[Correlation between insulin resistance and coronary collateral circulation in patients with chronic total coronary occlusion].

OBJECTIVE: To explore the impact of diabetes on collateral circulation (CC) development in patients with chronic total coronary occlusion (CTO) and the underlying regulatory mechanism. METHODS: This study was conducted among 87 patients with coronary heart disease (CHD), who had CTO in at least one vessel as confirmed by coronary angiography. Among them 42 patients were found to have a low CC level (Cohen-Rentrop grades 0-1) and 45 had a high CC level (grades 2-3). In the 39 patients with comorbid diabetes mellitus and 48 non-diabetic patients, insulin resistance (IR) levels were compared between the subgroups with different CC levels. The steady-state mode evaluation method was employed for calculating the homeostatic model assessment for insulin resistance index (HOMA-IR) using a mathematical model. During the interventional procedures, collateral and peripheral blood samples were collected from 22 patients for comparison of the metabolites using non-targeted metabolomics analysis. RESULTS: NT-proBNP levels and LVEF differed significantly between the patients with different CC levels (P<0.05). In non-diabetic patients, HOMA-IR was higher in low CC level group than in high CC level groups. Compared with the non-diabetic patients, the diabetic patients showed 63 upregulated and 48 downregulated metabolites in the collateral blood and 23 upregulated and 14 downregulated metabolites in the peripheral blood. The differential metabolites in the collateral blood were involved in aromatic compound degradation, fatty acid biosynthesis, and steroid degradation pathways; those in the peripheral blood were related with pentose phosphate metabolism, bacterial chemotaxis, hexanoyl-CoA degradation, glycerophospholipid metabolism, and lysine degradation pathways. CONCLUSION: The non-diabetic patients with a low level of CC had significant insulin resistance. The degradation pathways of aromatic compounds, fatty acid biosynthesis, and steroid degradation are closely correlated with the development of CC.

[Effect of asiaticoside on systolic blood pressure and relaxation of isolated thoracic aorta of rats].

OBJECTIVE: To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism. METHODS: SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes, and histological changes of the thoracic aorta were evaluated using HE staining. In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings, the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine (NE)- and KCl-induced constriction. The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester, indomethacin, zinc protoporphyrin Ⅸ, tetraethyl ammonium chloride, glibenclamide, barium chloride, Iberiotoxin, 4-aminopyridine, or TASK-1-IN-1. The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release. RESULTS: Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology. While not obviously affecting resting aortic rings with intact endothelium, asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE, but its effects differed between endothelium-intact and endothelium-denuded rings. In endothelium-intact aortic rings pretreated with indomethacin, ZnPP Ⅸ, barium chloride, glyburide, TASK-1-IN-1 and 4-aminopyridine, asiaticoside did not produce significant effect on NE-induced vasoconstriction, and tetraethylammonium, Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside. In KCland NE-treated rings, asiaticoside obviously inhibited CaCl2-induced vascular contraction. CONCLUSION: Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening, promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow, thereby reducing systolic blood pressure in rats.

[Correlation of serum ferredoxin 1 and lipoic acid levels with severity of coronary artery disease].

OBJECTIVE: To analyze the correlation of copper death inducer ferredoxin 1 (FDX1) and lipoic acid (LA) with the occurrence and severity of coronary atherosclerosis and explore their roles in coronary heart disease (CHD). METHODS: We analyzed the data of 226 patients undergoing coronary artery angiography (CAG) in our hospital between October, 2021 and October, 2022, including 47 patients with normal CAG findings (control group) and 179 patients with mild, moderate or severe coronary artery stenosis (CHD group). Serum FDX1 and LA levels were determined with ELISA for all the patients. We also examined pathological changes in the aorta of normal and ApoE-/- mice using HE staining and observed collagen fiber deposition with Sirius red staining. Immunohistochemistry was used to detect the expression and distribution of FDX1 and LA in the aorta, and RT-PCR was performed to detect the expressions of FDX1, LIAS and ACO2 mRNAs in the myocardial tissues. RESULTS: Compared with the control patients, CHD patients had significantly lower serum FDX1 and LA levels, which decreased progressively as coronary artery stenosis worsened (P < 0.01) and as the number of involved coronary artery branches increased (P < 0.05). Serum FDX1 and LA levels were positively correlated (r=0.451, P < 0.01) and they both negatively correlated with the Gensini score (r=-0.241 and -0.273, respectively; P < 0.01). Compared with normal mice, ApoE-/- mice showed significantly increased lipid levels (P < 0.01) and atherosclerosis index, obvious thickening, lipid aggregation, and collagen fiber hyperplasia in the aorta, and significantly reduced expressions of FDX1, LA, LIAS, and ACO2 (P < 0.05). CONCLUSION: Serum FDX1 and LA levels decrease with worsening of coronary artery lesions, and theirs expressions are correlated with coronary artery lesions induced by hyperlipidemia.

