Objective:To discuss the suitable concentration of D-galactose(D-gal)and modeling period,and establish its induced aging-related cognitive dysfunction model in the mice,and perform a comprehensive evaluation.Methods:Fifty C57BL/6J mice were randomly divided into control group and 100,200,400,and 800 mg·kg-1 D-gal groups,with 10 mice in each group.The mice in various D-gal groups were subcutaneously injected with the corresponding concentration of D-gal once daily;the mice in control group were injected with an equal volume of normal saline.The body mass and water consumption of the mice in various groups were monitored;forelimb grip strength test and experiment on the ability of pole climbing sports were used to evaluate the motor coordination ability of the mice in various groups;novel object recognition test,Y maze test,and Morris water maze test were used to evaluate the cognitive function of the mice in various groups;HE staining and Nissl staining were used to observe the pathomorphology of brain tissue of the mice in various groups;immunohistochemistry method was used to detect the expression of β-galactosidase(β-gal)protein in brain tissue of the mice in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of interleukin(IL)-1β,tumor necrosis factor-α(TNF-α),IL-18,and IL-4 in hippocampus tissue of the mice in various groups;Western blotting method was used to detect the expression levels of β-gal,p53,and p16 proteins in hippocampus tissue of the mice in various groups.Results:The body mass growth trends of the mice in control group and various D-gal groups were consistent and there was no statistically significant difference(P>0.05),and there was no statistically significant difference in water consumption(P>0.05).After 8 weeks of subcutaneous injection of D-gal,compared with control group,the forelimb grip strength values of the mice in 200 and 400 mg·kg?1 D-gal groups were significantly decreased(P<0.05 or P<0.01);the pole-climbing time of the mice in 200 mg·kg?1 D-gal group was significantly prolonged(P<0.05);the recognition indexes of the mice in 200 and 400 mg·kg?1 D-gal groups were significantly decreased(P<0.01);the spontaneous alternation rate of the mice in 100,200,400,and 800 mg·kg?1 D-gal group was significantly decreased(P<0.05 or P<0.01),the escape latency was significantly increased(P<0.05).Spatial probe test showed that compared with control group,the escape latency of the mice in 200 mg·kg?1 D-gal group was significantly increased(P<0.05).The HE staining and Nissl staining results showed that compared with control group,the hippocampus neurons of the mice in 200 mg·kg-1 D-gal group were arranged disorderly,with obvious nuclear pyknosis,nuclear condensation,and abnormal morphology and structure,and the number of Nissl staining positive cells was significantly decreased.The immunohistochemistry results showed that compared with control group,the β-gal expressions in CA1 region,CA3 region,and cortex region of hippocampus tissue of the mice in 200 mg·kg?1 D-gal group were strongly positive.The RT-qPCR results showed that compared with control group,the expression levels of IL-1β,IL-18,and TNF-α mRNA in hippocampus tissue of the mice in 200 mg·kg?1 D-gal group were significantly increased(P<0.05 or P<0.01),and the expression level of IL-4 mRNA was significantly decreased(P<0.01).The Western blotting results showed that compared with control group,the expression levels of β-gal,p53,and p16 proteins in hippocampus tissue of the mice in 200 mg·kg?1 D-gal group were significantly increased(P<0.05 or P<0.01).Conclusion:The aging-related cognitive dysfunction model in the mice can be established by subcutaneous injection of 200 mg·kg?1 D-gal daily for 8 weeks.

Objective This study aims to investigate the effects of transcatheter arterial chemoembolization(TACE)using EqualSpheres,CalliSpheres,and Lipiodol loaded with idarubicin on VX2 liver cancer in rabbits.Methods Twelve New Zealand white rabbits were randomly assigned to three groups:EqualSpheres group,CalliSpheres group,and Lipiodol group(n=4 per group).The VX2 liver cancer animal model was successfully established through ultrasound-guided percutaneous puncture.EqualSpheres,CalliSpheres,and Lipiodol were employed as embolization agents loaded with idarubicin for the embolization procedure.Peripheral blood samples were collected at intervals of 5 minutes,0.5,1,4,12 and 24 hours following embolization and were centrifuged to obtain serum.At 24 hours post-TACE treatment,the rabbits in both the experimental and control groups were euthanized,and both liver cancer tissues and normal liver tissues were collected.UPLC-MS/MS was used to measure the drug concentration of idarubicin in peripheral blood and tissue samples,and Graphpad software was used to construct drug concentration-time curves in peripheral blood.The pharmacokinetic curves were constructed to evaluate the dynamic in vivo distribution characteristics.Results The average drug concentration in the EqualSpheres group(920.06 ng/mL)was significantly higher than that in both the CalliSpheres group(79.47 ng/mL)and the Lipiodol group(118.71 ng/mL).However,the average drug concentration in normal liver tissue of all the three groups was lower,and the difference was not statistically significant.The peripheral blood drug concentration of the three groups decreased at 5 minutes post-TACE and increased over the next 24 hours.The average blood concentration curve of EqualSpheres group increased more steadily compared to the CalliSpheres group and the Lipiodol group.The Cmax of the Lipiodol group was reached at 0.5 hours,measuring 11.54 ng/mL.Both the CalliSpheres group and the EqualSpheres group achieved their Cmax at 5 minutes,with values of 7.82 and 8.36 ng/mL,respectively.Conclusion EqualSpheres loaded with idarubicin achieve a high drug concentration at the tumor site while maintaining a low concentration in peripheral blood over 24 hours.This study demonstrates the stable drug release capability of idarubicin-loaded EqualSpheres.

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 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 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.