Clinical study of the effect of 5 kinds of antiepileptic drugs on the postictal state.

OBJECTIVE: To compare the effects of levetiracetam（LEV）, lamotrigine(LTG), oxcarbazepine(OXC), topiramate(TPM) and valproate (VPA) on postictal state (PIS). METHODS: A total of 187 epilepsy patients undergoing monotherapy were enrolled in a long-term follow-up study at the Affiliated Hospital of Yangzhou College. This included 30 patients on levetiracetam, 41 on valproate, 30 on oxcarbazepine, 28 on topiramate, and 31 on lamotrigine. A control group of 28 newly diagnosed or previously untreated epilepsy patients was also included. The Liverpool Seizure Severity Scale 2.0 (LSSS2.0) and the Seizure Severity Questionnaire (SSQ) were utilized to evaluate the patients' condition, with comparison based on the results of the postictal status items. EEG during PIS termination was assessed using the Grand Total EEG score (GTE) as an objective tool to measure the impact of Antiseizure medications (ASMs) on the post-seizure state. RESULTS: The LSSS2.0 score indicated a statistically significant difference in post-seizure status score among the 5 groups (p < 0.05). The difference between the 5 groups and the control group was statistically significant (p < 0.05). Results of the SSQ demonstrated that all 5 drugs significantly reduced the post-seizure status score compared to the control group (p < 0.05). The GTE score revealed that, in the later stage of the seizure, the GTE score of the levetiracetam group, valproate group, oxcarbazepine group, and lamotrigine group significantly decreased compared to the control group (P < 0.05). There was no significant decrease in the GTE score in the topiramate group (P < 0.05). CONCLUSION: Levetiracetam, lamotrigine, oxcarbazepine, topiramate, and valproate demonstrate favorable efficacy in ameliorating the severity of post-seizure condition. Further investigations are warranted to assess the potential of other widely employed anti-seizure medications in enhancing post-seizure status.

Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1.

SARS-CoV-2 and filovirus enter cells via the cell surface angiotensin-converting enzyme 2 (ACE2) or the late-endosome Niemann-Pick C1 (NPC1) as a receptor. Here, we screened 974 natural compounds and identified Tubeimosides I, II, and III as pan-coronavirus and filovirus entry inhibitors that target NPC1. Using in-silico, biochemical, and genomic approaches, we provide evidence that NPC1 also binds SARS-CoV-2 spike (S) protein on the receptor-binding domain (RBD), which is blocked by Tubeimosides. Importantly, NPC1 strongly promotes productive SARS-CoV-2 entry, which we propose is due to its influence on fusion in late endosomes. The Tubeimosides' antiviral activity and NPC1 function are further confirmed by infection with SARS-CoV-2 variants of concern (VOC), SARS-CoV, and MERS-CoV. Thus, NPC1 is a critical entry co-factor for highly pathogenic human coronaviruses (HCoVs) in the late endosomes, and Tubeimosides hold promise as a new countermeasure for these HCoVs and filoviruses.

BushenHuoxue decoction suppresses M1 macrophage polarization and prevents LPS induced inflammatory bone loss by activating AMPK pathway.

Abnormal bone metabolism and subsequence osteoporotic fractures are common complications of chronic inflammatory diseases. No effective treatment for these bone-related complications is available at present. The chronic inflammatory state in these diseases has been considered as a key factor of bone loss. Therefore, the combination of inflammation inhibition and bone loss suppression may be an important strategy for reducing bone damage associated with inflammatory diseases. Bushen Huoxue Decoction (BSHXD) is a traditional Chinese herbal compound that has demonstrated the ability to improve bone quality and increase bone density. However, the efficacy of BSHXD on inflammatory bone loss and its underlying mechanisms remain unclear. This study aimed to investigate whether BSHXD inhibits inflammatory bone loss in mice and its potential molecular mechanisms. In the present study, the effect of BSHXD on lipopolysaccharide (LPS)-induced M1 polarization of RAW264.7 macrophage and on local inflammatory bone loss model of mouse skull was determined. The results showed that after treating RAW264.7 cells with LPS for 24 h, the expression levels of IL-1ß (39.42 ± 3.076 ng/L, p < 0.05), IL-6 (49.24 ± 1.766 mg/L, p < 0.05) and TNF-α (286.3 ± 27.12 ng/L, p < 0.05) were significantly increased. The addition of BSHXD decreased the expression levels of IL-1ß, IL-6, and TNF-α to 31.55 ± 1.296 ng/L, 37.94 ± 0.8869 mg/L, and 196.4 ± 25.25 ng/L, respectively (p < 0.05). The results of immunofluorescence staining, Western blotting (WB) and flow cytometry indicated that the proportion of M1 macrophages in RAW264.7 cells treated with BSHXD for 24 h was significantly lower than that in the LPS group (13.36% ± 0.9829% VS 24.80% ± 4.619%, p < 0.05). The evidence from in-vitro experiments showed that the immunomodulatory ability of BSHXD may be associated with the activation of AMP-dependent protein kinase (AMPK) pathway in LPS-treated macrophages. In addition, the results of micro-CT, H&E staining, immunohistochemical staining and immunofluorescence staining of mouse skull further demonstrated that BSHXD treatment significantly alleviated LPS-induced local bone loss and inflammatory damage in mouse skull model. All results indicated that BSHXD significantly inhibited inflammatory factors release and M1 polarization of macrophage through AMPK signaling pathway. Therefore, BSHXD may be a promising drug for the treatment of inflammatory bone loss.