[Quercetin improves pulmonary arterial hypertension in rats by regulating the HMGB1/RAGE/NF-κB pathway].

OBJECTIVE: To explore the mechanism through which quercetin improves pulmonary arterial hypertension (PAH). METHODS: Rat models of hypoxic pulmonary hypertension were established by exposure to hypoxia for 8-10 h each day (6 days a week for 4 weeks), and before each hypoxic exposure, the rats were given intragastric administration of 100 mg/kg quercetin or saline. After the treatments, the right ventricular systolic pressure (RVSP) and pulmonary artery systolic pressure of the rats were recorded. The right ventricular hypertrophy index (RVHI) was measured to evaluate right ventricular hypertrophy. HE staining was used to observe the remodeling of the pulmonary arterioles. The right cardiac function of the rats was evaluated by ultrasound. The protein levels of HMGB1, RAGE, NF-κB, Bax, Bcl-2 and cleaved caspase-3 in the lung tissue of the rats were detected using Western blotting. RESULTS: Compared with the rats maintained in normoxia, the rats with chronic hypoxic exposure showed significantly increased RVHI and RVSP (P<0.01), which were obviously lowered by quercetin treatment (P<0.01). HE staining showed significant pulmonary artery wall thickening with reduced lumen diameter in hypoxia group, and quercetin treatment effectively improved pulmonary vascular remodeling. Ultrasound examination revealed a significantly increased RVFW and a lowered PAT/PET ratio in hypoxia group (P<0.01), and such changes were ameliorated by quercetin treatment (P<0.01). Chronic hypoxia significantly increased the protein expressions of HMGB1 (P<0.01), RAGE, NF-κB and Bcl-2 (P<0.01) and lowered the protein expressions of Bax and cleaved caspase-3 (P<0.01); Quercetin treatment obviously lowered the protein expressions of HMGB1, NF-κB (P<0.05), RAGE (P<0.01) and (P<0.05) and increased the expressions of Bax and cleaved caspase-3 in the rat models (P<0.01). CONCLUSION: Quercetin improves pulmonary hypertension in rats possibly by promoting apoptosis through the HMGB1/RAGE/NF-κB pathway.

Comparison between ultrasound-guided pericapsular nerve group block and anterio quadratus lumborum block for total hip arthroplasty: a double-blind, randomized controlled trial.

OBJECTIVE: Peripheral nerve block can provide effective postoperative analgesia to patients undergoing total hip arthroplasty (THA). This study aimed to compare ultrasound-guided pericapsular nerve group (PENG) block against anterior quadratus lumborum (AQL) block for pain management in primary THA. PATIENTS AND METHODS: In this prospective, double-blind, randomized controlled trial, 90 patients undergoing primary THA under general anesthesia were randomly allocated to receive ultrasound-guided PENG block + sham AQL block ("PENG group") or ultrasound-guided AQL block + sham PENG block ("AQL" group). The primary outcome was the highest pain score on a visual analogue scale while the patient was in the recovery room. Secondary outcomes included pain scores after transfer out of the recovery room, morphine consumption, quadricep strength, duration of hospitalization, pain level one year after surgery, and incidence of complications. RESULTS: Patients in the PENG group reported significantly lower maximum pain scores in the recovery room (31.3±9.1 vs. 37.3±7.4, p=0.001), as well as significantly lower pain scores at rest at 3 h after surgery and during motion at 3 and 6 h after surgery. The two groups did not differ significantly in postoperative morphine consumption, length of hospitalization, pain level at one year after surgery, or incidence of complications. Neither block significantly weakened the quadriceps. CONCLUSIONS: PENG block may provide slightly more effective postoperative analgesia than AQL block during the early recovery period after primary THA.

[Serum levels of endothelin-1 and connective tissue growth factor are elevated in patients with atrial fibrillation and correlated with relapse following radiofrequency ablation].

