Serum metabolomics study of narcolepsy type 1 based on ultra-performance liquid chromatography-tandem mass spectrometry.

Narcolepsy is a chronic and underrecognized sleep disorder characterized by excessive daytime sleepiness and cataplexy. Furthermore, narcolepsy type 1 (NT1) has serious negative impacts on an individual's health, society, and the economy. Currently, many sleep centers lack the means to measure orexin levels in the cerebrospinal fluid. We aimed to analyze the characteristics of metabolite changes in patients with NT1, measured by ultra-performance liquid chromatography-tandem mass spectrometry. A principal component analysis (PCA), an orthogonal partial least square discriminant analysis (OPLS-DA), t tests, and volcano plots were used to construct a model of abnormal metabolic pathways in narcolepsy. We identified molecular changes in serum specimens from narcolepsy patients and compared them with control groups, including dehydroepiandrosterone, epinephrine, N-methyl-D-aspartic acid, and other metabolites, based on an OPLS-loading plot analysis. Nine metabolites yielded an area under the receiver operating curve > 0.75. Meanwhile, seven abnormal metabolic pathways were correlated with differential metabolites, such as metabolic pathways; neuroactive ligand‒receptor interaction; and glycine, serine, and threonine metabolism. To our knowledge, this is the first study to reveal the characteristic metabolite changes in sera from NT1 patients for the selection of potential blood biomarkers and the elucidation of NT1 pathogenesis.

Halomonas faecis sp. nov., a halophilic bacterium isolated from human faeces.

A novel moderately halophilic, Gram-stain-negative, catalase- and oxidase-positive, strictly aerobic, non-sporulating, non-motile rod, designated strain JSM 104105 T, was isolated from human faeces. Strain JSM 104105 T was able to grow with 0.5-18% (w/v) NaCl (optimum 4-9%), at pH 6-10.5 (optimum pH 7-8) and at 10-40 °C (optimum 30 °C) in complex media. The major cellular fatty acids were C18:1ω7c, C16:0, C16:1ω7c and/or C16:1ω6c, C19:0 cyclo ω8c and C12:0 3-OH. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unidentified aminophospholipid, an unidentified glycolipid and three unidentified phospholipids. The predominant respiratory quinone was Q-9 and the genomic DNA G + C content was 64.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain JSM 104105 T should be assigned to the genus Halomonas, and was most closely related to Halomonas gudaonensis SL014B-69 T (99.0% sequence similarity), followed by Halomonas azerbaijanica TBZ202T (98.6%) and Halomonas lysinitropha 3(2)T (97.3%). The whole genomic analysis showed that strain JSM 104105 T constituted a different taxon separated from the recognized Halomonas species. Combined data from phenotypic and genotypic studies demonstrated that strain JSM 104105 T represents a new species of the genus Halomonas, for which the name Halomonas faecis sp. nov. is proposed. The type strain is JSM 104105 T (= CCTCC AB 2014160 T = CGMCC 1.12945 T = KCTC 42146 T).

MOF-Derived Bifunctional Co0.85Se Nanoparticles Embedded in N-Doped Carbon Nanosheet Arrays as Efficient Sulfur Hosts for Lithium-Sulfur Batteries.

Lithium-sulfur batteries possess the merits of low cost and high theoretical energy density but suffer from the shuttle effect of lithium polysulfides and slow redox kinetics of sulfur. Herein, novel Co0.85Se nanoparticles embedded in nitrogen-doped carbon nanosheet arrays (Co0.85Se/NC) were constructed on carbon cloth as the self-supported host for a sulfur cathode using a facile fabrication strategy. The interconnected porous carbon-based structure of the Co0.85Se/NC could facilitate the rapid electron and ion transfer kinetics. The embedded Co0.85Se nanoparticles can effectively capture and catalyze lithium polysulfides, thus accelerating the redox kinetics and stabilizing sulfur cathodes. Therefore, the Co0.85Se/NC-S cathode could maintain a stable cycle performance for 400 cycles at 1C and deliver a high discharge specific capacity of 1361, 1001, and 810 mAh g-1 at current densities of 0.1, 1, and 3C, respectively. This work provides an efficient design strategy for high-performance lithium-sulfur batteries with high energy densities.

