Objective:To investigate the effect of the stress-induced protein sestrin 3(SESN3)on tumor proliferation and the sensitivity to endocrine therapy in hormone receptor-positive(HR+)breast cancer(BC)and its mechanism.Methods:The cancer genome atlas(TCGA)database was used to analyze the expression level of SESN3 in breast cancer tissue and paracancerous tissue.The clinical samples of breast cancer tissue and paracancerous tissue were collected,and immunohistochemistry(IHC)microarray was used to vali-date the expression of SESN3.Western blot was used to measure the protein expression level of SESN3 in BC cell lines with different pathological subtypes.HR+BC cell lines were used to establish the models of SESN3 overexpression and knockdown,and cell counting kit-8(CCK-8)assay and colony formation assay were used to assess the proliferative capacity of cells;Western blot was used to ana-lyze cell cycle alterations;a subcutaneous xenograft mouse model was used to validate the effect of SESN3 on proliferation in vivo.The bioinformatics analysis and Western blot were used to investigate the downstream mechanisms of SESN3 in regulating proliferation.Results:The analysis of TCGA database and clinical samples showed that the expression of the SESN3 gene in BC tissue was signifi-cantly lower than that in paracancerous tissue,and the patients with high SESN3 expression had a longer progression-free survival time.Compared with the other subtypes of BC cell lines,the HR+BC cells lines MCF-7 and T-47D had a relatively high expression level of SESN3.MCF-7 and T-47D cell lines were used to establish the cell models of knockdown(MCF-7KD and T-47DKD)and overexpres-sion(MCF-7OE and T-47DOE),and compared with the control group,MCF-7KD and T-47DKD cells showed increases in proliferative capacity and the proportion of cells arrested in the G2 and M phases.In vivo tumorigenesis experiments showed a significant increase in tumor growth in mice in the MCF-7KD group.The bioinfor-matics analyses showed a significant negative correlation between the mammalian Target of Rapamycin(mTOR)signaling pathway and SESN3 expression,and Western blot validation showed a significant increase in the expression of mTOR in MCF-7KD and T-47DKD cells,as well as reductions in the protein expression levels of autophagy-related genes.Subsequently,we further confirmed that the knockdown of MCF-7 and T-47D cells led to a decreased sensitivity to endocrine therapy.In addition,MCF-7、T-47D、MCF-7KD、and T-47DKD cell lines were treated with the mTOR inhibitor everolimus(EVE),and there was a significant reduction in proliferative capac-ity in the MCF-7KD group and the T-47DKD group;since the mTOR pathway reduced the sensitivity to endocrine therapy by reducing cell apopto-sis,there was a significant increase in the sensitivity to endocrine therapy with tamoxifen(TAM).Conclusion:The inte-grated database analysis,clinical sample validation,and in vivo/in vitro experimental models show that SESN3 inhibits the proliferation of HR+BC cells via the mTOR pathway and enhances the sensitivity to endocrine therapy.

Objective To investigate the role and mechanism of acyl-CoA syntbetase long chain family member 4(ACSL4)in Sevoflurane(Sev)induced neuronal cell damage.Methods Human neuroblastoma SH-SY5Y cells were used as the research object,and control group(dimethyl sulfoxide,10 μmol/L),Sev group and Sev+iron death inhibitor Ferrostatin-1(Fer-1,10 μmol/L)group were set up.CCK-8 method was used to detect cell activity in each group.4.1%Sev exposed postoperative cognitive dysfunction model was constructed in vitro and divided into Ctrol group,Sev group,Sev+si-NC group,Sev+si-ACSL4 group,and Sev+si-ACSL4+compound C group according to the transfection category.The contents of Malonaldehyde(MDA),4-hydroxynonenal(4-HNE),Glutathione(GSH)and Fe2+in each group were detected by colorimetry.The level of reactive oxygen species was detected using a 2',7'-dichlorofluorescein diacetate(DCFH-DA)fluorescent probe.Real time fluorescence quantitative PCR(qRT-PCR)was used to detect the mRNA expression of ACSL4,glutathione peroxidase 4(GPX4),and solute carrier family 7 member 11(SLC7A11).Protein immunoblotting was used to detect the expression of ACSL4,GPX4,adenosine 5'-monophosphate activated protein kinase(AMPK),phosphorylated(p)-AMPK,mammalian target of rapamycin(mTOR)and p-mTOR proteins.Results CCK-8 results showed that the cell viability of Sev group(0.41±0.11)was significantly lower than that of control group(0.98±0.07),and the cell viability of Sev+Fer-1 group(0.83±0.09)was significantly higher than that of Sev group(0.41±0.11),and the differences were statistically significant(t=7.572,5.118,all P<0.01).The levels of Fe2+,MDA,4-HNE,ROS and p-AMPK/AMPK ratios,as well as the mRNA and protein expression of ACSL4 in the Sev group cells,were higher than those in the Ctrol group(t=5.900,7.421,4.795,13.517,10.825,9.945,11.334),the GSH conten,p-mTOR/mTOR ratio,and mRNA and protein expression of SLC7A11 and GPX4 were lower than those in the Ctrol group(t=20.438,3.551,11.460,12.211,6.845,8.287),and the differences were statistically significant(all P<0.05)repectively.The levels of Fe2+,MDA,4-HNE,ROS,and p-AMPK/AMPK ratios,as well as the mRNA and protein expression of ACSL4 in the Sev+si-ACSL4 group,were lower than those in the Sev+si-NC group(t=3.818,3.164,3.054,4.465,13.088,7.918,9.737),the cell viability,GSH content,p-mTOR/mTOR ratio,and protein expression of SLC7A11 and GPX4 were higher than those in the Sev+si-NC group(t=2.912,7.248,7.574,20.092,5.915),and the differences were statistically significant(all P<0.05),respectively.The cell viability,GSH content,SLC7A11,and GPX4 protein expression in the Sev+si-ACSL4+compound C group were lower than those in the Sev+si-ACSL4 group(t=4.435,8.521,4.522,8.767),while the levels of Fe2+,MDA,4-HNE,and ROS were higher than those in the Sev+si-ACSL4 group(t=10.046,4.004,2.957,3.752),and the differences were statistically significant(all P<0.05).Conclusion Inhibiting ACSL4 expression attenuates Sev-induced iron death in SH-SY5Y cells by activating the AMPK/mTOR signaling pathway.

