Abnormal dynamics of functional connectivity density and effective connectivity in overactive bladder.

PURPOSE: The study aims to analyze alterations in dynamic functional connectivity density (dFCD) and effective connectivity (dEC) patterns using functional magnetic resonance imaging (fMRI), hypothesizing that overactive bladder (OAB) patients will exhibit distinct dFCD and dEC patterns, reflecting altered neural communication underlying the OAB. METHODS: Forty-three female OAB patients and 40 female healthy controls (HC) underwent resting-state fMRI. Sliding window correlation was used to calculate the variability of the dFCD. The changes in dFCD-based dEC between the two groups were examined using Granger causal analysis. To describe the time-varying Granger causality, a sliding-window approach was utilized to divide time courses into a group of windows. We adopted a k-means clustering method to cluster all matrices into discrete connectivity states. RESULTS: Compared with HC, OAB females consistently had a dFCD (decreased) in the left anterior cingulate cortex (ACC) and left medial prefrontal cortex (mPFC) (p < 0.05, GRF corrected). In state 1, OAB patients had excitatory effective connections from bilateral ACC to left mPFC in comparison to HC. In state 2, there was an increase in dEC from the SMA to the mPFC. Participants with OAB showed significantly more inhibitory dorsolateral prefrontal cortex (dlPFC) connections between the left ACC and the right ACC in state 4, as well as an excitatory dEC connection between the right dlPFC and the left ACC in state 2 (p < 0.05, GRF corrected). CONCLUSION: OAB patients demonstrate significant alterations in dFCD and dEC patterns, which may be indicative of the neural mechanisms involved in OAB pathophysiology.

Lateral Malleolus Reconstruction After Tumor Resection in Children: A Case Report and Literature Review.

BACKGROUND: Pediatric reconstruction of lateral malleolus was necessary and challengeable. Up to now, vascularized fibular was the optimal graft to reconstruct epiphyseal defection. However, the sophisticated microvascular operation has limited the wide application of this technique. CASE PRESENTATION: We present the case of a 9-year-old boy with Ewing sarcoma in left distal fibula. In order to restore the growth capacity, we used reverse-flow vascularized fibular epiphyseal graft with tibialis anterior artery to reconstruct the bone defect after tumor resection with no microvascular anastomosis. More than 4 years after the operation and adjuvant chemotherapy, the patient was free of pain and recurrence, and the function and stability of ankle joint was perfect. Radiology examination revealed satisfied bony union of fibula and normal growth of the fibular head transplant. CONCLUSIONS: The advantage of reverse-flow vascularized fibular epiphyseal graft is requiring no microvascular anastomosis which could not only shorten operating time, but also reduce factitious damage of vessels. This report presented that this technique might be an available option for reconstruction of lateral malleolus in children.

Abnormal resting-state brain activity and connectivity of brain-bladder control network in overactive bladder syndrome.

BACKGROUND: Neuroimaging studies have shown that the brain is involved in the mechanism of overactive bladder disease (OAB). PURPOSE: To explorer spatial patterns of spontaneous neural activities and functional integration in patients with OAB. MATERIAL AND METHODS: In total, 28 patients with OAB and 28 matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging and completed questionnaires to assess clinical symptoms. The amplitude of low-frequency fluctuation (ALFF) and ROI-based functional connectivity (FC) within the brain-bladder control network (BBCN) were calculated and compared between the two groups using a two-sample t-test. Pearson correlation analysis was performed to investigate the relationship between ALFF and the clinical score of patients with OAB. RESULTS: Compared with HCs, patients with OAB exhibited significantly decreased ALFF in the left superior medial middle gyrus (SFGmed) and superior dorsal frontal gyrus (SFGdor), and increased ALFF in the right hippocampus. Furthermore, ALFF values in the left SFGmed were negatively correlated with OABSS scores. FC in patients with OAB was significantly increased between the bilateral caudate nucleus (CAU) and bilateral SFGdor, the bilateral CAU and bilateral supplementary motor area (SMA), the bilateral thalamus and SMA; the left CAU and bilateral SFGmed, the left CAU and bilateral anterior cingulate gyrus, and the left CAU and left insula. Additionally, decreased FC was found between the bilateral amygdala and bilateral SFGmed and the left SMA and left insula. CONCLUSION: These abnormal activities and connectivities of BBCN may indicate impaired cortical control of micturition in OAB, suggesting a possible neural mechanism of OAB.