Clinical characteristics of cognitive impairment and its related risk factors in post-stroke epilepsy

Objective: Post-stroke epilepsy (PSE) patients are prone to cognitive impairment (CI) due to multiple factors. This study aimed to assess clinical characteristics of CI and its related risk factors in newly diagnosed Chinese Han adult epilepsy patients with ischaemic stroke. Methods: Data were collected on PSE patients hospitalized in the neurology ward of the Affiliated Hospital of Yangzhou University, from January 2016 to May 2019. Newly diagnosed PSE patients were followed for six months; their cognitive functions were then assessed according to the Chinese Beijing version of the Montreal Scale (MoCA) and patients were divided into a PSE+CI group (MoCA scale score <26) (n=81) or PSE-CI group (MoCA scale score ≥26) (n=36). Data collection tools also included the Chinese versions of the Zheng Self-assessment Anxiety Scale, the Zheng Self-assessment Depression Scale, the Barthel index and the National Hospital Seizure Severity Scale. We compared the basic clinical characteristics between the two groups of patients and investigated the factors of CI in PSE patients. Results: In total, CI was present in 81 (69%) and absent in 36 (31%) PSE patients. MoCA total score in the PSE+CI group was 20.85±4.13 and 27.53±1.34 in the PSECI group. The Bonferroni corrected significance level was 0.0013. Scores for multiple cognitive domains (visuospatial/executive skills, naming, attention, language and delayed recall) were lower in the PSE+CI group than the PSE-CI group. Moreover, the PSE+CI group had a higher incidence of depression and anxiety. Univariate analysis showed that diabetes (p= 0.000) and the number of antiepileptic drugs (AEDs) (p= 0.001) were associated with CI in PSE. Binary logistic regression analysis showed that diabetes (odds ratio [OR]: 5.242, 95% confidence interval [CI]: 1.680-16.363, p= 0.004), high homocysteine levels (OR: 1.103, 95% CI: 1.008-1.207, p= 0.033) and the number of AEDs (OR: 3.354, 95% CI: 1.225-9.180, p= 0.019) were associated with CI in PSE. Significance: Diabetes, high homocysteine levels and a higher number of AEDs may be risk factors for CI in PSE.

Urolithin B suppressed osteoclast activation and reduced bone loss of osteoporosis via inhibiting ERK/NF-κB pathway.

