Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic targets.In the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges.Within the scope of our study,high hetero-geneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples.Notably,TNBC exhibited significant specificity regarding cell prolif-eration,differentiation,and disease progression.Significant associations between tumor grade,prog-nosis,and TNBC oncogenes were established via pseudotime trajectory analysis.Consequently,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC.Additionally,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor growth.Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC.The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as pelitinib.We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model.Overall,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.

Objective To study the effects of intramedullary pressure on the fluid flow behavior in bones.Methods Multi-scale models of macro bone tissue and macro-meso osteon groups were established using the COMSOL Multiphysics software.Considering the interrelationship of different pore scales,such as the bone marrow cavity,Haversia canal,and bone lacunar-canaliculus,the pore pressure and flow rate of hollow bone tissues and bone tissues with intramedullary pressure were compared,and the effects of the amplitude and frequency of intramedullary pressure on the pressure and flow velocity of the liquid in the bone were analyzed.Results When intramedullary pressure was considered,the pore pressure in bone tissues with intramedullary pressure was 6.4 kPa higher than that in hollow bone tissues.The flow pressure increased significantly with an increase in the intramedullary pressure amplitude,but the flow velocity remained unchanged.The frequency of intramedullary pressure had little effect on pore pressure and flow velocity.Conclusions The multi-scale pore model established in this study can accurately analyze bone fluid flow behavior.These results are of great significance for an in-depth understanding of force conduction in the bone.

Background: and Purpose Intracranial vertebrobasilar atherosclerotic stenosis (IVBAS) is a major cause of posterior circulation stroke. Some patients suffer from stroke recurrence despite receiving medical treatment. This study aimed to determine the prognostic value of a new score for the posterior communicating artery and the P1 segment of the posterior cerebral artery (PCoA-P1) for predicting stroke recurrence in IVBAS. Methods: We retrospectively enrolled patients with severe IVBAS (70%–99%). According to the number of stroke recurrences, patients were divided into no-recurrence, single-recurrence, and multiple-recurrences groups. We developed a new 5-point grading scale, with the PCoA-P1 score ranging from 0 to 4 based on magnetic resonance angiography, in which primary collaterals were dichotomized into good (2–4 points) and poor (0 or 1 point). Stroke recurrences after the index stroke were recorded. Patients who did not experience stroke recurrence were compared with those who experienced single or multiple stroke recurrences. Results: From January 2012 to December 2019, 176 patients were enrolled, of which 116 (65.9%) had no stroke recurrence, 35 (19.9%) had a single stroke recurrence, and 25 (14.2%) had multiple stroke recurrences. Patients with single stroke recurrence (odds ratio [OR]= 4.134, 95% confidence interval [CI]=1.822–9.380, p=0.001) and multiple stroke recurrences (OR=6.894, 95% CI=2.489–19.092, p<0.001) were more likely to have poor primary collaterals than those with no stroke recurrence. Conclusions The new PCoA-P1 score appears to provide improve predictions of stroke recurrence in patients with IVBAS.

Objective:To analyze the clinical efficacy and safety of endoluminal treatment of complex renal artery aneurysm (RAA).Methods:The clinical data and follow-up results of 19 patients with complex RAA admitted to Renji Hospital, Shanghai Jiaotong University School of Medicine from November 2014 to September 2021 were retrospectively analyzed. Two patients were treated with simple spring coil embolization into the aneurysmal artery, 14 patients were treated with simple spring coil embolization of the aneurysmal cavity, and 3 patients were treated with stent-assisted + spring coil embolization technique. Based on the location of the aneurysm, RAA were classified into type Ⅰ, Ⅱ, and Ⅲ. 7 patients with type Ⅰ, 10 patients with type Ⅱ, and 2 patients with type Ⅲ were studied. Variance analysis was used to compare the differences in glomerular filtration rate(GFR) of the affected side when the tumor was located at different locations, and Pearson was used to analyze the correlation between the number of coils implanted and the size of the tumor and GFR.Results:Ten of the 19 patients who were underwent successful endoluminal intervention. The average size of the patients′ aneurysms was (20.89±6.65) mm, and the average number of spring coils implanted was 8.22±3.08. The preoperative and postoperative serum creatinine were in the normal range, and no RAA tumor enlargement or recurrence was found during the follow-up period. The postoperative GFR was abnormal in patients with type Ⅰ, type Ⅱ, and type Ⅲ renal aneurysms, and the mean GFR value differed among the three types of patients( P=0.003). There was a negative correlation between the postoperative GFR values of the affected kidney and the number of spring coils implanted ( P=0.047), and no significant relationship between GFR and aneurysm size. Conclusion:The endovascular technique is an effective and safe means of treating complex RAA.

