Preoperative and postoperative complications as risk factors for delayed gastric emptying following pancreaticoduodenectomy: A single-center retrospective study.

BACKGROUND: Mortality rates after pancreaticoduodenectomy (PD) have significantly decreased in specialized centers. However, postoperative morbidity, particularly delayed gastric emptying (DGE), remains the most frequent complication following PD. AIM: To identify risk factors associated with DGE after the PD procedure. METHODS: In this retrospective, cross-sectional study, clinical data were collected from 114 patients who underwent PD between January 2015 and June 2018. Demographic factors, pre- and perioperative characteristics, and surgical complications were assessed. Univariate and multivariate analyses were performed to identify risk factors for post-PD DGE. RESULTS: The study included 66 males (57.9%) and 48 females (42.1%), aged 33-83 years (mean: 62.5), with a male-to-female ratio of approximately 1.4:1. There were 63 cases (55.3%) of PD and 51 cases (44.7%) of pylorus-preserving pancreatoduodenectomy. Among the 114 patients who underwent PD, 33 (28.9%) developed postoperative DGE. Univariate analysis revealed significant differences in four of the 14 clinical indexes observed: pylorus preservation, retrocolonic anastomosis, postoperative abdominal complications, and early postoperative albumin (ALB). Logistic regression analysis further identified postoperative abdominal complications [odds ratio (OR) = 4.768, P = 0.002], preoperative systemic diseases (OR = 2.516, P = 0.049), and early postoperative ALB (OR = 1.195, P = 0.003) as significant risk factors. CONCLUSION: Postoperative severe abdominal complications, preoperative systemic diseases, and early postoperative ALB are identified as risk factors for post-PD DGE.

Morphological evaluation of the risk of posterior communicating artery aneurysm rupture: a mirror aneurysm model.

OBJECTIVE: The aim of this study was to use morphological parameters of mirror posterior communicating artery (PCoA) aneurysms to evaluate aneurysm rupture risk. METHODS: The morphological parameters of 45 pairs of ruptured mirror PCoA aneurysms were analyzed. Conditional univariate and multivariate logistic regression of the following paired morphological parameters was performed: aneurysm with a daughter sac, aneurysm height, aneurysm width, neck width, internal carotid artery diameter, PCoA diameter, flow angle, PCoA angle, aspect ratio, bottleneck factor, size ratio, height/width ratio, fetal posterior cerebral artery, and aneurysm with height > width. A scoring system was established according to the odds ratios (ORs). The receiver operating characteristic was used to test the prediction accuracy of this scoring system in the authors' database of 523 PCoA aneurysms and the threshold value was used to define higher risk. RESULTS: Aneurysm width (OR 1.676, p = 0.014), aneurysm with daughter sac (OR 7.775, p = 0.016), and aneurysm with height > width (OR 9.067, p = 0.012) were independent risk factors for rupture. The scoring system consisted of aneurysm width (1 point per mm), aneurysm with a daughter sac (5 points), and aneurysm with height > width (5 points). The area under the curve (AUC) of the scoring system was 0.842, and its threshold value was 7.97. A score ≥ 8 points was defined as higher risk. The AUC using this definition was 0.802. CONCLUSIONS: Aneurysm width, aneurysms with height > width, and aneurysms with a daughter sac were independent risk factors for PCoA aneurysm rupture. The scoring system devised in this study accurately predicts rupture risk.

Nonlinear Disturbance Observer-Based Fault-Tolerant Sliding-Mode Control for 2-D Plane Vehicular Platoon With UTVFD and ANAS.

This article investigates a nonlinear disturbance observer (NDO)-based fault-tolerant sliding-mode control (SMC) for 2-D plane vehicular platoon systems subjected to actuator faults with unknown time-varying fault direction (UTVFD), asymmetric nonlinear actuator saturation (ANAS), nonlinear unmodeled dynamics, and unknown external disturbance. The Nussbaum-type function approach is adopted to solve the problem of actuator faults with UTVFD. The designed NDO not only can estimate the lumped disturbance accurately but also can reduce the control peaking and chattering phenomena caused by the Nussbaum-type function. Then, an adaptive saturation compensator is designed to compensate for the influence of actuator saturation on the system. In addition, by combining SMC technology with the prescribed tracking performance (PTP) approach, a distributed fault-tolerant control scheme is developed to not only ensure collision avoidance and communication connectivity but also realize a variety of driving scenarios, such as multilane vehicle merging and vehicular platoon lane changing. Finally, simulation results are presented to show the proposed scheme's effectiveness and advantages.