OBJECTIVES: The main target of current drugs for alleviating bone loss is osteoclasts. However, the long-term application of such drugs will also cause side effects. Therefore, it is of great need to develop new and safer therapeutics for osteoporosis. In recent years, drug development based on gut microbiota has gradually attracted attention. This manuscript investigates the inhibitory effect of urolithin B (UB) on osteoclastogenesis and differentiation in vitro and in ovariectomized (OVX) mice. MATERIALS AND METHODS: CCK-8 was used to analyse the cytotoxicity of UB; BMMs cells were differentiated into osteoclasts by RANKL, and respectively treated with 1, 5, and 25 µmol/L UB during this process. After one week of intervention, tartrate-resistant acid phosphatase (TRAP) staining was used to analyse the number and average area of osteoclasts. F-actin staining and immunofluorescence staining were conducted to evaluate the morphology and function of osteoclasts. Bone resorption function of osteoclasts was detected by Pit Formation Assay. The expression of osteoclast-related protein genes in RAW264.7 cells were investigated via western blot and RT-PCR assays. Western blot analysis of RANKL-mediated activation of MAPK/NF-κB pathway after 0, 5, 15, 30, 60 min of intervention. For in vivo experiments, OVX mice received intraperitoneal injection of 10, 50 mg/kg every two days, 8 weeks later, the femurs of mice were taken for morphological analysis, and the serum content of CTX-1, a bone metabolism index, was analysed. RESULTS: UB could inhibit the osteoclast differentiation of rankl-induced bone marrow macrophages (BMMs) and RAW264.7 cells in vitro, suppress the uptake activity of hydroxyapatite and expression of osteoclast-related gene MMP9, CTSK, NFATc1 and c-fos. Furthermore, UB repressed the rankl-induced phosphorylation and degradation of IκB and the phosphorylation of P65 in the NF-κB pathway of RAW264.7 cells, and also down-regulated the phosphorylation level of ERK in the MAPK pathway. For in vivo studies, UB-treated OVX mice showed more significant improved various parameters of distal femur compared with the control group, with fewer NFATc1, MMP9 and TRAP-positive osteoclasts in bone tissues, and less serum content of CTX-1. CONCLUSION: Urolithin B attenuated bone loss in OVX mice by inhibiting the formation and activation of osteoclasts via down-regulation of the ERK/NF-κB signalling pathway.

Generation of SIV-resistant T cells and macrophages from nonhuman primate induced pluripotent stem cells with edited CCR5 locus.

Adoptive therapies with genetically modified somatic T cells rendered HIV resistance have shown promise for AIDS therapy. A renewable source of HIV-resistant human T cells from induced pluripotent stem cells (iPSCs) would further facilitate and broaden the applicability of these therapies. Here, we report successful targeting of the CCR5 locus in iPSCs generated from T cells (T-iPSCs) or fibroblasts (fib-iPSCs) from Mauritian cynomolgus macaques (MCM), using CRISPR-Cas9 technology. We found that CCR5 editing does not affect hematopoietic and T cell differentiation potentials of fib-iPSCs. However, T-iPSCs with edited CCR5 lost their capacity to differentiate into CD4+CD8+ T cells while maintaining myeloid differentiation potential. T cells and macrophages produced from CCR5-edited MCM iPSCs did not support replication of the CCR5-tropic simian immunodeficiency viruses SIVmac239 (T cell tropic) and SIVmac316 (macrophage-tropic). Overall, these studies provide a platform for further exploration of AIDS therapies based on gene-edited iPSCs in a nonhuman primate model.

A phthalocyanine-grafted MA-VA framework polymer as a high performance anode material for lithium/sodium-ion batteries.

A porous MA-VA-PcNi polymer was prepared by grafting nickel phthalocyanine (PcNi) onto the main chain of a maleic anhydride-vinyl acetate (MA-VA) polymer, and an MA-VA-PcNi electrode is prepared by electrospinning technology to inhibit the agglomeration of the active powder effectively, which produces spherical particles with a diameter of 100-300 nm. The synthesized MA-VA-PcNi polymer is used as the anode for lithium-ion and sodium-ion batteries, exhibiting excellent energy storage behaviors. The MA-VA-PcNi/Li battery displays a high capacity of 610 mA h g-1 and can still remain at 507 mA h g-1 with a retention rate of 83.1% after 400 cycles at a current density of 200 mA g-1. Even at a high current density of 2 A g-1, the specific capacity can remain at 195 mA h g-1. In addition, the MA-VA-PcNi/Na battery displays a high capacity of 336 mA h g-1 and can still remain at 278 mA h g-1 with a retention rate of 82.7% after 400 cycles at a current density of 100 mA g-1. A high specific capacity of 164 mA h g-1 can also be achieved at a high current density of 1 A g-1. After nickel phthalocyanine (PcNi) was grafted onto the MA-VA polymer, aggregation between phthalocyanine rings was effectively prevented, and this exposes more active sites. At the same time, the spherical particles obtained by electrospinning technology further improve the dispersion and increase the number of active sites of the active materials. Finally, the electrode materials show excellent energy storage behavior for lithium-ion and sodium-ion batteries, which provides a new idea for designing high-performance energy storage materials for organic electrodes.

1,4,5,8-Naphthalenetetracarboxylic dianhydride grafted phthalocyanine macromolecules as an anode material for lithium ion batteries.