OBJECTIVE: To investigate the changes in serum levels of endothelin-1 (ET-1) and connective tissue growth factor (CTGF) in patients with atrial fibrillation (AF) and their value for predicting recurrence of AF after radiofrequency ablation (RFCA). METHODS: Sixty-six patients with paroxysmal AF (PaAF) and 72 with persistent AF (PaAF) admitted in our hospital were recruited as AF group and 80 patients with sinus rhythm as the control group, and in all the participants, serum levels of ET-1 and CTGF were measured using ELISA and Western blotting. From 6 patients with AF and 6 with sinus rhythm undergoing cardiac surgery in our hospital, tissue samples of the right atrial appendage were taken intraoperatively for observation of structural changes of the cardiomyocytes, myocardial fibrosis and expression of ET-1 and CTGF protein. In AF group, the patients receiving RFCA were followed up for 6 months following the procedure for assessment of the outcomes. RESULTS: Compared with the control patients, the patients with AF showed obvious damages of the cardiomyocyte structure and myocardial fibrosis. Serum levels of ET-1 and CTGF levels were significantly higher in PaAF and PeAF groups than in the control group, and were higher in PeAF group than in PaAF group. In the patients with AF, serum ET-1 and CTGF levels were positively correlated with left atrial diameter (LAD) (P < 0.05), and ET-1 was positively correlated with CTGF levels (P < 0.05). In patients with postoperative AF recurrence, the serum levels of ET-1 and CTGF were significantly higher than those in patients without recurrence; serum ET-1 and CTGF levels before and after the operation were positively correlated with the recurrence of PeAF, and elevated serum levels of ET- 1 and CTGF were identified by logistic regression analysis as independent risk factors for postoperative recurrence of PeAF. CONCLUSION: Serum levels of ET-1 and CTGF are significantly elevated in AF patients in positive correlation with AF duration. ET-1 and CTGF levels are higher in AF patients with postoperative recurrence, and they both have predictive value for recurrence of PeAF following RFCA.

Abnormal hyperplasia of chondrocytes in a rat model of glucocorticoid-induced osteonecrosis of the femoral head.

OBJECTIVE: The aim of our study was to determine whether abnormal hyperplasia of chondrocytes occurs in glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) using a well-established rat model. MATERIALS AND METHODS: Rats were injected with lipopolysaccharide and methylprednisolone to induce GC-ONFH, while control animals were injected with saline (12 animals per group). Establishment of the disease model was confirmed using micro-computed tomography and hematoxylin-eosin (HE) staining of femoral head tissue sections. Chondrocyte hyperplasia was detected using HE staining and semi-quantitated using toluidine blue and saffron O staining. Expression of the autophagy marker LC3B was assessed in cartilage tissues of femoral head using immunohistochemistry. RESULTS: GC-ONFH animals showed significantly greater area of abnormal chondrocyte hyperplasia in femoral head tissue sections than control animals. They also showed significantly higher expression of LC3B in articular cartilage of the femoral head. CONCLUSIONS: GC-ONFH may be associated with abnormal chondrocyte hyperplasia in articular surface cartilage, which may be related to glucocorticoid-induced overactivation of autophagy.

[Medial parapatellar soft tissue overlapping suture in total knee arthroplasty for severe osteoarthritis with permanent patellar dislocation: early and mid-term results].

OBJECTIVE: To evaluate the early and mid-term clinical results of medial parapatellar soft tissue overlapping suture in total knee arthroplasty for treatment of severe osteoarthritis combined with permanent patellar dislocation. METHODS: We retrospectively analyzed the data of 12 patients (12 knees) diagnosed with severe knee osteoarthritis combined with permanent patellar dislocation undergoing total knee arthroplasty with medial parapatellar soft tissue overlapping suture. Knee Society Score (KSS), University of California Los Angeles (UCLA) activity-level rating, Visual Analog Scale (VAS) pain score, and knee range of motion of the patients were assessed before and 2 years after the surgery. Anteroposterior and lateral radiographs of the knee joint, full-length standing radiographs of the lower limbs and patellar axial radiographs were evaluated. RESULTS: The mean Knee Society Score of the patients increased from 34.2±11.1 before surgery to 73.5±6.3 at two years after the surgery (P < 0.001). The UCLA activity-level rating increased from an average of 3.8 ± 0.8 before surgery to 5.8 ± 0.6 at two years postoperatively (P=0.003). The mean VAS pain score decreased from 42.8±6.0 before surgery to 20.1±3.7 (P < 0.001) and the range of motion of the knee joint increased from 74.6±8.9 degrees to 97.5±4.5 degrees at two years (P < 0.001). The radiographs showed no signs of subluxation or dislocation of the patella in all the patients. CONCLUSIONS: Medial parapatellar soft tissue overlapping suture in total knee arthroplasty can achieve good early and mid-term clinical results for treatment of severe osteoarthritis combined with permanent patellar dislocation.