Effective treatment of anlotinib in giant delayed pulmonary metastasis of osteosarcoma: a case report and literature review.

Tumor relapse and pulmonary metastasis, especially unresectable lesions, are the major cause of poor prognosis of patients with osteosarcoma. Anlotinib, a novel small-molecule tyrosine kinase inhibitor (TKI), has been proved to have desirable anti-tumor effects via blocking VEGFR2 and PDGFRß phosphorylation in several tumors, including non-small cell lung cancer and soft tissue sarcoma. In this study, we presented a case of giant delayed pulmonary metastasis of osteosarcoma which was effectively treated by anlotinib. CT scan of this patient showed a giant neoplasm with the size of 1,366 cm3 in the left lung, clinically diagnosed as pulmonary metastasis of osteosarcoma. Due to refusing to chemotherapy and not eligible for surgery of the giant neoplasm, anlotinib was recommended. As a result, the tumor volume decreased more than 82% during 24-week anlotinib administration, from 1,366 to 247 cm3. Unfortunately, disease progression was observed at 27-week. Although argon-helium cryoablation (AHC) was performed followed by apatinib administration, the patient was dead in 16 weeks after disease progression. The progression-free survival (PFS) and overall survival since anlotinib administration of this patient was 27 weeks and 43 weeks, respectively. The toxicity included hypertension, fatigue and hand-foot skin syndrome in grade 1-2, which were controllable and well tolerated. Meanwhile, immunohistochemical staining showed that the expression of VEGFR2 and PDGFRß was decreased significantly and the whole exon sequencing revealed that c-MYC was duplicated, which was potentially associated with anlotinib resistance. Anlotinib had promising anti-tumor efficiency in the treatment of delayed pulmonary metastatic osteosarcoma. However, the potential mechanism of anlotinib resistance and the subsequent therapy after resistance were still challengeable and needed further investigation.

Advances in Chemical Constituents and Bioactivities of Macleaya cordata / 中国实验方剂学杂志

Macleaya cordata, a perennial plant in the genus Macleaya, it mainly distributed in most provinces and regions south of the Yangtze river and north of Nanling mountains of China and has been used as a Chinese traditional medicine. It is bitter, cold, warm, poisonous. M. cordata has the functions of dispelling wind, analgesia, detoxification and detumescence. It mainly treats poisonous abscess, cachexia, ulcer, scabies, trichomonal vaginitis, etc. It also has insecticidal and anti-itching activities. The main chemical constituents of M. cordata are isoquinoline alkaloids, sanguinarine, chelerythrine, protoopioid and allocrine alkaloids are the higher ones. In addition, it also contains phenylpropanoids, steroids, organic acids, phenols and volatile oils. The pharmacological effects of M. cordata are mainly anti-bacterial, anti-inflammatory, anti-tumor and improving liver function. In agriculture, it can be used as botanical insecticides and bacteriostasis, and also as feed additives for animal husbandry. By reviewing and analyzing domestic and foreign researches that isoquinolines were the main active constituents and characteristic components of M. cordata. This paper provides theoretical basis for the development and utilization of M. cordata extract and its' monomer compounds.

Quantitative evaluation of blood-brain barrier permeability in patients with ischemic white matter lesions with dynamic contrast-enhanced MRI / 中国医学影像技术

Objective To investigate the changes of blood-brain barrier (BBB) permeability and the correlation with cognitive function in patients with ischemic white matter disease with dynamic contrast-enhanced MRI (DCE-MRI).Methods Totally 71 subjects underwent routine MRI,DCE-MRI,mini-mental state examination (MMSE) and Fazekas scoring,and then were divided into patient group and control group according to the Fazekas scores.The leakage rate (K),area under the leakage curve (AUC) and fractional blood plasma volume (Vp) in cerebral white matter hyperintensities area and normal appearing white matter area were measured and compared between the two groups.The correlation between these parameters and MMSE scores were analyzed.Results K and AUC value of white matter hyperintensities area and normal appearing white matter area in patient group were significantly higher than those in control group (all P＜0.001).Vp value of normal appearing white matter area in patient group was lower than that in control group (P=0.015).K and AUC value of white matter hyperintensities area in patient group had significant negative correlation with MMSE scores (r=-0.440,--0.540,both P＜0.001).Conclusion BBB permeability increased in cerebral white matter hyperintensities and normal appearing white matter area in patients with ischemic white matter lesions,which correlated with cognitive function.

