[Association of urinary cadmium level with body mass index and body circumferences among older adults over 65 years old in 9 longevity areas of China].

Objective: To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China. Methods: Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 µg/g·creatinine, middle:0.77-1.69 µg/g·creatinine, high:≥1.69 µg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model. Results: The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) µg/g·creatinine, and the BMI was (22.70±3.82) kg/m2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 µg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI (Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference (Plinear<0.001), hip circumference (Plinear<0.001), and calf circumference (Plinear<0.001). Conclusion: Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

[Association of sleep duration and physical exercise with dyslipidemia in older adults aged 80 years and over in China].

Objective: To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China. Methods: The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia. Results: The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% (HR=1.22, 95%CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% (HR=0.67, 95%CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion: Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

[The mechanism by which hsa_circRNA_103124 highly expressed in peripheral blood of patients with active Crohn's disease regulates macrophage differentiation, pyroptosis and inflammation].

Objective: To investigate the role and related mechanism of the highly expressed circular RNA molecule 103124 (hsa_circRNA_103124) in macrophage differentiation, pyroptosis and inflammation in peripheral blood mononuclear cells (PBMC) of patients with active Crohn's disease (CD). Methods: Patients with active CD (CD group) admitted to the Affiliated Suzhou Hospital of Nanjing Medical University from April to September 2018 and healthy people (control group) from the physical examination center of the hospital from July to October 2018 were retrospectively selected. The levels of hsa_circRNA_103124 and Toll-like receptor 4 (TLR4) in PBMC of the two groups were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Tohoku hospital pediatrics-1 (THP1) cell line was used as a model for the study of hsa_circRNA_103124 regulating macrophage differentiation. Lentivirus infection was used to construct hsa_circRNA_103124 overexpressed or down-regulated THP1 cells to induce macrophage-like differentiation. According to the expression level of hsa_circRNA_103124, THP1 cell lines were divided into the following four groups: pLC5-ciR was overexpression control group; hsa_circRNA_103124 OE was the overexpression group; ShRNActrl was down-regulated expression control group; hsa_circRNA_103124 ShRNA was the down-regulated expression group. Flow cytometry was used to detect levels cluster of differentiation (CD) 68, CD80, interleukin (IL)-6, tumor necrosis factor α (TNF-α) and reactive oxygen species (ROS). The expression levels of IL-6, TNF-α, IL-1ß, TLR4 and myeloid differentiation factor 88 (MyD88) were detected by RT-qPCR. The levels of gasdermin D (GSDMD), IL-18 and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) were determined by immunofluorescence and RT-qPCR. Pearson correlation analysis was used to analyze the correlation between the abundance of hsa_circRNA_103124 and TLR4 expression level or Crohn's disease activity index (CDAI). Results: A total of 50 patients were included in the CD group, including 36 males and 14 females, aged (35±10) (19-64) years. A total of 30 subjects were included in the control group, including 22 males and 8 females, aged (38±9) (24-64) years. hsa_circRNA_103124 [(0.009±0.016) vs (0.003±0.002), P=0.042] and TLR4 [(0.005±0.003) vs (0.001±0.001), P<0.001] were all upregulated in the PBMC of patients in the CD group, compared with the control group. And hsa_circRNA_103124 was positively correlated with TLR4 (r=0.40, P=0.004). hsa_circRNA_103124 level was positively correlated with CDAI (r=0.32, P=0.024). The expression of CD68 (P=0.002) and CD80 (P<0.001) were enhanced. hsa_circRNA_103124 promoted production of ROS and the expression of IL-6, TNF-α, IL-1ß, TLR4, MyD88, GSDMD, IL-18 and NLRP3 in macrophage-like M1 differentiated THP1 cells (all P<0.05). Conclusion: High expresion of hsa_circRNA_103124 in PBMC of patients with active CD may promote macrophage M1 differentiation, pyroptosis and inflammation through enhancing the expression of TLR4, MyD88, NLRP3 and GSDMD.

Regulation of epidermal growth factor receptor tyrosine kinase inhibitor resistance via Ambra1-mediated autophagy in non-small cell lung cancer.

