimens. Methods A retrospective analysis was performed on all patients with primary untreated head and neck liposarcoma who were diagnosed and underwent surgical treatment at our hospital from January 2008 to January 2024. All patients were monitored during follow-up, and their prognoses were analyzed using SPSS software. Results A total of 30 patients were included in the study. Liposarcoma accounted for up to 60% of the cases in the orbit, while the remaining liposarcomas were primarily located in various interspaces of the neck. Dedifferentiated liposarcoma was the most common type, comprising 33%, while myxoid pleomorphic liposarcoma was the rarest at 4%. The tumor pathological type (P<0.001) and Ki67 (P=0.014) significantly affected the tumor control rate. However, an analysis of disease-specific survival rates revealed no significant differences across various factors (all P>0.05). Conclusion The prognosis of head and neck liposarcoma is better compared to that of liposarcomas in other parts of the body. However, myxoid pleomorphic liposarcoma, pleomorphic fat sarcoma, and high Ki67 levels are indicators of poor prognosis. Additionally, postoperative adjuvant radiotherapy does not significantly enhance disease-specific survival rates.

Objective:This study aimed to explore the molecular mechanisms of the maladaptation of H3N2 influenza virus in chicken embryos, provide a theoretical basis for the restoration of H3N2 influenza vaccine production in chicken embryos.Methods:Samples of respiratory secretions from patients with influenza-like symptoms (Influenza-like Illness, ILI) caused by H3N2 influenza virus were inoculated into chicken embryos and Madin-Darby Canine Kidney cells (MDCK), respectively. After isolating the virus, hemagglutination experiments were conducted to detect hemagglutination titers and hemagglutination inhibition experiments were used to compare antigenic differences; further, whole-genome sequencing of H3N2 influenza virus was performed using second-generation high-throughput gene sequencing (Next Generation High-Throughput Gene Sequencing, NGS), and key amino acid sites of mutations were identified through sequence alignment; combined with sialic acid receptor binding experiments, the differences in the binding of wild-type and mutant receptor binding sites (RBS) to sialic acid receptors were compared; finally, molecular docking and molecular dynamics simulation method were used to explore the specific molecular mechanisms of how mutation sites affect the differences in the affinity of the RBS pocket for sialic acid receptors.Results:The hemagglutination assay result indicated that both chicken embryos and MDCK cells could isolate the influenza virus, and the hemagglutination inhibition test showed that no antigenic differences were produced in the isolated strains. NGS analysis revealed that the H3N2 virus underwent an F195Y mutation in the (RBS) region of the hemagglutinin (HA) protein after adaptation through chicken embryo passages. Receptor-binding experiments demonstrated that the F195Y mutation enhanced the virus′s binding ability to α2, 3-linked sialic acid glycan (Neu5Acα2-3Galβ1-4GlcNAcβ-PAA, 3′SLN), while the mutation did not affect the affinity of the RBS pocket for α2, 6-linked sialic acid glycan (Neu5Acα2-6Galβ1-4GlcNAcβ-PAA, 6′SLN). Molecular docking and molecular dynamics simulation result indicate that the F195Y mutation, by replacing a hydrophobic amino acid with a hydrophilic one, leads to a significant decrease in the structure of the RBS pocket, enhancing the binding stability of the H3N2 influenza virus with α2, 3-sln. This is specifically manifested by an increase in binding time and an increase in the number of hydrogen bonds at the RBS site with the receptor. Furthermore, the F195Y mutation does not alter the binding of the virus to other receptors.Conclusions:The F195Y mutation in the RBS pocket of H3N2 influenza virus is a key site affecting the viral chicken embryo inadaptability.

Mass vaccination represents a highly effective strategy for accelerating disease control while simultaneously reducing incidence and mortality rates. By developing comprehensive plans and standards for mass vaccination, it is feasible to optimize resource allocation and swiftly enhance vaccination coverage, thereby preventing, controlling, or interrupting outbreaks or epidemics of specific infectious diseases. To standardize the mass vaccination process and establish a population immunity barrier in an orderly, efficient, and safe manner, a panel of experts was convened to develop the Recommendations on Mass Vaccination. These recommendations are grounded in the requirements of relevant policies and regulations in China, as well as the insights gained from the mass vaccination campaign for COVID-19 vaccines conducted in the country. The recommendations outline the system requirements pertaining to initiation conditions, departmental coordination, responsibilities, mobilization, operational specifications, and responses to vaccine reactions, among other aspects of mass vaccination implementation, so as to serve as a reference for future mass vaccination initiatives and the formulation of related policies.