For solving the problems of high solubility in electrolytes, poor conductivity and low active site utilization of organic electrode materials, in this work, 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTCDA) grafted nickel phthalocyanine (TNTCDA-NiPc) was synthesized and used as an anode material for lithium ion batteries. As a result, the dispersibility, conductivity and dissolution stability are improved, which is conducive to enhancing the performance of batteries. The initial discharge capacity of the TNTCDA-NiPc electrode is 859.8 mA h g-1 at 2 A g-1 current density, which is much higher than that of the NTCDA electrode (247.4 mA h g-1). After 379 cycles, the discharge capacity of the TNTCDA-NiPc electrode is 1162.9 mA h g-1, and the capacity retention rate is 135.3%, which is 7 times that of the NTCDA electrode. After NTCDA is grafted to the phthalocyanine macrocyclic system, the dissolution of the NTCDA in the electrolyte is reduced, and the conductivity and dispersion of the NTCDA and phthalocyanine ring are also improved, so that more active sites of super lithium intercalation from NTCDA and phthalocyanine rings are exposed, which results in better electrochemical performance. The strategy of grafting small molecular active compounds into macrocyclic conjugated systems used in this work can provide new ideas for the development of high performance organic electrode materials.

Sustained expression of MCP-1 induced low wall shear stress loading in conjunction with turbulent flow on endothelial cells of intracranial aneurysm.

Shear stress was reported to regulate the expression of AC007362, but its underlying mechanisms remain to be explored. In this study, to isolate endothelial cells of blood vessels, unruptured and ruptured intracranial aneurysm (IA) tissues were collected from IA patients. Subsequently, quantitative real-time PCR (qRT-PCR), Western blot and luciferase assay were performed to investigate the relationships between AC007362, miRNAs-493 and monocyte chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) exposed to shear stress. Reduced representation bisulphite sequencing (RRBS) was performed to assess the level of DNA methylation in AC007362 promoter. Accordingly, AC007362 and MCP-1 were significantly up-regulated while miR-493 was significantly down-regulated in HUVECs exposed to shear stress. AC007362 could suppress the miR-493 expression and elevate the MCP-1 expression, and miR-493 was shown to respectively target AC007362 and MCP-1. Moreover, shear stress in HUVECs led to the down-regulated DNA methyltransferase 1 (DNMT1), as well as the decreased DNA methylation level of AC007362 promoter. Similar results were also observed in ruptured IA tissues when compared with unruptured IA tissues. In conclusion, this study presented a deep insight into the operation of the regulatory network of AC007362, miR-493 and MCP-1 upon shear stress. Under shear stress, the expression of AC007362 was enhanced by the inhibited promoter DNA methylation, while the expression of MCP-1 was enhanced by sponging the expression of miR-493.

Correlation of sexual dysfunction with sex hormone and estrogen receptor gene polymorphism in Chinese Han women with epilepsy.

OBJECTIVE: Women with epilepsy (WWE) have a high risk of sexual dysfunction (SD). We aimed to investigate the incidence of SD, the correlation between SD, sex hormone and estrogen receptor (ER) gene polymorphism in Chinese Han WWE. METHODS: This cross-sectional study examined 112 married WWE in the Affiliated Hospital of Yangzhou University who were taking antiepileptic drugs (AEDs) for ≥1 year, and 120 healthy controls without epilepsy, all of Chinese Han nationality. The age, menstruation, fertility of all the subjects and disease details of WWE were recorded. The Chinese version of female sexual function index (FSFI) was used to investigate the sexual function of the subjects. The chemiluminescence method was used for the detection of sex hormones, while polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the ER gene polymorphism. The differences of the sexual function, sex hormone, ER genotype, and allele frequency were compared between the two groups. The correlation between SD, sex hormone and ER gene polymorphism was also analyzed. RESULTS: (1) A high rate (70.5%) of SD was detected in WWE. (2) The serum prolactin (PRL) level (P = 0.039) and the ratio of estradiol to progesterone (E2/P) (P＜0.001) in the WWE group were significantly higher than those in the control group. The allele frequencies of ERα-PvuII C (P = 0.001) and ERß-AluI A (P = 0.001) in the WWE group were significantly higher than those in the control group. (3) Binary logistic regression analysis showed that serum testosterone level [odds ratio (OR) = 0.412, 95 % confidence interval (CI): 0.201-0.842, P = 0.015], and PvuII CC genotype [odds ratio (OR) = 6.074, 95 % confidence interval (CI): 1.257-29.352, P = 0.025] were independently correlated with SD. CONCLUSION: The incidence of SD in Chinese Han WWE is high. High serum testosterone levels may exert a protective effect on sexual function. ERα-PvuII polymorphism is related to the susceptibility of SD, and PvuII CC genotype may be the risk genotype of SD.