To explore the molecular mechanisms related to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) resistance, along with potential therapeutic targets and strategies. The autophagy and Beclin 1 regulator 1 (Ambra1) short hairpin ribonucleic acid (shRNA) lentivirus vector and Ambra1 overexpression plasmid, constructed with a plasmid cloning deoxyribonucleic acid (pcDNA) 3.1 vector, were used to down-regulate and up-regulate Ambra1 expression in the human lung adenocarcinoma erlotinib-resistant cell line (PC9/ER), respectively, as well as to screen stable transgenic cell lines. The IC50 of Erlotinib in these cell lines were measured to determine their resistance status. The real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure messenger ribonucleic acid (mRNA) expression of resistance-related genes like multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 1 (MRP1), and lung drug-resistant-related protein (LRP). Western blot was performed to analyze the protein expressions of the autophagy-related genes Beclin 1, LC3II/I, and p62. Each stable transgenic line formed a tumor under the skin in nude mice; the mice with subcutaneous tumorigenesis of PC9/ER cells and shAmbra1-PC9/ER cells were subsequently treated with rapamycin (RAPA) and chloroquine (CQ), respectively. The mRNA expressions of MDR1, MRP1, and LRP in each tumor tissue sample were detected by qRT-PCR. The protein expressions of adenosine monophosphate-activated protein kinase (AMPK), phosphorylated-AMPK (p-AMPK), forkhead box O3 (FoxO3a), and phosphorylated forkhead box O3 (p-FoxO3a) in the AMPK/FoxO3a signaling pathway were analyzed via Western blot. The qRT-PCR result revealed that the level of Ambra1 in EGFR-TKI-resistant cells had increased. This was further exacerbated by the overexpression of Ambra1 and was reduced after its inhibition. Additionally, Ambra1 upregulated the mRNA expression of drug-resistant genes and the expression of autophagy-related proteins. Subcutaneous tumorigenesis of RAPA-treated shAmbra1-PC9/ER cells resulted in increased expression of drug resistance-related genes and a concomitant decrease in p-AMPK and increase in p-FoxO3a. The results revealed that Beclin-1/ß-actin, p62/ß-actin, and LC3II/I in the model group were all significantly increased compared to the control group, with P<0.05. Compared to the model group, Beclin-1/ß-actin, p62/ß-actin, and LC3II/I were all significantly higher in the pcDNA-Ambra1 group, with P<0.05. Compared to the model group, Beclin-1/ß-actin, p62/ß-actin, and LC3II/I were all significantly decreased in the shAmbra1 group, with P<0.05. Thus, these data suggest that Ambra1 promotes cellular autophagy. In addition, subcutaneous tumorigenesis of CQ-treated shAmbra1-PC9/ER cells resulted in reduced expression of drug resistance-related genes, and a concomitant increase in p-AMPK and decrease in p-FoxO3a. The results of this study revealed that Ambra1-mediated autophagy regulated EGFR-TKI resistance in NSCLC, most probably through the AMPK/FoxO3a signaling pathway.

[Study on the status of turnover intention and its influencing factors of 382 hemato-oncology nurses].

Objective: To explore the status of turnover intention and its influencing factors of hemato-oncology nurses. Methods: From September to November 2021, the convenience sampling method was used to select 382 hemato-oncology nurses from 8 tertiary grade A general hospitals in Shandong Province. The general information questionnaire, the Chinese Nurses' Work Stressor Scale, the Psychological Capital Questionnaire and the Turnover Intention Questionnaire were used to investigate the general situation, occupational stress, psychological capital and turnover intention of the objects. The correlations between the turnover intention, occupational stress and psychological capital of the objects were analyze by Pearson correlation. And the multiple linear regression was used to analyze the influencing factors of turnover intention. A structural equation model was used to analyze the effect path of occupational stress and psychological capital on turnover intention. Results: The total turnover intention score of hemato-oncology nurses was (14.25±4.03), with the average item score of (2.38±0.67). The occupational stress score of hemato-oncology nurses was (71.57±14.43), and the psychological capital score was (91.96±15.29). The results of correlation analysis showed that the turnover intention of hemato-oncology nurses was positively correlated with occupational stress, and was negatively correlated with psychological capital (r=0.599, -0.489, P<0.001). Multiple linear regression analysis showed that married (ß=-0.141), psychological capital (ß=-0.156) and occupational stress (ß=0.493) were the influencing factors of turnover intention of hemato-oncology nurses (P<0.05). The path analysis of structural equation model showed that the direct effect of occupational stress on turnover intention of hemato-oncology nurses was 0.522, and the intermediary effect of psychological capital on turnover intention was 0.143 (95%CI: 0.013-0.312, P<0.05), accounting for 21.5% of the total effect. Conclusion: The turnover intention of hemato-oncology nurses is at a high level, hospital and administrators should focus on the psychological state of unmarried nurses. By improving the psychological capital of nurses, to reduce occupational stress and turnover intention.

[The diagnostic and evaluation value of plasma interleukin 9 in the mucosal healing in patients with inflammatory bowel disease treated with biological agents].

Objective: To investigate the diagnostic and evaluation value of plasma interleukin 9 (IL9) in the mucosal healing (MH) in patients with inflammatory bowel disease (IBD) treated with biological agents. Methods: Cohort study. IBD patients (137 cases) treated in the Affiliated Suzhou Hospital to Nanjing Medical University (Suzhou Municipal Hospital) from September 2019 to January 2022 were prospective selected. Each patient was treated with biological agents [Infliximab (IFX, 56 cases), Adalimumab (ADA, 20 cases), Ustekinumab (UST, 18 cases), Vedolizumab (VDZ, 43 cases)]. According to different therapeutic drugs, the IFX, ADA, UST, and VDZ group were divided. Clinical symptoms, inflammatory indicators and imaging examinations etc. were evaluated every 8 weeks, and the degree of MH was evaluated by endoscopy at the 54th week. The expression of plasma IL9 was detected by ELISA after initial enrollment (W 0) and 8 weeks of biological treatment (W 8). Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of IL9 for MH. Select the cut off value for the optimal ROC threshold based on the highest value of the Youden index. Spearman's rank correlation was used to analyze the correlation between IL9 and Simple Endoscopic Score for CD (SES-CD) and Mayo Endoscopic Score (MES), so as to evaluate the predictive value of IL9 for MH in IBD patients treated with biologic agents. Results: Among the 137 patients, there were 97 Crohn's disease (CD) patients, 53 males and 44 females, aged (31.6±10.3) years (18-60 years). There were 40 ulcerative colitis (UC) patients, 22 males and 18 females, aged (37.5±14.7) years (18-67 years). Among the CD patients, 42 cases (43.3%) achieved MH on endoscopy at the 54th week, and 60 patients (61.9%) achieved clinical remission. Among the UC patients, 22 cases (55.0%) achieved MH and 30 cases (75.0%) achieved clinical remission. At W 0, the relative expression of IL9 in patients in IBD patients who achieved MH after 54 weeks of biological treatment was lower than that in the non-MH patients [x¯±s, (127.42±34.43) vs (146.82±45.64) ng/L, (113.01±44.88) vs (146.12±48.66) ng/L, respectively, both P<0.05]. At W 8, the relative expression of IL9 in the MH group was lower than that in the non-MH patients (both P<0.05). The relative expression of IL9 in the MH patients after IFX treatment was lower than that in the non-MH group (P<0.05). There was no significant difference among the other groups between MH and non-MH patients (all P>0.05). IL9 at W 8 showed high value in predicting MH in IBD [CD patients: area under curve (AUC)=0.716(95%CI: 0.616-0.817, P<0.001), sensitivity and specificity were 80.77%(95%CI:67.64%-88.45%) and 48.89%(95%CI: 35.53%-64.47%), respectively; UC patients: AUC=0.821, sensitivity and specificity were 77.78% and 72.73%, respectively]. At W 8, the cut off values for CD and UC patients were IL9>80.77 ng/L and IL9>77.78 ng/L, respectively. IL9 was positively correlated with endoscopic MH score parameters [M(Q1,Q3),SES-CD: 3.0(8.5, 18.5); MES: 2.0(1.0, 3.0)] (r=0.55, 0.72, respectively, both P<0.001) at W8. Conclusion: The plasma IL-9 at the week 8 after biological agents treatment can be used to diagnose and evaluate the MH of patients with IBD.

