The effect and mechanism of patchouli alcohol on cognitive dysfunction in AD mice induced by Aß1-42 oligomers through AMPK/mTOR pathway.

Alzheimer's disease (AD) is a neurodegenerative brain disorder that progressively impairs long-term and working memory. The function and mechanism of PA(Patchouli alcohol) in improving AD in the external treatment of encephalopathy remain unclear. This study aimed to investigate the therapeutic effect of PA on AD using an Aß1-42 induced AD mouse model with LPS(Lipopolysaccharide) stimulation of BV2 microglial cells. Additionally, we aimed to explore the potential mechanism of PA in enhancing autophagy and reducing neuroinflammation through the AMPK (AMP-activated protein kinase)/mTOR (Mammaliam target of rapamycin) signaling pathway. The Morris water maze was used to assess cognitive function, and cortical and hippocampal tissues were collected for further analysis of the corresponding signaling pathways and inflammatory changes through biological experiments. Our research findings demonstrate that PA has a significant positive impact on cognitive and memory impairments in mice that have been induced with Aß1-42-induced AD. Additionally, PA was also found to revert the activation of microglia induced by LPS. These effects may be attributed to the reduction of neuroinflammation and enhancement of the AMPK/mTOR autophagy pathway. Therefore, PA may serve as an effective therapeutic option to prevent or delay the progression of AD-associated memory dysfunction.

Meteorological factors and tick density affect the dynamics of SFTS in jiangsu province, China.

BACKGROUND: This study aimed to explore whether the transmission routes of severe fever with thrombocytopenia syndrome (SFTS) will be affected by tick density and meteorological factors, and to explore the factors that affect the transmission of SFTS. We used the transmission dynamics model to calculate the transmission rate coefficients of different transmission routes of SFTS, and used the generalized additive model to uncover how meteorological factors and tick density affect the spread of SFTS. METHODS: In this study, the time-varying infection rate coefficients of different transmission routes of SFTS in Jiangsu Province from 2017 to 2020 were calculated based on the previous multi-population multi-route dynamic model (MMDM) of SFTS. The changes in transmission routes were summarized by collecting questionnaires from 537 SFTS cases in 2018-2020 in Jiangsu Province. The incidence rate of SFTS and the infection rate coefficients of different transmission routes were dependent variables, and month, meteorological factors and tick density were independent variables to establish a generalized additive model (GAM). The optimal GAM was selected using the generalized cross-validation score (GCV), and the model was validated by the 2016 data of Zhejiang Province and 2020 data of Jiangsu Province. The validated GAMs were used to predict the incidence and infection rate coefficients of SFTS in Jiangsu province in 2021, and also to predict the effect of extreme weather on SFTS. RESULTS: The number and proportion of infections by different transmission routes for each year and found that tick-to-human and human-to-human infections decreased yearly, but infections through animal and environmental transmission were gradually increasing. MMDM fitted well with the three-year SFTS incidence data (P<0.05). The best intervention to reduce the incidence of SFTS is to reduce the effective exposure of the population to the surroundings. Based on correlation tests, tick density was positively correlated with air temperature, wind speed, and sunshine duration. The best GAM was a model with tick transmissibility to humans as the dependent variable, without considering lagged effects (GCV = 5.9247E-22, R2 = 96%). Reported incidence increased when sunshine duration was higher than 11 h per day and decreased when temperatures were too high (>28°C). Sunshine duration and temperature had the greatest effect on transmission from host animals to humans. The effect of extreme weather conditions on SFTS was short-term, but there was no effect on SFTS after high temperature and sunshine hours. CONCLUSIONS: Different factors affect the infection rate coefficients of different transmission routes. Sunshine duration, relative humidity, temperature and tick density are important factors affecting the occurrence of SFTS. Hurricanes reduce the incidence of SFTS in the short term, but have little effect in the long term. The most effective intervention to reduce the incidence of SFTS is to reduce population exposure to high-risk environments.

Feasibility of controlling hepatitis E in Jiangsu Province, China: a modelling study.

