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Background@#and Purpose This study aimed to construct an optimal dynamic nomogram for predicting malignant brain edema (MBE) in acute ischemic stroke (AIS) patients after endovascular thrombectomy (ET). @*Methods@#We enrolled AIS patients after ET from May 2017 to April 2021. MBE was defined as a midline shift of >5 mm at the septum pellucidum or pineal gland based on follow-up computed tomography within 5 days after ET. Multivariate logistic regression and LASSO (least absolute shrinkage and selection operator) regression were used to construct the nomogram. The area under the receiver operating characteristic curve (AUC) and decisioncurve analysis were used to compare our nomogram with two previous risk models for predicting brain edema after ET. @*Results@#MBE developed in 72 (21.9%) of the 329 eligible patients. Our dynamic web-based nomogram (https://successful.shinyapps.io/DynNomapp/) consisted of five parameters: basal cistern effacement, postoperative National Institutes of Health Stroke Scale (NIHSS) score, brain atrophy, hypoattenuation area, and stroke etiology. The nomogram showed good discrimination ability, with a C-index (Harrell’s concordance index) of 0.925 (95% confidence interval=0.890–0.961), and good calibration (Hosmer-Lemeshow test, p=0.386). All variables had variance inflation factors of 0.7, suggesting no significant collinearity among them. The AUC of our nomogram (0.925) was superior to those of Xiang-liang Chen and colleagues (0.843) and Ming-yang Du and colleagues (0.728). @*Conclusions@#Our web-based dynamic nomogram reliably predicted the risk of MBE in AIS patients after ET, and hence is worthy of further evaluation.
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ABSTRACT Background: Fibrinogen (Fib) to albumin (ALB) fibrinogen-to-albumin ratio as a prognostic index for esophageal cancer has been confirmed. A novel prognostic index was initially proposed with fibrinogen to prealbumin ratio (FPR) in patients with resectable esophageal squamous cell carcinoma (ESCC). Objective: The objective of the study was to study the prognostic role of the novel prognostic index (FPR) in patients with resectable ESCC without any neoadjuvant treatment. Methods: In this retrospective study, a total of 372 resectable ESCC patients without any neoadjuvant treatment were included. The best cutoff values were selected by the receiver operating characteristic curves. Two Cox regression analyses with forward stepwise (one for categorical variables and the other for continuous variables) were used to evaluate the overall survival (OS) and cancer-specific survival (CSS). Results: The best cutoff point was 0.014 for FPR. Patients with lower levels of FPR (≤0.014) had better CSS (50.7% vs. 18.0%, p < 0.001) and OS (48.0% vs. 17.6%, p < 0.001) than patients with higher levels of FPR (> 0.014). Multivariate Cox analyses (categorical and continuous) demonstrated that FPR was an independent prognostic factor in CSS (categorical: hazard ratio [HR]: 2.014, 95% confidence interval [CI]: 1.504-2.697, p < 0.001; continuous per 0.01: HR: 1.438, 95% CI: 1.154-1.793, p = 0.001) and OS (categorical: HR: 1.964, 95% CI: 1.475-2.617, p < 0.001; continuous per 0.01: HR: 1.429, 95% CI: 1.146-1.781, p = 0.002). Conclusions: Our study indicated that FPR served as an independent prognostic factor in patients with resectable ESCC.
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Humans , Male , Female , Middle Aged , Fibrinogen/metabolism , Prealbumin/metabolism , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/pathology , Prognosis , Esophageal Neoplasms/surgery , Retrospective Studies , Follow-Up Studies , Esophageal Squamous Cell Carcinoma/surgeryABSTRACT
OBJECTIVE: Therapeutic nucleic acids(siRNA etc.) have unique advantages such as high specificity, safety, and target diversity in the treatment of diseases. However, the naked siRNAs are easily degraded by nucleases(RNase), have short half-lives and low transfection efficiency, which limit their therapeutic application. To construct a mildly acidic microenvironment sensitive liposomal nanocarrier for the efficient localization and delivery of siRNA(small interfering RNA) at the tissue, cell and even organelle levels. METHODS: Blank liposomes were prepared by thin-film hydration using dioleoyl phosphatidylethanolamine(DOPE) and cholesteryl hemisuccinate(CHEMS). The siRNA was compressed with the amphiphilic material SA-R8 to obtain SA-R8/siRNA, which was then incubated with blank liposomes to prepare liposomes encapsulating siRNA. The terminally functionalized phospholipid(DSPE-PEG2000-MAL) was linked to the low pH insertion peptide(pHLIP). The product was then incubated with liposomes encapsulating siRNA to construct pHLIP-modified liposomes encapsulating siRNA. The particle size and distribution of liposomes were characterized by dynamic light scattering principle. The cellular uptake, intracellular transport and distribution were monitored by flow cytometry and confocal laser-scanning technique. RESULTS: The RESULTS showed that the average size of the prepared liposomes encapsulating siRNA was between 150 and 190 nm. The cell uptake of siRNA at pH 6.5 was significantly higher than that of pH 7.4. And the siRNA internalized was well localized in the cytoplasm. CONCLUSION: This carrier shows strong pH sensitivity and can significantly increase the cell uptake of siRNA in the tumor acidic environment.