[The incidence and time distribution of early transient intraocular pressure elevation after penetrating canaloplasty].

Objective: To report the incidence and time distribution of early transient intraocular pressure (IOP) elevation after penetrating canaloplasty. Methods: Retrospective case series study. Data of patients treated by penetrating canaloplasty for glaucoma in the Eye Hospital of Wenzhou Medical University from June 2015 to March 2020 were collected. Early transient IOP elevation was defined as an increase of IOP to over 21 mmHg on the first week to the third month after surgery followed by a decrease to 21 mmHg or less within 3 months. Main outcome measures included IOP, quantity of medication use, the occurrence time and duration of IOP elevation. Generalized estimating equations were used for statistical analysis, and measurement data with non-normal distribution was represented as M (Q1, Q3). Results: A total of 277 patients (315 eyes) achieved 360-degree catheterization of the canal successfully, and 299 eyes (94.9%) completed the postoperative 6-month follow-up. Thirty-four eyes (10.8%) had persistently high IOP, so the surgical treatment failed in them. Consequently, 234 patients (265 eyes) were enrolled in the analyses, including 161 males (184 eyes) and 73 females (81 eyes). The median age was 42 (26, 54) years, the mean preoperative IOP was (37.7±11.1) mmHg, and the mean number of drugs used was 3 (2, 4). The incidence of early transient IOP elevation was 43.0% (114/265) in all enrolled eyes, 42.7% (35/82) in eyes with primary open angle glaucoma, 37.8% (17/45) in eyes with primary angle closure glaucoma, 27.7% (13/47) in eyes with congenital glaucoma and 53.8% (49/91) in eyes with secondary glaucoma. The IOP began to increase on the first to fourth week in 91.2% (104/114) of eyes with early transient IOP elevation and reached the peak [21.3 mmHg to 54.8 mmHg; mean, (32.4±8.2) mmHg] in 88.6% (101/114) on the first to fifth week after surgery. The IOP elevation lasted for no more than 4 weeks in 69.3% (79/114) of eyes. Conclusions: Over 40.0% of patients with penetrating canaloplasty may experience postoperative transient IOP elevation. The incidence is relatively high in secondary glaucoma but low in congenital glaucoma. Most of the elevations and peak IOP occur within 1-4 weeks after surgery.

[Research advances on the promotive healing effect of hydrogel dressing for diabetic foot wound].

In recent years, the number of diabetic patients has gradually increased, and the number of patients with diabetic foot has also increased. Diabetic foot has a high rate of disability and death, seriously affects the patients' quality of life, shortens life expectancy, and brings heavy social burden. The current treatment methods for diabetic foot are insufficient. The concepts and methods of tissue engineering provide new thoughts and means for the treatment of diabetic foot. This article introduces the pathogenesis of diabetic foot wounds, the factors leading to non-healing of diabetic foot, the applications of functional hydrogel dressings in the treatment of diabetic foot and their technical methods of functional hydrogel dressings for treating skin wounds in diabetic animals, and the future development direction of functional hydrogel dressing for treating diabetic foot wounds is prospected.

[Effects of positive end-expiratory pressure setting of mechanical ventilation guided by esophageal pressure in the treatment of patients with traumatic craniocerebral injury combined with acute respiratory distress syndrome].

