Objectives:To investigate the impact of the Micra AV leadless pacemaker on cardiac function.Methods:A total of 76 patients who received the implantation of Micra AV leadless pacemaker due to sick sinus syndrome or atrioventricular block at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from September 2022 to April 2023 were included in this study.Among them,26 patients(34.2%)had sick sinus syndrome,and 50 patients(65.8%)had atrioventricular block.The patients were followed up for 1 year postoperatively.Cardiac function was evaluated by echocardiography,and the parameters of the pacemaker were collected through the outpatient clinic programming system.Results:After a follow-up of 120(87,181)days,compared with the preoperative state,the left ventricular ejection fraction(LVEF)decreased postoperatively([66.6±5.6]%vs.[63.8±5.2]%,P<0.001),and the cardiac output increased[(4.3±1.2)L/min vs.(5.3±1.5)L/min,P<0.001].There were no statistically significant differences in various cardiac function indexes of patients with sick sinus syndrome between the postoperative and preoperative states(all P>0.05).Compared with the preoperative state,in patients with atrioventricular block,the LVEF decreased postoperatively([67.0±5.1]%vs.[63.4±4.4]%,P<0.001),the cardiac output increased([4.2±1.1]L/min vs.[5.2±1.2]L/min,P<0.001),and the left ventricular end-diastolic diameter decreased[(49.9±5.4)mm vs.(48.6±5.0)mm,P=0.044].Firth's logistic regression analysis indicated that the preoperative LVEF(for every 1%increase,OR=1.56,95%CI:1.12-2.17,P=0.001),stroke volume(for every 1 ml increase,OR=1.15,95%CI:1.04-1.28,P=0.001),body mass index(for every 1 kg/m2 increase,OR=1.49,95%CI:1.02-2.17,P=0.020),and hypertension(OR=12.71,95%CI:1.11-145.13,P=0.039)were independent risk factors for the decrease in LVEF after surgery in patients with atrioventricular block.After the implantation of the MciraTM AV leadless pacemaker,the overall atrioventricular synchrony rate was 81.2%(68.8%,89.0%).The atrioventricular synchrony rates of patients with sick sinus syndrome and those with atrioventricular block were 70.6%(59.5%,83.4%)and 82.4%(74.2%,89.3%)respectively(P<0.05).Firth's logistic regression analysis indicated that sick sinus syndrome(OR=0.26,95%CI:0.07-0.89,P=0.029)and preoperative LVEF(for every 1%increase,OR=1.18,95%CI:1.03-1.35,P=0.015)were independent predictive factors for the atrioventricular synchrony rate>80%.Conclusions:There are differences in the impacts of the Micra AV leadless pacemaker on the LVEF and atrioventricular synchrony rate between patients with sick sinus syndrome and those with atrioventricular block.The preoperative LVEF,stroke volume,body mass index,and hypertension have independent predictive effects on the decrease in postoperative LVEF in patients with atrioventricular block.Sick sinus syndrome and preoperative LVEF are independent predictive factors for the atrioventricular synchrony rate>80%after surgery.

