Efficacy and safety of perampanel monotherapy in Chinese patients with focal-onset seizures: A single-center, prospective, real-world observational study.

OBJECTIVE: Efficacy and safety of perampanel monotherapy for treating focal-onset seizures (FOS) has been barely studied in China. This observational study aimed to evaluate the efficacy and safety of perampanel monotherapy in treating Chinese patients with FOS. METHODS: This single-center, prospective, real-world observational study enrolled patients aged ≥4 years with FOS who visited the Epilepsy Out-Patient Clinic of Nanjing Brain Hospital affiliated to Nanjing Medical University from January 2020 to December 2021. All patients were treated with perampanel monotherapy. Seizure-freedom rates after 6 and 12 months of treatment were calculated. Adverse events (AEs) were recorded. RESULTS: Seventy patients with FOS were enrolled. The mean maintenance perampanel dose was 4.64 ± 1.55 mg/day. The 6- and 12-month retention rates of perampanel monotherapy were 78.6% (55/70) and 70.0% (49/70), respectively. The 6- and 12-month seizure-freedom rates were 69.84% (44/63) and 65.08% (41/63), respectively. Patients with focal to bilateral tonic-clonic seizures had significantly higher 6-month and numerically higher 12-month seizure freedom rates than patients with focal impaired awareness seizures (P = 0.046 and P = 0.204, respectively). Twenty-six (37.1%) patients experienced treatment-emergent AEs, and the most common AE was dizziness. Four (5.7%) patients withdrew from the study due to AEs. No new safety concern was observed. SIGNIFICANCE: This is the first prospective study on the efficacy and safety of perampanel monotherapy in treating Chinese patients with FOS, and perampanel monotherapy was effective and safe in treating Chinese patients aged ≥4 years with FOS up to 12 months. More multicenter, real-world studies with large sample sizes and longer follow-ups are needed to further evaluate the long-term efficacy and safety of perampanel monotherapy.

Neurovascular coupling changes in patients with magnetic resonance imaging negative focal epilepsy.

Brain neuron activity is closely related to cerebral blood flow (CBF) changes. Alterations in the regional homogeneity (ReHo) and CBF occur in patients with magnetic resonance imaging negative focal epilepsy (FEP-MRI-). However, the coupling alterations of ReHo and CBF in FEP-MRI- remain unclear. The study aims to explore neurovascular coupling alterations and their clinical implication in FEP-MRI-. We collected resting-state magnetic resonance imaging (MRI) data from 31 healthy controls (HCs) and 48 patients with FEP-MRI-,including three-dimensional (3D) T1-weighted imaging, 3D arterial spin labeling (ASL) imaging,and resting-state functional MRI (rs-fMRI). The CBF and ReHo values were calculated from the ASL and rs-fMRI data, respectively. The CBF/ReHo ratio per voxel and whole-brain CBF-ReHo coupling were compared between the two groups. Correlation analysis involved the CBF/ReHo ratio and clinical indicators in FEP-MRI-. Patients with FEP-MRI- showed significantly increased cross-subject CBF-ReHo and global cross-voxel CBF-ReHo coupling. The CBF/ReHo ratio was higher in the bilateral orbitofrontal gyrus, right parietal lobe, and right middle frontal gyrus of patients with FEP-MRI-. Nevertheless, this ratio was lower in the bilateral supplementary motor areas, the left middle and posterior cingulate gyrus, and the right central sulcus cover. The CBF/ReHo ratio was markedly correlated with cognitive function, memory, intelligence, and epilepsy duration in the above abnormal brain regions. CBF/ReHo ratio may be useful as an indicator of neuropathological mechanisms. These results support the hypothesis that CBF/ReHo ratio relates to the neuropathological mechanisms of FEP-MRI-. Furthermore, it offers new perspectives for studying the mechanisms of MRI-negative epilepsy.

Immediate Effects of Vagal Nerve Stimulation in Drug-Resistant Epilepsy Revealed by Magnetoencephalographic Recordings.

