OBJECTIVES: To evaluate the therapeutic effect of gastrodin against hypoxic-ischemic brain damage (HIBD) in neonatal mice and explore the role of GPX4/SLC7A11/FTH1 signaling in mediating its effect. METHODS: Twenty-four 9- to 11-day-old C57BL/6J mice were randomized equally into 4 groups for sham operation, HIBD modeling by right common carotid artery ligation and subsequent exposure to hypoxia for 1 h, or gastrodin treatment at 100 or 200 mg/kg before and at 1 and 2 days after modeling. The mice then underwent neurological assessment (Zea-Longa scores), and the cerebral cortical penumbra tissue were collected for HE and Nissl staining, detection of ferroptosis biomarkers and protein expressions of GPX4, SLC7A11, and FTH1 with Western blotting and immunofluorescence co-localization, and observation of mitochondrial ultrastructure with electron microscopy. In cultured HT22 neuronal cells with oxygen-glucose deprivation (OGD) for 2 h, the effects of pretreatments with 0.5 mmol/L gastrodin, 10 μmol/L RSL3 (a GPX4 inhibitor), alone or in combination, were analyzed on expressions of ferroptosis-related proteins, cellular Fe²⁺, ROS, lipid peroxidation, MDA, and GSH levels, mitochondrial membrane potential (JC-1), and cell viability. RESULTS: Gastrodin treatment at the two doses both significantly ameliorated HIBD and neurological deficits of the mice, reduced mitochondrial damage and Fe²⁺, MDA and ROS levels, increased GSH level, and upregulated GPX4, SLC7A11, and FTH1 protein expressions. In HT22 cells, gastrodin pretreatment obviously attenuated OGD-induced ferroptosis and improved cell viability and mitochondrial function. Co-treatment with RSL3 potently abrogated the inhibitory effects of gastrodin on Fe²⁺, ROS, BODIPY-C11, and MDA levels and attenuated its protective effects on GSH level, cell viability, and mitochondrial membrane potential. CONCLUSIONS Gastrodin provides neuroprotective effects in neonatal mice with HIBD by suppressing neuronal ferroptosis via upregulating the GPX4/SLC7A11/FTH1 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Glucosides/pharmacology* ; Animals, Newborn ; Benzyl Alcohols/pharmacology* ; Amino Acid Transport System y+/metabolism*

Objective To investigate the value of a nomogram model constructed from intratumoral and peritumoral magnetic resonance imaging radiomics combined with clinical characteristics in predicting the status of lymphovascular space invasion(LVSI)in cervical cancer.Methods A retrospective analysis was conducted on 178 cervical cancer patients confirmed by postoperative pathology,with 70 cases of LVSI(+)and 108 cases of LVSI(-).The patients were divided into a training set[142 cases,including 54 cases of LVSI(+)and 88 cases of LVSI(-)]and a test set[36 cases,including 16 cases of LVSI(+)and 20 cases of LVSI(-)]at a ratio of 8:2.All underwent magnetic resonance imaging before surgery,and regions of interest were manually delineated layer by layer on the T2WI sequence,with the peritumoral region being uniformly expanded outward.Univariate logistic analysis was performed on clinical factors to select independent factors for cervical cancer LVSI(+).Radiomic features were extracted separately from the intratumoral region,the peritumoral region,and the intratumoral-peritumoral region to construct radiomics models,and the differences between the peritumoral and the intratumoral-peritumoral models were compared.A combined model was established based on the radiomics scores of the optimal intratumoral-peritumoral model and clinical independent predictive factors,and a nomogram was plotted.Receiver operating characteristic curves were used to evaluate the diagnostic performance of each model,and decision curve analysis was used to assess the clinical value of the models.Results The combined model demonstrated the best performance among the various models,with AUC of 0.970 in the training set and 0.803 in the test set.Conclusion Intratumoral and peritumoral magnetic resonance imaging radiomics combined with clinical characteristics can effectively predict LVSI in cervical cancer.