Impact of angiotensin II receptor antagonism on the sex-selective dysregulation of cardiovascular function induced by in utero dexamethasone exposure.

In utero exposure to glucocorticoids in late gestation programs changes in cardiovascular function. The objective of this study was to determine the degree to which angiotensin II mediates sex-biased changes in autonomic function as well as basal and stress-responsive cardiovascular function following in utero glucocorticoid exposure. Pregnant rats were administered the synthetic glucocorticoid dexamethasone (Dex; 0.4 mg/kg/day sc) or vehicle on gestation days 18-21. Mean arterial pressure, heart rate, and heart rate variability (HRV) were measured via radiotelemetry in freely moving, conscious adult rats. To evaluate the impact of stress, rats were placed in a restraint tube for 20 min. In a separate cohort of rats, restraint stress was performed before and after chronic treatment with the angiotensin type 1 receptor antagonist, losartan (30 mg/kg/day ip). Frequency domain analysis of HRV was evaluated, and data were integrated into low-frequency (LF, 0.20-0.75 Hz) and high-frequency (HF, 0.75-2.00 Hz) bands. Prenatal Dex resulted in an exaggerated pressor and heart rate response to restraint in female offspring that was attenuated by prior losartan treatment. HF power was higher in vehicle-exposed female rats compared with Dex females. Following losartan, HF power was equivalent between female vehicle and Dex-exposed rats. In utero exposure to Dex produced female-biased alterations in stress-responsive cardiovascular function, which may be indicative of a reduction in parasympathetic activity. Moreover, these findings suggest this autonomic dysregulation may be mediated, in part, by long-term changes in renin-angiotensin signaling.NEW & NOTEWORTHY Our findings reveal the involvement of angiotensin II on sex-selective cardiovascular function and autonomic changes in adult offspring exposed to dexamethasone during the last 4 days of gestation. We show that angiotensin II receptor blockade reverses the exaggerated pressor and heart rate response to acute restraint stress and the autonomic dysregulation observed in female, but not male, offspring exposed to dexamethasone in utero.

Sarcopenia predicts for long-term survival in patients with thoracoabdominal aortic aneurysms undergoing operative and nonoperative management.

OBJECTIVE: Sarcopenia, defined as a loss of muscle mass or poor muscle quality, is a syndrome associated with poor surgical outcomes. The prognostic value of sarcopenia in patients with thoracoabdominal aortic aneurysms (TAAAs) is unknown. The present study was designed to define sarcopenia in this patient population and assess its impact on survival among patients who had undergone operative and nonoperative management of TAAAs. METHODS: We retrospectively reviewed all patients with a diagnosis of a TAAA at an academic hospital between 2009 and 2017 who had been selected for operative and nonoperative management. Sarcopenia was identified by measuring the total muscle area on a single axial computed tomography image at the third lumbar vertebra. The muscle areas were normalized by patient height, and cutoff values for sarcopenia were established at the lowest tertile of the normalized total muscle area. Long-term patient survival was assessed using Kaplan-Meier and Cox regression models. RESULTS: A total of 295 patients were identified, of whom 199 had undergone operative management and 96 nonoperative management for TAAAs. The patients selected for nonoperative management were more likely to be women and to have chronic kidney disease, coronary artery disease, cerebrovascular disease, a higher modified frailty index, and a larger aortic diameter. The Kaplan-Meier analyses revealed significantly lower long-term survival for the patients with and without sarcopenia in the operative and nonoperative groups. In Cox regression analyses, sarcopenia was a significant predictor of shorter survival for both operative (hazard ratio, 0.96; 95% confidence interval, 0.94-0.99; P = .006) and nonoperative (hazard ratio, 0.95; 95% confidence interval, 0.90-1.00; P = .05) groups after adjusting for age, race, sex, maximum aortic diameter, modified frailty index, chronic kidney disease, and active smoking. Additionally, age was a significant predictor of shorter survival in the operative group, and smoking and aortic diameter were significant in the nonoperative group. CONCLUSIONS: In our cohort of patients who had received operative and nonoperative management of TAAAs, the patients with sarcopenia had had significantly lower long-term survival, regardless of whether surgery had been performed. These data suggest that sarcopenia could be used as a predictor of survival for patients with TAAAs and might be useful for risk stratification and decision making in the management of TAAAs.