Objective: Vagus nerve stimulation (VNS) has been a neuromodulatory option for treating drug-resistant epilepsy (DRE), but its mechanism remains unclear. To obtain insight into the mechanism by which VNS reduces epileptic seizures, the immediate effects of VNS in brain networks of DRE patients were investigated when the patients' vagal nerve stimulators were turned on. Methods: The brain network properties of 14 DRE patients with a vagal nerve stimulator and 14 healthy controls were evaluated using magnetoencephalography recordings for 6 main frequency bands. Results: Compared with healthy controls, DRE patients exhibited significant increases in functional connectivity in the theta, alpha, beta, and gamma bands and significant reductions in the small-world measure in the theta and beta bands. During periods when patients' vagal nerve stimulators were turned on, DRE patients showed significant reductions in functional connectivity in the theta and alpha bands and a significant increase in the small-world measure in the theta band when compared with periods when patients' vagal nerve stimulators were turned off. Conclusions: Our results indicate that the brain networks of DRE patients were pathologically hypersynchronous and instantaneous VNS can decrease the synchronization of brain networks of epileptic patients, which might play a key role in the mechanism by which VNS reduces epileptic seizures. In the theta band, instantaneous VNS can increase the network efficiency of DRE patients, and the increment in network efficiency may be helpful for improving brain cognitive function in epileptic patients. Impact statement For the first time, we investigated the immediate effects of vagus nerve stimulation (VNS) in the brain networks of drug-resistant epilepsy patients using magnetoencephalography. Our results show that instantaneous VNS can decrease the hypersynchronization of epileptic networks and increase the network efficiency of epileptic patients. Our results are helpful in understanding the mechanism of action by which VNS reduces epileptic seizures and improves the cognitive function in epileptic patients and the brain network reorganization caused by long-term VNS.

Summer dormancy of Myricaria laxiflora to escape flooding stress: Changes in phytohormones and enzymes induced by environmental factors.

Dormancy is an adaptation mechanism of plants to environmental stress. Myricaria laxiflora undergoes a long period of flooding stress every year. In order to determine whether this species escapes flooding stress through dormancy, young branches and leaves were collected at different time points before the onset of flooding, and changes in the content/activity of hormones/enzymes that are closely involved in plant growth were monitored. The inducing environmental factors of summer dormancy were identified. The branches and leaves of M. laxiflora showed the following trends as summer flooding approached: (1) gradual increase in the abscisic acid content; (2) gradual decrease in the gibberellin and cytokinin contents; and (3) a continuous decrease in the activities of malate dehydrogenase (MDH), ribulose diphosphate carboxylase (RuBisCo), and glycolate oxidase (GLO). Pearson correlation analysis revealed (1) daylight duration was highly correlated with the hormone content and enzyme activity; (2) the daily mean air temperature (DMAT) was significantly correlated with the cytokinin content. These findings suggest that daylight duration was the main environmental factor leading to changes in the phytohormone content and enzyme activity as well as leading to summer dormancy. M. laxiflora undergoes dormancy before the onset of summer flooding to escape summer flooding stress. Our data indicate that summer flooding does not impede the survival and growth of M. laxiflora.

Evaluation of Brain Network Properties in Patients with MRI-Negative Temporal Lobe Epilepsy: An MEG Study.

Abnormal functional brain networks of temporal lobe epilepsy (TLE) patients with structural abnormalities may partially reflect structural lesions rather than either TLE per se or functional compensatory processes. In this study, we sought to investigate the brain-network properties of intractable TLE patients apart from the effects of structural abnormalities. The brain network properties of 20 left and 23 right MRI-negative TLE patients and 22 healthy controls were evaluated using magnetoencephalographic recordings in six main frequency bands. A slowing of oscillatory brain activity was observed for the left or right TLE group vs. healthy controls. The TLE groups presented significantly increased functional connectivity in the delta, theta, lower alpha and beta bands, and significantly greater values in the normalized clustering coefficient and path length, and significantly smaller values in the weighted small-world measure in the theta band when compared to healthy controls. Alterations in global and regional band powers can be attributed to spectral slowing in TLE patients. The brain networks of TLE patients displayed abnormally high synchronization in multi-frequency bands and shifted toward a more regular architecture with worse network efficiency in the theta band. Without the contamination of structural lesions, these significant findings can be helpful for better understanding of the pathophysiological mechanism of TLE. The theta band can be considered as a preferred frequency band for investigating the brain-network dysfunction of MRI-negative intractable TLE patients.