Acute in-hospital blood pressure variability predicts early neurological deterioration in acute minor stroke or transient ischemic attack with steno-occlusive arterial disease.

It is generally known that acute minor stroke and transient ischemic attack (TIA) seem to be benign. However, their occurrence in patients with steno-occlusive arterial disease may result in early neurological deterioration (END). We aimed to elucidate the effect of blood pressure variability (BPV) on the development of END. Consecutive acute minor stroke and TIA patients within 24 hours of onset were prospectively recruited from the Affiliated Hospital of Yangzhou University between Aug 2015 and Feb 2019. END was defined as an NIHSS score increased ≥1 during the first 72 hours compared with the initial NIHSS score. During this period, the mean, maximum (max), the difference between the maximum and minimum (max-min), the SD, and coefficient of variation of BP (BPCV ) were calculated. Of the 160 total patients enrolled in the study (mean age, 68.01 ± 9.33 years; 50.6% female), 52 (32.5%) patients occurred END during the first 72h after admission. To express the BPV as a categorical variable, we classified the subjects into one of four groups, representing four quartiles of BPV. In the multivariable analyses, the lowest quartiles were considered as reference groups. The results showed that patients who fell in the fourth quartile (SBPmax-min :OR = 3.289, 95% CI 1.147-9.430; SBPSD :OR = 3.313, 95% CI 1.041-10.547; SBPCV :OR = 3.425, 95% CI 1.164-10.077; DBPSD :OR = 3.124, 95% CI 1.065-9.158) had a significantly higher risk of END after adjusting the variables (age, female, diabetes mellitus, atrial fibrillation, and CRP with P values <.1 in univariate analyses). Our study demonstrated that the acute in-hospital BPV was associated with the development of END in acute minor stroke and TIA with steno-occlusive arterial disease.

Relationship between high-sensitivity C-reactive protein and early neurological deterioration in stroke patients with and without atrial fibrillation.

BACKGROUND AND PURPOSE: The association of high-sensitivity C-reactive protein (hsCRP) with early neurological deterioration (END) is unclear, especially in stroke patients with atrial fibrillation (AF). In this study, we aimed to assess the association of baseline hsCRP levels with END in acute ischemic stroke with and without AF. METHODS: Consecutive acute ischemic stroke patients prospectively recruited from the Affiliated Hospital of Yangzhou University were analyzed and divided into two groups: AF related stroke (AF-S) and non-AF related stroke (Non-AF-S) groups. Plasma hsCRP levels on admission were categorized into three risk groups: low (<1.0 mg/L), average (1-3 mg/L) and high (>3 mg/L). RESULTS: A total of 655 consecutive patients diagnosed acute ischemic stroke were prospectively registered from our department in 2015-2018, which included 168 AF-S and 487 Non-AF-S cases. After standard therapy, 62 AF-S and 155 Non-AF-S cases developed END within 72 h of hospitalization. In AF-S cases, statistical differences between END and Non-END patients were found in age, gender, baseline National Institute of Health Stroke Scale (NIHSS) score, fasting blood glucose, responsible artery occlusion, CHA2DS2-VASc score and hsCRP level (p < 0.05). When variates showing p ≤ 0.1 in univariate analysis were adjusted, logistics regression analysis revealed following indexes as independent risk factors for END in AF-S patients: female (OR = 2.396, 95%CI:1.062-5.405, P = 0.035), fasting blood glucose (OR = 1.192, 95%CI:1.026-1.385, P = 0.022), responsible artery occlusion (OR = 3.589, 95%CI 1.425-9.036, P = 0.007), and high risk hsCRP (OR = 2.780, 95%CI 1.067-7.240, P = 0.036). In the Non-AF group, any level of hsCRP was not independently related to END after adjustment for age, sex, diabetes mellitus, smoking, baseline NIHSS, lesion size and responsible artery occlusion. CONCLUSION: High hsCRP level was independently correlated with END in patients with AF-S.

Porous diatomite-mixed 1,4,5,8-NTCDA nanowires as high-performance electrode materials for lithium-ion batteries.