Purpose: Effective predictors of the response to neoadjuvant chemotherapy (NAC) are still insufficient. This study aimed to investigate the predictive value of serum lipid profiles for the response to NAC in breast cancer patients. Methods: A total of 533 breast cancer patients who had received NAC were retrospectively studied. The pretreatment of serum lipids, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein-α, and clinicopathological characteristics were collected to assess their predictive roles. Results: Breast cancer patients had significantly lower TC, TG, HDL-C, and LDL-C levels than normal individuals. Among these indicators, TG and LDL-C levels and HDL-C level increased and decreased significantly after NAC, respectively. In estrogen receptor (ER)-positive patients, increased LDL-C level was associated with better outcomes. Moreover, the receiver operating characteristic curve analyses suggested that TG and HDL-C levels at diagnosis can be used as predictors of the response to NAC only in the ER-positive subgroup.According to univariate analyses, patients with low TG level (< 1.155 mmol/L) or high HDL-C level (≥ 1.305 mmol/L) in the ER-positive subgroup had more favorable clinical responses than the other patients in the subgroup. Furthermore, according to multivariate analyses, a high HDL-C level (≥ 1.305 mmol/L, p = 0.007) was an independent predictor of NAC efficacy. Conclusion High HDL-C level (≥ 1.305 mmol/L) before NAC and increased LDL-C level after NAC were associated with the better treatment response in ER-positive breast cancer patients.These results are potentially considered beneficial in establishing treatment decisions.

Objective To summarize the outcomes and experience of arterial switch operation (ASO) in the past 10 years in our center.Methods From September 2008 to July 2017,238 patients underwent ASO at Guangzhou Women and Children Medical Center for repair of transposition of the great arteries and Taussig-Bing anomaly.There were 193 male and 45 female.Median age at operation was 2 months (2 days to 10 years) and mean body weight was(4.2 ± 1.7) kg (1.8-20.6 kg).There were TGA and VSD 91 cases,TGA/IVS 110 cases,and Taussig-Bing anomaly 37 cases.Among them 24 patients had an aortic arch anomaly.Intramural coronary artery was found in 8 patients.Results All patients successfully completed the operation,one-stage ASO was perfonned in 232 patients.Two-stage ASO was performed in 6 patients.The mortality was 14.2％.The follow-up duration was 1-10 years (median time,46 mouths).There were 3 died.Two suffered sudden death,and another one arrhythmia.10-year survival rate was 92.8％.Conclusion The outcomes of ASO were satisfactory.The long-term reoperation rate was rare.

Objective To compare the value of serum cystatin C (CysC),urine β2-microglobulin (β2-MG),and neutrophil gelatinase-associated lipocalin (NGAL) as a test panel with that of traditional indicators,serum Cr and urea,for detection of early renal damage in lung cancer patients after chemotherapy.Methods This prospective study collected data at our hospital on levels of serum cystatin C (CysC),urine β2-microglobulin (β2-MG),and neutrophil-gelatinase associated lipocalin (NGAL) from 63 lung cancer patients aged 60 and over.In addition,levels of traditional indicators including serum Cr and urea were also measured.Participants were divided into three groups:a prechemotherapy group,an under chemotherapy group,and a post-chemotherapy group.Results Levels of serum CysC,urine β2-MG,and NGAL in the post-chemotherapy group markedly increased,whereas levels of serum Cr and urea had no significant increase;furthermore,levels of serum CysC,urine β2-MG,and NGAL went up steadily as the time of exposure to chemotherapy drugs increased.Pearson's test showed that the sensitivity of CysC,beta 2-MG and NGAL as a panel was statistically significant for both the under chemotherapy group and the post-chemotherapy group (x2 =31.32,P=0.00;x2 =60.38,P=0.00).Conclusions Serum CysC,urine β2-MG and NGAL as a panel have good diagnostic value for early renal function damage in lung cancer patients after chemotherapy and are superior to traditional renal function indicators such as serum creatinine and urea.