BACKGROUND: Hepatitis E, an acute zoonotic disease caused by the hepatitis E virus (HEV), has a relatively high burden in developing countries. The current research model on hepatitis E mainly uses experimental animal models (such as pigs, chickens, and rabbits) to explain the transmission of HEV. Few studies have developed a multi-host and multi-route transmission dynamic model (MHMRTDM) to explore the transmission feature of HEV. Hence, this study aimed to explore its transmission and evaluate the effectiveness of intervention using the dataset of Jiangsu Province. METHODS: We developed a dataset comprising all reported HEV cases in Jiangsu Province from 2005 to 2018. The MHMRTDM was developed according to the natural history of HEV cases among humans and pigs and the multi-transmission routes such as person-to-person, pig-to-person, and environment-to-person. We estimated the key parameter of the transmission using the principle of least root mean square to fit the curve of the MHMRTDM to the reported data. We developed models with single or combined countermeasures to assess the effectiveness of interventions, which include vaccination, shortening the infectious period, and cutting transmission routes. The indicator, total attack rate (TAR), was adopted to assess the effectiveness. RESULTS: From 2005 to 2018, 44 923 hepatitis E cases were reported in Jiangsu Province. The model fits the data well (R2 = 0.655, P < 0.001). The incidence of the disease in Jiangsu Province and its cities peaks are around March; however, transmissibility of the disease peaks in December and January. The model showed that the most effective intervention was interrupting the pig-to-person route during the incidence trough of September, thereby reducing the TAR by 98.11%, followed by vaccination (reducing the TAR by 76.25% when the vaccination coefficient is 100%) and shortening the infectious period (reducing the TAR by 50.05% when the infectious period is shortened to 15 days). CONCLUSIONS: HEV could be controlled by interrupting the pig-to-person route, shortening the infectious period, and vaccination. Among these interventions, the most effective was interrupting the pig-to-person route.

Modelling the transmission dynamics of severe fever with thrombocytopenia syndrome in Jiangsu Province, China.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is regionally distributed in Asia, with high fatality. Constructing the transmission model of SFTS could help provide clues for disease control and fill the gap in research on SFTS models. METHODS: We built an SFTS transmission dynamics model based on the susceptible-exposed-infectious-asymptomatic-recovered (SEIAR) model and the epidemiological characteristics of SFTS in Jiangsu Province. This model was used to evaluate the effect by cutting off different transmission routes and taking different interventions into account, to offer clues for disease prevention and control. RESULTS: The transmission model fits the reported data well with a minimum R2 value of 0.29 and a maximum value of 0.80, P < 0.05. Meanwhile, cutting off the environmental transmission route had the greatest effect on the prevention and control of SFTS, while isolation and shortening the course of the disease did not have much effect. CONCLUSIONS: The model we have built can be used to simulate the transmission of SFTS to help inform disease control. It is noteworthy that cutting off the environment-to-humans transmission route in the model had the greatest effect on SFTS prevention and control.

A novel tissue engineered nerve graft constructed with autologous vein and nerve microtissue repairs a long-segment sciatic nerve defect.

Veins are easy to obtain, have low immunogenicity, and induce a relatively weak inflammatory response. Therefore, veins have the potential to be used as conduits for nerve regeneration. However, because of the presence of venous valves and the great elasticity of the venous wall, the vein is not conducive to nerve regeneration. In this study, a novel tissue engineered nerve graft was constructed by combining normal dissected nerve microtissue with an autologous vein graft for repairing 10-mm peripheral nerve defects in rats. Compared with rats given the vein graft alone, rats given the tissue engineered nerve graft had an improved sciatic static index, and a higher amplitude and shorter latency of compound muscle action potentials. Furthermore, rats implanted with the microtissue graft had a higher density and thickness of myelinated nerve fibers and reduced gastrocnemius muscle atrophy compared with rats implanted with the vein alone. However, the tissue engineered nerve graft had a lower ability to repair the defect than autogenous nerve transplantation. In summary, although the tissue engineered nerve graft constructed with autologous vein and nerve microtissue is not as effective as autologous nerve transplantation for repairing long-segment sciatic nerve defects, it may nonetheless have therapeutic potential for the clinical repair of long sciatic nerve defects. This study was approved by the Experimental Animal Ethics Committee of Chinese PLA General Hospital (approval No. 2016-x9-07) on September 7, 2016.