A porous composite electrode composed of diatomite-mixed 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTCDA) is prepared by electrostatic spinning technology. Compared with traditional coated electrodes without diatomite mixing, the obtained composite electrode materials have higher porosity, larger specific surface area and faster lithium ion transport channels, which makes them exhibit better electrochemical performance, such as smaller impedance, higher capacity, and better cycling stability and rate performance. The electrospun diatomite-mixed 1,4,5,8-NTCDA composite (ED-1,4,5,8-NTCDA) electrode shows an initial coulombic efficiency of 77.2%, which is much higher than that of the electrospun 1,4,5,8-NTCA (E-1,4,5,8-NTCDA) electrode without diatomite mixing (63.8%) and the coated 1,4,5,8-NTCA (C-1,4,5,8-NTCDA) electrode (48.3%). Moreover, the ED-1,4,5,8-NTCDA electrode displays an initial discharge capacity of 1106.5 mA h g-1, which is much higher than that of the E-1,4,5,8-NTCDA electrode (546.0 mA h g-1) and the C-1,4,5,8-NTCDA electrode (185.4 mA h g-1). After 200 cycles, the capacity of the ED-1,4,5,8-NTCDA electrode remains at 1008.5 mA h g-1 with a retention ratio of 91.2%, which is also much higher than that of 753.2 mA h g-1 for the E-1,4,5,8-NTCDA electrode and 288.1 mA h g-1 for the C-1,4,5,8-NTCDA electrode. Even at a higher current density of 1500 mA g-1, its capacity remains above 508.9 mA h g-1. The ED-1,4,5,8-NTCDA electrode presents superior performance, which opens up a promising new approach for further utilization of organic materials as electrode materials in rechargeable lithium-ion batteries.

Macrophage Migration Inhibitory Factor Promotes Chemotaxis of Astrocytes through Regulation of Cholesterol 25-Hydroxylase Following Rat Spinal Cord Injury.

Oxysterol derived from cholesterol metabolism is involved in the inflammatory activation, and consequently in development of major chronic diseases. Multiple cytokines have been found to induce the expression of cholesterol metabolism-related enzymes. Several studies have shown that the protein level of cholesterol-25-hydroxylase (CH25H) is remarkably increased in response to injury of central nervous system (CNS), but little is known about the mechanisms of cytokine-induced expression of CH25H in specific cell types, and the resultant effects. In the present study, we demonstrated that ch25h expression was significantly upregulated in the astrocytes of rat injured spinal cord, in parallel with those of MIF. Administration of MIF inhibitor 4-IPP in the lesion sites attenuated injury-induced ch25h expression. MIF facilitated ch25h expression of astrocytes through interaction with CD74 membrane receptor, which in turn promoted production of chemokines, as identified by transcriptome profiles. MIF-induced release of oxysterol 25-hydroxycholesterol (25-HC) from astrocytes affects cell migration, but inhibited cell viability in dose-dependent manner, suggesting that MIF aggravates progressive neuropathology through regulation of cholesterol metabolism following CNS injury. These results have provided a novel mechanism and a potential therapeutic strategy for injured CNS.

Investigation of Nonmotor Symptoms in First-Degree Relatives of Patients with Different Clinical Types of Parkinson's Disease.

BACKGROUND: Nonmotor symptoms (NMS) are prodromal characteristics of Parkinson's disease (PD). The first-degree relatives (FDR) of PD patients had a higher risk of PD and also had more NMS. OBJECTIVE: To delineate NMS in FDR of patients with different clinical types of PD. METHODS: A total of 98 PD probands were recruited; 256 siblings of them were enrolled in the FDR group. Various scales were used to assess NMS, including depression, anxiety, cognitive impairment, insomnia, constipation, excessive daytime sleepiness, rapid eye movement sleep behavior disorder (RBD), and restless legs syndrome (RLS). The incidences of NMS were further compared between the FDR groups of PD with different types. RESULTS: The FDR of early-onset PD (EOP) showed a higher incidence of moderate to severe depression (OR = 4.08; 95% CI: 1.12-14.92; P=0.033), anxiety (OR = 4.22; 95% CI: 1.87-9.52; P=0.001), and excessive daytime sleepiness (OR = 3.40; 95% CI: 1.00-11.48; P=0.049) than the FDR of late-onset PD (LOP). It was also found that RBD (OR = 11.65; 95% CI: 3.82-35.54; P < 0.001), constipation (OR = 4.94; 95% CI: 1.85-13.21; P=0.001), sleep disorders (OR = 4.51; 95% CI: 1.73-11.78; P=0.002), cognitive impairment (OR = 3.55; 95% CI: 1.62-7.77; P=0.002), and anxiety (OR = 2.49; 95% CI: 1.32-4.71; P=0.005) were more frequent in FDR of tremor-dominant PD (TDP) than in FDR of non-tremor-dominant PD (NTDP). CONCLUSIONS: The siblings of patients with EOP and TDP have more NMS, presuming that they have a higher risk in the PD prodromal stage. Whether they have a greater possibility to progress into PD requires further investigation.