Risk factors for the rupture of mirror middle cerebral artery aneurysm using computer-assisted semiautomated measurement and hemodynamic analysis.

OBJECTIVES: To identify the morphologic and hemodynamic risk factor of mirror middle cerebral artery (MCA) aneurysms. METHODS: We conducted a retrospective analysis of 40 paired mirror MCA aneurysms. Aneurysms were divided into ruptured and unruptured groups. Seventeen morphological and nine hemodynamic parameters were measured using computer-assisted semiautomated measurement (CASAM) and computer flow dynamic (CFD) simulation. We performed a paired t-test (for normally distributed data) or a paired Wilcoxon rank-sum (for non-normally distributed data) to analyze all parameters between the groups. Multivariate conditional logistic regression analysis identified independent risk factors. The receiver operating characteristic curve was analyzed to acquire the area under the curve (AUC) and the cutoff values of the independent risk factors. RESULTS: There were significant differences in morphological and hemodynamic parameters between the ruptured and unruptured mirror aneurysms. The multivariate logistic analysis showed that the greater size (odds ratio [OR] = 9.807, p = 0.003), smaller neck diameter (OR = 0.285, p = 0.018) and maximum oscillatory shear index (OSI) (OR = 0.000001, p = 0.046) were independently correlated with aneurysm rupture. AUCs for size, N. and maximum OSI were 0.794, 0.695, and 0.701, respectively. The cutoff values of the size, neck diameter, and maximum OSI were 6.30, 5.07, and 0.356437, respectively. CONCLUSIONS: Morphology and hemodynamics can help predict aneurysm rupture risks. The more significant size, smaller neck diameter and maximum OSI were independent risk factors for the rupture of MCA aneurysms. The variables could aid practical risk evaluation.

Clip-reinforced wrapping using the Y-shaped temporalis fascia technique for intracranial aneurysms.

Objectives: This study aims to identify the effectiveness of the clip-reinforced wrapping using the Y-shaped temporalis fascia (CRYST) technique for treating intracranial aneurysms (IAs). Methods: We retrospectively reviewed five patients with ruptured IAs treated using the CRYST technique from July 2016 to May 2021. Three patients had blood blister-like aneurysms (BBAs) (one with intraoperative rupture), and two had anterior communicating artery (AcoA) aneurysms (one with intraoperative rupture). All patients had intraoperative indocyanine green angiography, and digital subtraction angiography (DSA) was reviewed 10-14 days after surgery. At 1 year postoperatively, three patients (two BBAs and one AcoA aneurysm) underwent DSA and two patients (one BBA and one AcoA aneurysm) underwent computed tomographic angiography (CTA). Results: Two aneurysms ruptured intraoperatively during the clipping, and no severe complications occurred. No patients had neurological deficits after surgery, and they had good outcomes. Four DSAs showed no aneurysms and no significant stenosis of the parent artery 10-14 days after surgery. One patient had mild stenosis of the parent artery on DSA 10 days after surgery; the stenosis improved on DSA 1 year after surgery. No other aneurysms recurred, and parent arteries were clear on CTA or DSA 1 year after surgery. Conclusions: Combining our accumulated experience in the work and literature, we described the CRYST technique to treat intractable IAs with specific morphologies and irregular wall structures in our patients. All outcomes and follow-up results were favorable.