Objective:To monitor and evaluate in vivo dose changes of intensity-modulated radiotherapy (IMRT) in patients with cervical cancer in a real-time manner. Methods:Twelve patients with cervical cancer admitted to our hospital were enrolled in this study. The in vivo doses were monitored by PerFRACTION?. Electronic portal imaging device (EPID) were collected in each treatment fraction for two-dimensional in vivo dose verification[γ index and dose difference (DD) index]. Log files were recorded for three-dimensional in vivo dose verification (γ index). The correlation between in vivo dose and treatment duration was analyzed by Pearson correlation analysis. Results:A total of 206 sets of EPID images and corresponding Log files were collected. The three-dimensional in vivo dose verification γ 1%/1mm of all patients was not correlated with treatment fraction ( P>0.05). Among them, the absolute difference of γ 1%/1mm of 94.66% fractions was< 1%. The mean DD 3% of two-dimensional in vivo dose verification of all patients was negatively correlated with treatment fraction ( P<0.05). Among which, the average γ 3%/3mm of 9 patients was>89% in the treatment fractions, and the average γ 3%/3mm of 98.57% fractions of these 9 patients was>93%. The other 3 patients had an average γ 3%/3mm ranged from 38% to 100%. CBCT images showed that the bladder volume of these 3 patients was significantly decreased with the relative changes by 82.08%, 84.41% and 73.59%, respectively, and the target area was retracted significantly with the relative changes by 38.12%, 59.79% and 24.46%, respectively. Conclusion:Combined with γ index and DD index, PerFRACTION? can monitor the mechanical stability of accelerator and MU delivery accuracy during treatment fractions, and monitor the changes of in vivo dose in patients with cervical cancer, which can improve the safety and quality assurance of IMRT for cervical cancer patients and provide guidance for patients with adaptive radiotherapy.

Objective: To study the expression and clinical significance of Vimentin and E-cadherin in human breast cancer tissues. Methods: : The clinical data of 56 cases of breast cancer patients, who underwent radical mastectomy in Chaohu Hospital Affiliated to Anhui Medical University from January 2014 to January 2016, were retrospectively analyzed. The protein and mRNAexpressions of Vimentin and E-cadherin in breast cancer tissues were detected by immunohistochemistry and qPCR, respectively; and the relationship between the expression of Vimentin and E-cadherin in breast cancer tissues and the clinicopathological characteristics was analyzed. Logistic multivariate regression was used to analyze the independent factors affecting the protein expressions of Vimentin and E-cadherin. Spearman was used to analyze the correlation between Vimentin and E-cadherin. Kaplan-Meier was used to analyze the relationship between protein expressions of Vimentin, E-cadherin and prognosis. ROC curve was used to analyze the diagnostic value of Vimentin and E-cadherin on prognosis. Results: The rates of breast cancer tissues with high positive expression of Vimentin and E-cadherin were 76.79% and 19.64%, respectively.Among them, 47 cases (47/56, 83.93%) of breast cancer tissues showed significantly higher Vimentin mRNA expression than adjacent tissues (P<0.05), and 46 cases (46/56, 82.14%) of breast cancer tissues showed significantly lower Ecadherin mRNA expression than adjacent tissues (P<0.05). Vimentin protein expression was associated with tumor size, lymph node metastasis, vascular invasion, histological grade, clinical stage, molecular typing, Ki67+, ER-, PR- and HER2- expression (P<0.05). And E-cadherin protein expression was associated with lymph node metastasis, vascular invasion, histological grade, clinical stage, molecular typing, Ki67+, ER-, PR- and HER2- expression (P<0.05). Tumor size, lymph node metastasis, vascular invasion, histological grading, clinical staging, molecular typing, Ki67+, ER-, PR- and HER2- expression were all independent factors affecting the expression of Vimentin and E-cadherin (P<0.05). There was a negative correlation between Vimentin and E-cadherin expression (P<0.05). The 3-year survival rate of patients with high expression of Vimentin protein was 67.44%, while that of patients with low expression of E-cadherin protein was 68.89%. Conclusion: The high expression of Vimentin and low expression of E-cadherin in breast cancer tissues may be related to the occurrence, development, invasion and metastasis of breast cancer. It can be used as a reliable indicator of clinical diagnosis and prognosis.