Sexual dysfunction and associated factors in Chinese Han women with epilepsy.

PURPOSE: Women with epilepsy (WWE) are believed to be at risk of sexual dysfunction (SD) and face many sexual challenges because of multiple factors. This study aimed to assess the factors associated with SD in Chinese Han WWE. METHODS: This cross-sectional study examined 112 married WWE in the Affiliated Hospital of Yangzhou University with focal (FE) or generalized epilepsy (GE) on antiepileptic drugs (AEDs), and 120 healthy controls without epilepsy, all of Chinese Han nationality. Data collection tools included the Chinese version of Female Sexual Function Index (FSFI), the Chinese version of Zung Self-Rating Anxiety Scale (SAS), the Chinese version of the Zung Self-Rating Depression Scale (SDS), the Chinese version of the revised Morisky Medication Adherence Scale (MMAS-8), and the Chinese version of the National Hospital Seizure Severity Scale (NHS3). Chi-square test, t-test, one-way analysis of variance (ANOVA), and binary logistic regression were used for statistical analysis. RESULTS: A high rate (70.5%) of SD was detected in WWE, with 24.2% in controls. Sexual dysfunction affected all dimensions: desire (85.7%), arousal (56.3%), lubrication (47.3%), orgasm (66.1%), satisfaction (58.9%), and pain (41.1%). Elevated rates of anxiety (40.2%) and depression (33%) and poor medication adherence (31.3%) were also found in WWE. Binary logistic regression found that poor economic status (odds ratio (OR) = 13.904, 95% confidence interval (CI): 2.025-95.472, P = 0.007 and OR = 6.350, 95% CI: 1.323-30.477, P = 0.021), anxiety (OR = 1.222, 95% CI: 1.055-1.415, P = 0.007), and poor medication adherence (OR = 0.297, 95% CI: 0.124-0.707, P = 0.006) were associated with SD. CONCLUSIONS: The associated factors of SD in Chinese Han WWE are multifactorial. The WWE have higher levels of anxiety, poor family economic status, and poor medication adherence. Medical professionals should not only better control seizures but also evaluate and improve patients' sexual function so as to improve the quality of life of WWE.

Optimization of Synthetic mRNA for Highly Efficient Translation and its Application in the Generation of Endothelial and Hematopoietic Cells from Human and Primate Pluripotent Stem Cells.

Identification of transcription factors that directly convert pluripotent stem cells (PSCs) into endothelial and blood cells and advances in the chemical modifications of messenger RNA (mRNA) offer alternative nucleic acid-based transgene-free approach for scalable production of these cells for drug screening and therapeutic purposes. Here we evaluated the effect of 5' and 3' RNA untranslated regions (UTRs) on translational efficiency of chemically-modified synthetic mRNA (modRNA) in human PSCs and showed that an addition of 5'UTR indeed enhanced protein expression. With the optimized modRNAs expressing ETV2 or ETV2 and GATA2, we are able to produce VE-cadherin+ endothelial cells and CD34+CD43+ hematopoietic progenitors, respectively, from human PSCs as well as non-human primate (NHP) PSCs. Overall, our findings provide valuable information on the design of in vitro transcription templates being used in PSCs and its broad applicability for basic research, disease modeling, and regenerative medicine.

Effect of blood pressure variability on early neurological deterioration in single small subcortical infarction with parental arterial disease.