Objective To summarize the revascularization surgery results of patients with unilateral absence of a pulmonary artery.Methods From November 2014 to July 2016,5 patients with unilateral absence of a pulmonary artery underwent surgical revascularization at Guangzhou Women and Children Medical Center.The age and body weight at surgery was 1-6 months and 3.9-5.8 kg.One patient was diagnosed with unilateral absence of left pulmonary artery.The other 4 patients were diagnosed with unilateral absence of right pulmonary artery.Three patients were diagnosed with isolated unilateral absence of a pulmonary artery.One was associated with Tetralogy of Fallot.One was associated with atrial septal defect.Revascularization was performed by connection of hilar artery and the main pulmonary artery,using direct anastomosis,Gore-Tex conduit or pericardial conduit.Results There was no mortality.The ICU stay after operation were 3-14 days.The follow-up duration was 14-34 months.All patients were alive and free from significant pulmonary stenosis.Conclusion Revascularization surgery for patients with unilateral absence of a pulmonary artery is effective and achieved satisfactory results.

Objective To analyze the application of intraoperative neurophysiological monitoring combined with neuronavigation multi-modal fusion technology in the brainstem glioma resection. Methods One hundred twenty patients with brainstem glioma were divided into observation group and control group. The control group was treated by traditional operation, while the observation group was treated by intraoperative nerve electrophysiological monitoring combined with neuronavigation multimodal fusion technology. The general condition, clinical efficacy, KPS score, complications and survival rate of the two groups were compared. Results The effect was significantly better in the observation group(76.66%)than in control group(53.33%)( x2=11.962,P=0.001).KPS scores were significantly higher in the observation group (27.91 ±1.98) than in the control group (12.11 ±2.13)(t=32.669, P<0.001). Conclusions Intraoperative nerve electrophysiological monitoring plus neuronavigation multimodality fusion technology can improve clinical efficacy and quality of life in patients with brainstem glioma.

Objective To find the expression level and the role of ENST00000460164 in luminal A breast cancer.Methods The expression level of ENST00000460164 in breast cancer tissues was detected by RT-qPCR.pll3.7-ENST00000460164-shRNA and empty vector,pll3.7,were transfected into MCF-7 cells.Cell cycle was measured by flow cytometry.Western blot was used to detect the expression of P16INK4A and cyclinD1.Results ENST00000460164 was highly expressed in luminal A breast cancer tissues as compared to the adjacent non-cancer tissues.The knockdown of ENST00000460164 resulted in the G1 cell-cycle arrested,cyclin D1 downregulated and P16INK4A upregulated in MCF-7 cells.Conclusions ENST00000460164 is overexpressed in luminal A breast cancer.ENST00000460164 may control G1/S transition by regulating P16INK4A or cyclin D1 expression.

Objective To establish the integrated prevention and control guide for multidrug-resistant organism (MDRO), guide nursing staff to strengthen prevention and control for MDRO and to compare the rate of implementation in preventive and control measures along with the discovery rate of MDRO before and after implementing guide.Methods The main problems of prevention and control management for MDRO were analyzed and induced with the methods of literature search, interviews with medical staff in ICU, referring to relevent clinical data and so on. The prevention and control guide was formulated according to expert consensus on MDRO, hospital infection management system of MDRO, clinical practice demand and so on. The prevention and control guide was implemented involving carrying out evidence-base training, building up prevention and control process, quality control and so on from July 2015 to June 2016. All patients of ICU in the Second Hospital of Jiaxing between July 2014 and June 2016 were divided into two groups before (n=622) and after (n=604) implementing prevention and control guide by purposive sampling. The discovery situation of MDRO was investigated. Besides, the implementation situation of preventive and control measures was evaluated by selecting 380 patients and 375 patients from two groups separately.Results After implementing prevention and control guide for MDRO, the rate of implementation in preventive and control measures (90.40%) significantly improved compared to that before implementation (70.00%) along with the discovery rate of MDRO (8.77%) decreased compared to that before implementation (16.08%) with significant differences (P<0.05). Conclusions The application of prevention and control guide for MDRO can effectively decrease the discovery rate of MDRO in ICU, make prevention and control work of MDRO more scientific, standardized, systematized and have a good clinical guidance role for prevention and control for MDRO of critical patients.