Objective To evaluate the feasibility of anticoagulant therapy for acute proximal deep vein thrombosis without inferior vena cava filter placement for femoral neck patients before hip arthroplasty.Methods From January 2013 to August 2017,9 femoral neck fractures patients with acute proximal deep vein thrombosis before hip arthroplasty were enrolled into this study.There were 3 men and 6 women.The average age was 76.44±5.39 years old (range,69 to 83 years old).The average injured time before admission was 4.00±4.06 days.All patients received anticoagulant therapy without placement of inferior vena cava filter before hip arthroplasty.Four patients received Rivaroxaban 10mg,two times per day,while two patients received Enoxaparin 0.4 ml,two times per day;3 cases received Batroxobin 0.5 ml,every other day combined with Rivaroxaban 10 mg one time per day or Enoxaparin 0.4 ml,one time per day.The size of thrombus before and after treatment,changes of coagulation markers,the outcome of thrombosis before surgery,during surgery,postoperatively and during follow-up,the related complications were recorded.Results The diagnosis time for proximal DVT was 3.89±3.01 days after admission.8 patients showed proximal DVT combined with distal thrombus and 1 patient showed isolated proximal DVT.The average length of proximal thrombus was 10.78±6.10 cm (range,4.0-20.0 cm).The mean duration of treatment was 14.22±7.03 days.The results showed 5 proximal DVTs have complete disappeared,3 cases significantly improved,and 1 case had no change but showed stable.After treatment,the length of the proximal thrombus was significantly decreased (10.77±6.10 cm vs.4.39±6.50 cm),there were statistically significant between two groups (t=3.429,P=0.009);D-dimer was significantly lower after treatment (10.47±4.87 μg/ml vs.2.59± 1.60 μg/ml) with statistical difference (t=4.970,P=O.O01).However,no statistical significance was found in other coagulation parameters such as plasma prothrombin time,the international normalized ratio,activated partial thromboplastin time,thrombin time,fibrinogen.Incision exudate occurred in one patient and anticoagulant therapy was paused,however,two days later,DVT recurred and then the patient received continuous therapy with drug anticoagulation.The average time for postoperative follow-up was 8.3±7.6 months.At the latest follow-up,4 cases had thoroughly recovered with the thrombi fully resolved;4 cases had significantly improved including three thrombi partly locating in the muscular veins and one partly locating in the infra-popliteal vein.One case became more severe after discharge and received continuous anticoagulant therapy.No death,symptomatic pulmonary embolism,bleeding and other adverse events occurred.Conclusion Inferior vena cava filter placement for femoral neck fracture patients with acute proximal venous thrombosis before hip arthroplasty may not be potent.Anticoagulant therapy which make the proximal thrombus completely dissolved or stabilized before surgery may be effective.

Objective To study the effect of stenting on intravascular pressure difference at both ends of stenosis in patients with symptomatic internal carotid artery stenosis (CAS).Methods Eleven patients with moderate-severe internal CAS were included in this study.Their distal mean arterial pressure was measured by pushing the pressure guide wire into the distal end of stenosis and the proximal mean arterial pressure was measured by placing the pressure receptor connecting pipe into the proximal end of stenosis.The intravascular pressure difference at both ends of stenosis was calculated.Correlation between the stenosis rate and intravascular pressure difference at both ends of stenosis was analyzed by Spearman correlation analysis.The intravascular pressure difference before and after stenting was analyzed according to the Wicoxon test.Results Complete intravascular pressure difference value was detected in 11 CAS patients before and after operation.No complications and adverse events occurred during the perioperative period.The stenosis rate was 64％-95％ (74.18％±8.70％) and 0％30％ (12.64％±11.07％) respectively before and after operation.The intravascular pressure was 5-72 (15.64±19.64) mm Hg before operation and was 0-9 (2.64±2.69) mm Hg after operation (P=0.035,P=0.000).Spearman correlation analysis showed that the stenosis rate was positively related with the intravascular pressure difference (r=0.767,P＜0.01).Conclusion Carotid artery stenting can reduce both the stenosis rate and intravascular pressure difference at both ends of stenosis.

Objective To analyze the characteristics of proximal deep vein thrombosis (DVT) after total joint arthroplasty.Methods 40 cases of proximal DVT were collected from May 2007 to October 2016 which were all diagnosed by lower limb venography or sonography.There were 9 males and 31 females aged from 38 to 86 years,average 67 years,and body mass index was from 16.94 to 31.25kg/m2,with an average of 24.3 kg/m2.29 cases of THA patients and 11 cases of TKA patients.The anatomical distribution,size,radiological performance,local physical findings were recorded and multivariable analysis was performed to evaluate the relationship between distribution of proximal DVT and related parameters including age,gender (male/female),side of leg(left/right),surgery type(knee and hip),preoperative diagnosis(femoral neck fracture/other disease),time of diagnosis with DVT (during hospitalization/after discharge).Results Among 40 proximal DVT cases,31 cases diagnosed by phlebography and 9 cases were diagnosed by ultrasound.2 cases were isolated proximal DVT while 38 cases connected with distal DVTs.9 cases of blood clots in the proximal and distal thrombosis connected discontinuously.There was no isolated proximal DVT in TKA group and 10 cases (90.9％) of blood clots in the proximal and distal thrombosis connected continuously while there were 2 cases (6.9％) isolated proximal DVTs in THA group and 21 (77.8％) of blood clots in the proximal and distal thrombosis connected discontinuously,and there was no statistic significant difference between the two groups.The average length of proximal was 8.85±9.3 1cm (range from 2-35cm) with 5.0±2.05 cm in TKA group and 10.31 ± 10.55 cmin THA group.A significant difference was found between the 2 groups (P=0.014).13 cases located in femoral veins and upper venous region which were all from THA group.There was a significant difference in the distribution between surgery type and preoperative diagnosis.However,there was no significant difference between other potential factors and distribution of proximal DVT.25 cases accepted the evaluation of symptom of DVT before scanning.However,no significant difference were found in edema,VAS score,Homans sign,Neuof sign between 9 TKA and 16 THA cases.Conclusion Proximal DVTs after knee and hip arthroplasty are more preferred to connect with distal DVT continuously.Surgery type and preoperative diagnosis have a significant effect on the distribution of proximal DVT.Proximal DVTs in THA and patients with preoperative femoral neck fracture could be more easily involving femoral veins and upper parts.