Sediminibacillus terrae sp. nov., a moderate halophile isolated from non-saline farm soil.

A Gram-stain-positive, moderately halophilic, strictly aerobic, endospore-forming, rod-shaped bacterium, strain JSM 102062T, was isolated from a non-saline farm soil sample collected from Dehang Canyon in Hunan, PR China. Growth occurred with 0.5-20 % (w/v) NaCl (optimum 4-7 %) at pH 5.5-11.0 (optimum pH 8.0) and at 20-50 °C (optimum 30-35 °C). Contained cell-wall peptidoglycan based on meso-diaminopimelic acid and possessed menaquinone-7 (MK-7) as the major respiratory isoprenoid quinone. The major cellular fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The polar lipid pattern consisted of diphosphatidylglycerol, phosphatidylglycerol, five unidentified phospholipids and an unidentified glycolipid. The DNA G+C content was 44.1 mol%. Phylogeny based on 16S rRNA gene sequences indicated that strain JSM 102062T belonged to the genus Sediminibacillus, sharing high 16S rRNA gene sequence similarities to Sediminibacillus halophilus EN8dT (99.4 %) and Sediminibacillus albus NHBX5T (98.3 %). The whole genomic analysis showed that strain JSM 102062T constituted a different taxon separated from the recognized Sediminibacillus species. Combined data from phenotypic and genotypic studies demonstrated that strain JSM 102062T represents a noval species of the genus Sediminibacillus, for which the name Sediminibacillus terrae sp. nov. is proposed; the type strain is JSM 102062T (=CCTCC AB 2014166T = CGMCC 1.12957T=DSM 28949T=KCTC 33541T).

Association between cytokines and fatigue in patients with type 1 narcolepsy.

BACKGROUND: Fatigue is a frequent complaint among patients with narcolepsy. Studies have shown that inflammatory cytokines are associated with fatigue in neurological disorders; however, this association has not been identified in patients with type 1 narcolepsy. The purpose of this study was to investigate the potential relationship between cytokines and fatigue in patients with type 1 narcolepsy. METHODS: We investigated the association between 12 inflammatory cytokines and fatigue in 49 patients with type 1 narcolepsy. The Multidimensional Fatigue Inventory-20 was used to assess the fatigue severity. The associations of fatigue were identified using Spearman and Pearson correlation analyses. A linear regression analysis model was used to adjust the confounding factors and evaluate the associations of fatigue. RESULTS: Correlation analysis showed that the plasma interleukin (IL)-2 level (r = 0.409, p = 0.004) was positively correlated with fatigue in patients with narcolepsy type 1. After adjusting for confounding factors, the linear regression model revealed a positive association between the IL-2 level (ß = 1.148, p = 0.04) and fatigue in individuals diagnosed with type 1 narcolepsy. CONCLUSION: IL-2 levels show a positive correlation with fatigue in type 1 narcolepsy, suggesting its potential role in the pathophysiology of fatigue.

The value of using ELISA to detect orexin-A in cerebrospinal fluid in the diagnosis of narcolepsy.