Objectives:To investigate the impact of the Micra AV leadless pacemaker on cardiac function.Methods:A total of 76 patients who received the implantation of Micra AV leadless pacemaker due to sick sinus syndrome or atrioventricular block at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from September 2022 to April 2023 were included in this study.Among them,26 patients(34.2%)had sick sinus syndrome,and 50 patients(65.8%)had atrioventricular block.The patients were followed up for 1 year postoperatively.Cardiac function was evaluated by echocardiography,and the parameters of the pacemaker were collected through the outpatient clinic programming system.Results:After a follow-up of 120(87,181)days,compared with the preoperative state,the left ventricular ejection fraction(LVEF)decreased postoperatively([66.6±5.6]%vs.[63.8±5.2]%,P<0.001),and the cardiac output increased[(4.3±1.2)L/min vs.(5.3±1.5)L/min,P<0.001].There were no statistically significant differences in various cardiac function indexes of patients with sick sinus syndrome between the postoperative and preoperative states(all P>0.05).Compared with the preoperative state,in patients with atrioventricular block,the LVEF decreased postoperatively([67.0±5.1]%vs.[63.4±4.4]%,P<0.001),the cardiac output increased([4.2±1.1]L/min vs.[5.2±1.2]L/min,P<0.001),and the left ventricular end-diastolic diameter decreased[(49.9±5.4)mm vs.(48.6±5.0)mm,P=0.044].Firth's logistic regression analysis indicated that the preoperative LVEF(for every 1%increase,OR=1.56,95%CI:1.12-2.17,P=0.001),stroke volume(for every 1 ml increase,OR=1.15,95%CI:1.04-1.28,P=0.001),body mass index(for every 1 kg/m2 increase,OR=1.49,95%CI:1.02-2.17,P=0.020),and hypertension(OR=12.71,95%CI:1.11-145.13,P=0.039)were independent risk factors for the decrease in LVEF after surgery in patients with atrioventricular block.After the implantation of the MciraTM AV leadless pacemaker,the overall atrioventricular synchrony rate was 81.2%(68.8%,89.0%).The atrioventricular synchrony rates of patients with sick sinus syndrome and those with atrioventricular block were 70.6%(59.5%,83.4%)and 82.4%(74.2%,89.3%)respectively(P<0.05).Firth's logistic regression analysis indicated that sick sinus syndrome(OR=0.26,95%CI:0.07-0.89,P=0.029)and preoperative LVEF(for every 1%increase,OR=1.18,95%CI:1.03-1.35,P=0.015)were independent predictive factors for the atrioventricular synchrony rate>80%.Conclusions:There are differences in the impacts of the Micra AV leadless pacemaker on the LVEF and atrioventricular synchrony rate between patients with sick sinus syndrome and those with atrioventricular block.The preoperative LVEF,stroke volume,body mass index,and hypertension have independent predictive effects on the decrease in postoperative LVEF in patients with atrioventricular block.Sick sinus syndrome and preoperative LVEF are independent predictive factors for the atrioventricular synchrony rate>80%after surgery.

Objective Evaluate the performance of the encephalon state index(ESI)in depth of anesthesia monitoring during clinical surgery,compared with the bispectral index(BIS).Methods ESI and BIS data were collected from 60 patients in a single-center clinical trial to compare their efficacy in measuring the depth of anesthesia.Results Consistency analysis revealed mean differences and standard deviations of-0.18±5.42 and-0.11±6.51 between ESI and BIS for awake and anesthetized states,respectively.Correlation analysis showed a correlation coefficient of 0.92 throughout the operative period.Prediction probability analysis indicated that both ESI and BIS had prediction probabilities of 0.97,effectively predicting anesthesia status.Conclusion ESI and BIS show good equivalence in monitoring depth of anesthesia during clinical surgery,which meet the requirements of clinical anesthesia.

Objective:To find the biomarkers that accurately predict the survival of patients with esophageal squamous cell carcinoma (ESCC).Methods:The immune related genes that were significantly related to the overall survival (OS) of patients with ESCC were screened from The Cancer Genome Atlas (TCGA) database to construct a prognostic risk score model. The prognoses of the high-risk and low-risk groups were compared by Kaplan-Meier method. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve. Tumor tissue samples of 83 patients with pathological diagnosis of ESCC were collected from Anyang Cancer Hospital for external verification. Cox regression analysis was used to comprehensively evaluate the effects of prognostic risk score and various clinical characteristics on OS of patients with ESCC.Results:Seven immune-related genes that were significantly related to survival prognosis were selected from the TCGA database and included in the prognostic risk score model, which were S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2. The 1- and 2-year survival rates of the low-risk group (40 cases) were 94.3% and 82.5%, respectively, while those of the high-risk group (40 cases) were 75.9% and 32.9%, respectively.The prognosis of the high-risk group was worse than that of the low-risk group ( P<0.001). The 83 external validation samples obtained consistent results by using the prognostic risk score model. The prognostic risk score was positively correlated with the content of CD4 + T lymphocytes in ESCC ( rs=0.259, P=0.020), but not correlated with the content of B lymphocytes, CD8 + T lymphocytes, neutrophils, macrophages or dendritic cells ( P>0.05). Conclusions:S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2 were risk genes significantly associated with OS of patients with ESCC. The prognostic risk score was an independent prognostic factor for the OS of patients with ESCC, and it was correlated with the content of CD4 + T lymphocytes in ESCC tissue.

