Identification of potent target and its mechanism of action of Tripterygium wilfordii Hook F in the treatment of lupus nephritis.

AIM: The Chinese anti-rheumatic herbal remedy Tripterygium wilfordii Hook F (TWHF) has been widely shown to be effective in treating lupus nephritis (LN), but the therapeutic targets and mechanisms of action are still unclear. In this study, we aimed to combine mRNA expression profile analysis and network pharmacology analysis to screen the pathogenic genes and pathways involved in LN and to explore the potential targets of TWHF in the treatment of LN. METHODS: The mRNA expression profiles of LN patients were used to screen differentially expressed genes (DEGs) and to predict associated pathogenic pathways and networks via the Ingenuity Pathway Analysis database. Through molecular docking, we predicted the mechanism by which TWHF interacts with candidate targets. RESULTS: A total of 351 DEGs were screened from the glomeruli of LN patients and were mainly concentrated in the role of pattern recognition receptors in the recognition of bacteria and viruses and interferon signaling pathways. A total of 130 DEGs were screened from the tubulointerstitium of LN patients, which were concentrated in the interferon signaling pathway. TWHF might be effective in treating LN by hydrogen bonding to regulate the functions of 24 DEGs (including HMOX1, ALB, and CASP1), which are mainly concentrated in the B-cell signaling pathway. CONCLUSION: The mRNA expression profile of renal tissue from LN patients revealed a large number of DEGs. TWHF has been shown to interact with the DEGs (including HMOX1, ALB and CASP1) through hydrogen bonding to treat LN.

The correlations between C-reactive protein and MRI-detected inflammation in patients with axial spondyloarthritis: a systematic review and meta-analysis.

BACKGROUND: C-reactive protein (CRP) and magnetic resonance imaging (MRI) are widely used to monitor inflammation in patients with axial spondyloarthritis (axSpA), but the relationship between CRP and MRI-detected inflammation is incompletely understood. The present study was undertaken to assess correlations between CRP and MRI-detected inflammation in axSpA. MATERIALS AND METHODS: A systematic literature search was performed (Medline, Embase, and Cochrane Library) to identify relevant studies concerning CRP and MRI-detected inflammation in axSpA patients. The MRI-detected inflammation was evaluated by MRI-based disease activity score (DAS). The correlation between CRP and MRI-based DAS was integrated by random-effect models. RESULTS: Eighteen studies reported a total of 1392 axSpA patients which were included in this meta-analysis. CRP was significantly associated with spinal MR DAS (r=0.226, 95%CI [0.149, 0.291], p<0.001, I2=23%). We also found a moderate correlation between CRP change and spinal MR DAS change (r[ASspiMRI-a]=0.354, 95%CI [0.282, 0.422], p<0.001, I2=48%; r[SPARCC]=0.544, 95%CI [0.345, 0.701], p<0.001, I2=19%). CRP at baseline was negatively associated with improvement in spinal MR DAS (r= - 0.327, 95%CI [-0.397, -0.264], p<0.001, I2=0%). However, no significant association was found between CRP and sacroiliac joint (SIJ) MR DAS. CONCLUSIONS: In axSpA patients, CRP is associated with MRI-detected inflammation in the spine but not in SIJ. We speculate that CRP could be a reasonable index to reflect spinal inflammation. Therefore, we suggest it is not essential to repeat spinal MRI in a short term, while SIJ MRI may be necessary to provide additional information on inflammation. Key Points • CRP is associated with MRI-detected inflammation in the spine but not in sacroiliac joints. • CRP at baseline was negatively associated with improvement in spinal MR DAS. • It was not essential to repeat spinal MRI frequently, while SIJ MRI may be necessary to provide additional information on inflammation.

Genotype-phenotype correlation of deletions and duplications of 4p: case reports and literature review.