[RIP1/RIP3-MLKL signaling pathway correlates with occurrence, progression and prognosis of chronic heart failure].

OBJECTIVE: To detect plasma levels of receptor-interacting protein kinase 1 (RIP1), RIP3 and mixed lineage kinase domain-like protein (MLKL) in patients with chronic heart failure and explore the expression pattern of programmed necrosis signaling pathway RIP1/RIP3-MLKL in the progression of heart failure. METHODS: The patients with chronic heart failure (NYHA class Ⅱ-Ⅳ) admitted in our hospital between February, 2020 and March, 2021 were prospectively enrolled in this study, with 21 healthy volunteers as the control group. The enrolled patients included 20 with grade Ⅱ, 33 with grade Ⅲ, and 43 with grade Ⅳ cardiac function. Fasting venous blood was collected from all the participants for detecting plasma levels of RIP1, RIP3, and MLKL and protein expressions of RIP1/RIP3-MLKL pathway using enzyme-linked immunosorbent assay (ELISA) and Western blotting. The patients with grade Ⅳ cardiac function were followed up for 5 months to evaluate the clinical prognostic indicators. RESULTS: Compared with the healthy volunteers, the patients with grade Ⅱ, Ⅲ and Ⅳ cardiac function had significantly increased plasma levels of RIP1, RIP3, and MLKL (P < 0.01), and their levels were significantly higher in grade Ⅲ/Ⅳ patients than in those with grade Ⅱ cardiac function (P < 0.01); the plasma levels of RIP1 and MLKL were significantly higher in grade Ⅳ patients than in grade Ⅲ patients (P < 0.05). The results of Western blotting also showed increased expressions of the proteins in the RIP1/RIP3-MLKL pathway in patients with heart failure. Pearson correlation analysis suggested that in patients with heart failure, the expression levels of RIP1, RIP3, and MLKL were positively correlated with SCR, AST, LVEDD and NT-proBNP (P < 0.05). Follow-up study of the patients with grade Ⅳ cardiac function showed that higher expression levels of RIP1/RIP3-MLKL were associated with a poorer prognosis of the patients. CONCLUSION: The expressions of RIP1, RIP3 and MLKL are significantly upregulated in patients with heart failure in positive correlation with the severity of the disease condition, and the activation of the RIP1/RIP3-MLKL signaling pathway may contribute to the occurrence, development and prognosis of chronic heart failure.

[Exploring the therapeutic mechanism of quercetin for heart failure based on network pharmacology and molecular docking].

OBJECTIVE: To investigate the molecular mechanism of quercetin in the treatment of heart failure (HF) based on network pharmacology and molecular docking. METHODS: Quercetin and HF-related targets were obtained using TCMSP, PharmMapper, CTD and GeneCards databases, and quercetin-HF intersection targets were obtained through the online website Venn; the protein interaction network was constructed and imported into Cytoscape 3.7.2 to identify the core targets of quercetin in the treatment of HF.GO and KEGG pathway enrichment analyses were performed using R package, and molecular docking was performed using Auto Dock Vina.The protein levels of AKT1, phospho-AKT(Ser473), eNOS, MMP9, and caspase-3 in quercetin-treated HF cell models were detected using protein immunoblotting. RESULTS: We identified 80 quercetin-HF intersectional targets (AKT1, CASP3, MAPK1, MMP9, and MAPK8) and 5 core targets of quercetin for treatment of HF.GO analysis suggested that the therapeutic effect of quercetin for HF was mediated mainly by such biological processes as responses to peptide hormones, phosphatidylinositol-mediated signalling, responses to lipopolysaccharides, responses to molecules of bacterial origin and regulation of inflammatory responses.KEGG pathway enrichment analysis identified lipid and atherosclerosis pathway, proteoglycans in cancer, PI3K-AKT signaling pathway, diabetic cardiomyopathy and MAPK signaling pathway as the most significantly enriched signaling pathways.Molecular docking showed a good binding activity of quercetin to the 5 core targets.The results of protein immunoblotting showed that 100 µmol/L quercetin significantly reduced AKT1, phospho-AKT (Ser473), eNOS, MMP9 and caspase-3 levels in the cell models of HF (P < 0.01). CONCLUSION: Quercetin improves the pathological changes in HF possibly by regulating the AKT1-eNOS-MMP9 pathway to inhibit cell apoptosis.