Changes in resting-state cerebral blood flow and its connectivity in patients with focal to bilateral tonic-clonic seizures.

Arterial spin labeling (ASL) is an important tool for understanding cerebral perfusion in epilepsy patients. The aim of this study was to explore patterns of change in cerebral blood flow (CBF) and CBF connectivity in patients with focal to bilateral tonic-clonic seizures (FBTCS). High-resolution three-dimensional (3-D) T1-weighted and 3-D pseudo-continuous ASL magnetic resonance imaging (MRI) was collected from 32 patients with FBTCS and 16 healthy volunteers using a 3.0 T MRI scanner. Cerebral blood flow and its connectivity were compared between the FBTCS and control group. Correlation analysis was used to explore relationships of CBF and its connectivity changes with clinical parameters. Cerebral blood flow data of spatial standardization and normalization were used to improve statistical power. Patients with FBTCS exhibited increased CBF in the bilateral thalamus, caudate nucleus, olfactory cortex, and gyrus rectus, but decreased CBF in the bilateral supplementary motor areas (SMA) and middle cingulate cortex (MCC). Patients with FBTCS showed significant positive correlation between CBF and gray matter volume (GMV) in bilateral SMA and MCC. No significant correlations between CBF and clinical parameters were found among FBTCS patients. The anterior cingulate cortex (ACC) showed positive CBF connectivity with the bilateral SMA and MCC, and these CBF connectivity measures differed significantly between groups (cluster-level, FWE-corrected, P < 0.001). These findings suggest that patients with FBTCS have changes in cerebral CBF and CBF connectivity, which may relate to the underlying neuropathology of FBTCS.

Carbohydrate saving or biomass maintenance: which is the main determinant of the plant's long-term submergence tolerance?

It is hypothesized that plant submergence tolerance could be assessed from the decline of plant biomass due to submergence, as biomass integrates all eco-physiological processes leading to fitness. An alternative hypothesis stated that the consumption rate of carbohydrate is essential in differing tolerance to submergence. In the present study, the responses of biomass, biomass allocation, and carbohydrate content to simulated long-term winter submergence were assessed in four tolerant and four sensitive perennials. The four tolerant perennials occur in a newly established riparian ecosystem created by The Three Gorges Dam, China. They had 100% survival after 120 days' simulated submergence, and had full photosynthesis recovery after 30 days' re-aeration, and the photosynthetic rate was positively related to the growth during the recovery period. Tolerant perennials were characterized by higher carbohydrate levels, compared with the four sensitive perennials (0% survival) at the end of submergence. Additionally, by using a method which simulates posterior estimates, and bootstraps the confidence interval for the difference between strata means, it was found that the biomass response to post-hypoxia, rather than that to submergence, could be a reliable indicator to assess submergence tolerance. Interestingly, the differences of changes in carbohydrate content between tolerant and sensitive perennials during submergence were significant, which were distinct from the biomass response, supporting the hypothesis that tolerant perennials could sacrifice non-vital components of biomass to prioritize the saving of carbohydrates for later recovery. Our study provides some insight into the underlying mechanism(s) of perennials' tolerance to submergence in ecosystems such as temperate wetland and reservoir riparian.

The effect of Elymus nutans sowing density on soil reinforcement and slope stabilization properties of vegetation-concrete structures.