Structural rearrangements of chromosome 4p gives rise to a group of rare genomic disorders that mainly result in two different clinical entities: Wolf-Hirschhorn syndrome (WHS) and partial 4p trisomy. The severity of the phenotype depends on the size of the deletion or locus duplication. Here, we present two unrelated individuals with a copy number variation of chromosome 4p. Inverted duplication deletions (inv dup-del) in 4p are particularly rare. Case 1 describes a 15-year-old girl with a 1.055 Mb deletion of terminal 4p, distal to the recognized critical region of WHS, and a large duplication of 9.6 Mb in size from 4p16.3 to p16.1. She had postnatal development delay, intellectual disability (especially pronounced in speech), seizure/electroencephalogram anomalies, and facial dysmorphic features. This unusual chromosomal imbalance resulted in the WHS phenotype rather than the 4p trisomy syndrome phenotype. Case 2 describes a 21-month-old boy with a 1.386 Mb terminal 4p deletion who presented with slight developmental delay, borderline intellectual disability, and seizures. Combined with previous reported cases of 4 pter del-dup or pure 4p terminal deletions, our observations suggest that terminal chromosome 4p deletion is more pathogenic than the concomitant partial 4p duplication, and some regions of the 4p terminal may have regulatory effects on the remaining region of 4p. About nine cases have been reported thus far to date, and our study delineates further genotype-phenotype correlations about terminal 4p duplication-deletions for predicting disease prognosis and patient counseling.

Correlation between scalp high-frequency oscillations and prognosis in patients with benign epilepsy of childhood with centrotemporal spikes.

AIMS: The study aimed to explore whether high-frequency oscillations (HFOs) can predict seizure risk and atypical manifestations of benign epilepsy of childhood with centrotemporal spikes (BECTS). METHODS: We recruited 60 patients and divided them into three groups: (1) seizure-free BECTS, (2) active typical BECTS, and (3) active atypical forms of BECTS. Electroencephalogram was used to record the number, location, average amplitude, and duration of spikes, and spike ripples were analyzed using time-frequency technology. Multivariable logistic regression analysis was used to investigate independent predictive factors for prognosis. RESULTS: The number of sleep spike ripples, rather than spikes, was an independent risk factor for the active period of the disease (odds ratio [OR] = 4.714, p = 0.003) and atypical forms of BECTS (OR = 1.455, p = 0.049); the optimal thresholds for the spike ripple rate were >0 (area under the curve [AUC] = 0.885, sensitivity = 96.15%, specificity = 73.33%) and >0.6/min (AUC = 0.936, sensitivity = 84.21%, specificity = 96.15%), respectively. Furthermore, in typical BECTS, the spike ripple rate showed significant negative correlations with time since the last seizure (ρ = -0.409, p = 0.009) and age (ρ = -0.379, p = 0.016), while the spike rate did not. CONCLUSION: Spike ripple was a marker for distinguishing typical and atypical forms of BECTS and reflected the risk of seizure recurrence better than the spike alone. The present findings might assist clinicians in BECTS treatment.

Chemical-microbial effects of acetic acid, oxalic acid and citric acid on arsenic transformation and migration in the rhizosphere of paddy soil.

Low-molecular-weight organic acids (LMWOAs) are essential components of rice roots exudates and an important source of soil organic carbon. The chemical-microbial pathway by which LMWOA affects arsenic (As) cycling in the rhizosphere of paddy soils is still unclear. In this study, three typical LMWOAs (acetic acid (AA), oxalic acid (OA), and citric acid (CA)) in rice root exudates were added to As-contaminated soil at a concentration of 10 mM, mimicking the rhizosphere environment. The results showed that the addition of AA and OA inhibited the mobilization of As in the rhizosphere soil. After 14 days of incubation, the content of As in the porewater of AA and OA decreased by 40% and 22%, respectively, compared with the control. AA hindered the mobilization of As in soil via promoting the formation of secondary minerals. The addition of OA inhibits the mobilization of As via increasing the proportion of As (V) in porewater and promoting the formation of secondary minerals in soil. In addition, OA addition not only significantly increased the aioA gene abundance but also notably enriched the microorganisms containing As (III) methylation functional genes (arsM). The addition of CA greatly expedited the release of As from the soil solid phase through the solubilization of Fe/Mn minerals via the effects of both soil chemistry and microbial action. Furthermore, linear discriminant analysis effect size (LEfSe) revealed the possibility that bacteria such as Burkholderia, Magnetospirillum, and Mycobacterium were involved in the reduction or methylation of As in the rhizosphere of paddy soil. This study revealed the internal causes of LMWOAs regulating As transformation and mobilization in flooded paddy soil and provided theoretical support for reducing As accumulation in rice by breeding rice varieties with high AA and OA secretions.