Objective To analyze the effect of carotid artery stenting (CAS) on cerebralblood flow and cerebrovascular reactivity in patients with severe carotid stenosis.Methods Twenty patients with unilateral severe internal carotid artery stenosis,conformed by carotid color ultrasonography or MR angiography in our hospital from August 2014 to December 2015,were chosen in our study.CAS was performed;relative cerebral blood flow (rCBF) detection and relative cerebrovascular reactivity (rCVR) assessment were performed by single photon emission computed tomography (SPECT) combined with carbon dioxide (CO2) inhalation within one week before surgery and 3 months after surgery.Four regions of interest (ROIs) in the bilateral middle cerebral artery (MCA) territory of internal carotid stenosis were selected for data analysis.The changes of rCBF and rCVR before and after CAS between the ipsilateral and contralateral ROIs of these patients were compared.Results In these 20 patients,80 ROIs from each patient were obtained.Preoperative ipsilateral rCBF averaged 0.883±0.075,and contralateral rCBF averaged 0.929±0.033;preoperative ipsilateral rCVR averaged 0.010±0.055,and contralateral rCBF averaged 0.124±0.053;postoperative ipsilateral rCBF and rCVR averaged 0.927±0.040 and 0.092±0.058,and contralateral rCBF averaged 0.938±0.038 and 0.127±0.054.Postoperative ipsilateral rCBF and rCVR were significantly improved as compared with preoperative ones (P＜0.05).Postoperative contralateral rCBF and rCVR were improved as compared with preoperative ones,without significant differences (P＞.05).Conclusions CAS can not only improve rCBF and rCVR of the MCA in the carotid artery stenosis,but also improve the contralateral side.

Objective To investigate the significance of intravascular ultrasound (IVUS) in diagnosis and treatment of carotid stenosis.Methods IVUS was performed before and after carotid arterial stenting (CAS) in 12 patients with moderate or severe carotid stenosis,admitted to our hospital from July 2014 to April 2016 and diagnosed by digital subtraction angiography (DSA).The severity of carotid stenosis,expansion and adherence of the stent were observed,respectively.Results DSA indicated 17 vessels having pathological changes,including 4 (23.5％) eccentric lesions and 13 (76.5％) concentric lesions;IVUS indicated 23 vessels having pathological changes,including 13 (56.5％) eccentric lesions and 10 (43.5％) concentric lesions;the rate of eccentric plaque detected by IVUS was significantly higher than that by DSA (P＜0.05).The carotid diameter stenosis degree measured by DSA was smaller than the stenosis degree by IVUS (P＜0.05).In 4 patients underwent CAS,DSA showed that the residual stenosis was more than 30％,and IVUS showed stent underexpansion or poor adherence;in other 5 patients undewent CAS,IVUS showed poor stent symmetry,however,IVUS showed that the stent expansion,symmetry and adherence became better after the balloon expansion.Conclusion IVUS is useful for evaluation before and after stenting in patients with moderate or severe carotid stenosis.

Objective To observe the correlation between degrees ofextracranial cerebral artery stenosis and pressure ratio across stenosis.Methods The patients with ≥ 50％ stenosis,admitted to our hospital and conformed by DSA from September 2015 to February 2017,were collected in this study.Collateral circulation compensation was assessed by DSA.The distal stenosis pressure (Pd) and stenosis pressure (Pa) were measured by pressure wire system;the pressure ratio across stenosis was recorded.Correlations of pressure ratio with stenosis rate and collateral circulation compensation were analyzed by Spearman correlation.Results Thirty one stenotic extracranial cerebral arteries (9 of carotid stenosis,12 of vertebral artery stenosis and 10 of subclavian artery stenosis) in 28 patients were collected.There were no perioperative complications or adverse events.The vascular stenosis rate showed negative correlation with pressure ratio (r=-0.615,P=0.000).In the subgroups,pressure gradient was negatively correlated with carotid artery stenosis rate (r=-0.948,P=-0.000),vertebral artery stenosis rate (r=-0.757,P=0.004) and subclavian artery stenosis (r=-0.759,P=0.011).Pressure ratio and collateral circulation compensation showed negative correlated relation (r=-0.475,P=0.007).Conclusion The pressure ratio across stenosis gets worse impairment with increase of severity of stenosis,and the collateral circulation influences the pressure ratio.