Use of nimotuzumab combined with cisplatin in treatment of nasopharyngeal carcinoma and its effect on expressions of VEGF and MMP-2

Purpose This paper aims to observe the expressions of VEGF and MMP-2 in patients with nasopharyngeal carcinoma treated by nimotuzumab combined with cisplatin. Methods Altogether, 104 patients with nasopharyngeal carcinoma treated in our hospital from April 2014 to August 2016 were selected as research subjects. Among them, 50 patients treated with cisplatin were divided into a control group and 54 patients treated with nimotuzumab combined with cisplatin were divided into an observation group. The two groups of patients were compared in terms of efficacy after treatment and incidence of adverse reactions. Changes of serum VEGF and MMP-2 concentrations before and after treatment were detected using enzyme-linked immunosorbent assay (ELISA), and the 3-year overall survival (OS) of patients was observed. Results Compared with the control group, patients in the observation group had significantly higher total remission rate (RR) (P < 0.05) and significantly lower incidence of adverse reactions (P < 0.05). Before treatment, there was no significant difference between the observation and control groups in the concentrations of VEGF and MMP-2 (P > 0.05). After treatment, the concentrations in the two groups were significantly lower than those before treatment (P < 0.05), and the concentrations in the observation group were significantly lower than those in the control group (P < 0.05). There was no significant difference in the 3-year OS between the observation and control groups (P > 0.05). Conclusions Nimotuzumab combined with cisplatin could improve the conditions of patients with nasopharyngeal carcinoma. After treatment, the expression of VEGF and MMP-2 decreased significantly. We speculated that it improves the survival rate of patients by reducing the expression of VEGF and MMP-2 (AU)

[Subgroup identification based on accelerated failure time model combined with adaptive elastic net].

OBJECTIVE: To solve the problem of identifying subgroup in a randomized clinical trial with respect to survival time, we present a strategy based on accelerated failure time model to identify the subgroup with an enhanced treatment effect. OBJECTIVE: We fitted and compared univariate accelerated failure time (AFT) models and penalized AFT models regularized by adaptive elastic net to identify the candidate covariates. Based on these covariates, we utilized change-point algorithm to classify the patient subgroups. A two-stage adaptive design was adopted to verify the treatment effect in certain subgroups. Simulations were conducted across different scenarios to evaluate the performance of the models. OBJECTIVE: As the correlation between covariates differed, the power of the models with an adaptive design was stable. In the two-stage adaptive design, the power of the models was the highest when the two significance levels (α1 and α2) were allocated to be 0.035 and 0.015, respectively. A better effect of the responder subgroup was associated with a higher power of the models. For a fixed sample size, the power decreased as the covariate number to sample size ratio increased, but the power showed a stable trend when the ratio was above 1. The univariate models showed different distribution patterns of the parameters for different survival time, while their distribution was relatively stable in the penalized AFT models. OBJECTIVE: The correlation between the covariates does not affect the performance of univariate AFT models and penalized AFT models. (0.035, 0.015) can be used as a reference for the significance level of an adaptive design. For small differences in the treatment effect between the responder and the non-responder, the penalized AFT model including the main effect of covariate (Penalized, Eq_in) outperforms the univariate AFT model excluding the main effect of covariate (Univariate, Eq_ex). Univariate, Eq_ex performs better when the covariate number to sample size ratio is less than 1, but is outperformed by Penalized, Eq_in when the ratio is above 1. The parameter distribution of survival time has a greater impact on the univariate models but a smaller impact on the penalized models.

Use of nimotuzumab combined with cisplatin in treatment of nasopharyngeal carcinoma and its effect on expressions of VEGF and MMP-2.