Auditory verbal hallucination can be evoked by prefrontal epileptic seizure.

Auditory verbal hallucinations (AVHs) have been reported in neocortical temporal epileptic seizures and have been considered highly associated with implication of auditory cortex by epileptic discharges or electrical stimulation. Herein, we report two rare frontal epilepsy cases in which AVHs featured the habitual seizures. The epileptogenic zones of these two patients were localized in the dorsal and orbitomedial prefrontal cortex, respectively by stereoelectroencephalography (SEEG) monitoring. Comparing with the AVHs in schizophrenia, we postulated that the phenomenological similarities between the two sets of AVHs imply homology in mechanisms. Ictal SEEG confirmed that the wide involvement of prefrontal-cingulate-auditory cortical network by low-voltage fast activity corresponded the occurrence with AVHs during frontal epileptic seizures. Electrical stimulation study of one of the two cases highlighted the causal role of prefrontal-cingulate cortex in the emergence of AVHs. Based on our clinical observation, SEEG findings, and electrical cortical stimulation, we supposed that wide implication of prefrontal-cingulate-auditory cortical network during epileptic seizure underlie the emergence of AVHs, and further hypothesized that AVHs could be yielded by transient deficit of self-monitoring for inner speech in focal epileptic seizures.

Correlations Between Structural Brain Abnormalities, Cognition and Electroclinical Characteristics in Patients With Juvenile Myoclonic Epilepsy.

Objective: To explore the structural brain abnormality and its relationship with neuropsychological disorders and electroclinical characteristics in juvenile myoclonic epilepsy (JME) patients. Methods: Sixty-seven patients diagnosed with JME and 56 healthy controls were enrolled. All subjects underwent MRI using T1-weighted 3D brain structural images with 1 mm thickness. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses were performed. They also underwent a series of neuropsychological tests to assess cognitive function. The correlation analyses were conducted between structural changes, neuropsychological outcomes, and electroclinical features. Results: The gray matter concentration (GMC) was decreased in the bilateral pre-central and post-central gyrus, right anterior cingulate gyrus, left posterior orbital region, bilateral occipital regions, bilateral hippocampus and bilateral caudate nucleus in the JME groups (corrected P < 0.05). The evaluation of gray matter volume (GMV) showed significant decrease respectively in bilateral pre-central and post-central gyrus, left paracentral lobule, left orbital gyrus, left amygdala, left basal ganglia and left thalamus of JME patients (P < 0.05). The cortex thicknesses of the right inferior temporal gyrus, right insular gyrus, and right cingulate gyrus had negative correlations with the disease duration significantly. At the same time, the whole-brain white matter volume was positively associated with the course of the disease (P < 0.05). Patients with persistent abnormal EEG discharges had significantly less whole-brain gray matter volume than JME patients with normal EEG (P = 0.03). Correlation analyses and linear regression analyses showed that, in addition to the gray matter volumes of frontal and parietal lobe, the temporal lobe, as well as the basal ganglia and thalamus, were also significantly correlated with neuropsychological tests' results (P < 0.05). Conclusion: The JME patients showed subtle structural abnormalities in multiple brain regions that were not only limited to the frontal lobe but also included the thalamus, basal ganglia, parietal lobe, temporal lobe and some occipital cortex, with significant involvement of the primary somatosensory cortex and primary motor cortex. And we significantly demonstrated a correlation between structural abnormalities and cognitive impairment. In addition, the course of disease and abnormal discharges had a specific negative correlation with the structural changes.

Post-traumatic stress disorder in patients with rheumatic disease during the COVID-19 outbreak: a cross-sectional case-control study in China.