Elymus nutans is an herbaceous plant that can be used to restore degraded alpine and subalpine ecosystems. Here, we evaluated how sowing density affects soil reinforcement and slope stabilization properties of vegetation-concrete structures. To investigate the optimal sowing density of E. nutans in vegetation-concrete applications for slope protection, six experimental treatments were established with different plant densities: control, I (1100 seeds/m2), II (2200 seeds/m2), III (3300 seeds/m2), IV (4400 seeds/m2), and V (5500 seeds/m2). Several parameters of plant growth in addition to soil reinforcement and slope stabilization properties were measured in each treatment, as well as the associations among parameters. As density increased, aboveground biomass continually increased, and plant heights, root surface areas, root lengths, and underground biomass all first increased and then decreased. In contrast, tiller numbers and the average root diameter gradually decreased with increasing density. Increased density also resulted in increased maximum water interception levels by aboveground stems and leaves. The maximum water interception by the aboveground stems and leaves was 41.75% greater in the highest density treatment (V) compared to the lowest density treatment (I). However, the enhancement of erosion resistance and soil shear strength first increased and then decreased as density increased, with maximal values observed in the medium-high density treatment (IV). Sowing density was highly correlated with aboveground biomass, plant heights, tiller numbers, and the maximum level of water interception by stems and leaves. Thus, sowing density directly influenced soil reinforcement and slope stabilization properties of aboveground plant components. However, density was not significantly correlated with belowground biomass, root lengths, root surface areas, the enhancement of erosion resistance, and soil shear strengths. Therefore, sowing density indirectly influenced soil reinforcement and slope stabilization of belowground plant components. Following from these results, we suggest that the optimal sowing density of E. nutans is approximately 4400 plants/m2 in their application within vegetation-concrete structures used for slope protection.

Growth and respiratory metabolic adaptation strategies of riparian plant Distylium chinense to submergence by the field study and controlled experiments.

Submergence tolerance is crucial when thinking in promising species for restoration of ecosystems prone to suffer extreme flooding events. In this study, two-year-old seedlings of Distylium chinense were subjected to one field study and five controlled experiments: unsubmerged and watered daily as controls (CK) and completely submerged for 30, 60, 90 and 120 days, respectively followed by a 60-day recovery period to test the submergence tolerance. The results showed that the survival decreased with the increasing flooding duration. Different submergence duration treatments affected dry mass accumulation and carbohydrate content of roots, stems and leaves. Flooding stress affected the activities of pyruvate decarboxylase (PDC), ethanol dehydrogenase (ADH) and lactic dehydrogenase (LDH) enzymes, which indicated the roots and leaves adapt to long-term flooding by reinforcing their anaerobic respiration and activities of ADH were higher than those of LDH for roots and leaves with stronger alcoholic fermentation mainly. After de-submergence, the recovery patterns of carbohydrate were coincided with those of dry mass accumulation of the roots, stems and leaves. A significant regression equation analysis showed root starch content and dry mass accumulation were the major factors affecting the seedling survival. And D. chinense accumulated substantial amounts of carbohydrate before submergence and invested more in roots and stems than in leaves, which enhances long-term survival under submergence. Carbohydrate storage is a key functional trait that can explain high survival under submergence. D. chinense may have adopted a suite of growth and respiratory metabolic adaptation strategies to survive long-term submergence.

Factors influencing the long-term prognosis of patients with temporal lobe epilepsy: a single center study.