Objective: To investigate the effects of positive end-expiratory pressure (PEEP) setting of mechanical ventilation guided by esophageal pressure in the treatment of patients with traumatic craniocerebral injury combined with acute respiratory distress syndrome (ARDS). Methods: The retrospective cohort study was conducted. From June 2016 to June 2018, 55 patients with traumatic craniocerebral injury combined with ARDS who met the inclusion criteria were admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University. According to PEEP setting method, 28 patients were allocated to esophageal pressure group (17 males and 11 females, aged (40±13) years) and 27 patients were allocated to PEEP-fractional concentration of inspired oxygen (FiO2) table group (18 males and 9 females, aged (38±10) years). Patients in the 2 groups were treated with mechanical ventilation guided by lung protective ventilation strategy, and the optimal PEEP at 0 (immediately), 24, 48, and 72 h after treatment was determined according to esophageal pressure and PEEP-FiO2 table, respectively. The mechanical ventilation parameters in the 2 groups were adjusted according to the optimal PEEP. The transpulmonary end-expiratory pressure, pulmonary compliance, oxygen index, central venous pressure, mean arterial pressure, and intracranial pressure at 24, 48, and 72 h after treatment were recorded. Data were statistically analyzed with analysis of variance for repeated measurement, chi-square test, independent sample t test, and Bonferroni correction. Results: The optimal PEEP of patients in esophageal pressure group at 0, 24, 48, and 72 h after treatment was (12.4±3.9), (11.2±3.5), (13.4±2.6), and (13.2±3.6) cmH2O (1 cmH2O=0.098 kPa), respectively, which was significantly higher than (8.2±2.5), (7.4±2.2), (8.3±2.3), and (8.5±2.5) cmH2O in PEEP-FiO2 table group, respectively (t=4.702, 4.743, 7.849, 5.623, P<0.01). The transpulmonary end-expiratory pressure and pulmonary compliance at 24, 48, and 72 h after treatment and oxygen index at 48 and 72 h after treatment of patients in esophageal pressure group were significantly higher than those in PEEP-FiO2 table group (t=17.852, 20.586, 19.532, 4.752, 5.256, 7.446, 2.342, 4.178, P<0.05 or P<0.01). The central venous pressure of patients in esophageal pressure group at 24, 48, and 72 h after treatment was significantly higher than that in PEEP-FiO2 table group (t=12.632, 5.247, 8.994, P<0.01), and there was no statistically significant difference in mean arterial pressure of patients between the 2 groups at 24, 48, and 72 h after treatment (P>0.05). The intracranial pressure of patients in esophageal pressure group was higher than that in PEEP-FiO2 table group at 24, 48, and 72 h after treatment, but there was no statistically significant difference between the 2 groups (P>0.05). Conclusions: For patients with traumatic craniocerebral injury combined with ARDS, the optimal PEEP can be set under the guidance of esophageal pressure method, and the mechanical ventilation parameters adjusted according to the optimal PEEP can improve lung compliance and accelerate recovery of lung function more effectively, with no adverse effect in mean arterial pressure and intracranial pressure.

[Alteration on hepatocyte nuclear factor 1α expressions and significance in the process of occurrence and development of liver inflammation and fibrosis in patients with chronic hepatitis B].

Objective: To investigate the relationship between the expression of hepatocyte nuclear factor-1 α (HNF-1α) and the occurrence and development of liver inflammation and fibrosis in liver tissues of patients with chronic hepatitis B. Methods: Sixty-four patients with chronic hepatitis B who were diagnosed and treated in our hospital from 2011 to 2018 were selected. All patients underwent ultrasound-guided aspiration liver biopsy. The pathological results of liver biopsy were collected for inflammation grading and fibrosis staging. The liver puncture biopsies was collected by paraffin sectioning. The expression of HNF1α in the liver tissue was detected by immunohistochemical staining. Mantel-Haenszel χ(2) test was used for bidirectional ordered grouping data, and Spearman's rank-correlation test was used for rank correlation analysis. Results: There were varying degrees of inflammatory necrosis and fibrosis in the liver tissues of patients with chronic hepatitis B. There was a linear relationship between the expression of HNF1α and the level of inflammation in liver tissues (χ (2)(MH) = 40.70, P < 0.05). The expression of HNF1α in liver tissues of patients with chronic hepatitis B was decreased with the increase of liver inflammation. The expression intensity of HNF1α was negatively correlated with the inflammation grade (r(s) = -0.815, P < 0.05). There was a linear relationship between the expressions of HNF1α and the degree and stage of liver fibrosis (χ (2)(MH) = 31.95, P < 0.05). The expression level of HNF1α in liver tissue was gradually decreased with the aggravation of liver fibrosis. The expression intensity of HNF1α was negatively correlated with fibrosis stage (r(s) = -0.713, P < 0.05). Conclusion: HNF1α is closely related to the occurrence and development of liver tissue inflammation and fibrosis, and is expected to be a sensitive indicator for evaluating the level of liver tissue inflammation and fibrosis in patients with chronic hepatitis B. In addition, its down-regulation may be involved in the process of occurrence and development of liver inflammation and liver fibrosis, and may become a new target for the treatment of chronic hepatitis B.

[Layer-specific strain assessment on left ventricular function before and after PCI in patients with ST segment elevation myocardial infarction].