Orexin in cerebrospinal fluid (CSF) is a neuropeptide synthesized by a cluster of neurons in the lateral hypothalamus. It mainly functions to maintain arousal, regulate feeding, and participate in reward mechanisms. Radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) can detect CSF orexin. At present, RIA is widely used but is limited by various conditions, which is not conducive to its widespread development. We aimed to determine whether ELISA can replace RIA in detecting orexin in CSF. We investigated the results of 20 patients with central disorders of hypersomnolence, including 11 with narcolepsy type 1, 2 with narcolepsy type 2, 5 with idiopathic hypersomnia, and 2 with other causes of somnolence. RIA and ELISA were used to detect CSF orexin, and P values <.05 were considered to be significant. In the narcolepsy and non-narcolepsy type 1 groups, there was no correlation between the RIA and ELISA results (P > .05). In the narcolepsy type 1 group, the ELISA and RIA results were significantly different (P < .05), but this was not observed in the non-narcolepsy type 1 group (P > .05). The accuracy of ELISA to detect CSF orexin was lower than that of RIA (P < .05). ELISA cannot replace RIA in the measurement of CSF orexin, and RIA is recommended as the first choice when narcolepsy is suspected.

Cell-based vs enzyme-linked immunosorbent assay for detection of anti-Tribbles homolog 2 autoantibodies in Chinese patients with narcolepsy.

STUDY OBJECTIVES: Narcolepsy type 1 is attributed to a deficiency in cerebrospinal fluid orexin and is considered linked to autoimmunity. The levels of anti-Tribbles homolog 2 (TRIB2) autoantibodies are elevated in the sera of some patients with narcolepsy with cataplexy. Additionally, injecting mice with serum immunoglobulin from patients with narcolepsy with positive anti-TRIB2 antibodies can induce hypothalamic neuron loss and alterations in sleep patterns. Consequently, we hypothesized the existence of a potential association between anti-TRIB2 antibodies and narcolepsy. To test this possibility, we used cell-based assays (CBAs) and enzyme-linked immunosorbent assays (ELISAs) to detect the presence of anti-TRIB2 antibodies in Chinese patients with narcolepsy. METHODS: We included 68 patients with narcolepsy type 1, 39 patients with other central disorders of hypersomnolence, and 43 healthy controls. A CBA and a conventional ELISA were used to detect anti-TRIB2 antibody levels in patients' sera. RESULTS: CBA was used to detect serum anti-TRIB2 antibodies in Chinese patients with narcolepsy, and the results were negative. However, when the ELISA was used, only 2 patients with narcolepsy type 1 had TRIB2 antibody titers higher than the mean titer plus 2 standard deviations of the healthy controls. CONCLUSIONS: In our study, ELISA identified TRIB2 autoantibodies in sera of patients with narcolepsy where CBA failed to demonstrate them. Contrary to our hypothesis, this intriguing finding deserves further research to elucidate the potential association between TRIB2 and narcolepsy type 1. Exploring the implications of TRIB2 autoantibodies in narcolepsy and disparate outcomes between ELISA and CBA could provide crucial insights. CITATION: Zhong X, Yuan Y, Zhan Q, et al. Cell-based vs enzyme-linked immunosorbent assay for detection of anti-Tribbles homolog 2 autoantibodies in Chinese patients with narcolepsy. J Clin Sleep Med. 2024;20(6):941-946.

Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial.

Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable--mean adjusted total daily off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

Tribological behaviors of laser textured surface under different lubrication conditions for rotary compressor.

Tribological behaviors of laser textured surface with elliptical dimples were experimentally compared with that of the smooth one under different lubrication conditions, including the poor-oil, rich-oil and dry lubrication. The lubrication regime was analyzed with the increasing operating load by ring-on-ring tribological tests. Finally, the performance impact of rolling piston rotary compressor with textures fabricated on the thrust surfaces was investigated. Results show that the tribological improvement strongly depends on lubrication condition. With the increase of applied loads under rich-oil and poor-oil lubrication, the effect of micro dimple promotes the critical load transforming lubrication regime, and expands the range of hydrodynamic lubrication, meanwhile maintains a similar minimum of friction coefficient as the smooth surface but enhances wear resistance. However, it is reverse to increase the friction coefficient and surface wear for the textured surfaces under dry lubrication. The compressor performance can be improved significantly by laser surface texturing with a 2% reduction of friction power consumption and a 2.5% enhancement of energy efficiency ratio.

Vertical Graphene Film Enables High-Performance Quasi-Solid-State Planar Zinc-Ion Microbatteries.