OBJECTIVE: The COVID-19 pandemic is not only a traumatic event, but a collective stressor unfolding over time, causing devastating implications for the mental health. This study aimed to shed light on the mental health status of patients with rheumatic disease (RD) during the massive outbreak of COVID-19 in China, especially the prevalence and severity of post-traumatic stress disorder (PTSD) compared with healthy individuals. METHODS: A total of 486 patients with RD and 486 age-matched and sex-matched healthy individuals were recruited into the study. For each participant, we collected demographic and clinical characteristics data. The PTSD Checklist for DSM-5 (PCL-5) and four items from the Pittsburgh Sleep Quality Index (PSQI) were used to investigate the prevalence and severity of PTSD and sleep quality, respectively. RESULTS: Compared with healthy control subjects (n=486), patients with RD (n=486) had a higher prevalence of PTSD (12.1% vs 4.1%; p<0.001). Higher total scores on the PCL-5 and on all four items from the PSQI (p≤0.001) were also observed. Female, old age, poor sleep quality, long duration of RD, poor subjective evaluation of the disease and pessimistic subjective perception of the epidemic were identified as risk factors of PTSD in patients with RD during the COVID-19 epidemic. CONCLUSION: During the COVID-19 outbreak, patients with RD presented a higher prevalence and severity of PTSD and showed more sleep disturbances. Our findings confirm the importance of psychological assessment and mental healthcare out of regular clinical care for patients with RD during the pandemic.

Accumulation and subcellular distribution of cadmium in rygegrass induced by Aspergillus niger TL-F2 and Aspergillus flavus TL-F3.

Although plant growth-promoting fungi can greatly accelerate the ryegrass bioaccumulation of cadmium (Cd), the underlying mechanisms are not yet well documented. Therefore, we performed a 20-days hydroponic experiment to investigate the effects of Aspergillus niger TL-F2 (A. niger TL-F2) and Aspergillus flavus TL-F3 (A. flavus TL-F3) on accumulation/subcellular distribution of Cd by annual ryegrass Dongmu 70 at different Cd concentrations (0, 2.5, and 5 mg L-1). Results indicated that both fungal strains promoted ryegrass biomass/growth by about 60%. Furthermore, we found that ryegrass roots (17.8-37.1 µg pot-1) had a significantly higher capability for Cd uptake than the shoots (1.66-5.45 µg pot-1) (p < 0.05). Of total Cd in ryegrass plants, 44-67% was in soluble form, 24-37% was in cell wall, and 8.5-25.5% was in organelles. Compared with non-fungus ryegrass, cell wall and soluble Cd fractions in fungus-inoculated roots increased and decreased by 13.5-44% and 21.5-26.4%, respectively. Besides, fungus inoculation generally increased the content of cell wall and soluble Cd fractions in ryegrass shoots. Altogether, the study concludes that inoculation of fungus in ryegrass is a promising approach to improve phytoremediation of Cd contaminated environments.Novelty statement Previous study by Han et al. (2018) examined the resistance of ryegrass plant to Cd stress after its inoculation with Aspergillus aculeatus. In this study, using a hydroponic experiment, we examined the effects of co-application of two species of Aspergillus fungi. i.e. A. niger TL-F2 and A. flavus TL-F3 on ryegrass growth/biomass, Cd absorption by ryegrass shoots and roots, and subcellular distribution of Cd in ryegrass roots and shoots.

Assessment of Neuropathic Pain in Ankylosing Spondylitis: Prevalence and Characteristics.

INTRODUCTION: Pain in ankylosing spondylitis is currently considered an inflammatory pain (IP). However, it was found that some patients still had the sensation of pain even without inflammation. Our study was to investigate the prevalence and characteristics of neuropathic pain (NeP) in Chinese Han ankylosing spondylitis (AS) patients. METHODS: The study consisted of three parts. Firstly, we assessed the prevalence and clinical data of NeP in 182 AS patients. Secondly, we evaluated pain improvement after etanercept therapy in 63 patients. Finally, serum neurotransmitters were measured for 20 AS patients and ten healthy controls (HC). RESULTS: Out of 182 AS patients, our study showed that 14 patients (7.70%) had likely NeP and 55 (30.21%) had uncertain NeP. There were significant differences among the three groups with respect to nocturnal pain (NP), peripheral pain (PP), total back pain (TBP), BASDAI, ASDAS-CRP, HAD-A, HAD-D, and BASDAI-fatigue except fort CRP concentrations. Principal component analysis (PCA) of AS pain revealed that the weight of NeP was greater than PP in the first principal component (0.703 vs. 0.639). Structural equation modeling (SEM) revealed that NeP altered disease activity (ß = 0.62, P < 0.001), which influenced psychological status (ß = 0.42, P < 0.001). Of 63 patients who used etanercept for 3 months, significant improvement was found in NP, TBP, and PP (all P < 0.0001) but not in PDQ (10.60 ± 6.85 vs. 9.98 ± 6.40, P = 0.0671). Serum norepinephrine concentrations in patients with PDQ > 19 were higher than those in patients with PDQ ≤ 19 and HC. CONCLUSIONS: We conclude that NeP contributes to pain in AS patients.