Objective:To evaluate the improvement of papilledema and visual acuities in patients with idiopathic intracranial hypertension (IIH) after venous sinus stenting.Methods:The clinical data of 8 IIH patients who met the inclusion criteria underwent venous sinus stenting between January 2013 and December 2016 at Department of Neurosurgery, Tianjin Huanhu Hospital were analyzed retrospectively. There were 6 females and 3 males,aged (32.9±14.4)years (range:19 to 57 years).The thickness of the retinal nerve fiber layer (RNFL) was measured by optical coherence tomography. Fundus,visual acuity and visual field examination were performed before and after operation. If pressure gradient ≥10 mmHg(1 mmHg=0.133 kPa) across the venous stenosis was indicated by intraoperative pressure measurement,the patient would be treated with venous sinus stenting. Intracranial pressure was measured by lumbar puncture 3 to 7 days after operation. RNFL thickness and eye examination were detected 6 months after surgery. CT venogram was used to observe the sinus venous conditions. Paired t test was used to compare the data before and after surgery. Results:All the 8 patients underwent venous sinus stenting successfully. The mean pressure gradient across the venous stenosis was reduced from (24±9.2) mmHg to (2.6±2.0) mmHg ( t=8.02, P<0.01). Intracranial pressure decreased from preoperative (41.4±12.7) cmH 2O(1 cmH 2O=0.098 kPa) to postoperative (12.9±3.3) cmH 2O ( t=7.08, P<0.01). The RNFL thickness decreased from (275.3±68.3)μm to (131.4±31.8)μm( t=5.80, P<0.05) 6 months after surgery and the baseline visual acuity was improved from( M( Q R))0.24 (0.25) to 0.65 (0.23)( Z=-2.52, P<0.05).Papilledema was significantly improved in 6 patients,and no significant change in 2 patients. CT venogram indicated adjacent stent restenosis in 1 patient. Conclusion:Venous sinus stenting can effectively improve papilledema and visual acuity caused by IIH.

Objective:To evaluate the efficacy and safety of drug-coated balloon (DCB) with paclitaxel in the treatment of femoropopliteal arteriosclerosis obliterans (ASO).Methods:From Dec 2016 to Dec 2018, clinical data of femoropopliteal artery disease patients treated with paclitaxel DCB in Renji Hospital, School of Medicine, Shanghai Jiaotong University were retrospectively analyzed.Results:A total of 83 patients (95 lower limbs) underwent DCB therapy. Including 50 chronic total occlusion (CTO) lesions (52.6%) with mean lesion length of (18.35±10.61) cm. Twenty-four lesions (25.3%) were moderately or severely calcified. Bail-out stent implantation was performed in 29.5% cases. The mean follow-up time was 17.5 months. Twelve months after intervention, the all-cause mortality rate was 6.0%, the major amputation rate was 4.3%, the primary patency rate was 60.6%, the primary assisted patency rate was 72.4%, the secondary patency rate was 83.4%, and the freedom rate from clinically-driven target lesion revascularization(F-TLR) was 77.0%. Moderate to severe calcification was an independent risk factor for the primary patency of DCB therapy.Conclusion:DCB is a safe and effective endovascular therapy for femoropopliteal artery disease.