Bioinformatic analysis of cytokine expression in the proximal and distal nerve stumps after peripheral nerve injury.

In our previous study, we investigated the dynamic expression of cytokines in the distal nerve stumps after peripheral nerve injury using microarray analysis, which can characterize the dynamic expression of proteins. In the present study, we used a rat model of right sciatic nerve transection to examine changes in the expression of cytokines at 1, 7, 14 and 28 days after injury using protein microarray analysis. Interleukins were increased in the distal nerve stumps at 1-14 days post nerve transection. However, growth factors and growth factor-related proteins were mainly upregulated in the proximal nerve stumps. The P-values of the inflammatory response, apoptotic response and cell-cell adhesion in the distal stumps were higher than those in the proximal nerve stumps, but the opposite was observed for angiogenesis. The number of cytokines related to axons in the distal stumps was greater than that in the proximal stumps, while the percentage of cytokines related to axons in the distal stumps was lower than that in the proximal nerve stumps. Visualization of the results revealed the specific expression patterns and differences in cytokines in and between the proximal and distal nerve stumps. Our findings offer potential therapeutic targets and should help advance the development of clinical treatments for peripheral nerve injury. Approval for animal use in this study was obtained from the Animal Ethics Committee of the Chinese PLA General Hospital on September 7, 2016 (approval No. 2016-x9-07).

Different protein expression patterns in rat spinal nerves during Wallerian degeneration assessed using isobaric tags for relative and absolute quantitation proteomics profiling.

Sensory and motor nerve fibers of peripheral nerves have different anatomies and regeneration functions after injury. To gain a clear understanding of the biological processes behind these differences, we used a labeling technique termed isobaric tags for relative and absolute quantitation to investigate the protein profiles of spinal nerve tissues from Sprague-Dawley rats. In response to Wallerian degeneration, a total of 626 proteins were screened in sensory nerves, of which 368 were upregulated and 258 were downregulated. In addition, 637 proteins were screened in motor nerves, of which 372 were upregulated and 265 were downregulated. All identified proteins were analyzed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of bioinformatics, and the presence of several key proteins closely related to Wallerian degeneration were tested and verified using quantitative real-time polymerase chain reaction analyses. The differentially expressed proteins only identified in the sensory nerves were mainly relevant to various biological processes that included cell-cell adhesion, carbohydrate metabolic processes and cell adhesion, whereas differentially expressed proteins only identified in the motor nerves were mainly relevant to biological processes associated with the glycolytic process, cell redox homeostasis, and protein folding. In the aspect of the cellular component, the differentially expressed proteins in the sensory and motor nerves were commonly related to extracellular exosomes, the myelin sheath, and focal adhesion. According to the Kyoto Encyclopedia of Genes and Genomes, the differentially expressed proteins identified are primarily related to various types of metabolic pathways. In conclusion, the present study screened differentially expressed proteins to reveal more about the di?erences and similarities between sensory and motor nerves during Wallerian degeneration. The present findings could provide a reference point for a future investigation into the differences between sensory and motor nerves in Wallerian degeneration and the characteristics of peripheral nerve regeneration. The study was approved by the Ethics Committee of the Chinese PLA General Hospital, China (approval No. 2016-x9-07) in September 2016.

Protein microarray analysis of cytokine expression changes in distal stumps after sciatic nerve transection.

A large number of chemokines, cytokines, other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration. This microenvironment is one of the major factors for regenerative success. Therefore, it is important to investigate the key molecules and regulators affecting nerve regeneration after peripheral nerve injury. However, the identities of specific cytokines at various time points after sciatic nerve injury have not been determined. The study was performed by transecting the sciatic nerve to establish a model of peripheral nerve injury and to analyze, by protein microarray, the expression of different cytokines in the distal nerve after injury. Results showed a large number of cytokines were up-regulated at different time points post injury and several cytokines, e.g., ciliary neurotrophic factor, were downregulated. The construction of a protein-protein interaction network was used to screen how the proteins interacted with differentially expressed cytokines. Kyoto Encyclopedia of Genes and Genomes pathway and Gene ontology analyses indicated that the differentially expressed cytokines were significantly associated with chemokine signaling pathways, Janus kinase/signal transducers and activators of transcription, phosphoinositide 3-kinase/protein kinase B, and notch signaling pathway. The cytokines involved in inflammation, immune response and cell chemotaxis were up-regulated initially and the cytokines involved in neuronal apoptotic processes, cell-cell adhesion, and cell proliferation were up-regulated at 28 days after injury. Western blot analysis showed that the expression and changes of hepatocyte growth factor, glial cell line-derived neurotrophic factor and ciliary neurotrophic factor were consistent with the results of protein microarray analysis. The results provide a comprehensive understanding of changes in cytokine expression and changes in these cytokines and classical signaling pathways and biological functions during Wallerian degeneration, as well as a basis for potential treatments of peripheral nerve injury. The study was approved by the Institutional Animal Care and Use Committee of the Chinese PLA General Hospital, China (approval number: 2016-x9-07) in September 2016.