Yisaipu® Provide AS Patients With an Economical Therapeutic Option While Original Biologicals are More Advantageous in the COVID-19 Epidemic Situation.

Objectives: Anti-tumor necrosis factor (TNF) agents have been regarded as the most effective treatment for ankylosing spondylitis (AS) so far. However, economic factors limited the prescription of original biologicals in China. Yisaipu® is a biosimilar for etanercept as pre fill syringes (PFS), which has entered China's national medical insurance catalog for more than 10 yr and was widely used because it greatly reduced the economic burden of AS patients. Yisaipu® is provided subcutaneous injection in hospital setting only. We collected clinical data of AS patients before, during and after COVID-19 epidemic, in an attempt to investigate the advantages and disadvantages of original biologicals and Yisaipu® during regular follow up and COVID-19 epidemic. Methods: AS patients who received original biologicals or Yisaipu® in our department for more than 1 yr were included in our study. General data, demographic characteristics, disease activity, quality of life and medical compliance were collected from regular visits. The patients were followed up through telephone interviews from April 20th to 27th, 2020 about the overall impact of the COVID-19 epidemic. Results: There was no significant difference in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP) between the two groups. Health Assessment Questionnaire for Spondyloarthropathies (HAQ-s) showed that Yisaipu® group was superior to original biological group in terms of eating, gripping and driving. In addition, the medical cost of Yisaipu® was lower than that of original biologicals. The overall impact of the COVID-19 epidemic on patients of original biological group was comparatively smaller than that on Yisaipu® group. Conclusions: Yisaipu® provided AS patients with an economical selection during regular follow-up, while original biologicals had certain advantages in the COVID-19 epidemic setting, including a longer time interval between two drug administrations and the self-injection dose form of medication.

A semiological marker of emotional insulo-cingulate network activation in epileptic human brain.

There are limited reports on the "chapeau de gendarme" (CDG) sign, which is considered reliable evidence for the verification of frontal epilepsy. However, several recent reports of scattered cases of extra-frontal epilepsy suggest the complexity of the cortical networks underlying CDG generation. The present study aimed to investigate the anatomo-electro-clinical correlations and explore the cortical mechanisms of the generation of CDG via video-stereoelectroencephalography (SEEG). Patients with focal epilepsy who underwent SEEG and epilepsy surgery in our center from March 2017 to December 2019 were retrospectively reviewed. Ten patients with epilepsy with habitual seizures presenting with CDG were included. Most CDG signs were discerned visually into two chronological components referred to as the "prodromal component" and the "major component." The CDG signs occurred at 2.4-26.1 s after electrical onset and lasted for 2.2-16.6 s. The two sequential components were visually discerned in 64 included seizures of the six patients. The epileptogenic zones were diverse in distribution. Cluster analysis was performed based on the neurophysiological features of distinct cortical areas, and the agranulo-dysgranular insular and cingulate cortices were emphasized. Pearson correlation and linear regression showed a linear relationship between the latencies of CDG onset and the latencies of co-activation of agranulo-dysgranular cingulate and insular cortex in gamma bands. Our results suggest that (1) the CDG sign should be interpreted as a type of facial behavior with social-emotional features and considered a semiological marker of emotional insulo-cingulate cortex involvement in focal epilepsy, and (2) epileptic discharges arising directly from or propagating indirectly into this anterior limbic network have a high likelihood of evoking the CDG sign.

Transitional pattern as a potential marker of epileptogenic zone in focal epilepsy - Clinical observations from intracerebral recordings.