Objective: To evaluate the changes of left ventricular function in patients with ST segment elevation myocardial infarction (STEMI) before PCI and within 24 hours after PCI by layer-specific strain, and to explore the value of this new assessment method for quantitative monitoring on the myocardial function in STEMI patients. Methods: A total of 40 patients with acute anterior wall myocardial infarction, who underwent PCI in Affiliated Hospital of Jiangsu University during July 2017 to July 2018, were included in this prospective cohort study. According to the symptom to balloon time (STB), the patients were divided into STB ≤6 hours group (26 cases) and STB 6-12 hours group (14 cases). Echocardiography was performed before, immediately, 3 hours and 24 hours after PCI. Echocardiographic indexes including endocardial myocardial longitudinal strain (LS-endo), 18-segment full-thickness myocardial longitudinal strain (LS) of left ventricle and left ventricular global longitudinal strain (GLS) were measured. The mean LS-endo and LS values of myocardial segments in infarcted area (IALS-endo, IALS) and the mean LS-endo and LS values of myocardial segments in non-infarcted area (NIALS-endo, NIALS) were calculated. Results: There were 34 males and 6 females in this cohort and age was (62±10) years. In STB≤6 hours group, the IALS-endo value ((13.7±4.9)% vs. (10.0±2.7)%, P<0.05) and NIALS-endo value ((17.0±2.9)% vs. (14.6±2.9)%, P<0.05) were significantly higher at 24 hours after PCI than those before PCI. In the group of STB 6-12 hours, IALS-endo decreased immediately after PCI ((6.7±3.3)% vs. (11.9±6.5)%, P<0.05), and there was a rising trend at 3 hours after PCI (P>0.05). At 24 hours after PCI, the index was higher than that immediately after PCI ((13.6±8.4)% vs. (6.7±3.3)%, P<0.05). The NIALS-endo value was significantly higher at 24 hours after PCI than that before PCI ((17.1±2.1)% vs. (14.5±3.2)%, P<0.05). In the STB 6-12 hours group, the decrease rate of IALS-endo immediately after PCI was higher than that in the STB ≤6 hours group (93% (13/14) vs. 35% (9/26), P<0.001). In STB ≤6 hours group, the NIALS value at 24 hours after PCI was higher than that before PCI (P<0.05), and there was no significant difference in IALS, NIALS and GLS at other time points (P>0.05). Conclusions: Layered LS is superior to full-thickness LS and GLS in evaluating left ventricular function in STEMI patients. LS measured by echocardiography can continuously and quantitatively evaluate the changes of left ventricular myocardial function in STEMI patients before and after PCI.

[Analysis of prognosis and pregnancy outcomes of fertility-preserving treatment for patients with stage â a, grade 2 endometrial cancer].

Objective: To investigate the efficacy and pregnancy outcome of fertility-preserving treatment for patients with stage Ⅰa, grade 2 endometrial cancer (EC). Methods: Clinical data was retrospectively collected for EC or atypical endometrial hyperplasia (AEH) patients treated in Peking University People's Hospital, Foshan First People's Hospital of Guangdong Province and First Affiliated Hospital of Sun Yat-sen University, from 2010 to 2019. Inclusion criteria for fertility-preserving treatment included: (1) Age ≤45 years. (2) EC with histological differentiation of G(1), G(2) or endometrial AEH. (3) EC disease should be stage Ⅰa, confined to the endometrium without myometrial invasion, lymph node or extrauterine metastasis. Treatment regimen: patients were given oral progestin therapy and endometrial pathology was evaluated every three months. Patients were divided into three groups as G(2) EC group, G(1) EC group and AEH group based on the histological differentiation. Oncological and pregnancy outcomes were compared among them. Results: (1) Totally 57 eligible patients were included in this study, including 11 cases with G(2) EC, 22 cases with G(1) EC, and 24 cases with AEH. (2) Oncological outcome: among the three groups of G(2) EC, G(1) EC and AH, the complete remission rates (9/11, 91% and 96%, respectively) and recurrence rates (3/9, 30% and 22%, respectively) were not significantly different (all P>0.05). Median remission time was significantly longer in the G(2) EC group than those in the other two groups (8, 6 and 4 months; P=0.046). Among 9 G(2) EC patients who recurred after complete remission, three patients relapsed at 7, 18 and 53 months, respectively. All 3 patients chose fertility-sparing treatment again, and all achieved complete remission after retreatment. (3) Pregnancy outcome: among the three groups, the assisted reproduction technology rates (4/8, 5/18 and 36%, respectively) and pregnancy rates (6/8, 5/18 and 36%, respectively) had no significant difference (P>0.05). However, time interval to pregnancy was shorter in G(2) EC patientsthan the other two groups (4, 9 and 22 months, respectively; P=0.006). Conclusions: Fertility-preserving treatment for patients with stageⅠa, G(2) endometrial cancer, may obtain a relatively high remission rate and an acceptable pregnancy rate. However, further exploration is needed due to the limited number of cases.

IL-6 stimulates lncRNA ZEB2-AS1 to aggravate the progression of non-small cell lung cancer through activating STAT1.

OBJECTIVE: To illustrate the role of interleukin 6 (IL-6) in the progression of non-small cell lung cancer (NSCLC) via activating STAT1. PATIENTS AND METHODS: The level of IL-6 mRNA in 48 paired NSCLC tissues and matched normal ones was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Kaplan-Meier curves were depicted for assessing the overall survival of NSCLC patients with high or low level of IL-6 mRNA. Subsequently, the ZEB2-AS1 level in A549 cells treated with different doses of IL-6 for different time points was determined. After A549 cells were treated with different doses of IL-6, wound closure assays were performed to assess the migration of cells. Protein levels of pSTAT1 and STAT1 in IL-6-treated A549 cells were detected by Western blot. The regulatory effect of STAT1 on IL-6-induced migration of A549 cells was also evaluated. The interaction between ZEB2-AS1 and STAT1 was explored through Chromatin Immunoprecipitation (ChIP) assay. Finally, the role of ZEB2-AS1/STAT1 axis in regulating NSCLC cells was investigated through rescue experiments. RESULTS: Our results indicated that IL-6 was upregulated in NSCLC tissues and cancer cell lines. NSCLC patients with T3-T4 or accompanied with lymphatic metastasis had a higher IL-6 abundance than those with T1-T2 or without metastatic foci. The worse prognosis was identified in NSCLC patients with high expression of IL-6 compared to those with low expression. ZEB2-AS1 showed dose-dependent and time-dependent increase in IL-6-treated A549 cells. IL-6 treatment gradually enhanced the migration ability of A549 cells in a dose-dependent manner. In IL-6-treated A549 cells, protein level of pSTAT1 was remarkably upregulated, and knockdown of STAT1 significantly reversed the promotive effect of IL-6 on migration ability of A549 cells. The results of ChIP assay verified the interaction between ZEB2-AS1 and STAT1. In addition, ZEB2-AS1 could reverse the regulatory effect of STAT1 on the migration ability of A549 cells. CONCLUSIONS: IL-6 was upregulated in NSCLC and accelerated the progression of NSCLC via activating STAT1/ ZEB2-AS1.