[The role and mechanism of autophagy in lipopolysaccharide-induced inflammatory response of A549 cells]. / 自噬在脂多糖诱导的A549ç»†èƒžç‚Žç—‡ååº”ä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To study the role and mechanism of autophagy in lipopolysaccharide (LPS)-induced inflammatory response of human alveolar epithelial A549 cells. METHODS: A549 cells were stimulated with LPS to establish a cell model of inflammatory response, and were then grouped (n=3 each) by concentration (0, 1, 5, and 10 µg/mL) and time (0, 4, 8, 12, and 24 hours). The A549 cells were treated with autophagy inhibitor 3-methyladenine (3-MA) to be divided into four groups (n=3 each): control, LPS, 3-MA, and 3-MA+LPS. The A549 cells were treated with autophagy agonist rapamycin (RAPA) to be divided into four groups (n=3 each): control, LPS, RAPA, and RAPA+LPS. The A549 cells were transfected with the Toll-like receptor 4 (TLR4) overexpression plasmid to be divided into four groups (n=3 each): TLR4 overexpression control, TLR4 overexpression, TLR4 overexpression control+LPS, and TLR4 overexpression+LPS. The A549 cells were transfected with TLR4 siRNA to be divided into four groups (n=3 each): TLR4 silencing control,TLR4 silencing, TLR4 silencing control+LPS, and TLR4 silencing+LPS. CCK-8 assay was used to measure cell viability. Western blot was used to measure the protein expression levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4. RESULTS: After stimulation with 1 µg/mL LPS for 12 hours, the levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4 increased and reached the peak (P<0.05). Compared with the LPS group, the 3-MA+LPS group had reduced expression of autophagy-related proteins and increased expression of inflammation-related proteins and TLR4, while the RAPA+LPS group had increased expression of autophagy-related proteins and reduced inflammation-related proteins and TLR4 (P<0.05). The TLR4 overexpression+LPS group had reduced autophagy-related proteins and increased inflammation-related proteins compared with the TLR4 overexpression control+LPS group, and the TLR4 silencing+LPS group had increased autophagy-related proteins and reduced inflammation-related proteins compared with the TLR4 silencing control+LPS group (P<0.05). CONCLUSIONS: In the LPS-induced inflammatory response of human alveolar epithelial A549 cells, autophagic flux has a certain protective effect on A549 cells. TLR4-mediated autophagic flux negatively regulates the LPS-induced inflammatory response of A549 cells.

A predictive hemodynamic model based on risk factors for ruptured mirror aneurysms.

Objectives: To identify hemodynamic risk factors for intracranial aneurysm rupture and establish a predictive model to aid evaluation. Methods: We analyzed the hemodynamic parameters of 91 pairs of ruptured mirror aneurysms. A conditional univariate analysis was used for the continuous variables. A conditional multivariate logistic regression analysis was performed to identify the independent risk factors. Differences where p < 0.05 were statistically significant. A predictive model was established based on independent risk factors. Odds ratios (ORs) were used to score points. The validation cohort consisted of 189 aneurysms. Receiver operating characteristic curves were generated to determine the cutoff values and area under the curves (AUCs) of the predictive model and independent risk factors. Results: The conditional multivariate logistic analysis showed that the low shear area (LSA) (OR = 70.322, p = 0.044, CI = 1.112-4,445.256), mean combined hemodynamic parameter (CHP) (>0.087) (OR = 3.171, p = 0.034, CI = 1.089-9.236), and wall shear stress gradient (WSSG) ratio (>893.180) (OR = 5.740, p = 0.003, CI = 1.950-16.898) were independent risk factors. A prediction model was established: 23*LSA + 1*CHP mean (>0.087: yes = 1, no = 0) + 2 * WSSG ratio (>893.180: yes = 1, no = 0). The AUC values of the predictive model, LSA, mean CHP (>0.087), and WSSG ratio (>893.180) were 0.748, 0.700, 0.654, and 0.703, respectively. The predictive model and LSA cutoff values were 1.283 and 0.016, respectively. In the validation cohort, the predictive model, LSA, CHP (>0.087), and WSSG ratio (>893.180) were 0.736, 0.702, 0.689, and 0.706, respectively. Conclusions: LSA, CHP (>0.087), and WSSG ratio (>893.180) were independent risk factors for aneurysm rupture. Our predictive model could aid practical evaluation.

Early Follow-Up of Arthroscopic Latarjet Procedure with Screw or Suture-Button Fixation for Recurrent Anterior Shoulder Instability.