Objective:To find the biomarkers that accurately predict the survival of patients with esophageal squamous cell carcinoma (ESCC).Methods:The immune related genes that were significantly related to the overall survival (OS) of patients with ESCC were screened from The Cancer Genome Atlas (TCGA) database to construct a prognostic risk score model. The prognoses of the high-risk and low-risk groups were compared by Kaplan-Meier method. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve. Tumor tissue samples of 83 patients with pathological diagnosis of ESCC were collected from Anyang Cancer Hospital for external verification. Cox regression analysis was used to comprehensively evaluate the effects of prognostic risk score and various clinical characteristics on OS of patients with ESCC.Results:Seven immune-related genes that were significantly related to survival prognosis were selected from the TCGA database and included in the prognostic risk score model, which were S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2. The 1- and 2-year survival rates of the low-risk group (40 cases) were 94.3% and 82.5%, respectively, while those of the high-risk group (40 cases) were 75.9% and 32.9%, respectively.The prognosis of the high-risk group was worse than that of the low-risk group ( P<0.001). The 83 external validation samples obtained consistent results by using the prognostic risk score model. The prognostic risk score was positively correlated with the content of CD4 + T lymphocytes in ESCC ( rs=0.259, P=0.020), but not correlated with the content of B lymphocytes, CD8 + T lymphocytes, neutrophils, macrophages or dendritic cells ( P>0.05). Conclusions:S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2 were risk genes significantly associated with OS of patients with ESCC. The prognostic risk score was an independent prognostic factor for the OS of patients with ESCC, and it was correlated with the content of CD4 + T lymphocytes in ESCC tissue.

Objective:To investigate the effects of combined exposure of fluorine, arsenic, and fluorine-arsenic on the signaling pathway related protein expression of tumor necrosis factor receptor-related factor 6 (TRAF-6)/nuclear factor κB1(NF-κB1) in a co-culture system of mouse osteoblasts MC3T3-E1 and mouse monocyte macrophage RAW264.7.Methods:MC3T3-E1 cells were co-cultured with RAW264.7 cells after induction with osteogenic inducers. The cells were cultured for 7 days in vitro, and different doses of sodium fluoride (0.0, 0.1, 0.4, 1.6 mmol/L NaF, F), sodium arsenite (0.0, 0.5, 2.5, 12.5 μmol/L NaAsO 2, As) and different doses of fluorine and arsenic were added to the culture medium and cultured for 24 h using factorial design. The expression levels of nuclear factor κB receptor activating factor (RANK), TRAF-6, NF-κB1, T cell activating factor (NFATc1), and tartrate-resistant acid phosphatase (TRAP) protein were detected by Western blotting. Results:When fluorine was used alone, compared with the control group (F 0.0As 0.0, 1.00 ± 0.00), the expressions of RANK, NF-κB1 and TRAP proteins (1.11 ± 0.04, 1.29 ± 0.05, 1.38 ± 0.04, 1.24 ± 0.04, 1.13 ± 0.03, 1.34 ± 0.05, 1.12 ± 0.03, 1.24 ± 0.04, 1.61 ± 0.06) were increased ( P < 0.05); TRAF-6 protein expressions in F 0.1 and F 1.6 groups (1.23 ± 0.04, 1.35 ± 0.03) were increased ( P < 0.05). When arsenic was used alone, compared with the control group (F 0.0As 0.0), the expressions of RANK, TRAF-6, NF-κB1 proteins were increased in As 0.5 group ( P < 0.05), the expressions of RANK and NFATc1 proteins were reduced in As 12.5 group ( P < 0.05). When fluorine was combined with arsenic, at the same dose of fluorine, RANK protein expression in F 0.1As 0.5 group and TRAF-6 protein expression in F 0.1As 12.5, F 0.4As 0.5, F 0.4As 2.5 groups, NF-κB1 protein expression in F 0.1As 0.5 F 0.4As 2.5, F 0.4As 12.5 groups, NFATc1 protein expression in F 0.1As 0.5 and F 0.4As 0.5 groups, TRAP protein expression in F 0.1As 12.5 group were higher than the corresponding fluorine groups alone (F 0.1, F 0.4, P < 0.05), but lower than the sum of fluorine and arsenic alone. At the same dose of arsenic, RANK protein expression in F 0.1As 12.5 group, TRAF-6 protein expression in F 0.1As 12.5 and F 0.4As 2.5 groups, and NF-κB1 protein expression in F 0.1As 12.5, F 0.4As 2.5, F 0.4As 12.5, and F 1.6As 2.5 groups, TRAP protein expression in F 1.6As 2.5 and F 1.6As 12.5 groups were higher than the corresponding arsenic groups alone (As 2.5, As 12.5, P < 0.05), but lower than the sum of fluorine and arsenic alone. Fluorine had a major effect on the expressions of RANK, TRAF-6, NF-κB1, NFATc1, and TRAP proteins ( F=3.41, 341.73, 66.01, 56.49, 147.40, P < 0.05); arsenic also had a main effect on all protein indicators ( F=686.71, 174.96, 107.32, 235.80, 331.37, P < 0.05); the combined effect of fluorine and arsenic had an interaction effect on each protein indicator ( F=50.39, 234.94, 116.72, 67.77, 36.56, P < 0.05). Conclusions:In the co-culture system of MC3T3-E1 and RAW264.7 cells, fluorine can activate TRAF-6-mediated expression of NF-κB1 signaling pathway-related proteins, thereby promoting osteoclast differentiation; the effects of arsenic on the expression of related proteins are not completely consistent. The interaction of fluorine and arsenic exposure on TRAF-6-mediated expression of NF-κB1 signaling pathway-related proteins is mainly antagonistic.

