Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Objective:To develop a tetramer probe targeting fibroblast activation protein (FAP), named 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-4P(FAP inhibitor (FAPI)) 4, evaluate its biodistribution and PET image in FAP-positive-tumor bearing nude mice, and explore its feasibility as a novel radio-regent for treatment of FAP-positive tumor. Methods:FAP tetramer probe was constructed on the FAPI-46 motif with four mini-polyethylene glycol (PEG)(PEG 3) spacers between the four FAPI motifs, denoted as 4P(FAPI) 4. DOTA was used as the chelator for radiolabeling with 68Ga and 177Lu. The FAP binding characteristics were test by in vitro cell competitive binding experiment. Small-animal PET, in vivo biodistribution, and radionuclide targeting therapy were performed in HT-1080-FAP tumor bearing nude mice ( n=39). Independent-sample t test was performed to analyze tumor uptake data, and two-factor repeated measures analysis of variance was utilized to compare tumor volume data in radioactive isotope therapy. Results:Cell experiment showed that FAPI-tetramer and FAPI-monomer had similar half maximal inhibitory concentration values (3.29 and 2.15 nmol/L). 68Ga/ 177Lu radiolabeled FAPI-tetramer had better tumor uptake and retention than FAPI-monomer in small-animal PET and in vivo biodistribution experiment, with the tumor uptake for 177Lu-DOTA-4P(FAPI) 4 and 177Lu-FAPI-46 at 48 h of (18.72±1.32) vs (2.72±1.20) percentage activity of injection dose per gram of tissue (%ID/g) ( t=15.55, P<0.001). 177Lu-DOTA-4P(FAPI) 4 group showed best anti-tumor efficacy compared with 177Lu-FAPI-46 and control group in radionuclide targeting therapy. On the 2nd day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the control group (mean difference 67.19 mm 3, P=0.049); on the 14th day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the monomer treatment group (mean difference 414.33 mm 3, P=0.005). Conclusion:FAPI-tetramer can improve tumor uptake and retention ability compared with FAPI-46, and 177Lu-DOTA-4P(FAPI) 4 can be a promising radio-agent for FAP-positive tumor therapy.

The internal iliac artery originating from the common iliac artery is an important branch, and communicating with the branches of the abdominal aorta, such as lumbar artery and sacral median artery, forming rich collateral circulation and nourishing the blood supply of gluteal muscle and pelvic floor viscera. Surgical intervention is recommended when the maximum diameter of internal iliac artery aneurysms>2 cm. A variety of treatment modalities are available, particularly, endovascular technique has been successfully applied in the clinical treatment of internal iliac artery aneurysms, which can significantly improve the cure and reduce complications and deaths. This article reviews the previous literature and summarizes the progress of internal iliac artery aneurysms treatment.

Objective:To explore the clinical value of extra-long subcutaneous tunnel ventricular drainage in patients with hydrocephalus.Methods:From March 2016 to March 2020, 33 patients who were not suitable for ventriculoperitoneal shunt, who would have expected time of external ventricular drainage longer than 7 d, who had external ventricular drainage reaching for 7 d and still could not expect for drainage tube drawing for the next 7 d, or who had hydrocephalus after external ventricular drainage were chosen in our study. These patients accepted extra-long subcutaneous tunnel ventricular drainage. The curative effects in the patients were analyzed retrospectively.Results:The drainage tube was kept for a maximum of 24 months and the shortest time was 13 d, with average of 69.3 d; 32 patients (97%) had drainage time longer than 14 d. There was no secondary infection after operation.Conclusion:Extra-long subcutaneous tunnel extraventricular drainage tube has a long duration of catheter placement, could avoid multiple drainage and secondary intracranial infection, so it is a safe and effective new technology for hydrocephalus.

Objective :To explore influence of ticagrelor on levels of serum high sensitive C reactive protein (hsCRP) and plasma homocysteine (Hcy) in patients with acute coronary syndrome (ACS).Methods :A total of 135 ACS pa‐ tients hospitalized in our department from Jan 2016 to Feb 2017 were selected .Based on routine treatment ,Patients were randomly and equally divided into routine group ,clopidogrel group and ticagrelor group (based on routine treatment respectively received clopidogrel or ticagrelor ) for four weeks .Levels of serum hsCRP and plasma Hcy were measured and compared among all groups before and after treatment .Results :Compared with before treat‐ment ,after four‐week treatment , there were significant reductions in levels of serum hsCRP and plasma Hcy in three groups (P＜0. 05 or ＜0.01).Compared with routine group and clopidogrel group after four‐week treatment , there were significant reductions in levels of serum hsCRP [ (12.95 ± 1.99) mg／L , (8. 56 ± 1. 24) mg／L vs.(4. 47 ± 1. 92) mg／L] and plasma Hcy [ (13.48 ± 2.12) μmol／L , (9.55 ± 0. 94) μmol／L vs.(6. 61 ± 1. 15) μmol／L] in ticagrelor group ( P＜0.05 or ＜0.01).Conclusion :Ticagrelor can significantly reduce levels of serum hsCRP and plasma Hcy while effective antiplatelet therapy ,then significantly inhibit inflammatory response ,improve vascular endothelial function ,contribute to stabilizing atherosclerotic plaques ,improve prognosis in ACS patients .