OBJECTIVE: To evaluate the early clinical and radiographic results of arthroscopic Latarjet procedure using screw or suture-button fixation in patients with recurrent anterior shoulder dislocation. METHODS: Twelve patients who underwent arthroscopic Latarjet procedure between January 2015 and December 2018 at our institution were retrospectively studied. Data of the patients' history, including age, gender, side of affected arm, body mass index (BMI), and the number of dislocations since fist dislocation were collected. Preoperative and postoperative clinical follow-up data were evaluated using Walch-Duplay score, American Shoulder and Elbow Society (ASES) score, and modified Rowe score. Active external rotation and active internal rotation at 90° of abduction as well as active elevation were evaluated preoperatively and postoperatively. The position and healing condition of the transferred coracoid bony graft were also assessed using computed tomography (CT) and Mimics 19.0 software. RESULTS: Mean follow-up was 24.9 months (range, 13 to 53 months) of all patients. At final follow-up, the average ASES score (preoperative vs postoperative values) had improved from 68.9 ± 7.9 to 91.1 ± 6.1 in screw fixation group and 68.9 ± 8.9 to 87.5 ± 6.7 in suture-button fixation group; the average Rowe score (preoperative vs postoperative values) had improved from 25.0 ± 8.4 to 92.5 ± 4.2 in screw fixation group and 21.7 ± 13.7 to 93.3 ± 4.1 in suture-button fixation group; the average of Walch-Duplay score (preoperative vs postoperative values) had improved from 12.5 ± 15.1 to 91.7 ± 4.1 in screw fixation group and 18.3 ± 20.7 to 88.3 ± 7.5 in button fixation group. The forward flexion was 175.0° ± 8.4° preoperatively and 178.3° ± 4.1° postoperatively in screw fixation group while 174.8° ± 10.2° preoperatively and 175.0° ± 5.5° postoperatively in suture-button fixation group. The active external rotation was 77.5° ± 5.2° preoperatively and 71.7° ± 4.1° postoperatively in screw fixation group while 72.5° ± 6.9° preoperatively and 68.3° ± 7.5° postoperatively in suture-button fixation group. The average of active internal rotation was 66.7° ± 6.1° preoperatively and 67.5° ± 6.1° postoperatively in screw fixation group while 68.3° ± 11.3° preoperatively and 66.7° ± 7.5° postoperatively in suture-button fixation group. In postoperative CT scan, 91.7% grafts midline center were located at or under the equator in the en face view; 75% of the bone blocks were flush to the glenoid face in the axial view, with only two grafts exhibiting slight medial placement in screw fixation group (33.3%) and one graft exhibiting slight lateral placement in suture-button fixation group (16.7%). All grafts achieved bone union. Graft absorption mostly occurred outside of the "best-fit" circle. The average bony absorption rates of the coracoid grafts were 25.2% and 10.18% in screw fixation group and suture-button fixation group, respectively, at 6 months postoperative follow-up. CONCLUSION: Both suture-button fixation and screw fixation techniques in arthroscopic Latarjet procedure revealed excellent clinical outcomes with low complication rates in the early follow-up. The suture-button fixation exhibited a flexible fixation pattern that allowed for self-correction to some extent, even slight lateralization could finally remodel over time.

Autophagic blockage by bismuth sulfide nanoparticles inhibits migration and invasion of HepG2 cells.

The biological effects of nanoparticles are of great importance for the in-depth understanding of safety issues in biomedical applications. Induction of autophagy is a cellular response after nanoparticle exposure. Bismuth sulfide nanoparticles (Bi2S3 NPs) are often used as a CT contrast agent because of their excellent photoelectric conversion ability. Yet there has been no previous detailed study other than a cell toxicity assessment. In this study, three types of Bi2S3 NPs with different shapes (Bi2S3 nano rods (BSNR), hollow microsphere Bi2S3 NPs (BSHS) and urchin-like hollow microsphere Bi2S3 NPs (ULBSHS)) were used to evaluatecytotoxicity, autophagy induction, cell migration and invasion in human hepatocellular carcinoma cells (HepG2). Results showed that all three Bi2S3 NPs lead to blockage in autophagic flux, causing p62 protein accumulation. The cell death caused by these Bi2S3 NPs is proved to be autophagy related, rather than related to apoptosis. Moreover, Bi2S3 NPs can reduce the migration and invasion in HepG2 cells in an autophagy-dependent manner. ULBSHS is the most cytotoxic among three Bi2S3 NPs and has the best tumor metastasis suppression. These results demonstrated that, even with relatively low toxicity of Bi2S3 NPs, autophagy blockage may still substantially influence cell fate and thus significantly impact their biomedical applications, and that surface topography is a key factor regulating their biological response.

Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury.