OBJECTIVES: To investigate the characteristics of transition from interictal to ictal phase in intracranial recordings and further to determine the potential marker of epileptogenic zone. METHODS: Eighteen patients with drug-refractory epilepsy who underwent stereo-electroencephalography (SEEG) evaluation and subsequent resective surgery were included. All patients were seizure-free post-operatively. The recorded seizures were retrospectively reviewed and time episodes including 5 min before electrographic onset were selected for further analysis to verify the presence of a transitional pattern in the transitional phase, which was distinct from interictal background and ictal onset. Besides, the components of transitional patterns which characterized by different pathological waveforms were identified by visual analysis and time-frequency analysis. The prevalence of transitional patterns between resection and non-resection, lesion and non-lesion sites were compared. In addition, the association between transitional patterns and types of epilepsy was explored. RESULTS: Six transitional patterns characterized by different combinations of multiple pathological waveforms by visual analysis combined with time-frequency analysis were identified: spike/spike-waves/polyspikes; spike superimposed by HFOs; spike superimposed by gamma oscillations; spike followed by suppression; spike superimposed by HFOs and followed by suppression; and spike superimposed by gamma oscillations and followed by suppression. A higher prevalence of transitional patterns in resection than non-resection (p < 0.001) and in lesion than non-lesion contacts (p < 0.001). The pattern characterized by spike superimposed by HFOs and followed by suppression was more prevalent in resection than non-resection sites (p = 0.004). Further, there was an association between the complexity of transitional patterns and the location of contacts. Patterns with higher degree of complexity were more likely to be inside the resection area (p = 0.035). Besides, we found the pattern with spike superimposed by HFOs was associated more with limbic epilepsy than neocortical epilepsy (p < 0.001), whereas another 3 patterns, spike superimposed by gamma oscillation, spike followed by suppression and spike combined with HFOs and suppression, were observed more frequently in neocortical epilepsy than limbic epilepsy (p = 0.018, 0.011 and < 0.001, respectively). CONCLUSION: Transitional patterns from interictal to ictal state were characterized by different combinations of multiple pathological waveforms, which may be a potential marker of epileptogenic zone. Our findings support that the interaction of different neuronal oscillations or waveforms generated by different neuronal populations may be the potential mechanism of seizure generation.

The chapeau de gendarme sign can be evoked by lateral prefrontal epileptic seizures.

PURPOSE: The 'chapeau de gendarme' (CDG) sign, characterised by a symmetric down-turned mouth, has been considered as a semiological hallmark of focal epileptic seizures with cingulate or insular involvement. We report three cases in which the CDG sign featured in habitual seizures. METHODS: The epileptogenic zones of these three patients were localized in the lateral prefrontal cortex by video-stereoelectroencephalography monitoring. A sulcal resection has led to a seizure-free outcome in each patient. RESULTS: Ictal stereoelectroencephalography demonstrated that ictal discharges arising from the lateral prefrontal cortices were immediately followed by low-voltage fast activity, concomitantly involving the anterior insulo-cingulate cortices, and preceding the onset of the CDG signs. Limited sulcal resection and seizure freedom after surgery confirmed the restricted distributions of the epileptogenic zones in the lateral prefrontal cortex. CONCLUSION: Our observations led us to speculate that the epileptic discharges could enter the emotional insulo-cingulate cortical system through the prefrontal-cingulate inhibitory projections (feedforward pattern) -arising from the supragranular layers of the lateral prefrontal cortex-and proceed to the deeper layers of the anterior-middle cingulate cortex, trigger the co-occurrence of gamma bands, and evoke a set of exaggerated behaviours, which is often accompanied by the unique facial sign.

Case of Childhood Absence Epilepsy with Focal Spikes.

BACKGROUND: Childhood absence epilepsy is a common generalized epilepsy syndrome characterized by childhood onset of frequent sporadic absence seizures. During onset, the electroencephalogram exhibits bilateral, symmetric, and synchronous discharges of approximately 3 Hz of generalized spike-and-wave complexes. Focal spikes are often found in children with focal epilepsy but are not common in absence epilepsy. CASE DESCRIPTION: In the case patient, focal spikes were observed during active onset of absence epilepsy and at 5 years after the first hospital visit, at which time absence epilepsy was controlled and medication was withdrawn without focal seizure attack in the interim. CONCLUSIONS: This case demonstrates that focal spikes associated with childhood absence epilepsy do not require specific treatment in the absence of focal seizures.

Genetic and clinical markers for predicting treatment responsiveness in rheumatoid arthritis.