Objective:To evaluate the improvement of papilledema and visual acuities in patients with idiopathic intracranial hypertension (IIH) after venous sinus stenting.Methods:The clinical data of 8 IIH patients who met the inclusion criteria underwent venous sinus stenting between January 2013 and December 2016 at Department of Neurosurgery, Tianjin Huanhu Hospital were analyzed retrospectively. There were 6 females and 3 males,aged (32.9±14.4)years (range:19 to 57 years).The thickness of the retinal nerve fiber layer (RNFL) was measured by optical coherence tomography. Fundus,visual acuity and visual field examination were performed before and after operation. If pressure gradient ≥10 mmHg(1 mmHg=0.133 kPa) across the venous stenosis was indicated by intraoperative pressure measurement,the patient would be treated with venous sinus stenting. Intracranial pressure was measured by lumbar puncture 3 to 7 days after operation. RNFL thickness and eye examination were detected 6 months after surgery. CT venogram was used to observe the sinus venous conditions. Paired t test was used to compare the data before and after surgery. Results:All the 8 patients underwent venous sinus stenting successfully. The mean pressure gradient across the venous stenosis was reduced from (24±9.2) mmHg to (2.6±2.0) mmHg ( t=8.02, P<0.01). Intracranial pressure decreased from preoperative (41.4±12.7) cmH 2O(1 cmH 2O=0.098 kPa) to postoperative (12.9±3.3) cmH 2O ( t=7.08, P<0.01). The RNFL thickness decreased from (275.3±68.3)μm to (131.4±31.8)μm( t=5.80, P<0.05) 6 months after surgery and the baseline visual acuity was improved from( M( Q R))0.24 (0.25) to 0.65 (0.23)( Z=-2.52, P<0.05).Papilledema was significantly improved in 6 patients,and no significant change in 2 patients. CT venogram indicated adjacent stent restenosis in 1 patient. Conclusion:Venous sinus stenting can effectively improve papilledema and visual acuity caused by IIH.

Objective To investigate the clinical value of fetal echocardiography in prenatal diagnosis , classification and outcome of abnormal origin of pulmonary artery from ascending aorta ( AOPA) . Methods From January 2014 to June 2018 ,18 cases of AOPA diagnosed by echocardiography in 43966 fetuses from Shaanxi Fetal Congenital Heart Disease Diagnostic Center were retrospectively analyzed . The echocardiographic features ,pathological and anatomical classification ,genetic characteristics and outcome of postnatal echocardiography were summarized . Results Abnormal origin of pulmonary artery branches could be demonstrated by color Doppler imaging system in 18 cases . Ten cases ( 55 .6％ ) of right pulmonary artery abnormalities originated from ascending aorta ( AORPA ) ,in which 6 cases ( 60％ ) were distal pulmonary artery abnormalities ,4 cases ( 40％ ) were proximal pulmonary artery abnormalities . Eight cases( 44 .4％ ) of left pulmonary artery abnormalities originated from ascending aorta ( AOLPA ) ,including 7 cases ( 87 .5％ ) of distal pulmonary artery abnormalities and 1 case ( 12 .5％ ) of proximal pulmonary artery abnormalities . Twelve AOPAs were associated with other intracardiac malformations with 6 right ventricular double outlet (DORV) accompanying with pulmonary stenosis ,3 tetralogy of fallots( TOF) ,2 atrioventricular septal defects( AVSD) ,1 single ventricle with single atrium ,and 1 Berry syndrome ,and no casese were associated with extracardiac malformations .Amniocentesis karyotype analysis and gene chip detection in 5 cases showed normal results . Four of 18 cases were born ,in which 3 cases died and 1 case was progressively suffered with right pulmonary artery atresia ,10 cases were inducted of labor ( 4 autopsy) and following-up was lost in 4 cases . Conclusions Incidence of AOLPA and distal type in fetal AOPA is higher than that in child and adult from references ,DORV is abnormal type mostly associated with intracardiac malformation . AOPA has no obvious genetic result for less cases . The main risk after AOPA birth is pulmonary infection . Echocardiography is of great value for AOPA in prenatal diagnosis , outcome observation and surgical planning after birth .

Objective To discuss the application of Chaperon guiding catheter system in endovascular treatment of intracranial aneurysms. Methods A total of 20 patients with intracranial aneurysms were enrolled in this study. The patients hadⅡorⅢtype of aortic arch (n=11) or sclerotic plague at the orifice of internal carotid or vertebral artery (n = 9). Endovascular embolization of the intracranial aneurysm was carried out in all patients. By using Cordis guiding catheter system the catheter was placed into the target artery. Chaperon guiding catheter system was used during the procedure in order to determine whether the Chaperon guiding catheter could be smoothly placed into the target artery or not. Results When the Chaperon guiding catheter system was employed in the endovascular procedure, the difficulties of catheterization caused by the distortion of the aorta or by the plagues on the walls of arteries could be basically overcome. The Guiding catheter could be smoothly placed into the target arteries. Conclusion The Chaperon guiding catheter system can be successfully used in the endovascular treatment for the intracranial aneurysms, especially when the patient has tortuous aorta or there is sclerotic plague on the artery wall. (J Intervent Radiol, 2014, 23:281-283).