BACKGROUND: Aucubin (Au), an iridoid glycoside from natural plants, has antioxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in an H2O2-induced oxidant damage in primary cortical neurons and weight-drop induced-TBI in a mouse model. METHODS: In vitro experiments, the various concentrations of Au (50 µg/ml, 100 µg/ml, or 200 µg/ml) were added in culture medium at 0 h and 6 h after neurons stimulated by H2O2 (100 µM). After exposed for 12 h, neurons were collected for western blot (WB), immunofluorescence, and M29,79-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In vivo experiments, Au (20 mg/kg or 40 mg/kg) was administrated intraperitoneally at 30 min, 12 h, 24 h, and 48 h after modeling. Brain water content, neurological deficits, and cognitive functions were measured at specific time, respectively. Cortical tissue around focal trauma was collected for WB, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl staining, quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry, and enzyme linked immunosorbent assay (ELISA) at 72 h after TBI. RNA interference experiments were performed to determine the effects of nuclear factor erythroid-2 related factor 2 (Nrf2) on TBI mice with Au (40 mg/kg) treatment. Mice were intracerebroventricularly administrated with lentivirus at 72 h before TBI establishment. The cortex was obtained at 72 h after TBI and used for WB and q-PCR. RESULTS: Au enhanced the translocation of Nrf2 into the nucleus, activated antioxidant enzymes, suppressed excessive generation of reactive oxygen species (ROS), and reduced cell apoptosis both in vitro and vivo experiments. In the mice model of TBI, Au markedly attenuated brain edema, histological damages, and improved neurological and cognitive deficits. Au significantly suppressed high mobility group box 1 (HMGB1)-mediated aseptic inflammation. Nrf2 knockdown in TBI mice blunted the antioxidant and anti-inflammatory neuroprotective effects of the Au. CONCLUSIONS: Taken together, our data suggest that Au provides a neuroprotective effect in TBI mice model by inhibiting oxidative stress and inflammatory responses; the mechanisms involve triggering Nrf2-induced antioxidant system.

Safety and efficacy of different therapeutic strategies in the endovascular treatment of anterior cerebral artery aneurysms with different features: A single centre experience.

BACKGROUND: Outcomes of endovascular treatment of anterior cerebral artery (ACA) aneurysms are still not well-characterized. OBJECTIVE: The study aimed to review the clinical effect, procedure-related complications and follow-up outcomes and to evaluate the safety and efficacy of endovascular treatment of ACA aneurysms in our center experience. METHODS: From August 2014 to August 2018, a total of 75 consecutive patients with 77 ACA aneurysms were treated via the endovascular approach after providing informed consent. A retrospective review of the clinical, radiological, and endovascular details of these patients was conducted. RESULTS: The mortality and the morbidity in this study were 4% and 9.3%, respectively. Compared with A1 and A2 aneurysms, intraoperative rupture was more common in A3 aneurysms (P = 0.029). Difference between the ruptured and unruptured aneurysms in the distribution of therapeutic strategy (P = 0.003) and immediate embolization degree (P = 0.004) was also significant. Statistical analysis demonstrated that the larger aneurysm (P = 0.031) was, the greater the ratio of aneurysm size to parent artery diameter (P = 0.029) was, the more likely the unruptured aneurysms were to occur ischemic events. Higher Hunt-Hess grade (P = 0.0066) was an independent risk factor for poor clinical outcome. CONCLUSION: Endovascular treatment is feasible and effective for ACA aneurysms.

Inhibition of AIM2 inflammasome activation alleviates GSDMD-induced pyroptosis in early brain injury after subarachnoid haemorrhage.

Only a few types of inflammasomes have been described in central nervous system cells. Among these, the absent in melanoma 2 (AIM2) inflammasome is primarily found in neurons, is highly specific and can be activated only by double-stranded DNA. Although it has been demonstrated that the AIM2 inflammasome is activated by poly(deoxyadenylic-deoxythymidylic) acid sodium salt and leads to pyroptotic neuronal cell death, the role of AIM2 inflammasome-mediated pyroptosis in early brain injury (EBI) after subarachnoid haemorrhage (SAH) has rarely been studied. Thus, we designed this study to explore the mechanism of gasdermin D(GSDMD)-induced pyroptosis mediated by the AIM2 inflammasome in EBI after SAH. The level of AIM2 from the cerebrospinal fluid (CSF) of patients with SAH was detected. The pathway of AIM2 inflammasome-mediated pyroptosis, the AIM2/Caspase-1/GSDMD pathway, was explored after experimental SAH in vivo and in primary cortical neurons stimulated by oxyhaemoglobin (oxyHb) in vitro. Then, we evaluated GSDMD-induced pyroptosis mediated by the AIM2 inflammasome in AIM2 and caspase-1- deficient mice and primary cortical neurons generated through lentivirus (LV) knockdown. Compared with that of the control samples, the AIM2 level in the CSF of the patients with SAH was significantly increased. Pyroptosis-associated proteins mediated by the AIM2 inflammasome were significantly increased in vivo and in vitro following experimentally induced SAH. After AIM2 and caspase-1 were knocked down by an LV, GSDMD-induced pyroptosis mediated by the AIM2 inflammasome was alleviated in EBI after SAH. Intriguingly, when caspase-1 was knocked down, apoptosis was significantly suppressed via impeding the activation of caspase-3. GSDMD-induced pyroptosis mediated by the AIM2 inflammasome may be involved in EBI following SAH. The inhibition of AIM2 inflammasome activation caused by knocking down AIM2 and caspase-1 alleviates GSDMD-induced pyroptosis in EBI after SAH.