With the advantages of low cost, high safety, and environmental friendliness, quasi-solid-state zinc-ion microbatteries (ZIMBs) have received widespread attention in the field of flexible wearable devices and on-chip integratable energy storage. However, hysteresis Zn-ion transport kinetics and inhomogeneous growth of the zinc anode result in the poor capacity reversibility and cycling stability. Herein, a quasi-solid-state planar zinc-ion cell was developed by employing a vertical graphene (VG) film as an effective conductive modification layer for both the cathode and anode. The VG distinctly induces uniform Zn deposition/stripping, accelerates the charge transport, and enhances the adhesion between the active materials and current collectors. As a result, planar Zn@VG//MnO2@VG exhibits a high areal capacity of 159 µAh cm-2, a remarkably high areal energy/power density of 201.5 µWh cm-2/67.16 µW cm-2, and a high capacity retention of 95.6% at a bending angle of 180°. The proposed facile strategy for electrode modification provides a new insight into the design of high-performance flexible and planar ZIMBs.

Highly effective transfer of micro-LED pixels to the intermediate and rigid substrate with weak and tunable adhesion by thiol modification.

Based on transfer printing technology, micro-LED pixels can be transferred to different types and sizes of driving substrates to realize displays with different application scenarios. To achieve a successful transfer, GaN-based micro-LEDs first need to be separated from the original epitaxial substrate. Here, micro-LED pixels (each size 25 µm × 30 µm) on the sapphire substrate were transferred to a flexible semiconductor wafer processing (SWP) tape that is strongly sticky by conventional laser lift-off (LLO) techniques. The pixels on the SWP tape were then transferred by using a sacrificial layer of non-crosslinked oligomeric polystyrene (PS) film onto the intermediate and rigid substrate (IRS) with weak and tunable adhesion by thiol (-SH) modification. The electrode of the micro-LED is Au metal, which forms Au-S bonds with the surface of the IRS to fix the pixels. The rigid substrate helps ensure that the pixel spacing is almost unchanged during the stamp transfer process, and the weak and tunable adhesion facilitates the pixels being picked up by the stamp. The experimental results demonstrate that the pixels can be efficiently transferred to the IRS by LLO and sacrificial layer-assistance, which will provide the possibility of achieving the further transfer of pixels to different types and sizes of driving substrates by a suitable transfer stamp. The transfer process details are discussed, which can provide insights into the transfer of micro-nano devices through polymer sacrificial layers.

Changed epidemiology of narcolepsy before, during, and after the 2009 H1N1 pandemic: a nationwide narcolepsy surveillance network study in mainland China, 1990-2017.

STUDY OBJECTIVES: Increased incidence of narcolepsy was reported in children during the 2009 H1N1 pandemic following Pandemrix, a H1N1 flu vaccine. A link with A(H1N1) pdm09 infections remains controversial. Using nationwide surveillance data from China (1990 to 2017), the epidemiology of narcolepsy was analyzed. METHODS: Individual records of narcolepsy patients were collected from 15 of 42 hospitals across China known to diagnose cases. Incidence was estimated assuming the representativeness of these hospitals. Age-specific incidence, epidemiological and clinical characteristics of patients were evaluated before, during, and after the 2009 H1N1 pandemic. Sensitivity analyses were conducted by including NT1 cases only and excluding the effect of the 2009 H1N1 vaccination. RESULTS: Average annual incidence was 0.79 per 100 000 person-years (PY) from 1990 to 2017 and 1.08 per 100 000 PY from 2003 to 2017. Incidence increased 4.17 (95% CI 4.12, 4.22) and 1.42 (95% CI 1.41, 1.44) fold during and after the 2009 H1N1 pandemic when compared to baseline. These results were robust in sensitivity analyses. Patients with the onset of narcolepsy during the pandemic period were younger (notably in 5-9-year-old strata), and the age shift toward younger children reversed to baseline following the pandemic. CONCLUSIONS: Increased incidence of narcolepsy was observed during the 2009 H1N1 pandemic period. This is likely to be associated with the circulation of the wild type A(H1N1)pdm09 virus. This observation should be considered for future influenza pandemic preparedness plans.