[Association between plasma HDL-C levels and coronary artery severity and impact on outcomes of patients underwent percutaneous coronary intervention].

Objective: To analyze the association between plasma high-density lipoprotein cholesterol (HDL-C) levels and the severity of coronary artery disease, and to evaluate the impact of HDL-C levels on long-term outcomes in patients underwent percutaneous coronary intervention (PCI). Methods: A total of 10 458 consecutive patients underwent PCI from January 2013 to December 2013 at Fuwai hospital were enrolled in this study. Patients were divided into three groups according to HDL-C tertiles: low HDL-C group (HDL-C≤0.89 mmol/L, n=3 525), median HDL-C group (HDL-C>0.89-1.11 mmol/L, n=3 570) and high HDL-C group (HDL-C>1.11 mmol/L, n=3 363). SYNTAX score was used to evaluate the severity of coronary artery disease, linear regression was used to analyze the relationship of HDL-C and SYNTAX score. Kaplan-Meier survival analysis was used to compare the outcomes among the three groups. Multivariate Cox regression was used to define the potential associations of HDL-C and outcomes. Results: The HDL-C level was (1.03±0.28) mmol/L and the SYNTAX score was 11.7±8.1. Patients were older, proportion of female, stable angina pectoris, successful PCI and left ventricular eject fraction value were higher, while incidence of diabetes mellitus was lower, hyperlipidemia, old myocardial infraction, smoking history and left main and three vessels disease were lower in high HDL-C group (all P<0.05). Patients in high HDL-C group also had the lowest SYNTAX score (12.2±8.4 vs. 11.7±8.1 vs. 11.2±7.8, P<0.001). Both univariate and multivariate linear regression analysis showed that HDL-C was negatively associated with SYNTAX score, e.g. Univariate analysis: ß=-0.046, P<0.001; Multivariate analysis: ß=-0.058, P=0.001. And 10 400 (99.4%) patients completed 2-year follow up. At 2-year follow-up, there were no difference in all-cause death, cardiac death, myocardial infarction, revascularization, stroke, major adverse cardiovascular and cerebral events (MACCE) and stent thrombosis among three groups (P for trend>0.05), while patient in high HDL-C group experienced the highest BARC type 2 bleeding events (P for trend=0.018). Multivariate Cox regression analysis showed that HDL-C level was not an independent risk factor of 2-year adverse ischemia events (P>0.05) and 2-year bleeding events (P>0.05). Conclusion: In patients underwent PCI, plasma HDL-C level is negatively associated with SYNTAX score, but not an independent risk factor of ischemic and bleeding events post PCI.

Serum miR-133 as a novel biomarker for predicting treatment response and survival in acute myeloid leukemia.

OBJECTIVE: MiRNA-133 (miR-133) has been identified as a tumor suppressor in many types of human cancers. However, its clinical significance in acute myeloid leukemia (AML) is still unclear. The purpose of this study was to assess the correlation of miR-133 expression with clinical variables and prognosis in AML patients. PATIENTS AND METHODS: Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) was performed to analyze blood samples from 145 patients with AML and 70 healthy volunteers. RESULTS: Decreased miR-133 levels were observed in AML patients and closely associated with aggressive clinical parameters, such as white blood cells and poor Karyotype subgroups. In addition, receiver operator characteristic (ROC) analysis revealed that serum miR-133 could efficiently screen AML patients from normal controls with high sensitivity and specificity. More interestingly, serum miR-133 levels were remarkably elevated in the patients with favorable response after standard induction chemotherapy or achieving a complete remission. Furthermore, patients in the high serum miR-133 expression group had better overall survival and recurrence-free survival than those in the low serum miR-133 expression group. Meanwhile, multivariate analysis identified serum miR-133 as a significant independent predictor for survival. CONCLUSIONS: Low miR-133 expression was a common event and correlated with worse clinical outcome in AML, suggesting that serum miR-133 might serve as a promising indicator for the early detection and prognosis evaluation of AML.

[Impact of short-time anticoagulant therapy after selective percutaneous intervention on prognosis of patients with coronary artery disease].