BACKGROUND AND PURPOSE: Early neurological deterioration (END) is not uncommon in acute single small subcortical infarct (SSSI), especially in those with parental arterial disease (PAD). The purpose of this study was to elucidate the effect of BP variability on the development of END as well as functional outcome at 90 days in SSSI and to determine whether the effect is linked to the status of parent artery. METHODS: Consecutive patients with acute SSSI were prospectively recruited from the First People's Hospital of Yangzhou between Aug 2013 and Jul 2016. END was defined as an NIHSS score increased ≥ 2 during the first 72 h compared with the initial NIHSS score. Functional outcome at 90 days after onset was assessed using the modified Rankin Score (mRS) and dichotomized as good (0-2) and poor (≥ 3). During this period, the parameters of BP variability such as BPmax-min, BPSD, and BPCV (equal to [SD × 100] / mean) were calculated. RESULTS: A total of 296 patients were included in the analysis. Of these, 30 (38.5%) SSSI associated with PAD and 53 (24.3%) without developed END respectively. Logistic regression analysis demonstrated that SBPmax (OR 1.036, 95% CI 1.005-1.069), SBPSD (OR 1.177, 95% CI 1.021-1.356), SBPcv (OR 1.306, 95% CI 1.049-1.626), DBPmax (OR 1.141, 95% CI 1.042-1.250), DBPmax-min (OR 1.085, 95% CI 1.015-1.160), DBPSD (OR 1.369, 95% CI 1.032-1.816), and DBPCV (OR 1.281, 95% CI 1.028-1.597) were all the independent predictors of END after acute SSSI associated with PAD. However, for those without PAD, none of the BP parameters was found significantly associated with END. Also, BP parameters were not related to the poor outcome at 90 days after onset. CONCLUSIONS: Our study demonstrated that the acute in-hospital BP variability was associated with the development of END in patients with acute SSSI. However, its impact varies depending on the status of parent artery.

StemRegenin 1 selectively promotes expansion of Multipotent Hematopoietic Progenitors derived from Human Embryonic Stem Cells.

Human embryonic stem cell (hESC)-derived hematopoietic stem/progenitor cells hold tremendous potential as alternative cell sources for the treatment of various hematological diseases, drug discovery and toxicological screening. However, limited number of hematopoietic stem/progenitor cells generated from the differentiation of hESCs hinders their downstream applications. Here, we show that aryl hydrocarbon receptor antagonist StemRegenin 1 (SR1) selectively promotes expansion of hESC-derived lin-CD34+ hematopoietic progenitors in a concentration-dependent manner. The colony-forming cell (CFC) activity was found to be enriched in the CD34+ cells that were expanded with SR1; however, these cells have less colony-forming activity as compared to unexpanded cells (1,338 vs. 7 of CD34+ cells to form 1 colony, respectively). Interestingly, SR1 showed a bipotential effect on the proliferation of CD34 negative population, that is low dose of SR1 (1 µM) enhanced cell proliferation, whereas it was repressed at higher doses (>5 µM). In summary, our results suggest that SR1 has the potential to facilitate expansion of hESC-derived lin-CD34+ hematopoietic progenitors, which further retain the potential to form multilineage hematopoietic colonies.

Using in silico techniques: Isolation and characterization of an insect cuticle-degrading-protease gene from Beauveria bassiana.

Cuticle-degrading-proteases (CDPs) secreted by Beauveria spp. are pivotal biocontrol substances, possessing commercial potential for developing bio-pesticides. Therefore, a thoughtful and contemplative understanding and assessment of the structural and functional features of these proteases would markedly assist the development of biogenic pesticides. Computational molecular biology is a new facile alternative approach to the tedious experimental molecular biology; therefore, by using bioinformatics tools, we isolated and characterized an insect CDP gene from Beauveria bassiana 70 s.l. genomic DNA. The CDP gene (1240 bp with GeneBank accession no. KT804651.1) consisted of three introns and four CDS exons, and shared 74-100% sequence identity to the reference CDP genes. Its phylogenetic tree results showed a unique evolution pattern, and the predicted amino acid peptide (PAAP) consisted of 344 amino acid residues with pI, molecular weight, instability index, grand average hydropathicity value and aliphatic index of 7.2, 35.4 kDa, 24.45, -0.149, and 76.63, respectively. The gene possessed 74-89% amino acid sequence similarity to the 12 reference strains. Three motifs (Peptidase_S8 subtilase family) were detected in the PAAP, and the computed 3D structure possessed 79.09% structural identity to alkaline serine proteases. The PAAP had four (three serine proteases and one Pyridoxal-dependent decarboxylase) conserved domains, a disulfide bridge, two calcium binding sites, MY domain, and three predicted active sites in the serine family domains. These results will set the groundwork for further exploitation of proteases and understanding the mechanism of disease caused by cuticle-degrading-serine-proteases from entomopathogenic fungi.