Although many drugs and therapeutic strategies have been developed for rheumatoid arthritis (RA) treatment, numerous patients with RA fail to respond to currently available agents. In this review, we provide an overview of the complexity of this autoimmune disease by showing the rapidly increasing number of genes associated with RA.We then systematically review various factors that have a predictive value (predictors) for the response to different drugs in RA treatment, especially recent advances. These predictors include but are certainly not limited to genetic variations, clinical factors, and demographic factors. However, no clinical application is currently available. This review also describes the challenges in treating patients with RA and the need for personalized medicine. At the end of this review, we discuss possible strategies to enhance the prediction of drug responsiveness in patients with RA.

Absorption, translocation, and detoxification of Cd in two different castor bean (Ricinus communis L.) cultivars.

Cadmium (Cd) is considered to be the most phytotoxic heavy metal pollutant. The selection of castor bean cultivars with Cd tolerance and the exploration of the physiological mechanisms involved in Cd tolerance are critical steps for improving phytoremediation performance. In this study, a hydroponic experiment was used to investigate variations in Cd transportation, chelation, and subcellular distribution in two different castor bean cultivars, namely JX-22 and ZB-9. Both cultivars had high tolerance index scores, indicating that both cultivars were tolerant to Cd. The findings of the present study indicate that Cd is significantly more mobile in JX-22 than in ZB-9 during xylem and phloem transportation, resulting in the accumulation of Cd in the shoots of JX-22 was 7.67 times that in ZB-9. Subcellular distribution assessment verified that more Cd was bound to the biologically detoxified metal fractions than the metal sensitive fractions in JX-22. The contents of the non-protein thiol pool and glutathione in the leaves were higher in JX-22 than ZB-9 when exposed to Cd. These results indicate that JX-22 has a greater ability to accumulate Cd, and well-coordinated physiological changes in JX-22 afford greater Cd tolerance in comparison to ZB-9 under Cd exposure, indicating that JX-22 is suitable for use in the remediation of Cd-contaminated soils.

Analysis of heart rate variability-related indexes in the interictal period in patients with focal epilepsy.

AIMS: Changes in cardiac autonomic nervous function have been evaluated by studying the related indexes of heart rate variability (HRV) in patients with focal epilepsy (FE) in the interictal period. MAIN METHODS: A total of 30 FE patients who were treated in our department from July 2015 to May 2017, were included into this study. These patients were divided into three pairs of groups: less frequent seizure group and more frequent seizure group; medication group and non-medication group; <10 years disease group and ≥10 years disease group. In addition, 16 normal healthy subjects were enrolled as the control group. The time domain and frequency domain indexes of HRV indexes between subgroups and the control group were retrospectively analyzed. KEY FINDINGS: The low-frequency/high-frequency ratio (LF/HF) in the interictal period was higher in the more frequent seizure group than in the control group and less frequent seizure group (P < 0.05). Furthermore, differences in interictal LF/HF and very low frequency (VLF) between the medication group and non-medication group and control group were statistically significant (P < 0.05). SIGNIFICANCE: In interictal period FE patients who present with an imbalance in autonomic nervous function, LF/HF can serve as an indicator to evaluate the interictal cardiac sympathetic activity of FE patients. Furthermore, the dynamic observation of changes in the HRV-related indexes of FE patients can prevent the choice of antiepileptic drugs that affect heart function, which is of guiding significance for evaluating autonomic nervous function.

Segmental neurofibromatosis type 1 complicated with multiple intracranial arteriovenous fistulas: A case study.

Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disorder that primarily affects the skin and the nervous system. This condition is called segmental NF1 (also called neurofibromatosis type V) when clinical features are limited to one area of the body. Segmental NF1 is generally thought to result from somatic mosaicism due to a postzygotic mutation in the NF1 gene, thus a test for NF1 gene abnormalities in peripheral blood is usually negative. Here we report a 31-year-old male presenting with epileptic seizures, who had a history of neurofibromas confirmed by biopsy, but lacked a family history of neurofibromatosis. Multiple signs highly suggestive of NF1 and cerebrovascular abnormities were seen, including distended scalp vessels, gingival hyperplasia, cutaneous masses, skin nodules, and café-au-lait macules. Cerebral computed tomography angiography and venography revealed multiple intracranial arteriovenous fistula. However, NF1 genetic testing of peripheral blood failed to detect mutations, deletions or rearrangements in any of the coding exons or neighboring splice sites. A diagnosis of segmental NF1 was still warranted. To the best of our knowledge, this is the first case study of segmental NF1 complicated with multiple intracranial arteriovenous fistulas.