Aligned fibers enhance nerve guide conduits when bridging peripheral nerve defects focused on early repair stage.

Nerve conduits enhance nerve regeneration in the repair of long-distance peripheral nerve defects. To help optimize the effectiveness of nerve conduits for nerve repair, we developed a multi-step electrospinning process for constructing nerve guide conduits with aligned nanofibers. The alignment of the nerve guide conduits was characterized by scanning electron microscopy and fast Fourier transform. The mechanical performance of the nerve guide conduits was assessed by testing for tensile strength and compression resistance. The biological performance of the aligned fibers was examined using Schwann cells, PC12 cells and dorsal root ganglia in vitro. Immunohistochemistry was performed for the Schwann cell marker S100 and for the neurofilament protein NF200 in PC12 cells and dorsal root ganglia. In the in vivo experiment, a 1.5-cm defect model of the right sciatic nerve in adult female Sprague-Dawley rats was produced and bridged with an aligned nerve guide conduit. Hematoxylin-eosin staining and immunohistochemistry were used to observe the expression of ATF3 and cleaved caspase-3 in the regenerating matrix. The recovery of motor function was evaluated using the static sciatic nerve index. The number of myelinated fibers, axon diameter, fiber diameter, and myelin thickness in the distal nerve were observed by electron microscopy. Gastrocnemius muscle mass ratio was also determined. The analyses revealed that aligned nanofiber nerve guide conduits have good mechanical properties and can induce Schwann cells, PC12 cells and dorsal root ganglia to aggregate along the length of the nanofibers, and promote the growth of longer axons in the latter two (neuronal) cell types. The aligned fiber nerve conduits increased the expression of ATF3 and cleaved caspase-3 at the middle of the regenerative matrix and at the distal nerve segment, improved sciatic nerve function, increased muscle mass of the gastrocnemius muscle, and enhanced recovery of distal nerve ultrastructure. Collectively, the results show that highly aligned nanofibers improve the performance of the nerve conduit bridge, and enhance its effectiveness in repairing peripheral nerve defects.

Optimal projection method determination by Logdet Divergence and perturbed von-Neumann Divergence.

BACKGROUND: Positive semi-definiteness is a critical property in kernel methods for Support Vector Machine (SVM) by which efficient solutions can be guaranteed through convex quadratic programming. However, a lot of similarity functions in applications do not produce positive semi-definite kernels. METHODS: We propose projection method by constructing projection matrix on indefinite kernels. As a generalization of the spectrum method (denoising method and flipping method), the projection method shows better or comparable performance comparing to the corresponding indefinite kernel methods on a number of real world data sets. Under the Bregman matrix divergence theory, we can find suggested optimal λ in projection method using unconstrained optimization in kernel learning. In this paper we focus on optimal λ determination, in the pursuit of precise optimal λ determination method in unconstrained optimization framework. We developed a perturbed von-Neumann divergence to measure kernel relationships. RESULTS: We compared optimal λ determination with Logdet Divergence and perturbed von-Neumann Divergence, aiming at finding better λ in projection method. Results on a number of real world data sets show that projection method with optimal λ by Logdet divergence demonstrate near optimal performance. And the perturbed von-Neumann Divergence can help determine a relatively better optimal projection method. CONCLUSIONS: Projection method ia easy to use for dealing with indefinite kernels. And the parameter embedded in the method can be determined through unconstrained optimization under Bregman matrix divergence theory. This may provide a new way in kernel SVMs for varied objectives.