Close-spaced thermally evaporated 3D Sb2Se3 film for high-rate and high-capacity lithium-ion storage.

As a key factor for fast-charging lithium-ion batteries (LIBs), high-rate anode materials that can recharge in a few minutes have aroused increasing attention. However, high-rate performance is always accompanied by low theoretical capacities, such as the widely known high-rate electrode of Li4Ti5O12 (175 mA h g-1), which severely limits its large-scale implementation in the development of high power density LIBs. Here, we report a modified close-spaced thermal evaporation process to deposit 3D-structured Sb2Se3 films (3D-SSF) with tunable morphology as an additive-free anode for LIBs. After a high-rate activation process, 3D-SSF exhibits a flatter discharge plateau than the reported results and could deliver a high capacity of 471 mA h g-1 at an ultrahigh current density of 21 440 mA g-1, which is superior to the widely known high-rate Li4Ti5O12 anode (over 150 mA h g-1 at 8750 mA g-1). Moreover, we reveal a current-regulated Li-ion storage mechanism where 3D-SFF undergoes a synergistic conversion and alloying reaction at low current densities, while an alloying reaction-dominated process at high rates. Beyond that, full batteries with excellent rate performance were successfully assembled by pairing with homemade LiFePO4 (LFP) as the cathode.

Molecular mechanism of an antagonistic antibody against glucose-dependent insulinotropic polypeptide receptor.

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone involved in regulating glucose and lipid metabolism. GIP receptor (GIPR) antagonism is believed to offer therapeutic potential for various metabolic diseases. Pharmacological intervention of GIPR, however, has limited success due to lack of effective antagonistic reagents. Previously we reported the discovery of two mouse anti-murine GIPR monoclonal antibodies (mAbs) with distinctive properties in rodent models. Here, we report the detailed structural and biochemical characterization of these two antibodies, mAb1 and mAb2. In vitro and in vivo characterizations demonstrated mAb2 is a full GIPR antagonistic antibody and mAb1 is a non-neutralizing GIPR binder. To understand the molecular basis of these two antibodies, we determined the co-crystal structures of GIPR extracellular domain in complex with mAb1 and with mAb2 at resolutions of 2.1 and 2.6 Å, respectively. While the non-neutralizing mAb1 binds to GIPR without competing with the ligand peptide, mAb2 not only partially occludes the ligand peptide binding, but also recognizes the GIPR C-terminal stalk region in a helical conformation that acts as a molecular mimic of the ligand peptide and locks GIPR in a novel auto-inhibited state. Furthermore, administration of mAb2 in diet-induced obesity mice for 7 weeks leads to both reduction in body weight gain and improvement of metabolic profiles. In contrast, mAb1 has no effect on body weight or other metabolic improvement. Together, our studies reveal the unique molecular mechanism of action underlying the superior antagonistic activity of mAb2 and signify the promising therapeutic potential of effective GIPR antagonism for the treatment of metabolic disorders.

A Hierarchical Copper Oxide-Germanium Hybrid Film for High Areal Capacity Lithium Ion Batteries.

Self-supported electrodes represent a novel architecture for better performing lithium ion batteries. However, lower areal capacity restricts their commercial application. Here, we explore a facial strategy to increase the areal capacity without sacrificing the lithium storage performance. A hierarchical CuO-Ge hybrid film electrode will not only provide high areal capacity but also outstanding lithium storage performance for lithium ion battery anode. Benefiting from the favorable structural advance as well as the synergic effect of the Ge film and CuO NWs array, the hybrid electrode exhibits a high areal capacity up to 3.81 mA h cm-2, good cycling stability (a capacity retention of 90.5% after 150 cycles), and superior rate performance (77.4% capacity remains even when the current density increased to 10 times higher).