Morphology parameters for rupture in middle cerebral artery mirror aneurysms.

OBJECTIVE: To identify the morphological parameters correlated with the rupture of middle cerebral artery (MCA) aneurysms. METHODS: We retrospectively analyzed the digital subtraction angiography (DSA) data of 48 patients with ruptured mirror MCA aneurysms. Morphological parameters included aneurysm with wall protrusion, maximum diameter (Dmax), height, neck width, aneurysm width, dome projection, parent artery average diameter (Dp), aspect ratio (AR), bottleneck factor (BNF), size ratio (SR), M1/M2 ratio, and height/width (H/W) ratio. These paired parameters were analyzed by conditional univariate and multivariate logistic regressions to screen out the independent risk factors. We established a score based on the independent risk factors. Receiver operating characteristics (ROC) were generated to estimate the prediction performance of the score in our large database of 763 aneurysms. RESULTS: In the univariate regressions, Dmax, height, aneurysm width, neck width, AR, BNF, H/W ratio, SR, anterior dome projection and aneurysm with wall protrusion were significant risk factors. Aneurysm width (OR 3.296, p=0.015), AR (OR 11.594, p=0.014) and anterior dome projection (OR 9.385, p=0.016) were independent risk factors in multivariate regression. The area under the curve (AUC) value of the score based on the three independent risk factors was 0.829. CONCLUSION: Aneurysm width, AR and anterior dome projection were independent risks factors of rupture.

Preliminary results on anal cancer by applying intensity modulated radiotherapy and synchronous capecitabine chemotherapy simultaneously.

BACKGROUND: Anal cancer is a rare clinical disease with the incidence rate of 1-2/10 million. The present study aims to assess the feasibility, safety and short-term outcome of the simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) schedule with oral capecitabine in patients with anal cancer. METHODS: From September 2009 to February 2014, a total of 10 patients with anal carcinoma were treated with SIB-IMRT in 32 daily fractions of 1.8 Gy to the primary tumor and macroscopically involved lymph nodes and 32 fractions of 1.55 Gy electively to the bilateral iliac and inguinal lymph node areas with concurrent capecitabine 625 mg/m2 twice daily 5 days/week. Two patients received a sequential radiation boost dose of 2×1.8 Gy on macroscopic residual tumor in week 5 of treatment. Acute and late toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. RESULTS: All patients completed chemoradiation without any treatment break. Grade 3 acute skin toxicity was observed in 4 patients (40%). No grade 4 toxicity was observed. Mean follow-up was 20 months (range: 6-60 months). The 2-year-local control, colostomy-free survival, distant metastases-free survival and overall survival (OS) rates were 100% (10/10), 90% (9/10), 90% (9/10), and 90% (9/10), respectively. CONCLUSIONS: SIB-IMRT with concomitant capecitabine 625 mg/m2 b.i.d. on irradiation days resulted in an acceptable safety profile, and proved to be a tolerable and effective treatment regimen for locally advanced anal cancer. However, a larger number of patients and a longer follow-up are required to assess its potential superiority.

Inhibition of Elevated Hippocampal CD24 Reduces Neurogenesis in Mice With Traumatic Brain Injury.