Purpose To explore the feasibility of low radiation dose combined with lowdose contrast agent in thyroid CT enhanced scan and investigate the benefit of reducing radiation hazard and contrast agent damage to thyroid.Materials and Methods 120 patients assigned for thyroid enhanced CT scan were prospectively and randomly divided into four groups (each group was 30 patients).Group A:radiation dose 120 kV,180 mA,contrast agent dose 1.2 ml/kg;group B:radiation dose 120 kV,180 mA,contrast agent dose 1.0 ml/kg;group C:radiation dose 100 kV,100 mA,contrast agent dose 1.2 ml/kg;group D:radiation dose 100 kV,100 mA,contrast agent dose 1.0 ml/kg.CT values,background sign,background noise of thyroid were measured;signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated;CT dose index of volume (CTDIvol),dose length product (DLP),and the effective dose (ED) were recorded and calculated.The image quality was evaluated and the data was statistically analyzed by two radiologists.Results CT values,background sign and background noise of thyroid,as well as CTDIvol,DLP,ED among four groups were statistical significant (P＜0.05);there was no significant difference in SNR,CNR and image quality scores among four groups (P＞0.05).Conclusion It is beneficial of reducing radiation hazard and side-effect of contrast agent from low radiation dose combined with low-dose contrast agent under the condition of ensuring diagnostic image quality.

Objective To evaluate the value of multi-slice spiral CT Low-dose scanning technology in thyroid enhanced scan. Methods Eighty patients were randomly divided into four groups including Group A:120 kV,180 mA;Group B:120 kV,100 mA;Group C:100 kV,180 mA and Group D:100 kV,100 mA.The subjective image quality was evaluated and scored.Thyroid CT val-ue,image background noise (N),image signal to noise ratio (SNR),CT dose index (CTDIvol),dose length product (DLP),and the effective radiation dose (ED)were measured and compared.Results The subjective image scores and SNR of these four groups were 3.90±0.31 and 26.34±3.13,3.75±0.44 and 25.08 ±1.87,3.70 ±0.47 and 25.86 ±2.38,3.60 ±0.60 and 24.87 ±2.20 respectively.There were no significantly statistical differences among the subjective image scores and SNR (P > 0.05 )of the 4 Groups.Thyroid CT values,N,CTDIvol,DLP and ED were (1 68.55 ± 13.39)HU,(6.48 ±0.84)HU,(10.95 ±0.00)mGy, (145.67±8.79)mGy·cm,(0.73±0.04)mSv in Group A,(170.70±11.34)HU,(6.83±0.45)HU,(6.08±0.00)mGy,(84.58± 4 .9 4)mGy· cm,(0 .4 2 ±0 .0 3 )mSv in Group B,(1 8 5 .2 0 ±2 2 .3 5 )HU,(7 .1 9 ±0 .8 6 )HU,(6 .5 9 ±0 .0 0 )mGy,(8 9 .8 6 ± 3 .2 6 )mGy· cm,(0 .4 5 ±0 .0 3 )mSv in Group C,(1 9 0 .5 5 ±2 1 .3 8 )HU,(7 .6 6 ± 1 .0 1 )HU,(3 .6 6 ±0 .0 0 )mGy,(5 0 .2 0 ± 1 .8 9 )mGy·cm,(0.25±0.01)mSv in Group D respectively.There were significantly statistical differences among different thyroid CT values,N,CTDIvol,DLP and ED (P <0.05).Conclusion Multi-slice spiral CT low-dose scanning technology in thyroid en-hanced scan can guarantee the image quality and effectively reduce thyroid radiation dose.