Objective:To identify risk factors influencing clinical efficacy of endoscopic resection of small rectal neuroendocrine tumor (NETs).Methods:A retrospective analysis was conducted on patients with rectal NETs ≤10 mm who underwent endoscopic resection from 2013 to 2022. Patients were divided into the endoscopic submucosal dissection (ESD) group and the endoscopic mucosal resection with ligation (EMRL) group according to the treatment methods. After comparing the baseline data, propensity score matching was performed to compare the rates of R1 resection and adequacy of vertical margin distance.Results:A total of 186 patients were included in this study, with 139 receiving ESD and 47 receiving EMRL. The R1 resection rates were 12.2% (17/139) and 2.1% (1/47) in the ESD and EMRL group, respectively ( χ2=3.027, P=0.082). A significant difference in vertical margin adequacy was observed between the two groups [69.1% (96/139) VS 85.1% (40/47), χ2=4.598, P=0.032]. After propensity score matching, 46 pairs of cases were included, and there were no significant differences in the R1 resection rate [6.5% (3/46) VS 2.2% (1/46), χ2=0.261, P=0.609] and vertical margin adequacy [78.3% (36/46) VS 84.8% (39/46), χ2=0.649, P=0.420] between the two groups. Univariate and multivariate Logistic regression analyses revealed that operator experience and preoperative biopsy were independent risk factors for inadequate margin. Conclusion:Treatment method may not be the key factor affecting the distance of the vertical margin after endoscopic resection, but preoperative biopsy and operator experience have a significant impact on margins. Biopsy before endoscopic resection should be avoided, and less experienced doctors are recommended to use EMRL method for small NETs due to its ease of execution.

Objective To explore the influencing factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial internal carotid artery(ICA)stenosis and to construct a nomogram prediction model.Methods This study retrospectively and consecutively enrolled patients diagnosed with unilateral moderate-to-severe extracranial ICA stenosis and exhibited indications for carotid endarterectomy(CEA)hospitalized in the Department of Neurosurgery at the First Affiliated Hospital of Soochow University,between August 2019 and September 2024.The patients were divided into a stroke group and a non-stroke group,based on their clinical presentation and head MRI results.Baseline characteristics and clinical data including age,sex,body mass index,blood pressure(systolic and diastolic pressure[＜140 mmHg,140-＜160 mmHg,≥160 mmHg]),hypertension,diabetes,smoking and alcohol consumption history,use of statin and antiplatelet medication,fasting blood glucose,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglycerides(TG),total cholesterol(TC)were collected and ratios between LDL-C/HDL-C,TG/HDL-C,non-HDL-C(calculated according to equation:non-HDL-C=TC-HDL-C),and non-HDL-C/HDL-C(nHHR)were calculated based on aforementioned data.The clinical and baseline data were then compared between two groups.Imaging data included side of carotid artery stenosis(identified through neck vascular ultrasound,CT angiography and/or DSA),degree of carotid stenosis(with 50％-69％categorized as moderate stenosis,and,70％-99％as severe stenosis),plaque echogenicity(predominantly low,medium or high),plaque calcification(surface and basal calcification),plaque ulceration(exists or not),bilateral middle cerebral artery(MCA)hemodynamic parameters measured by transcranial Doppler ultrasound(including,mean flow velocity[Vm],peak systolic velocity[Vs],end-diastolic velocity[Vd]),and the pulsatility index(PI,calculated via formula:PI=[Vs-Vd]/Vm).The hemodynamic parameter differences(△Vm,△Vs,△Vd,△PI)between the healthy and affected MCA were calculated.The baseline,clinical and imaging data with P＜0.05 in univariate analysis were included in multivariate Logistic regression analysis using forward stepwise selection to identify influencing factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis,and a nomogram prediction model was then constructed base on the analyzed results.Receiver operating characteristic curves were plotted,and the area under the curve(AUC)was calculated to evaluate the predictive performance of the nomogram.Delong's test was used to compare AUC differences between single indicators and the combined model.Results A total of 166 patients with unilateral moderate-to-severe extracranial ICA stenosis and CEA indication were included.In which,99 patients were in the stroke group and 67 patients were in the non-stroke group.The stroke group had a significantly higher proportion of hypertension patients(78.8％[78/99]vs.59.7％[40/67],P=0.008),higher systolic blood pressure([152±15]mmHg vs.[137±18]mmHg,P＜0.01),higher diastolic blood pressure([84±10]mmHg vs.[80±10]mmHg,P=0.042),higher TG(1.33[0.95,1.77]mmol/L vs.1.10[0.87,1.48]mmol/L,P=0.019),higher TG/HDL-C(1.35[0.97,2.08]vs.1.07[0.81,1.52],P=0.003),and higher nHHR(2.89[2.25,3.61]vs.2.48[1.93,3.27],P=0.027)than the non-stroke group.The HDL-C was significantly lower in the stroke group(0.96[0.80,1.15]mmol/L vs.1.03[0.91,1.16]mmol/L,P=0.014).Statistically significant differences were also observed in the distribution of systolic blood pressure between the groups(P＜0.01).No significant differences were found in other clinical data(all P＞0.05).The proportion of patients with carotid plaque ulceration was higher in the stroke group(35.4％[35/99]vs.16.4％[11/67],P=0.007),while stenosis side,stenosis degree,plaque echogenicity,and plaque calcification type showed no significant differences between the groups(all P＞0.05).△Vm(19[4,32]cm/s vs.10[-3,21]cm/s,P=0.001),△Vs(32[9,55]cm/s vs.24[3,40]cm/s,P=0.005),and △Vd(10[-1,19]cm/s vs.6[-3,12]cm/s,P=0.006)were significantly higher in the stroke group.No significant difference was found in △PI(P=0.076).Multivariate Logistic regression analysis identified high systolic blood pressure(OR,1.063,95％CI 1.036-1.090,P＜0.01),high TG/HDL-C(OR,2.802,95％CI 1.551-5.061,P=0.001),high △Vm(OR,1.032,95％CI 1.010-1.055,P=0.004),and plaque ulceration(OR,2.777,95％CI 1.123-6.871,P=0.027)as independent risk factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis.Systolic blood pressure,TG/HDL-C,△Vm and plaque ulceration were involved in the construction of a combined predictive model for ischemic stroke in the targeted patient group(with unilateral moderate-to-severe extracranial ICA stenosis).The AUC of the combined prediction model was 0.828(95％CI 0.765-0.892,P＜0.01),which was significantly higher than the predictive efficacy of any single factor(all P＜0.01).Conclusions High systolic blood pressure,high TG/HDL-C ratio,high △Vm,and plaque ulceration are independent risk factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis.The nomogram prediction model based on these factors demonstrates good predictive value for assessing ischemic stroke risk in this patient population.