Chain elongation analog of resveratrol as potent cancer chemoprevention agent

Resveratrol is identified as a natural cancer chemoprevention agent. There has been a lot of interest in designing and developing resveratrol analogs with cancer chemoprevention activity superior to that of parent molecule and exploring their action mechanism in the past several decades. In this study, we have synthesized resveratrol analogs of compounds A-C via conjugated chain elongation based on isoprene unit retention strategy. Remarkably, cytotoxic activity analysis results indicated that compound B possesses the best proliferation inhibition activity for NCI-H460 cells in all the test compounds. Intriguingly, compound B displayed a higher cytotoxicity against human non-small cell lung cancer cells (NCI-H460) compared to normal human embryonic lung fibroblasts (MRC-5). Afterward, flow cytometry analysis showed that compound B would induce cell apoptosis. We further researched the action mechanism. When NCI-H460 cells were incubated by compound B for 6 or 9 h, respectively, the intracellular reactive oxygen species (ROS) level was enhanced obviously. With elevation of intracellular ROS level, flow cytometry measurement verified mitochondrial transmembrane potential collapse, which was accompanied by the up-regulation of Bax and down-regulation of Bcl-2. More interestingly, compound B increased the expression of caspase-9 and caspase-3, which induced cell apoptosis. Moreover, compound B arrested cell cycle in G0/G1 phase. These are all to provide useful information for designing resveratrol-based chemoprevention agent and understanding the action mechanism (AU)

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Chain elongation analog of resveratrol as potent cancer chemoprevention agent.

Resveratrol is identified as a natural cancer chemoprevention agent. There has been a lot of interest in designing and developing resveratrol analogs with cancer chemoprevention activity superior to that of parent molecule and exploring their action mechanism in the past several decades. In this study, we have synthesized resveratrol analogs of compounds A-C via conjugated chain elongation based on isoprene unit retention strategy. Remarkably, cytotoxic activity analysis results indicated that compound B possesses the best proliferation inhibition activity for NCI-H460 cells in all the test compounds. Intriguingly, compound B displayed a higher cytotoxicity against human non-small cell lung cancer cells (NCI-H460) compared to normal human embryonic lung fibroblasts (MRC-5). Afterward, flow cytometry analysis showed that compound B would induce cell apoptosis. We further researched the action mechanism. When NCI-H460 cells were incubated by compound B for 6 or 9 h, respectively, the intracellular reactive oxygen species (ROS) level was enhanced obviously. With elevation of intracellular ROS level, flow cytometry measurement verified mitochondrial transmembrane potential collapse, which was accompanied by the up-regulation of Bax and down-regulation of Bcl-2. More interestingly, compound B increased the expression of caspase-9 and caspase-3, which induced cell apoptosis. Moreover, compound B arrested cell cycle in G0/G1 phase. These are all to provide useful information for designing resveratrol-based chemoprevention agent and understanding the action mechanism.

MR Tracer Diffusion in Cerebral Interstitial Fluid of Elderly SD Rats / 中国医学影像学杂志

Purpose With the progression of brain tissue aging, the transport and drainage characteristics of metabolites and secretory products for neurons in extracellular space occurs irreversible change. This paper aims to investigate and quantify MR tracer diffusion characteristics in cerebral interstitial fluid of elderly SD rats. Materials and Methods MR contrast agent Gd-DTPA was injected into the caudate nucleus of two groups of rats including 8 in experimental group (15-17 month old) and 15 in control group (7-10 month old). MR scan was performed at 0.25 h, 0.5 h, 1 h, 2 h, 3 h and 4 h to observe the dynamic distribution in the caudate and measure the diffusion and clearance rate. Results There was no statistically significant difference in diffusion rate and D* between control group with (3.32±0.70)×10-4 mm2/s and experimental group with (3.25±0.46)×10-4 mm2/s (t=1.739, P>0.05). The clearance rate k' was significantly different between control group (0.62±0.12)×10-4/s and experimental group (0.29±0.08)×10-4/s (t=11.602, P<0.05). Conclusion The degeneration of aging brain tissue changes the composition of extracellular space resulting in decreased speed of ISF clearance. This may cause accumulation of metabolites which eventually triggers a variety of age-related diseases.