PURPOSE: This paper aims to observe the expressions of VEGF and MMP-2 in patients with nasopharyngeal carcinoma treated by nimotuzumab combined with cisplatin. METHODS: Altogether, 104 patients with nasopharyngeal carcinoma treated in our hospital from April 2014 to August 2016 were selected as research subjects. Among them, 50 patients treated with cisplatin were divided into a control group and 54 patients treated with nimotuzumab combined with cisplatin were divided into an observation group. The two groups of patients were compared in terms of efficacy after treatment and incidence of adverse reactions. Changes of serum VEGF and MMP-2 concentrations before and after treatment were detected using enzyme-linked immunosorbent assay (ELISA), and the 3-year overall survival (OS) of patients was observed. RESULTS: Compared with the control group, patients in the observation group had significantly higher total remission rate (RR) (P < 0.05) and significantly lower incidence of adverse reactions (P < 0.05). Before treatment, there was no significant difference between the observation and control groups in the concentrations of VEGF and MMP-2 (P > 0.05). After treatment, the concentrations in the two groups were significantly lower than those before treatment (P < 0.05), and the concentrations in the observation group were significantly lower than those in the control group (P < 0.05). There was no significant difference in the 3-year OS between the observation and control groups (P > 0.05). CONCLUSIONS: Nimotuzumab combined with cisplatin could improve the conditions of patients with nasopharyngeal carcinoma. After treatment, the expression of VEGF and MMP-2 decreased significantly. We speculated that it improves the survival rate of patients by reducing the expression of VEGF and MMP-2.

Anatomic Eligibility for Commercial Branched Endograft Repair of Thoracoabdominal Aortic Aneurysms.

BACKGROUND: First-generation "off-the-shelf" branched endovascular stent grafts are in development for treatment of thoracoabdominal aortic aneurysms (TAAAs). Prior studies have assessed eligibility rates among highly selected cohorts of patients referred for endovascular treatment, and the broader applicability of these devices to all patients with TAAA is unknown. The aims of this study were to assess the overall suitability of the 3 commercial 4-branched devices with or without adjunct procedure(s) in an unselected cohort of patients with TAAA and to identify areas for improvement in the next generation of devices. METHODS: A retrospective review of three-dimensional centerline reconstructions of contrast-enhanced computed tomography (CT) imaging was performed in consecutive patients with TAAA seen between 2013 and 2017. All patients with contrast-enhanced CT imaging were included, regardless of prior evaluation for suitability for endovascular repair. Eligibility for a device was assessed based on instructions for use (IFU) from the device manufacturer along with prespecified anatomic criteria. Adjunct procedures were defined as carotid-subclavian revascularization, target vessel endovascular intervention, and iliac conduit/revascularization. RESULTS: Of 165 patients with TAAA, 122 had CT scans adequate for study inclusion. Eighteen patients (14.8%) were eligible for at least 1 device by IFU, and 41 (33.6%) could have been made eligible for at least 1 device by an adjunct procedure. Sixty-three (51.6%) were not eligible for any device within IFU even with adjunct procedures, including 31 of 32 patients with TAAA due to dissection. The most common reasons for ineligibility were perivisceral flow channel diameter <20 mm (n = 43) and an inadequate proximal seal zone (n = 29). Women were significantly less likely to be eligible for an off-the-shelf device (P = 0.03) and were more likely to require an iliac procedure to become eligible (P = 0.006). Almost none of the patients with dissection could receive a device even if adjunct procedures were used. CONCLUSIONS: Over half of patients with TAAA could not be made eligible for an off-the-shelf device based on manufacturers' criteria, even with adjunct procedures. Women and patients with TAAA due to dissection had higher rates of ineligibility. These data demonstrate that custom fenestrated devices and low-profile devices are needed to expand eligibility for endovascular repair of TAAA.

CircRNA_001010 adsorbs miR-5112 in a sponge form to promote proliferation and metastasis of non-small cell lung cancer (NSCLC).