In the adult rodents' brain, CD24 expression is restricted to immature neurons located in the neurogenesis areas. Our previous studies have confirmed that CD24 expression could be markedly elevated in the cerebral cortex after traumatic brain injury (TBI) both in humans and in mice. Although there is a close relationship between CD24 and neurogenesis, it remains unknown about the specific role of CD24 in neurogenesis areas after TBI. Here, the expression of CD24 was detected in the ipsilateral hippocampus by the Western blotting and real-time quantitative polymerase chain reaction. RNA interference was applied to investigate the effects of CD24 on post-traumatic neurogenesis. Brain sections were labeled with CD24 and doublecortin (DCX) via immunofluorescence. The Morris water maze test was used to assess cognitive functions. The results indicated that both mRNA and protein levels of CD24 were markedly elevated in the hippocampus after TBI. Meanwhile, TBI could cause a decrease of DCX-positive cells in the dentate gyrus of the hippocampus. Downregulation of CD24 significantly inhibited the phosphorylation of Src homology region 2-containing protein tyrosine phosphatase 2 in the ipsilateral hippocampus. Meanwhile, inhibition of CD24 could reduce the number of DCX-positive cells in the dentate gyrus area and impair cognitive functions of the TBI mice. These data suggested that hippocampal expression of CD24 might positively regulate neurogenesis and improve cognitive functions after TBI.

Receptor-Mediated Delivery of Astaxanthin-Loaded Nanoparticles to Neurons: An Enhanced Potential for Subarachnoid Hemorrhage Treatment.

Astaxanthin (ATX) is a carotenoid that exerts strong anti-oxidant and anti-inflammatory property deriving from its highly unsaturated molecular structures. However, the low stability and solubility of ATX results in poor bioavailability, which markedly hampers its application as therapeutic agent in clinic advancement. This study investigated a promising way of transferrin conjugated to poly (ethylene glycol) (PEG)-encapsulated ATX nanoparticles (ATX-NPs) on targeted delivery and evaluated the possible mechanism underlying neuroprotection capability. As a result, the ATX integrated into nanocarrier presented both well water-dispersible and biocompatible, primely conquering its limitations. More than that, the transferrin-containing ATX-NPs exhibited enhanced cellular uptake efficiency than that of ATX-NPs without transferrin conjugated in primary cortical neurons. Additionally, compared to free ATX, transferrin-containing ATX-NPs with lower ATX concentration showed powerful neuroprotective effects on OxyHb-induced neuronal damage. Taken together, the improved bioavailability and enhanced neuroprotective effects enabled ATX-NPs as favorable candidates for targeted delivery and absorption of ATX. We believe that these in vitro findings will provide insights for advancement of subarachnoid hemorrhage therapy.

Targeting an Autocrine Regulatory Loop in Cancer Stem-like Cells Impairs the Progression and Chemotherapy Resistance of Bladder Cancer.

PURPOSE: Cancer stem-like cells (CSCs) contribute to bladder cancer chemotherapy resistance and progression, but the associated mechanisms have not been elucidated. This study determined whether blocking an autocrine signaling loop in CSCs improves the therapeutic effects of cis-platinum on bladder cancer. EXPERIMENTAL DESIGN: The expression of the epithelial marker OV6 and other markers in human bladder cancer specimens was examined by IHC. The CSC properties of magnetic-activated cell sorting (MACS)-isolated OV6+ and OV6- bladder cancer cells were examined. Molecular mechanisms were assessed through RNA-Seq, cytokine antibody arrays, co-immunoprecipitation (co-IP), chromatin immunoprecipitation (ChIP) and other assays. An orthotopic bladder cancer mouse model was established to evaluate the in vivo effects of a YAP inhibitor (verteporfin) and a PDGFR inhibitor (CP-673451) on the cis-platinum resistance of OV6+ CSCs in bladder cancer. RESULTS: Upregulated OV6 expression positively associated with disease progression and poor prognosis for bladder cancer patients. Compared with OV6- cells, OV6+ bladder cancer cells exhibited strong CSC characteristics, including self-renewal, tumor initiation in NOD/SCID mice, and chemotherapy resistance. YAP, which maintains the stemness of OV6+ CSCs, triggered PDGFB transcription by recruiting TEAD1. Autocrine PDGF-BB signaling through its receptor PDGFR stabilized YAP and facilitated YAP nuclear translocation. Furthermore, blocking the YAP/TEAD1/PDGF-BB/PDGFR loop with verteporfin or CP-673451 inhibited the cis-platinum resistance of OV6+ bladder cancer CSCs in an orthotopic bladder cancer model. CONCLUSIONS: OV6 could be a helpful indicator of disease progression and prognosis for patients with bladder cancer, and targeting the autocrine YAP/TEAD1/PDGF-BB/PDGFR loop might serve as a remedy for cis-platinum resistance in patients with advanced bladder cancer.