Objective To investigate the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in Chinese patients with ischemic stroke . Methods In this multi‐center study ,2 310 continuously inpatients with ischemic stroke diagnosed in 20 stroke screening and prevention project base hospitals from June 2015 to M ay 2016 were enrolled . Carotid ultrasonography and transcranial color‐coded sonography or transcranial Doppler were performed in all patients to confirm the presence of cerebral artery stenosis or occlusion . According to the distribution of lesions ,the subjects were divided into 2 groups :the simple intracranial artery stenosis group and the simple extracranial artery stenosis group . T he difference of risk factors between the two groups was compared . Results Of the 2 310 patients with ischemic stroke ,1 516 ( 65 .6% ) had simple intracranial artery stenosis and 794 ( 34 .4% ) had simple extracranial artery stenosis . T he incidence of anterior circulation artery stenosis was higher in the group of intracranial artery stenosis than that in the extracranial artery stenosis group ( 68 .1% vs 48 .7% , P ＜0 .001) . Posterior circulation artery stenosis and combined anterior with posterior circulation artery stenosis were more common in patients with extracranial artery stenosis group than those in intracranial artery stenosis group ( 36 .4% vs 22 .1% ,14 .9% vs 9 .8% ;all P ＜0 .001) . Univariate analysis of risk factors for stroke showed that patients with intracranial arterial stenosis had a higher prevelence of hypertension , diabetes ,obesity ,and family history of stroke ,and their systolic blood pressure ,diastolic blood pressure , body mass index ( BM I) ,fasting blood‐glucose ,glycosylated hemoglobin ,triacylglycerol ,total cholesterol , and low‐density lipoprotein cholesterol were significantly higher than those in the extracranial arterial stenosis group ( all P ＜ 0 .05 ) . T he proportion of elderly ( ≥ 65 years old ) ,male and smokers in the extracranial arterial stenosis group was significantly higher than that in the intracranial arterial stenosis group ( all P ＜0 .05) . Multivariate logistic regression analysis showed that elderly ( ≥65 years old) ,male , and smoking history were independent risk factors for extracranial arterial stenosis ( OR＝ 2 .012 ,1 .637 , 1 .325 ,respectively ;all P ＜0 .05) . While hypertension ,diabetes ,less physical activity ,and high BM I levels were independent risk factors for simple intracranial arterial disease ( OR ＝ 1 .301 ,1 .252 ,1 .248 ,1 .030 , respectively ;all P ＜0 .05) . Conclusions There are significant differences in the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in patients with ischemic stroke in China .