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<p><b>Background</b>Sleep disturbance is one of the major non-motor symptoms which cause the disability of Parkinson's disease (PD) patients. Cystatin C (CysC) is a more sensitive biomarker than serum creatinine or estimated glomerular filtration rate. Previous studies have reported altered CysC levels in neurodegenerative disorders and sleep disorders. This study aimed to explore the correlations of serum CysC levels and objective sleep disturbances in early PD.</p><p><b>Methods</b>We recruited 106 early PD patients and 146 age- and sex-matched controls. All participants underwent clinical investigation and video-polysomnography. Sleep parameters and serum levels of CysC were measured. Then, we investigated the relationships between CysC and clinical variables and objective sleep disturbances in early PD patients.</p><p><b>Results</b>The mean serum level of CysC was significantly higher in patients with early PD (1.03 ± 0.19 mg/L) compared to controls (0.96 ± 0.15 mg/L, P = 0.009). There were significantly positive correlations between serum CysC levels and age (r = 0.334, P < 0.001), gender (r = 0.264, P = 0.013), and creatinine levels (r = 0.302, P = 0.018) in early PD patients. Increased serum CysC levels in early PD patients were significantly associated with higher apnea and hypopnea index (AHI) (r = 0.231, P = 0.017), especially hypopnea index (r = 0.333, P < 0.001). In early PD patients, elevated serum CysC levels were positively correlated with oxygen desaturation index (r = 0.223, P = 0.021), percentage of time spent at oxygen saturation (SaO) <90% (r = 0.644, P < 0.001), arousal with respiratory event during sleep (r = 0.247, P = 0.013). On the contrary, the elevated serum CysC levels were negatively correlated with mean and minimal SaO(r = -0.323, -0.315, both P = 0.001) in PD patients.</p><p><b>Conclusions</b>The level of serum CysC was higher in early PD patients. PD patients with elevated serum CysC levels had more respiratory events and more severe oxygen desaturation. Therefore, the serum CysC levels may predict the severities of sleep-disordered breathing problems in early PD patients.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Cystatin C , Blood , Glomerular Filtration Rate , Physiology , Parkinson Disease , Blood , Polysomnography , Sleep Wake Disorders , BloodABSTRACT
Objective:Vacuolar ATPase (V-ATPase) was found within the membranes and internal organelles of a vast array of eukaryotic cells,and was related to various kinds of highly metastatic tumors.LASS2/TMSG1 gene was a novel tumor metastasis suppressor gene cloned from human prostate cancer cell line PC-3M in 1999 by our laboratory.It was found out that protein encoded by LASS2/TMSG1 could interact with the c subunit of V-ATPase (ATP6V0C).In this study,To use RNA interference to suppress the expression of ATP6V0C and try to further investigate the molecular mechanism of ATP6V0C in tumor metastasis and its relationship with LASS2/TMSG1 gene.Methods and Results:The expression level of ATP6V0C mRNA and protein in high metastatic potential prostate cancer cell lines (PC-3M-1E8 and PC-3M) was significantly higher than that in low metastatic potential prostate cancer cell lines (PC-3M-2B4 and PC-3),the expression level in PC-3M-1E8 being the highest.Follow-up tests selected PC-3M-1E8 cells for gene silencing.The expression and secretion of MMP-2 and the expression of MMP-9 in ATP6V0C siRNA transfected PC-3M-1E8 cells displayed no obvious change,but the activity of secreted MMP-9 was abated noticeably compared with the controls (P ＜ 0.05).Extracellular hydrogen ion concentration and V-ATPase activity in interference group were both reduced significantly compared with the controls (P ＜ 0.05).The migration and invasion capacity of ATP6V0C siRNA interfered cells in vitro were diminished significantly compared with the controls (P ＜ 0.05).Furthermore,a dramatic reduction of LASS2/TMSG1 mRNA and protein level after transfection of siRNA in PC-3M-1 E8 cells was discovered (P ＜ 0.05).Confocal immunofluorescence showed a vast co-localization of ATP6V0C protein and LASS2/TMSG1 protein in plasma and membrane.The co-localization signals of control group were much stronger than those of interference group.Conclusion:Specific siRNA silencing of ATP6V0C gene inhibits the invasion of human prostate cancer cells in vitro by mechanism of inhibiting V-ATPase activity and then reducing the extracellular hydrogen ion concentration,inhibiting MMP-9 activation and affecting ECM degradation and reconstruction.Meanwhile,ATP6V0C and LASS2/TMSG1 have interaction and it is likely that ATP6V0C functions as a feedback regulator of LASS2/TMSG1.