Hypoxic-ischemic brain damage (HIBD) is one of the main causes of disability in middle-aged and elderly people, as well as high mortality rates and long-term physical impairments in newborns. The pathological manifestations of HIBD include neuronal damage and loss of myelin sheaths. Tau protein is an important microtubule-associated protein in brain, exists in neurons and oligodendrocytes, and regulates various cellular activities such as cell differentiation and maturation, axonal transport, and maintenance of cellular cytoskeleton structure. Phosphorylation is a common chemical modification of Tau. In physiological condition, it maintains normal cell cytoskeleton and biological functions by regulating Tau structure and function. In pathological conditions, it leads to abnormal Tau phosphorylation and influences its structure and functions, resulting in Tauopathies. Studies have shown that brain hypoxia-ischemia could cause abnormal alteration in Tau phosphorylation, then participating in the pathological process of HIBD. Meanwhile, brain hypoxia-ischemia can induce oxidative stress and inflammation, and multiple Tau protein kinases are activated and involved in Tau abnormal phosphorylation. Therefore, exploring specific molecular mechanisms by which HIBD activates Tau protein kinases, and elucidating their relationship with abnormal Tau phosphorylation are crucial for future researches on HIBD related treatments. This review aims to focus on the mechanisms of the role of Tau phosphorylation in HIBD, and the potential relationships between Tau protein kinases and Tau phosphorylation, providing a basis for intervention and treatment of HIBD.
Humans ; tau Proteins/physiology* ; Phosphorylation ; Hypoxia-Ischemia, Brain/physiopathology* ; Animals ; Oxidative Stress

This study aims to delve into the influences and underlying mechanisms of Banxia Xiexin Decoction(BXD) on the proliferation, apoptosis, invasion, and migration of colon cancer cells. Firstly, the components of BXD in blood were identified by UPLC-MS/MS, and subsequently the content of these components were determined by HPLC. Then, different concentrations of BXD were used to treat both the normal intestinal epithelial cells(NCM460) and the colon cancer cells(HT29 and HCT116). The cell viability and apoptosis were examined by the cell counting kit-8(CCK-8) and flow cytometry, respectively. Western blot was employed to determine the expression of the apoptosis regulators B-cell lymphoma-2(Bcl-2) and Bcl-2-associated X(Bax). The cell wound healing assay and Transwell assay were employed to measure the cell migration and invasion, respectively. Additionally, Western blot was employed to determine the expression levels of epithelial-mesenchymal transition(EMT)-associated proteins, including epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), and vimentin. The protein and mRNA levels of the factors in the poly(ADP-ribose) glycohydrolase(PARG)/poly(ADP-ribose) polymerase 1(PARP1)/nuclear factor kappa-B p65(NF-κB p65) signaling pathway were determined by Western blot and RT-qPCR, respectively. The results demonstrated that following BXD intervention, the proliferation of HT29 and HCT116 cells was significantly reduced. Furthermore, BXD promoted the apoptosis, enhanced the expression of Bcl-2, and suppressed the expression of Bax in colon cancer cells. At the same time, BXD suppressed the cell migration and invasion and augmented the expression of E-cadherin while diminishing the expression of N-cadherin and vimentin. In addition, BXD down-regulated the protein and mRNA levels of PARG, PARP1, and NF-κB p65. In conclusion, BXD may inhibit the malignant phenotypes of colon cancer cells by mediating the PARG/PARP1/NF-κB signaling pathway.
Colonic Neoplasms/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Phenotype ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Apoptosis ; Cell Movement/drug effects* ; Neoplasm Invasiveness ; HCT116 Cells ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; Humans ; Poly (ADP-Ribose) Polymerase-1 ; Glycoside Hydrolases ; bcl-2-Associated X Protein ; NF-kappa B p50 Subunit

This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals ; Tryptophan/metabolism* ; Colonic Neoplasms/pathology* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred BALB C ; Humans ; Cell Line, Tumor ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Female ; Disease Progression ; Cell Proliferation/drug effects* ; Proto-Oncogene Mas ; Male