Objective: To observe the safety and impact of short-term anticoagulant therapy on prognosis after selective percutaneous coronary intervention (PCI) in patients with coronary artery disease. Methods: From January 2013 to December 2013, 9 769 consecutive patients underwent selective PCI in Fuwai Hospital were retrospectively included in this study. Patients were divided into two groups, including non-post-PCI anticoagulant therapy group and low-dose and short-time post-PCI anticoagulant therapy group (enoxaparin 0.4 ml/12 h or fondaparinux 2.5 mg/day by subcutaneous injection for 2-3 days after PCI). All patients were evaluated at 30 days, 180 days and 12 months for major adverse coronary and cerebral events (MACCE) including all-cause death, myocardial infarction, revascularization and stroke as well as in-stent thrombosis and bleeding events. Data from 1 755 pairs of patients were analysis after propensity score matching. The clinical outcomes were compared between groups by using Kaplan-Meier survival analysis before and after propensity score matching. Multivariable Cox analysis was used to define the impact and determinants of post-PCI anticoagulation on clinical outcomes. Results: one thousand seven hundred and fifty-five (18.0%) patients didn't receive post-PCI anticoagulation and 8 014 (82.0%) patients received post-PCI anticoagulation, 5 666 (58.0%) patients received enoxaparin and 2 348 (24.0%) patients received fondaparinux. Patients were younger and incidence of female patients was less, incidence of renal dysfunction and acute coronary syndrome were higher in low-dose and short-time post-PCI anticoagulant therapy group than in non-post-PCI anticoagulation group (all P<0.05). Similarly, patients with post-PCI anticoagulation were associated with more left main coronary artery lesion and branch lesion (P<0.05). Post-PCI anticoagulation patients were associated with less trans-femoral process, more drug-eluting stents implantation and less simple balloon dilatation (all P<0.05). Nine thousand seven hundred and seventeen (99.5%) patients completed 2 years follow up. Post-PCI anticoagulation patients had significantly lower 30-day all-cause death (0.05% (4 cases) vs. 0.46% (8 cases), P<0.001) and stroke (0 vs. 0.11% (2 cases), P=0.003), lower 180-day all-cause death (0.17% (14 cases) vs. 0.57% (10 cases), P=0.002), revascularization (2.07% (166 cases) vs. 3.71% (65 cases), P<0.001) and MACCE (3.49% (280 cases) vs. 5.47% (96 cases), P<0.001), lower 2-year revascularization (7.61% (610 cases) vs. 12.84% (225 cases), P<0.001) and MACCE (10.92 (875 cases) vs. 16.01% (281 cases), P<0.001). Multivariable Cox regression analysis showed that post-PCI anticoagulant therapy was an independent protective factor of 30-day (HR=0.17, 95%CI 0.05-0.62, P=0.007), 180-day all-cause death (HR=0.37, 95%CI 0.16-0.87, P=0.023) and MACCE (HR=0.74, 95%CI 0.58-0.94, P=0.013), 2-year MACCE (HR=0.71, 95%CI 0.62-0.81, P<0.001). After propensity score matching, post-PCI anticoagulation therapy remained as an independent protective factor of 30-day all-cause death (HR=0.11, 95%CI 0.01-0.92, P=0.042) and 2-year MACCE (HR=0.81, 95%CI 0.68-0.96, P=0.015). Conclusions: Low-dose and short-time post-PCI anticoagulant therapy may decrease 30-day all-cause death, 180-day all-cause death and MACCE and 2-year MACCE, and meanwhile this option does not increase bleeding risk in patients underwent selective PCI.

[Impact of coronary artery lesion calcification on the long-term outcome of patients with coronary heart disease after percutaneous coronary intervention].

Objective: To investigate the impact of coronary lesion calcification on the long-term outcome of patients with coronary heart disease after percutaneous coronary intervention. Methods: In this prospective observational study, a total of 10 119 consecutive patients with coronary heart disease undergoing percutaneous coronary intervention from January 1 to December 31, 2 103 in our hospital were enrolled. The patients were divided into non/mild calcification group (8 268 cases) and moderate/severe calcification group (1 851 cases) according to the angiographic results. The primary endpoint was one-year major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, and target vessel revascularization. Results: The patients were (58.3±10.3) years old, and there were 2 355 females (23.3%). Compared with non/mild calcification group, patients in the moderate/severe calcification group were older ((60.0±10.6) years vs. (57.9±10.2) years, P<0.01), and had higher proportion of female (25.4% (470/1 851) vs. 22.8% (1 885/8 268), P=0.02), debates (33.9% (628/1 851) vs. 29.0% (2 399/8 268), P<0.01), hypertension (68.0% (1 259/1 851) vs. 63.7% (5 264/8 268), P<0.01), coronary artery bypass grafting (4.6% (85/1 851) vs. 3.2% (268/8 268), P<0.01), stroke (12.6% (233/1 851) vs. 10.4% (861/8 268), P=0.01), and renal dysfunction (6.2% (115/1 851) vs. 3.7% (303/8 268), P<0.01). Compared with non/mild calcification group, patients in themoderate/severe calcification group experienced longer procedure time (37 (24, 61) min vs. 27 (17,40) min, P<0.01) and stent length was longer (32 (23,48) mm vs. 27 (18,38) mm, P<0.01), and percent of rotational atherectomy was higher (2.56%(57/2 229) vs. 0.03% (3/11 930), P<0.01). One-year follow-up results showed that MACE (7.5% (139/1 846) vs. 4.9% (402/8 243), P<0.01), all-cause death (1.0% (19/1 846) vs. 0.6% (49/8 243), P=0.04), myocardial infarction (2.2% (41/1 846) vs. 1.4% (114/8 243), P=0.01), and target vessel revascularization (5.0% (92/1 846) vs. 3.2% (266/8 243), P<0.01) were all significantly higher in moderate/severe calcification group than in non/mild group. Multivariate Cox regression analysis showed that moderate/severe calcification was an independent predictor of MACE at one-year after the procedure (HR=1.41, 95%CI 1.16-1.72, P<0.01). Conclusion: Moderate/severe calcification in coronary lesion is an independent predictor of long-term poor prognosis in coronary heart disease patients undergoing percutaneous coronary intervention.

DUXAP10 regulates proliferation and apoptosis of chronic myeloid leukemia via PTEN pathway.