Physical and functional interaction of Snapin with Cav1.3 calcium channel impacts channel protein trafficking in atrial myocytes.

The L-type Ca2+ channel (LTCC) Cav1.3 plays a critical role in generating electrical activity in atrial myocytes and cardiac pacemaker cells. However, the molecular and functional basis of Cav1.3 modulation in atrial myocytes has not yet been fully understood. By using the yeast two-hybrid system (Y2H), a Cav1.3-associated protein was screened, which was identified as Snapin. Physical interaction and co-localization between Snapin and Cav1.3 were then confirmed in both the heterologous expression system and mouse atrial myocytes. Direct interaction between them was additionally addressed in a GST pull down assay. Furthermore, both total and membrane expressions of Cav1.3 were significantly impaired by Snapin overexpression, resulting in the ubiquitin-proteasomal degradation of Cav1.3 and a consequent reduction of the densities of whole-cell ICa-L. Snapin-induced down-regulation of Cav1.3 was reversed by SNAP-23 competitively. What is more important is that the depressed-expression of Cav1.3 paralleled with enhanced-expression of Snapin was documented in atrial samples from atrial fibrillation (AF) patients. Our results provide the evidence of a direct regulatory role of Snapin on Cav1.3 channels in atrial myocytes, and highlight a potential role of Snapin in the regulation of Cav1.3 in atrial arrhythmogenesis.

Pathological concentration of zinc dramatically accelerates abnormal aggregation of full-length human Tau and thereby significantly increases Tau toxicity in neuronal cells.

A pathological hallmark of Alzheimer disease and other tauopathies is the formation of neurofibrillary tangles mainly composed of bundles of fibrils formed by microtubule-associated protein Tau. Here we study the effects of Zn2+ on abnormal aggregation and cytotoxicity of a pathological mutant ΔK280 of full-length human Tau. As revealed by Congo red binding assays, transmission electron microscopy, immunofluorescence, Western blot, and immunogold electron microscopy, pathological concentration of Zn2+ dramatically accelerates the fibrillization of ΔK280 both in vitro and in SH-SY5Y neuroblastoma cells. As evidenced by annexin V-FITC apoptosis detection assay and MTT reduction assay, pathological concentration of Zn2+ remarkably enhances ΔK280 fibrillization-induced apoptosis and toxicity in SH-SY5Y cells. Substitution of Cys-291 and Cys-322 with Ala, however, essentially eliminates such enhancing effects of Zn2+ on the fibrillization and the consequent cytotoxicity of ΔK280. Furthermore, Zn2+ is co-localized with and highly enriched in amyloid fibrils formed by ΔK280 in SH-SY5Y cells. The results from isothermal titration calorimetry show that Zn2+ binds to full-length human Tau by interacting with Cys-291 and Cys-322, forming a 1:1 Zn2+-Tau complex. Our data demonstrate that zinc dramatically accelerates abnormal aggregation of human Tau and significantly increases Tau toxicity in neuronal cells mainly via bridging Cys-291 and Cys-322. Our findings could explain how pathological zinc regulates Tau aggregation and toxicity associated with Alzheimer disease.

Whole-brain CT perfusion combined with CT angiography for ischemic complications following microsurgical clipping and endovascular coiling of ruptured intracranial aneurysms.

Ischemic complications associated with microsurgical clipping and endovascular coiling affects the outcome of patients with intracranial aneurysms. We prospectively evaluated 58 intracranial aneurysm patients who had neurological deterioration or presented with poor grade (Hunt-Hess grades III and IV), aneurysm size >13 mm and multiple aneurysms after clipping or coiling. Thirty patients had ischemic complications (52%) as demonstrated by whole-brain CT perfusion (WB-CTP) combined with CT angiography (CTA). Half of these 30 patients had treatment-associated reduction in the diameter of the parent vessels (n=6), ligation of the parent vessels or perforating arteries (n=2), and unexplained or indistinguishable vascular injury (n=7); seven of these 15 (73%) patients suffered infarction. The remaining 15 patients had disease-associated cerebral ischemia caused by generalized vasospasm (n=6) and focal vessel vasospasm (n=9); six of these 15 (40%) patients developed infarction. Three hemodynamic patterns of ischemic complications were found on WB-CTP, of which increased time to peak, time to delay and mean transit time associated with decreased cerebral blood flow and cerebral blood volume were the main predictors of irreversible ischemic lesions. In conclusion, WB-CTP combined with CTA can accurately determine the cause of neurological deterioration and classify ischemic complications. This combined approach may be helpful in assessing hemodynamic patterns and monitoring operative outcomes.