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Objective To evaluate the clinical feasibility of localization CT enhanced image replacing plain CT scan image for target delineation and dose calculation.Methods Forty cases of NPC were collected and divided into two groups with different concentrations of contrast agents.The contours of planning target volume (PTV) and organs at risk (OARs) of each case were delineated in the plain scan image,and the contours of PTV and OARs were copied to the enhanced image.Two plans based on the plain scan image and the enhanced image were designed in the planning system of Eclipse.The dose distribution and OARs and MU were compared between the groups.Results No statistical differences were found in the dosimetry of PTV,OARs and MU (P＞0.05).Conclusion The image intensifier has little effect on the dose calculation of Eclipse for NPC.In the radiotherapy for NPC,the localization CT enhanced image can be used to replace the plain CT scan image for target delineation and dose calculation.
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<p><b>OBJECTIVE</b>To investigate the effects of metoprolol on cardiomyocyte apoptosis and caspase-8 activation after coronary microembolization(CME) in rats.</p><p><b>METHODS</b>Adult rats were randomly assigned into CME group (intraventricular injection of 3000 microspheres with 42 µm in diameter), sham-operated group (0.1 ml saline) and CME plus metoprolol group (pretreatment with 3 bolus metoprolol 2.5 mg/kg intravenous injection at 10 minutes interval at 30 minutes before microspheres injection, n = 15, each group). Cardiac function was evaluated by echocardiography at 6 hours post various treatments. Cardiomyocyte apoptosis was detected with TUNEL staining and the expression of caspase-3 and caspase-8 was detected with Western blot analysis.</p><p><b>RESULTS</b>Compared with sham-operated group, LVEF (72.68% ± 3.26% vs. 82.64% ± 3.43%, P < 0.05), fractional shortening (FS) (37.46% ± 2.38% vs. 42.85% ± 3.25%) and cardiac output (CO) [(0.101 ± 0.006) L/min vs. (0.162 ± 0.008) L/min] were significantly reduced while left ventricular end-diastolic diameter (LVEDd) [(6.22 ± 0.17) mm vs. (5.18 ± 0.43) mm] was significantly increased in CME group (all P < 0.05). Cardiac function [LVEF:73.94% ± 4.22%, FS:38.53% ± 2.03%, CO:(0.120 ± 0.012) L/min, LVEDd:(6.18 ± 0.27) mm] was similar in CME plus metoprolol group compared to CME group (all P > 0.05). The cardiomyocytes apoptosis rates (3.19% ± 1.23% vs. 0.18% ± 0.10%) and the levels of activated caspase-3 and caspase-8 proteins were significantly increased in CME group than in sham-operated group (all P < 0.05). The cardiomyocyte apoptosis rate (1.32% ± 0.28%) and the levels of activated caspase-3 and caspase-8 proteins were significantly lower in CME plus metoprolol group than in CME group (all P < 0.05).</p><p><b>CONCLUSIONS</b>Metoprolol pretreatment reduced post-CME myocardial apoptosis possibly through downregulating death receptor-mediated apoptotic pathway.</p>
Subject(s)
Animals , Male , Rats , Apoptosis , Caspase 8 , Metabolism , Coronary Occlusion , Drug Therapy , Disease Models, Animal , Embolism , Drug Therapy , Ischemic Preconditioning, Myocardial , Metoprolol , Therapeutic Uses , Myocytes, Cardiac , Metabolism , Pathology , Rats, Sprague-DawleyABSTRACT