Aim To investigate whether nicorandil (Nic)protects H9c2 cardiac cells against high glucose (HG)-induced injury and inflammation by inhibiting nuclear factor-κB (NF-κB )/cyclooxygenase-2 (COX-2 )pathway.Methods Cell viability was measured by cell counter kit-8 (CCK-8)assay.The expression lev-els of NF-κB,COX-2 and cleaved caspase-3 were de-termined by Western blot.The activity of lactate dehy-drogenase (LDH)in the culture medium was measured with commercial kits.The intracellular level of reactive oxygen species (ROS)was detected by 2′,7′-dichlor-fluorescein-diacetate (DCFH-DA)staining followed by photofluorography.The number of apoptotic cells was observed by Hoechst 33258 nuclear staining followed by photofluorography.Mitochondrial membrane poten-tial (MMP)was examined by rhodamine 123 staining followed by photofluorography.The secretion levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA.Results After H9 c2 cardiac cells were treated with 35 mmol · L-1 glucose (high glucose,HG)for 24 h,the cell viability was significantly decreased .Pre-treatment of the cells with 20~100 μmol·L-1 Nic for 60 min or 50 μmol· L-1 Nic for 30~120 min before exposure to HG signif-icantly attenuated the decrease in viability induced by HG.On the other hand,HG increased the expression levels of phosphorated (p)-NF-κB p65 and cyclooxy-genase-2 (COX-2 )in H9c2 cardiac cells.Pre-treat-ment of the cells with 50 μmol·L-1 Nic for 60 min at-tenuated the up-regulation of p-NF-κB p65 and COX-2 expression levels induced by HG.Furthermore,HG induced considerable injuries and inflammatory re-sponse,leading to increases in LDH activity,ROS generation,MMP loss,the number of apoptotic cells, the expression of cleaved caspase-3 as well as the se-cretion levels of IL-1βand TNF-α.Pre-treatment of the cells with 50 μmol·L-1 Nic for 60 min before HG exposure,or co-treatment of the cells with 100 μmol· L-1 PDTC (an inhibitor of NF-κB)or 10 μmol·L-1 NS-398 (an inhibitor of COX-2)and HG for 24 h ob-viously reduced the above injuries and inflammatory re-sponse induced by HG. Conclusion Nic protects H9 c2 cardiac cells against HG-induced injury and in-flammation by inhibiting NF-κB/COX-2 pathway.

AIM:To investigate whether angiotensin-(1-7) [Ang-(1-7)] protects H9c2 cardiac cells against high glucose (HG)-induced injury and inflammation by inhibiting the interaction between Toll-like receptor 4 (TLR4) acti-vation and necroptosis .METHODS:The expression levels of receptor-interacting protein 3 ( RIP3;an indicator of necrop-tosis) and TLR4 were determined by Western blot .Cell viability was measured by CCK-8 assay.The activity of lactate de-hydrogenase ( LDH) in the culture medium was measured with a commercial kit .The releases of interleukin-1β( IL-1β) and tumor necrosis factor-α( TNF-α) were measured by ELISA .The intracellular level of reactive oxygen species ( ROS) was analyzed by 2 ’ , 7 ’-dichlorfluorescein-diacetate ( DCFH-DA ) stating followed by photofluorography .Mitochondrial membrane potential ( MMP) was examined by rhodamine 123 staining followed by photofluorography .RESULTS:After the H9c2 cardiac cells were treated with HG (35 mmol/L glucose) for 24 h, the expression of RIP3 was obviously increased . Co-treatment of the cells with 30μmol/L TAK-242 (an inhibitor of TLR4) attenuated the up-regulation of RIP3 induced by HG.Furthermore, the expression of TLR4 was significantly increased after the cells were exposed to HG for 24 h, and co-treatment of the cells with 100μmol/L necrostatin-1 ( Nec-1;a specific inhibitor of necroptosis ) and HG for 24 h attenua-ted the up-regulation of TLR4 expression induced by HG .Moreover, 1μmol/L Ang-(1-7) simultaneously blocked the up-regulation of the RIP3 and TLR4 induced by HG.On the other hand, co-treatment of the cells with 1μmol/L Ang-(1-7), 30 μmol/L TAK-242 or 100 μmol/L Nec-1 and HG for 24 h attenuated HG-induced injuries and inflammatory response , leading to the increase in the cell viability , and the decreases in the activity of LDH , ROS generation , MMP loss as well as the releases of IL-1βand TNF-α.CONCLUSION:Ang-(1-7) protects H9c2 cardiac cells against HG-induced injury and inflammation by inhibiting the interaction between TLR 4 activation and necroptosis .

Objective To compare the consistency and correlation of multiple breath-hold (BH) with respiratory-triggered (RT) 1H-MRS for quantification of hepatic lipid content. Methods Sixty subjects were underwent RT 1H-MRS of the liver (Couinaud segment VII) and BH 1H-MRS at 1.5 Tesla Magnetic Resonace Imaging (MRI). The peak areas of water and methylene obtained on RT and BH 1H-MRS were recorded respectively and the liver fat fraction was calculated. Pearson correlation coefficient , Bland-Altman 95% limit of agreement, and concordance correlation coefficient were calculated. Results Mean liver fat fraction measured in RT and BH 1H-MRS were (8.6 ± 8.7)% and (9.4 ± 9.3)% respectively. There was a strong correlation between RT and BH 1H-MRS(r = 0.973, P < 0.000 1, concordance correlation coefficient = 0.95). With the Bland-Altman method, 91.7% data points were within the 95% limits of agreement. Conclusion RT and BH 1H-MRS are alternative tools for intrahepatic lipid quantification. These two methods have a strong correlation and perfect consistency.