Cerebral Hemodynamic Evaluation of Parent Artery Occlusion for Giant Intracranial Aneurysm in Patients who Tolerated Balloon Test Occlusion: Two Case Reports.

Parent artery occlusion is an effective treatment for giant intracranial aneurysms that cannot be clipped directly by surgery in patients who tolerate balloon test occlusion. However, concern remains that impaired hemodynamics after parent artery occlusion may cause delayed ischemic events in the ipsilateral hemisphere. We used computed tomography perfusion studies to evaluate the cerebral hemodynamics before and after parent artery occlusion in two patients with giant intracranial aneurysms who tolerated balloon test occlusion. In the first case, significant vortex flow in the aneurysm cavity prevented distal vascular engorgement and caused severe ischemic changes. After parent artery occlusion, the vortex flow was eliminated, circle of Willis compensatory flow was restored, and cerebral hemodynamics were significantly improved. In the second case, cerebral hemodynamics were normal on preoperative computed tomography perfusion. After parent artery occlusion, the time-to-peak was prolonged in the cerebral hemisphere on the occluded side compared with the contralateral hemisphere.

Sequence-dependent abnormal aggregation of human Tau fragment in an inducible cell model.

A pathological hallmark of Alzheimer disease (AD) is the accumulation of misfolded hyperphosphorylated microtubule-associated protein Tau within neurons, forming neurofibrillary tangles and leading to synaptic dysfunction and neuronal death. Here we study sequence-dependent abnormal aggregation of human fragment Tau244-372 in an inducible cell model. As evidenced by confocal laser scanning microscopy, Western blot, and immunogold electron microscopy, fibril-forming motifs are essential and sufficient for abnormal aggregation of Tau244-372 in SH-SY5Y neuroblastoma cells induced by Congo red: when its two fibril-forming segments PHF6 and PHF6* are deleted, Tau244-372 does lose its ability to form fibrils in SH-SY5Y cells, and the replacement of PHF6 and PHF6* with an unrelated amyloidogenic sequence IFQINS from human lysozyme does rescue the fibril-forming ability of Tau244-372 in SH-SY5Y cells. By contrast, insertion of a non-fibril forming peptide GGGGGG does not drive the disabled Tau244-372 to misfold in SH-SY5Y cells. Furthermore, as revealed by quantum dots based probes combined with annexin V staining, annexin V-FITC apoptosis detection assay, and immunofluorescence, fibril-forming motifs are essential and sufficient for early apoptosis of living SH-SY5Y cells induced by abnormal aggregation of Tau244-372. Our results suggest that fibril-forming motifs could be the determinants of Tau protein tending to misfold in living cells, thereby inducing neuronal apoptosis and causing the initiation and development of AD.

Hemodynamic alterations in unilateral chronic middle cerebral artery stenosis patients and the effect of percutaneous transluminal angioplasty and stenting: a perfusion-computed tomography study.

BACKGROUND: The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial indicated that most patients with symptomatic intracranial atherosclerosis are not good candidates for percutaneous transluminal angioplasty and stenting (PTAS) because of a higher complication risk than with conservative treatment. However, enrollment of SAMMPRIS patients was based on lesion severity only, without functional imaging. PURPOSE: To determine whether perfusion computed tomography (PCT) can effectively evaluate hemodynamic compromise in unilateral chronic middle cerebral artery stenosis and the alterations of hemodynamics after PTAS. MATERIAL AND METHODS: In this prospective study, 89 patients with unilateral middle cerebral artery (MCA) stenosis/occlusion were enrolled and classified into four groups according to the degree of stenosis. Cerebral hemodynamics was evaluated by measuring cerebral blood flow (CBF), cerebral blood volume (CBV), and time to peak (TTP) in the ipsilateral and contralateral hemispheres by PCT before and after intervention with PTAS. Differences in hemodynamic parameters before and after intervention were analyzed. RESULTS: Three different hemodynamic patterns were observed in these patients. Patients with severe MCA stenosis (70-99%) or MCA occlusion demonstrated a significant increase of ipsilateral CBV and TTP, indicating hemodynamic compromise. Ten severe stenosis patients with recurrent ischemic symptoms despite of maximal conservative therapy were selected for PTAS. PTAS induced a rapid recovery of cerebral hemodynamics (especially TTP) at 1 week post intervention. CONCLUSION: PCT appears to be a valuable noninvasive technique to evaluate hemodynamic compromise in unilateral chronic MCA stenosis and the improvements after PTAS.