Simplified Chinese version of hip and knee replacement expectations surveys in patients with osteoarthritis and ankylosing spondylitis: cross-cultural adaptation, validation and reliability.

BACKGROUND: The Hospital for Special Surgery Hip Replacement Expectations Survey (HSS-THRES) and Knee Replacement Expectations Survey (HSS-TKRES) are widely used tools developed to assess patients' preoperative expectations for total hip and knee arthroplasty. This study aimed to translate and adapt the HSS-THRES and HSS-TKRES into Chinese versions (SC-THRES/TKRES) and evaluate their psychometric properties in patients with osteoarthritis (OA) and ankylosing spondylitis (AS). METHODS: Patients scheduled for total hip (104 hip OA and 51 AS) or knee replacements (101 knee OA) were recruited in this study. Confirmatory Factor Analysis (CFA) was used to evaluate structural validity. The internal consistency was assessed by the Cronbach's α coefficient. The intraclass correlation coefficient (ICC) was used to assess test-retest reliability. The construct validity was analyzed by evaluating the correlations between SC-THRES/TKRES and the Expectation WOMAC. The correlations with the Expectation WOMAC were tested against our hypotheses. We additionally compared preoperative expectations of AS patients to those of hip OA patients. RESULTS: The results of CFA for the SC-THRES and SC-TKRES demonstrated good fit. The results for the SC-THRES/TKRES revealed good test-retest reliability and good internal consistency (AS: ICC = 0.893, Cronbach's α = 0.815; hip OA: ICC = 0.878, Cronbach's α = 0.814; knee OA: ICC = 0.806, Cronbach's α = 0.808). The correlations between the SC-THRES/TKRES and the Expectation WOMAC were moderate (0.541 for AS, 0.490 for hip OA and 0.465 for knee OA), which were consistent with the hypotheses. CONCLUSION: The SC-THRES/TKRES are reliable, valid for the evaluation of Chinese patients with OA and AS undergoing total hip and knee arthroplasty. The surveys can be used as part of preoperative assessments. Meanwhile, additional research is needed to replicate these findings and to assess the content validity in a larger sample.

Cross-cultural adaptation and validation of the Chinese version of the shoulder pain and disability index in patients with symptomatic shoulder pain: A prospective case series.

The aim of this study is to cross-culturally adapt and translate the original version of SPADI into Chinese (C-SPADI), and to test the reliability, validity, and responsiveness of the C-SPADI.This research was a test of previously developed diagnostic criteria in a series of consecutive patients with universally applied gold standard. The original version was translated into Chinese according to international recognized standards. Patients who were diagnosed with a shoulder disorder and underwent shoulder arthroscopic treatments from 2014 to 2015 were enrolled in our study. Each participant was asked to finish the C-SPADI, the Short-Form 36 (SF-36), and the Oxford Shoulder score (OSS) at first visit. The C-SPADI was completed a second time with an interval of 7 days. Six months after arthroscopic treatments, the C-SPADI was completed a third time for responsiveness evaluation. The Cronbach alpha, intraclass correlation coefficient (ICC), standard error of measurement (SEM), minimally detectable change (MDC), Pearson correlation coefficient (r), effect size (ES), and standardized response mean (SRM) were calculated to evaluate the reliability, validity, and responsiveness of C-SPADI respectively.The original version of the SPADI was well adapted and translated into Chinese. The Cronbach alpha ranged from 0.812 to 0.912 in all subscales and total scale of the C-SPADI, indicating good or excellent internal consistency. The test-retest reliability (ICC = 0.887-0.915, SEM = 5.47, MDC = 15.16) was proved to be good or excellent. Moderate or good correlations (r = 0.556-0.672) were obtained between the C-SPADI and the OSS, physical subscales of SF-36; and poor, fair, or moderate correlations (r = 0.038-0.492) were obtained between the C-SPADI and mental subscales of SF-36, which, adequately illustrated good discriminant validity in the C-SPADI. Additionally, the responsiveness was considered good in the C-SPADI (SRM = 1.58-2.44, ES = 1.79-2.17).The C-SPADI was documented to be a reliable, valid, and responsible instrument for self-assessment of patients with shoulder disorders in China. LEVEL OF EVIDENCE: Level II.