Morroniside protects against cerebral ischemia/reperfusion injury by inhibiting neuron apoptosis and MMP2/9 expression.

The aim of the present study was to investigate the effect of morroniside against matrix metalloproteinase (MMP)2/9 and focal cerebral ischemia/reperfusion (I/R) injury in rats. A rat model of focal cerebral I/R injury rats was established and rats were administered with 30, 90 or 270 mg/kg/day morroniside for 7 days. The expression of MMP2/9 and neuronal apoptosis were assessed. In addition, the expression of active caspase-3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were measured. The results revealed that MMP2 and MMP9 expression was upregulated and the percentage of apoptotic neurons was increased in rats with focal cerebral I/R injury compared with the control. However, treatment with morroniside significantly inhibited I/R-induced MMP2/9 expression and neuron apoptosis compared with the untreated I/R injury group. Morroniside administration also decreased the expression of active caspase-3 and increased the Bcl-2/Bax ratio compared with untreated rats with focal cerebral I/R injury. The inhibitory effect of morroniside on MMP2/9 expression and neuron apoptosis was dose dependent. In summary, the results of the present study suggest that morroniside is able to protect against cerebral I/R injury in the brain and may have potential as a therapeutic treatment for patients who have suffered a stroke.

Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models.

Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) has been identified in multiple genome-wide association studies (GWAS) as a contributor to obesity, and GIPR knockout mice are protected against diet-induced obesity (DIO). On the basis of this genetic evidence, we developed anti-GIPR antagonistic antibodies as a potential therapeutic strategy for the treatment of obesity and observed that a mouse anti-murine GIPR antibody (muGIPR-Ab) protected against body weight gain, improved multiple metabolic parameters, and was associated with reduced food intake and resting respiratory exchange ratio (RER) in DIO mice. We replicated these results in obese nonhuman primates (NHPs) using an anti-human GIPR antibody (hGIPR-Ab) and found that weight loss was more pronounced than in mice. In addition, we observed enhanced weight loss in DIO mice and NHPs when anti-GIPR antibodies were codosed with glucagon-like peptide-1 receptor (GLP-1R) agonists. Mechanistic and crystallographic studies demonstrated that hGIPR-Ab displaced GIP and bound to GIPR using the same conserved hydrophobic residues as GIP. Further, using a conditional knockout mouse model, we excluded the role of GIPR in pancreatic ß-cells in the regulation of body weight and response to GIPR antagonism. In conclusion, these data provide preclinical validation of a therapeutic approach to treat obesity with anti-GIPR antibodies.

A Novel Fc-FGF21 With Improved Resistance to Proteolysis, Increased Affinity Toward ß-Klotho, and Enhanced Efficacy in Mice and Cynomolgus Monkeys.

Fibroblast growth factor (FGF) 21 is a natural hormone that modulates glucose, lipid, and energy metabolism. Previously, we engineered an Fc fusion FGF21 variant with two mutations, Fc-FGF21(RG), to extend the half-life and reduce aggregation and in vivo degradation of FGF21. We now describe a new variant developed to reduce the extreme C-terminal degradation and improve the binding affinity to ß-Klotho. We demonstrate, by introducing one additional mutation located at the C terminus of FGF21 (A180E), that the new molecule, Fc-FGF21(RGE), has gained many improved attributes. Compared with Fc-FGF21(RG), Fc-FGF21(RGE) has similar in vitro potency, preserves ß-Klotho dependency, and maintains FGF receptor selectivity and cross-species reactivity. In vivo, Fc-FGF21(RGE) showed reduced susceptibility to extreme C-terminal degradation and increased plasma levels of the bioactive intact molecule. The circulating half-life of intact Fc-FGF21(RGE) increased twofold compared with that of Fc-FGF21(RG) in mice and cynomolgus monkeys. Additionally, Fc-FGF21(RGE) exhibited threefold to fivefold enhanced binding affinity to coreceptor ß-Klotho across mouse, cynomolgus monkey, and human species. In obese and diabetic mouse and cynomolgus monkey models, Fc-FGF21(RGE) demonstrated greater efficacies to Fc-FGF21(RG), resulting in larger and more sustained improvements in multiple metabolic parameters. No increased immunogenicity was observed with Fc-FGF21(RGE). The superior biophysical, pharmacokinetic, and pharmacodynamic properties, as well as the positive metabolic effects across species, suggest that further clinical development of Fc-FGF21(RGE) as a metabolic therapy for diabetic and/or obese patients may be warranted.