OBJECTIVE: To investigate the role of DUXAP10 in chronic myelogenous leukemia (CML) and its underlying mechanism. PATIENTS AND METHODS: We detected DUXAP10 expression in 82 CML patients, 12 normal controls, and CML cell line by qRT-PCR (quantitative real-time polymerase chain reaction). After transfection of si-DUXAP10 or si-PTEN in CML cell lines (K652, KG-1), we detected proliferation, cell cycle, and apoptosis by CCK-8 (cell counting kit-8), colony formation assay, and flow cytometry, respectively. Finally, protein expressions of p21, CDK2, Bcl-2, Bax, and PTEN were detected by Western blot. RESULTS: DUXAP10 was upregulated in CML tissues and cells, which was gradually increased in the chronic phase (CP), acceleration phase (AP), and blast phase (BP) of CML. Knockdown of DUXAP10 in K652 and KG-1 cells can remarkably inhibit cell proliferation, promote cycle arrest and apoptosis. Western blot and flow cytometry results demonstrated that DUXAP10 can reduce apoptosis by inhibiting PTEN expression. CONCLUSIONS: Overexpressed DUXAP10 accelerates the development and progression of CML by promoting cell proliferation, reducing cell cycle arrest and apoptosis via inhibiting PTEN expression.

Effect of miR-363 on the proliferation, invasion and apoptosis of laryngeal cancer by targeting Mcl-1.

OBJECTIVE: To investigate the potential effect of miR-363 on the development of laryngeal cancer and to reveal the relevant mechanism. PATIENTS AND METHODS: The expression level of miR-363 was detected in laryngeal cancer tissues and cells (TU-177), respectively. Luciferase assay was performed to evaluate the interaction between miR-363 and myeloid cell leukemia-1 (Mcl-1). The effect of the miR-363/Mcl-1 axis on TU-177 cells was determined by subsequent experiments including cell proliferation, invasion, apoptosis and the expression level of Mcl-1. RESULTS: In the present study, we found that miR-363 was both repressed in laryngeal cancer tissues and cells (TU-177). To find the regulating target of miR-363, we searched three publicly available algorithms, including TargetScan, miRDB, and microRNA. Results showed that Mcl-1 was a direct target of miR-363, and the Luciferase assay confirmed our suggestion. Subsequent experiments indicated that the decreased expression of Mcl-1 resulting from the up-regulation of miR-363 could deaccelerate cell proliferation and invasion, and accelerate cell apoptosis in laryngeal cancer cells. CONCLUSIONS: Our research revealed the suppressed function of miR-363 in laryngeal cancer by targeting Mcl-1. Meanwhile, we found that the restoration of miR-363 could serve as a potential therapeutic strategy for the treatment of laryngeal cancer.

[Safety and efficacy of a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent for the treatment of de novo coronary lesions: 5-year results of the TARGET â ¡ trial].

Objective: This study sought to evaluate the safety and efficacy of FIREHAWK, a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent (SES) in patients with moderate-complex coronary lesions (including patients with small vessel disease, long lesion and multi vessel disease), and to validate the ability of the SYNTAX score (SS) to predict clinical outcomes in patients treated with FIREHAWK stent. Methods: TARGETⅡ was a prospective, multicenter, single-arm clinical trial, a total of 730 patients who underwent percutaneous coronary intervention (PCI) of de novo lesions in native coronary arteries in 24 medical centers in China from August 2011 to February 2012 were enrolled in this study. All patients were exclusively treated with the FIREHAWK stent. Clinical data including patients with diabetes, small vessel disease, long lesion and multi vessel disease were analyzed. The primary composite endpoint was the target lesion failure (TLF) of cardiac death, target vessel-related myocardial infarction (TV-MI), or target lesion revascularization (TLR). The secondary composite endpoint was patient-oriented endpoint (PoCE), a composite of all death, all myocardial in farction (MI), or any repeat revascularization; definite/probable stent thrombosis (ST) (including acute, late, and very late thrombosis) . SS was calculated in lesions with stenosis more than 50% with coronary artery diameter greater than 1.5 mm. Patients were grouped by tertiles of SS (≤7, >7 to ≤12, >12). Follow-up was performed up to 5 years. Results: A total of 730 patients were enrolled in the TARGET Ⅱ trial. The average SS was 10.9±6.9. 683 (93.6%) patients completed 5-year clinical follow-up. The 5-year incidence of TLF was 8.5%(58/683). The incidence of TLF components was as follows: cardiac death 2.0%(14/683), TV-MI 4.4%(30/683), TLR 3.4%(23/683). The incidence of PoCE was 16.4%(112/683). The incidence of definite/probable stent thrombosis was 0.7%(5/683).Multivariable Cox regression analysis showed that the diabetes subgroup (HR=1.123, 95%CI 0.623-2.026, P=0.699), the small vessel disease subgroup (HR=0.909, 95%CI 0.526-1.570, P=0.732), the long lesion subgroup (HR=1.561, 95%CI 0.922-2.640, P=0.097), and the multi vessel disease subgroup (HR=1.062, 95%CI 0.611-1.846, P=0.830) did not increase the HR of TLF compared with the counterpart subgroups. Multivariable Cox regression analysis showed that the hazard of TLF was not increased in the middle and high SS groups as compared with the low SS group (HR=1.203,95%CI 0.607-2.385,P=0.597;HR=1.548,95%CI 0.829-2.892,P=0.171). Conclusions: The 5 years follow-up results of TARGET Ⅱ trial shows that the biodegradable polymer of FIREHAWK stents have long-lasting safety and efficacy for patients with moderate-complex coronary lesions. SS is not the predicting factor for the occurrence of TLF in FIREHAWK treated patients with moderate-complex coronary lesions. Trial Registration Clinical Trials.gov, NCT0141264.