This study examined the clinical features of complications of congenital retinoschisis and the clinical efficacy of vitreoretinal surgery in the treatment of these complications. The clinical efficacy of surgical treatments was retrospectively analyzed in 10 patients with congenital retinoschisis (10 eyes) complicated with rhegmatogenous retinal detachment (n=5), vitreous hemorrhage (n=2) and macula- involving schisis (n=1). All the patients suffered foveal and peripheral schisis. They were treated with scleral buckling (n=1) or vitrectomy (n=9). After the surgical treatment, the retina was reattached in patients with rhegmatogenous retinal detachment; the refractive media became transparent in those with vitreous hemorrhage; the visual acuity in 80% of patients was improved; no remarkable progression of schisis was found; no severe operative complications occurred. It was concluded that vitreoretinal surgery in the treatment of complications of congenital retinoschisis is safe and effective, and helps improve and maintain the visual function.
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OBJECTIVE@#To determine the effect of photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV).@*METHODS@#Eleven patients (11 eyes) with PCV who were diagnosed by fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and optic coherence tomography (OCT) were given PDT. The changes of best corrected visual acuity (BCVA), fundus photography, FFA and ICGA before and after the PDT were compared. Follow-up time varied from 6 to 30 months.@*RESULTS@#One month after the PDT, the BCVA was stable in 3 eyes, increased in 1 line in 3 eyes, increased in 2 lines in 2 eyes, and decreased in 2 lines in 3 eyes. FFA and ICGA showed no leakage in 5 eyes, leakage reduced in 3 eyes, and slight leakage in 3 eyes. At the last follow-up, the BCVA was stable in 5 eyes, increased in 1 line in 2 eyes, increased in 2 lines in 2 eyes, and decreased in 2 lines in 2 eyes. FFA and ICGA showed no leakage in 6 eyes, leakage reduced in 3 eyes, and slight leakage in 2 eyes. No severe systemic or local adverse effect was found during or after the PDT, except that 1 eye had vitreous hemorrhage 2 months after the PDT.@*CONCLUSION@#PDT may stop or reduce leakage of the lesion, facilitate the absorption of hemorrhage, edema and exudates, and stabilize or increase the patients' visual acuity. It could be a choice for PCV.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Choroid , Pathology , Choroid Diseases , Drug Therapy , Choroidal Neovascularization , Drug Therapy , Peripheral Vascular Diseases , Diagnosis , Drug Therapy , Photochemotherapy , Photosensitizing Agents , Therapeutic Uses , Porphyrins , Therapeutic Uses , Verteporfin , Visual AcuityABSTRACT
OBJECTIVE@#To examine the effect of genistin on traumatic proliferative vitreoretinopathy (PVR) in rabbits.@*METHODS@#Traumatic PVR was induced in pigmented rabbits by intravitreal injection of platelet rich plasma. The eyes then received an intravitreal injection of dimethyl sulfoxide (0.1 mL), 2 or 40 μg genistin (0.1 mL), and 1 mg fluorouracil(0.1 mL), respectively to form 4 groups. The eyes were examined ophthalmoscopically on distinct days after the surgery and the stage of PVR was evaluated. The model eyes and normal eyes in the 40 μg genistin group carried ERG test on the 28th day. All model eyes in the 4 groups were observed by light microscope on the 28th day.@*RESULTS@#In the control eyes, the retina was detached after 10 d, the PVR had progressed to higher stages with time. In the eyes injected 40 μg genistin or fluorouracil, the PVR also developed; however, the severity of PVR was lower than that in the control eyes. PVR was significantly inhibited in the 40 μg genistin group compared with the control eyes after 14 d (P<0.05). Histological examination of the genistin-treated eyes disclosed no morphological changes, and ERG analysis revealed no significant functional changes.@*CONCLUSION@#Intravitreal injection of genistin is safe and effective in reducing traumatic PVR in clinical treatment.