OBJECTIVETo explore the association between rs659366 polymorphisms and the outcomes of patients after surgery for colorectal cancer.

METHODSThe study was conducted among a cohort of 501 patients with primary colorectal cancer who had surgery in Sichuan Cancer Hospital during March 2010 and July 2013. The outcomes of the patients were followed up. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect rs659366 genotypes. The log-rank test was performed to analyze the effects of clinical features on patients' outcomes. The correlation between rs659366 polymorphisms and the outcomes of patients was analyzed using the Cox proportional hazard model.

RESULTSIn this study, the median of follow-up time was 44.23(0.13-78.53)months, and 101 out of 501 (20.2%) patients failed to follow-up. The log-rank test showed the tumor site, TNM stage, vascular invasion, perineural invasion and the preoperative carcino-embryonic antigen(CEA) level were significantly associated with the outcome of colorectal cancer (<0.05 or <0.01). The overall survival rate of patients with AA, GA and GG genotypes were 62.7%, 69.9% and 75.5%, respectively. Multivariate analysis according to Cox proportional hazard model taking the GG genotype as the reference indicated that the AA genotype increased risks for survival of patients (=1.823); under the dominant genetic model taking GG genotype as reference, GA+AA genotypes increased risks for the poorer outcomes of patients (=1.498); the addictive genetic model showed that allele A increased the hazard for the poorer outcomes (=1.787).

CONCLUSIONSThe rs659366 polymorphisms are significantly associated with the outcome of patients with colorectal cancer.

ARNTL Transcription Factors ; deficiency ; metabolism ; Animals ; Cyclic AMP ; metabolism ; Gluconeogenesis ; Glucose ; biosynthesis ; HEK293 Cells ; Histone Deacetylases ; metabolism ; Humans ; Liver ; metabolism ; Mice ; Mice, Knockout

Objective To propose a new suggestion for the clinical downstaging of nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT) without changing the current T,N,and M staging system.Methods We reviewed the records of 536 NPC patients treated in Sun Yat-Sen University Cancer Center from January 2002 to December 2006.The Kaplan-Meier method was used to calculate the disease-specific survival (DSS) rate,and the log-rank test was used for survival difference analysis.The Cox regression model was used to calculate the hazard ratio (HR) of each subset.ResultsAccording to the 7th edition of UICC/AJCC staging system,the 5-year DSS rates of stage Ⅰ-Ⅲ patients (except T3N2M0) were all more than 85%(P>0.05),those of stage ⅣA and ⅣB patients were 71.8% and 46.2%,respectively (P=0.171),and that of stage ⅠVC patients was only 24.0%.In stage Ⅲ,the 5-year DSS rate of non-T3N2M0 patients (91.5%) was significantly higher than that of T3N2M0 patients (78.6%)(P=0.042),but there was no significant difference in DSS between T3N2M0 patients and stage ⅣA and ⅣB patients.Based on the above results,new stage Ⅰ included T1-3N0-1M0 and T1-2N2M0,new stage Ⅱ included T3N2M0,T4N0-2M0,and TxN3M0,and new stage Ⅲ included TxNxM1.The 5-year DSS rates of new stage Ⅰ,Ⅱ,and Ⅲ patients were 93.3%,72.7%,and 24.0%,respectively (P=0.000).Compared with new stage Ⅰ patients,new stage Ⅱ and Ⅲ patients had HRs of 4.01 and 16.76,respectively,for 5-year DSS.Conclusions In the era of IMRT,the new clinical staging system (stages Ⅰ,Ⅱ,and Ⅲ) helps with prognostic evaluation and clinical treatment.