Extracellular space diffusion during progression of rat C6 glioma quantificated by magnetic resonance imaging / 中国比较医学杂志

Objective To compare the extracellular space diffusion at different stages of rat C6-gliomas determined by MRI tracer method and analyze the influencing effect of extracellular matrix ( ECM) on the diffusion process.Methods Introducing adolinium-diethylene triaminepentaacetic acid ( Gd-DTPA) into extracellular space ( ECS) as a tracer.The diffusion parameters and half-life time were quantified according to mathematical model of diffusion.The main ECM components ( e.g. chordroitin sulfate proteoglycans ( CSPGs ) , collagen IV tenascin C ) were detected by immunohistochemical and immunoblot analysis.Results Gd-DTPA introduced into 20-day glioma in the rats diffused more slowly [(6.67 ±1.78) ×10 -5 mm2/s vs.(1.26 ±0.27) ×10-4 mm2/s; t =4.265; P<0.01)], deriving a larger tortuosity [(3.99 ±0.57) vs.(2.83 ±0.29);t=4.11;P<0.01)], localized within the tumor with a smaller clearance rate [(7.67 ±2.29) ×10 -5mm2/s)vs.(1.46 ±0.36) ×10 -4mm2/s);t=3.87;P<0.05), and a longer half-life time ((0.86 ±0.23 h)vs.(1.64 ±0.12 h);(t=5.91;p<0.01)] compared with 10-day gliomas in the rats.The increased levels of extracellular matrix of glioma were associated with different diffusion and clearance parameters of 20-day gliomas in the rats in comparision with those in the 10-day rat gliomas, in which the chordroitin sulfate proteoglycans[(0.48 ±0.07) vs.(0.32 ±0.09);t=4.663;P<0.01)], tenascin C [(0.29 ±0.04) vs.(0.58 ±0.11);t =6.50;P<0.01] and collagen IV [(0.24 ±0.07)vs.(0.33 ±0.06);t=3.81;P<0.05] were tested.Conclusions The ECS parameters are changed with the C6 glioma progression due to the increased ECM content.The results of our study may help us to better understanding the glioma micro-environment and provide beneficial references for the brain interstitial drug delivery to treat gliomas.

Efficacy and safety of CT perfusion-guided patient selection for intra-arterial thrombolysis of anterior circulation ischemic stroke beyond the time window / 中华神经医学杂志

Objective To observe the safety and efficacy ofintra-arterial thrombolysis guided by CT perfusion in patients with anterior circulation ischemic stroke presenting with symptoms longer than 6 h.Methods The clinical data of patients with anterior circulation ischemic stroke presenting with symptoms longer than 6 h (n=36) and shorter than or equal to 6 h (n=30),performed intra-arterial thrombolysis in our hospitals from July 2003 to December 2012,were retrospectively evaluated.Patients of the former group were evaluated the ischemic penumbra and core region of infarction and the mismatch between the two regions based on CT perfusion.The clinical features,clinical outcomes and complications were compared between the two groups.Results As compared with those in patients of symptoms shorter than or equal to 6 h,the early neurological improvement rate (13.3％ vs.22.2％) and long-term neurological improvement rate (86.7％ vs.77.7％),recanalization rate (80.0％ vs.88.9％) and 3-month mortality (6.7％ vs.16.7％) of patients of symptoms longer than were not significantly different (P=0.665,P=0.665,P=0.639 and P=0.607).Conclusions To patients with anterior circulation ischemic stroke presenting with symptoms longer than 6 h,the neurological function at 3-month significantly improves after intra-arterial thrombolysis guided by CT perfusion.Although the incidence of symptomatic intracranial hemorrhage increases,the mortality rate does not significantly increase.