BACKGROUND: This study aimed to explore the risk factors influencing the long-term prognosis of temporal lobe epilepsy (TLE) patients treated with drug therapy or surgical treatment. METHODS: A total of 112 patients who were diagnosed with TLE were retrospectively enrolled. All of the patients were initially treated with antiepileptic drugs (AEDs). Patients who met the criteria of drugresistant TLE were evaluated for treatment with temporal lobectomy. The main outcome was whether the patients achieved seizure-free status. This was defined as when a patient experienced no seizures for at least 24 months of follow-up. The independent predictors of the outcome were evaluated using a multiple logistic regression model. RESULTS: The median follow-up period was 5 years (range, 2-13 years). At the end of follow-up, 26 patients had not achieved seizure freedom after treatment with AEDs, including 22 cases of monotherapy, 4 cases of duotherapy (1 case of drug-resistant epilepsy after continuous drug treatment). AED treatment was withdrawn in 6 patients. Overall, 23.2% TLE patients (26/112) achieved seizure freedom after treatment with AEDs alone, while the remaining 76.8% (86/112) of patients were diagnosed as drug-resistant epilepsy (DRE). Of the 45 DRE patients who subsequently received surgical treatment, 77.8% (35/45) achieved seizure freedom, with successful AED withdrawal in 11 patients. The proportion of patients who achieved seizure-free status was higher among those who underwent temporal lobectomy than among those who continued with AED treatment (77.8% vs. 23.2%, P<0.001). Effective early monotherapy was an independent predictor for good therapeutic effect in all TLE patients (OR: 0.16; 95% CI: 0.04-0.66; P=0.007). Multivariate logistic regression analysis showed the predictors of good prognosis in DRE patients after surgery to be unilateral origin of discharges in electroencephalogram (EEG, OR =0.20, 95% CI: 0.06-0.74, P=0.016), no secondary generalized tonic-clonic seizures (GTCS, OR =0.08, 95% CI: 0.01-0.67, P=0.002), and not needing a subdural electrode (OR =15.4, 95% CI: 1.36-174.38, P=0.027). CONCLUSIONS: Effective early monotherapy was an independent protective factor for the favorable prognosis of TLE. Unilateral origin of discharges in EEG, no secondary GTCS, and not needing a subdural electrode were independent factors associated with favorable prognosis after TLE surgery.

Spatiotemporal photosynthetic physiology responses of remnant Myricaria laxiflora populations to regulated water level fluctuations.

The construction of the Three Gorges-Gezhouba Dam cascade hydropower station has changed the water level fluctuation pattern of the habitats for remnant rare and endangered Myricaria laxiflora populations downstream of the dam. The present study utilized biochemical markers of photosynthetic physiology to evaluate the spatiotemporal responses of remnant populations to human-regulated water level fluctuations. The results showed that the photosynthetic physiological activities of remnant M. laxiflora populations underwent a period of rapid growth, followed by a gradual decline in the growth recovery phase after flooding. During the entire experimental period, photosynthetic physiological activities of remnant M. laxiflora populations changed with prolongation of emergence time: specifically, net photosynthetic rate and stomatal conductance initially decreased and then subsequently increased, intercellular carbon dioxide concentrations peaked at mid-phase and transpiration rate continuously increased. The maximum net photosynthetic rate, apparent photosynthetic quantum efficiency and dark respiration rate in the light-response curves of the plants continuously increased during growth. The water level gradient also significantly affected the photosynthetic physiological activities in the remnant populations, i.e. the photosynthetic physiological activities of high-altitude plants were significantly higher than the middle- and low-altitude plants. The changes in photosynthetic pigment content of plants in remnant populations during the growth recovery phase and the entire growth period were similar to those occurring in photosynthetic activities in plants. Further, canonical correspondence analysis showed that photosynthetic physiological activities in the plants were significantly correlated with changes in water levels, emergence time, elevation gradient, soil water and soil nitrogen contents. Therefore, the artificial regulation of water level fluctuations by large hydropower stations will inevitably affect the photosynthetic activities and growth of remnant M. laxiflora populations.

Correction to: Diffuse leptomeningeal glioneuronal tumor in a Chinese adult: a novel case report and review of literature.

The article "Diffuse leptomeningeal glioneuronal tumor in a Chinese adult: a novel case report and review of literature", written by "Honghao Xu, Fangqing Chen, Haitao Zhu, Lei Luo, and Rui Zhang", was originally published electronically on the publisher's internet portal (currently SpringerLink) on 24th December 2019 with open access.

LncRNA CASC2 inhibits astrocytic activation and adenosine metabolism by regulating PTEN in pentylenetetrazol-induced epilepsy model.