[Current situation related to antiretroviral therapy and related influential factors on HIV infected injection drug users in the methadone maintenance treatment clinics].

OBJECTIVE: To find out the current coverage of antiretroviral therapy (ART) among HIV positive subjects and to identify the major influential factors associated with the participation in ART among them. METHODS: 291 HIV positive subjects from 6 methadone maintenance treatment (MMT) clinics in Guangxi and Yunnan province were surveyed by questionnaires. RESULTS: 217 males (74.6%) and 74 females (25.4%) were under investigation, with the average age of 38.4 +/- 5.9. Most of them received less than senior high school education, married and unemployed. Results from the single factor logistic regression analysis showed that: working status, living alone, self-reported history of drinking alcohol in the last month, negative attitude towards MMT among family members,poor self-reported compliance to MMT in the last month,lack of incentives in the MMT clinics, reluctance on disclosure of their own HIV status, good self-perception on their health status, lack of communication on ART related topics among family members in the last 6 months, lack of correct attitude and knowledge on ART etc. appeared as the main factors that influencing the participation in ART program among the patients. Data from the multivariate logistic regression analysis showed that factors as: living alone, unwilling to tell others about the status of HIV infection, poor self-perception on HIV infection, lack of discussion of ART related topics within family members in the last 6 months and poor awareness towards ART among the family members etc., were associated with the low participation rate of ART. Conclusion Strengthening the publicity and education programs on HIV positive patients and their family members at the MMT clinics seemed to be effective in extending the ART coverage. Attention should also be paid to increase the family support to the patients.

Quantitative perfusion computed tomography measurements of cerebral hemodynamics: correlation with digital subtraction angiography identified primary and secondary cerebral collaterals in internal carotid artery occlusive disease.

BACKGROUND: The aim of the present study was to assess hemodynamic variations in symptomatic unilateral internal carotid artery occlusion (ICAO) patients with primary collateral flow via circle of Willis or secondary collateral flow via ophthalmic artery and/or leptomeningeal collaterals. METHODS: Thirty-eight patients with a symptomatic unilateral ICAO were enrolled in the study. Based on digital subtraction angiography (DSA) findings, patients were classified into 2 groups: primary collateral (n = 14) and secondary collateral (n = 24) groups. Collateral flow hemodynamics were investigated with perfusion computed tomography (PCT) by measuring the cerebral blood flow (CBF), cerebral blood volume (CBV) and time to peak (TTP) in the hemispheres ipsilateral and contralateral to ICAO. Based on the measurements, the ipsilateral to contralateral ratio for each parameter was calculated and compared. RESULTS: Irrespective of the collateral patterns, ipsilateral CBF was not significantly different from that of the contralateral hemisphere (P = 0.285); ipsilateral CBV and TTP was significantly increased compared with those of the contralateral hemisphere (P=0.000 and P = 0.000 for CBV and TTP, respectively). Furthermore, patients with secondary collaterals had significantly larger ipsilateral-to-contralateral ratios for both CBV (rCBV, P = 0.0197) and TTP (rTTP, P = 0.000) than those of patients with only primary collaterals. These two groups showed no difference in ipsilateral-to-contralateral ratio for CBF (rCBF, P = 0.312). CONCLUSION: Patients with symptomatic unilateral ICAO in our study were in an autoregulatory vasodilatation status. Moreover, secondary collaterals in ICAO patients were correlated with ipsilateral CBV and delayed TTP that suggested severe hemodynamic impairment, presumably increasing the risk of ischemic events.