OBJECTIVE: It has been demonstrated that circular RNA (circRNA) plays an important regulatory role in a series of diseases. The purpose of this study is to investigate the expression of circRNA_001010 and its facilitating effects on proliferation and invasion of non-small cell lung cancer (NSCLC) by regulating oncogene CDK4 through sponging with miR-5112. PATIENTS AND METHODS: qRT-PCR was performed to detect the expressions of circRNA_001010 and CDK4 in human NSCLC tissues and cells. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate the A549 cells proliferation and transwell assay was performed to evaluate the A549 cells migration. Correlation analysis between circRNA_001010 and miR-5112 was detected by statistical analysis. Bioinformatics prediction was made to detect the binding site of GTL and miR-5112 and Luciferase activity was conducted to investigate the interaction between circRNA_001010 and miR-5112. Furthermore, we cloned the mice CDK4 3'-UTR into the Luciferase reporter vector and constructed miR-5112 binding mutants to validate the inhibited modulation of miR-5112 to the CDK4 expression. RESULTS: Results showed that the expressions of circRNA_001010 and CDK4 were upregulated in human NSCLC tissues and cells. qRT-PCR and CCK-8 assay showed that circRNA_001010 expression is associated with the proliferation of NSCLC cells, and that upregulated circRNA_001010 contributed to cell proliferation of A549. Transwell assay showed that circRNA_001010 was associated with the migration ability of tumor cells, and that increased expression of circRNA_001010 promoted the migration and invasion of NSCLC cells. The bioinformatics prediction and Luciferase assay demonstrated that by sponging with miR-5112, circRNA_001010 can serve as a ceRNA for miR-5112 to further regulate the expression of CDK4. CONCLUSIONS: For the first time, we found that circRNA_001010 was upregulated in human NSCLC patients, which could accelerate tumor proliferation, migration and invasion as a molecular sponge by modulating the inhibitory effect of miR-5112 on oncogene CDK4.

Effects of nalmefene hydrochloride on TLR4 signaling pathway in rats with lung ischemia-reperfusion injury.

OBJECTIVE: To investigate the effect of nalmefene hydrochloride on TLR4 signaling pathway in rats with lung ischemia-reperfusion injury. MATERIALS AND METHODS: Altogether 64 pure inbred male SD rats were divided into groups A, B, C, and D according to the principle of body weight similarity, with 24 rats in each group. Four groups of rats were respectively twisted on the left testis to establish unilateral testicular torsion rats. Group A was the control group, treated with normal saline, group B was the nalmefene hydrochloride high-dose group, treated with 20 µg/kg of nalmefene hydrochloride, group C was the nalmefene hydrochloride low-dose group, treated with 10 µg/kg of nalmefene hydrochloride, and group D was the sham operation group. Lung tissue was collected 60 h later. Western blotting was used to detect the expression levels of HMGB1, TLR4, CD14, and NF-κB protein, qPCR was used to detect the mRNA expression level, and enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of inflammatory factors IL-17, IL-6, and ICAM-1. RESULTS: The expression levels of HMGB1, TLR4, CD14, NF-κB protein, mRNA, IL-17, IL-6, and ICAM-1 in group A were significantly higher than those in groups B, C, and D (p<0.05), while were significantly lower in group D than in groups B and C (p<0.05), and were significantly lower in group B than in group C (p<0.05). CONCLUSIONS: Nalmefene hydrochloride can effectively inhibit the signal pathway of TLR4, and can effectively reduce the injury caused by lung ischemia-reperfusion. The large dose is closely related to the good effect, which is worthy of promotion.

Nurses' knowledge, beliefs and practices regarding the screening and treatment of postpartum depression in maternal and child health clinics: A cross-sectional survey.

BACKGROUND: Postpartum depression (PPD) affects 10-15% of women worldwide, and screening is recommended by clinical guidelines. In Malaysia, nurses in maternal and child health (MCH) clinics provide postpartum care. AIM: To determine nurses' level of knowledge, beliefs and practices regarding PPD and factors associated with screening practices. METHODS: A cross-sectional study using universal sampling was conducted on nurses from seven government MCH clinics in Malaysia. Data was collected from March until April 2016 through a self-reported questionnaire. Univariate and multivariate analyses were performed to identify factors associated with having ever performed PPD screening. RESULTS: Of the 108 nurses, 55.6% scored above the median total knowledge score (17 out of 24 points). Despite a high proportion of nurses believing that they were responsible for PPD screening (72.2%), counselling depressed mothers (72.2%) and referring mothers for further treatment (87.0%), only 64.8% and 51.9% were confident in recognizing PPD and counselling depressed mothers, respectively. Only 25.9% had ever practiced PPD screening, which was associated with beliefs concerning screening taking too much time (adjusted odds ratio [AOR]=0.13, 95% confidence interval [CI]= 0.02-0.74, P=0.022) and that screening is their responsibility (AOR=14.12, 95%CI=1.65-120.75, P=0.016). CONCLUSION: More than half of the nurses scored above the median total knowledge score and had positive beliefs towards PPD screening. However, PPD screening practices were poor, and this outcome was associated with their beliefs regarding time and responsibility.