Growing evidence has indicated that long noncoding RNAs (lncRNAs) are closely implicated in the progress of epilepsy. However, the expression profile and potential function of long noncoding RNAs cancer susceptibility candidate 2 (lncRNA CASC2) in epilepsy are poorly studied. The aim of this study was to testify the influence of lncRNA CASC2 on epilepsy in rat and cell models of epileptic seizure. We adopted qRT-PCR on the hippocampus of rats following pentylenetetrazol (PTZ)-stimulated epilepsy. To further examine the correlation between lncRNA CASC2 and Phosphatase and tensin homolog (PTEN), we detected the effects of lncRNA CASC2 on PTEN expression. We found that lncRNA CASC2 and PTEN expression were positively correlated in PTZ-induced epileptic rat. Overexpression of lncRNA CASC2 prolonged the latency and reduced the frequency of epileptic seizure, suppressed the activation of astrocytes and the release of adenosine in epileptic rat, whereas downregulation of lncRNA CASC2 exhibited the opposite effects. Meanwhile, lncRNA CASC2 decreased the adenosine metabolism related proteins expression of p38, Equilibrative nucleoside transporter 1 (ENT1) and Adenosine Kinase (ADK). In PTZ-treated astrocytes, PTEN was found to be a direct target of lncRNA CASC2. Additionally, downregulation of PTEN attenuated the protective effect of lncRNA CASC2 overexpression in epileptic seizure. Our findings manifested the key role of lncRNA CASC2 in the occurrence of epilepsy by targeting PTEN, which provided a novel target for epilepsy therapy.

Diffuse leptomeningeal glioneuronal tumor in a Chinese adult: a novel case report and review of literature.

Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare glioma tumor classified by the World Health Organization as a central nervous system tumor in 2016. DLGNT is most common in children and adolescents but is rare in adults. A 25-year-old male patient was admitted due to recurrent seizures. Head magnetic resonance imaging revealed lesions in the right temporal lobe, which were considered to be intracranial tumors with variable properties. The patient was admitted for surgical treatment. After admission, it was confirmed that seizures were associated with right temporal lobe lesions. Right temporal epileptogenic focus resection was performed by craniotomy. Immunohistochemistry revealed that tumor cells were reactive for oligodendrocyte transcription factor 2, synaptophysin, S100 proteins, and α-thalassemia mental retardation X-linked; and partially reactive for neuronal nuclei, glial fibrillary acidic protein, and nestin. The vascular wall was reactive for vimentin, CD34, CD31, and smooth muscle actin. Ki-67 was 4%. Molecular detection demonstrated 1p36 deletion, O6-methylguanine-DNA-methyltransferase methylation, and positive v-raf murine sarcoma viral oncogene homolog B mutation. DLGNT. The patient recovered well after surgery and received 54 Gy/27f radiotherapy without neurological dysfunction and seizures. In this study, onset age, tumor site, tumor increment coefficient, molecular detection, treatment methods, and prognosis of 54 patients were summarized from 19 studies. DLGNT patients are characterized by more singular tumor site, smaller volume, lower increment coefficient, and longer stable disease period. Patients with DLGNT may also have a longer stable condition in cases of molecular detection of 1p/19q deletion, or BRAF fusion.

Gentiopicroside inhibits RANKL-induced osteoclastogenesis by regulating NF-κB and JNK signaling pathways.

Gentiopicroside, a main active component from the traditional Chinese herb medicine Gentiana manshurica Kitag, has been shown to possess anti-arthritis effect. However, the molecular mechanism of gentiopicroside on the osteoclast formation remains unclear. The present study was designed to investigate the effects and mechanisms of gentiopicroside on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. The results showed that pre-treatment with gentiopicroside significantly inhibited RANKL-induced osteoclast formation from mouse bone marrow macrophages (BMMs). In addition, we observed that gentiopicroside efficiently suppressed osteoclastogenesis-related marker genes expression in RANKL-stimulated BMMs. Mechanistically, gentiopicroside suppressed RANKL-induced the activation of JNK and NF-κB signaling pathways in BMMs. Taken together, the present study demonstrated that gentiopicroside inhibits RANKL-induced osteoclastogenesis through the inactivation of JNK and NF-κB signaling pathways. Thus, gentiopicroside may be a promising agent for the treatment of osteoporosis.