Effects of valproate on the carotid artery intima-media thickness in epileptics.

OBJECTIVE: The objective was to explore the effects of valproate (VPA) on the carotid artery intima-media thickness (CA-IMT) in epileptics. MATERIALS AND METHODS: A total of 30 epileptic patients treated with VPA was included as disease group, while 33 healthy people who matched general basic demographic details were the control group. The IMTs of the left and right carotids of the both groups were measured, and the average CA-IMT was calculated. The IMT-related risk factors were acquired for the univariate and multivariate analysis. RESULTS: The bilateral carotid and average CA-IMTs of the disease group were significantly higher than the control group (P < 0.001). The multivariant gradual regressive analysis screened out two CA-IMT-related factors, namely the disease duration and the drug administration duration were positively correlated with the average CA-IMT. The epileptic patients with disease course of more than 3 years had much higher average CA-IMT than that of the epileptics with ≤3 years disease (P < 0.001). The average CA-IMT of the patients with VPA-administration duration >1 year was also higher than that of the patients with VPA-administration duration <1 year, while the difference was not statistically significant (P = 0.196). CONCLUSIONS: The average CA-IMT of the epileptic patients treated with VPA was higher than that of healthy people.

[Impact of obstructive sleep apnea-hypopnea syndrome on cerebral microbleeds in patients with cerebral infarction].

OBJECTIVE: To investigate the impact of obstructive sleep apnea-hypopnea syndrome (OSAHS) on cerebral microbleeds (CMBs) in patients with cerebral infarction. METHODS: Consecutive patients with acute cerebral infarction who had cerebral microbleeds shown by susceptibility-weighted imaging (SWI) were enrolled to undergo polysomnography (PSG). The patients were divided into two groups, namely non-OSAHS group with apnea-hypopnea index (AHI) less than 5 and OSAHS group with greater AHI, and the clinical and radiological features of cerebral microbleeds were compared between them. RESULTS: Forty-nine patients were enrolled in this study, including 27 (55.1%) with both cerebral infarction and OSAHS and 22 (44.9%) with cerebral infarction but not OSAHS. A comparison of the risk factors showed that hypertension, a smoking history, and a history of stroke were more prevalent in patients with OSAHS than in those without OSAHS (P<0.05). The incidences of subclinical stroke in OSAHS and non-OSAHS patients were 37.0% (10/27) and 9.0% (2/22) (P<0.05), respectively. Neurological imaging revealed a greater number of cerebral microbleeds in OSAHS group than in non-OSAHS group (P<0.05). In OSAHS patients, 77.8% of the microbleeds were distributed in cortical-subcortical areas, 55.6% in the basal ganglia area, and 25.9% in the infratentorial area, as compared to the percentages of 50.0%, 40.9% and 50.0% in non-OSAHS patients, respectively (P<0.05). In OSAHS patients, 40.7% also had leukoaraiosis, and 48.1% had two or more causes, as compared to the percentages of 13.6% and 18.2% in non-OSAHS patients, respectively (P<0.05). CONCLUSIONS: OSAHS can be a risk factor for cerebral microbleeds. Patients with both cerebral infarction and OSAHS tend to have greater and more extensive lesions of cerebral microbleeds, more complicated cause of the disease, and a grater likeliness of stroke recurrence.