Clinical features of serotonin syndrome and its curative effects: an analysis of 15 cases / 中华神经医学杂志

Objective To investigate the clinical features of serotonin syndrome (SS) and observe its curative effects. Methods Retrospective analysis was performed on the clinical features of 15 patients with SS admitted to our hospital from January 2006 to December 2011; 9 mild-ill cases,5 moderately-ill cases,and 1 severe-ill case were noted in these patients.After the serotonin drugs were removed and cyproheptadine and supportive treatment were given, curative effects were analyzed.Results The clinical manifestations of SS were highly variable: irritability was noted in 4 patients,tachyrhythmia in 12,hyperactive bowel sounds in 5,diarrhea in 4,diaphorisis in 12,febricity in 5,hypertension in 6,ocular ataxia in 4, mydfiasis in 4, musculature tremor in 6, hypermyotonia in 8,myoclonus in 4,tendon hyperreflexia in 8,ataxia in 2 and seizure attack in 2.The symptoms of 9 mild-ill cases were recovered within 72 h.The major of duration of symptoms was 126 h and the mean time of therapy was (86.9±21.7) h in 5 moderate-ill cases and 1 severe-ill case. Conclusion SS is characterized by mental status changes,autonomic instability,and neuromuscular hyperactivity.The key point of prevention and cure is early diagnosis,appropriate management and being early aware of the serotonergic drug side effect by clinicians.

Neuroprotective effects of edaravone on early brain injury in rats after subarachnoid hemorrhage / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The underlying mechanism of early neurobiological impairment after subarachnoid hemorrhage (SAH) is not well understood, but the system of reactive oxygen superoxide (ROS) might be involved. Edaravone (MCI-186), a potent free radical scavenger that prevents apoptosis of neurons, was thus used in this study to see its possible therapeutic effect in early brain injury due to SAH in a rat model.</p><p><b>METHODS</b>One hundred and twenty male Sprague-Dawley rats were randomly assigned to four groups: group 1, control rats receiving sham operation only; group 2, rats with SAH treated by saline; group 3, rats with SAH treated with 1 mg/kg MCI-186 injected intraperitoneally; and group 4, rats with SAH treated with 3 mg/kg MCI-186. Treated with either saline or MCI-186 twice daily for two consecutive days after SAH, the rats were sacrificed for measurements of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) and histological analysis of caspase-3 protein by Western blotting and immunohistochemical staining. In addition, mortality and neurological scores were statistically analyzed by the chi-square test and Dunn's procedure respectively for each group. One-way analysis of variance followed by the Tukey's procedure was also used in data analysis.</p><p><b>RESULTS</b>The rats in group 2 that received saline only showed neurological impairment as well as elevated mortality, and were found to have significantly increased levels of MDA and caspase-3, but reduced SOD activities in brain tissues (P < 0.05). When treated with MCI-186 at two different dosages, the rats in groups 3 and 4 had markedly decreased levels of MDA and caspase-3 but increased SOD activities in the brain tissue (P < 0.05), along with improved scores of neurological evaluation (P < 0.05).</p><p><b>CONCLUSIONS</b>This study sheds some lights on the therapy of SAH-induced early brain injury by providing the promising data indicating that MCI-186, a radical scavenger, can efficiently diminish apoptosis of neurons and thus prevent the function loss of the brain in rats with SAH.</p>

Study of removal effect on Mesocyclops leukarti with oxidants / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Cyclops of zooplankton propagates prolifically in eutrophic waterbody and it cannot be exterminated by conventional disinfection process. The mutagenicity of Mesocyclops leukarti and its extermination with oxidants in a drinking waterworks in China were studied. Among five oxidants for use in bench-scale, chlorine dioxide is the most effective and the potassium permanganate is the weakest against Mesocyclops leukarti under the same conditions. Full-scale results showed that Mesocyclops leukarti could be effectively removed from water by 1.0 mg/L chlorine dioxide preoxidation combined with conventional removal physical process. After filtration, chlorite, a by-product of prechlorine dioxide, is stable at 0.45 mg/L, which is lower than the critical value of the USEPA. GC-MS examination and Ames test further showed that the quantity of organic substance and the mutagenicity in water treated by chlorine dioxide preoxidation are obviously less than those of prechlorination.