Effects of the seasonal flooding on riparian soil seed bank in the Three Gorges Reservoir Region: a case study in Shanmu River.

INTRODUCTION: The water-level fluctuation in the Three Gorges Reservoir Region has changed dramatically as a result of the hydroelectric project for flood control and power generation. The riparian seasonal hydrological environment also has changed from summer flooding with winter drought to summer drought with winter flooding. The changes of riparian seed bank and vegetation were investigated to determine the effects of the seasonal flooding on the composition and spatial distribution of riparian soil seed bank and the similarity of seed bank to standing vegetation. CASE DESCRIPTION: We conducted intensive riparian soil sampling (525 samples) along altitude gradient in the Shanmu River, a tributary of the Yangzi River in the reservoir region of China. Seed bank density, species richness and composition of soil seed bank were examined using the seedling-emergence method. The seasonal hydrological conditions resulted in a decrease in species diversity and an increase in the distribution heterogeneity of the soil seed bank. The soil seed bank was composed of 48 species from 22 families and 40 genera. Most species were annual and perennial herbaceous Polygonaceae, Asteraceae, and Poaceae. Rumex dentatus was the predominant species accounting for 27.0 % of the total seeds. Diversity and composition of the seed bank changed along an altitude gradient and soil depth. Maximum species richness was found in the top soil layer at 165 m and 175 m above sea level. The mean overall seed density of the soil seed bank was 13,475.3 ind m(-2). Density and the number of seeds increased initially and then decreased with increased altitude. Maximum seed density (22,500.2 ind m(-2)) was found at 165 m above sea level in the intermediately flooded riverbank, with the seed number accounting for 27.8 % of the total soil seed bank. Average seed density declined significantly with soil depth. The similarity of seed bank to standing vegetation was relatively high. DISCUSSION AND EVALUATION: The environmental heterogeneity created by the wide range and seasonal flooding led to the changes in biodiversity and seed density along altitude gradient. The seasonal flooding also led to the increase in the similarity of seed bank to standing vegetation as their composition both degraded. CONCLUSIONS: The seasonal flooding due to the dam reshape the composition and spatial distribution of riparian soil seed bank and limit the vegetation to a grassland dominated by a few annuals and perennials in the Three Gorges Reservoir Region.

Population pharmacokinetics of rhTNFR-Fc in Chinese patients with rheumatic arthritis.

OBJECTIVE: We aimed to investigate the population pharmacokinetics (PK) of soluble recombinant human tumor necrosis factor receptor fusion protein (rhTNFR- Fc) in Chinese patients with rheumatic arthritis (RA). The PK differences between Chinese patients with RA and healthy Chinese subjects were also compared. METHODS: 40 patients were randomized to a single subcutaneous (SC) injections of 12.5 mg (n = 10), 25 mg (n = 10), and 50 mg (n = 10) of rhTNFR-Fc, and six SC injection of rhTNFR- Fc at 25 mg once in 3 days (n = 10) respectively. A total of 550 serum concentration data points were collected in the RA patients. The population PK analysis was performed by NONMEM. Based on the population PK parameters obtained herein and those reported in healthy Chinese subjects, simulation was conducted to compare the difference of rhTNFR-Fc exposure between these populations. RESULTS: The PK data of Chinese patients with RA were best described by a one compartment model with lag time. A higher CL/F was noted in RA patients compared with that of the healthy Chinese subjects (1.64 L/h vs. 1.10 L/h), and a lower Ka was noticed in the RA patients compared with that of the healthy subjects (0.0317 h-1 vs. 0.0605 h-1). The simulate results showed that rhTNFR-Fc exposure in Chinese patients with RA was significantly lower than that in healthy subjects. The mean patients/healthy subjects C(max) and AUC(ss) ratios were 0.870 and 0.890, respectively. CONCLUSIONS: A population PK model of rhTNFR- Fc was developed in Chinese patients with RA. Statistical difference was noted in the PK of rhTNFR-Fc between Chinese patients with RA and healthy Chinese subjects.

[Soil heterotrophic respiration and its sensitivity to soil temperature and moisture in Liquidambar formosana and Pinus massoniana forests in hilly areas of southeast Hubei Province, China].

Field monitoring was conducted to study the annual dynamics of soil heterotrophic respiration and soil temperature and moisture in Liquidambar formosana and Pinus massoniana forests in hilly areas of southeast Hubei Province, China. At the same time, laboratory experiment was performed to study the heterotrophic respiration rate along soil profile, and the sensitivity of surface soil (0-5 cm) heterotrophic respiration to soil temperature and moisture. Then, a model was established to valuate the potential effects of warming change on the soil heterotrophic respiration in study area. In L. formosana and P. massoniana forests, the soil heterotrophic respiration rate in 0-5 cm layer was 2.39 and 2.62 times, and 2.01 and 2.94 times of that in 5-10 cm and 10-20 cm layers, respectively, illustrating that soil heterotrophic respiration mainly occurred in 0-5 cm surface layer. The temperature sensitivity factor (Q10) of soil heterotrophic respiration in 0-5 cm, 5-10 cm, and 10-20 cm layers was 2.10, 1.86, and 1.78 in L. formosana forest, and 1.86, 1.77, and 1.44 in P. massoniana forest, respectively. The relationship between surface soil heterotrophic respiration and temperature (T) well fitted exponential function R = alphaexp (beta3T), and that between surface soil heterotrophic respiration and moisture (W) well fitted quadratic function R = a+bW+cW2. Therefore, the relationship of surface soil heterotrophic respiration with soil temperature and moisture could be described by the model lnR = a+bW+cW2 +dT+eT2, which suggested that the response of soil heterotrophic respiration to soil moisture was depended on soil temperature, i.e., the sensitivity decreased with decreasing soil temperature. The calculation of the annual soil heterotrophic respiration rate in the two forests with the established model showed that the calculated respiration rate was a slightly higher in L. formosana forest but close to the measured one in P. massoniana forest, illustrating the applied importance of the model. Our results suggested that the soil heterotrophic respiration in the L. formosana and P. massoniana forests in hilly areas of southeast Hubei Province would have an obvious increase under the background of global warming.

[Effects of waterlogging on ecophysiological characteristics of Salix variegate seedlings].

Salix variegate, a widely distributed species along the riverbank in Three Gorges Reservoir area, plays an important role in soil conservation and riverbank stabilization. Waterlogging from April to May was simulated in 2006 to test the adapting ability and mechanism of S. variegate seedlings to water environment change resulted from the construction of Three Gorges Project. The results showed that under waterlogging, all of the S. variegate seedlings could survive, but their maximum photosynthesis (Pmax), transpiration rate (Tr), water use efficiency (WUE), and stomatal conductance (Gs) decreased significantly with the prolongation of waterlogging. In the early period of waterlogging (20 days), these indices changed little, with the Pmax and Tr decreased by 18.5% and 2.2%, respectively, compared with the control. After 30 days, Pmax and Tr decreased by 53.4% and 23.7%, respectively, and then, kept stable. The contents of chlorophyll and carotenoid and their ratio decreased significantly with the prolongation of waterlogging, while the ratio of chlorophyll a to b increased significantly. The ratio of chlorophyll to carotenoid ranged in 4.873-6.883, and that of chlorophyll a to b ranged in 2.855-3.912. Adventitious roots were developed after waterlogging, which would benefit the oxygen supply for the plants. It was suggested that S. variegate had good adaptability to waterlogging, and could be used as a pioneer species in the restoration of degraded water-level fluctuation zone.