Tandem phospha-Michael addition/cyclization/dehydration of 2-hydroxychalcones with H-phosphine oxides for the synthesis of 4-phosphorylated 4H-chromenes.

A Hg(OTf)2-catalyzed tandem phospha-Michael addition/cyclization/dehydration of 2-hydroxychalcones with H-phosphine oxides is presented. This protocol provides a new and supplementary approach for the preparation of 4-phosphorylated 4H-chromenes in good yields (up to 99%). In addition, this domino reaction allows the successful construction of two new C-P and C-O bonds in a one-pot operation.

Clinical features of patients with anti-leucine-rich glioma inactivated-1 protein associated encephalitis: a Chinese case series.

Purpose: Antibodies against leucine-rich glioma inactivated 1 (LGI1) are associated with limbic encephalitis and faciobrachial dystonic seizures (FBDS). We present a large series of Han Chinese patients for further clinical refinement. Materials and methods: Serum and cerebrospinal fluid samples from patients were tested. Clinical information of patients with serum anti­LGI1antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed. Results: The median onset age of the 24 patients was 56.9 years. Among these cases, 18 (75%) patients presented with new­onset refractory seizures, 18 (75%) patients had memory deficits, eight (33.3%) patients had a personality changes and five (20.8%) patients had a disturbance of consciousness. FBDS was observed in nine (37.5%) patients and five of them presented with FBDS as the initial symptom. No cancer was detected in any patient by CT scans. Fourteen (58.3%) patients had hyponatremia. Lymphocytic pleocytosis and protein concentration elevation in CSF were detected in four (16.7%) and six (25%) patients, respectively. Twelve (50%) patients showed paroxysmal sharp/spike waves and slow waves on EEG and seven (29.2%) patients showed mesial temporal region abnormalities by MRI scans. All patients received antiepileptic drugs and immunotherapy. After treatments, the modified Rankin scores of all patients were decreased. Conclusions: Our study showed that Han Chinese patients with anti­LGI1 antibody associated encephalitis had prominent clinical manifestations including seizures, memory deficits and FBDS. They showed neurological improvement with timely immunotherapy. Prompt treatments after rapid clinical recognition is important to improve the prognosis of patients.

[The Clinical Study of Comorbidities and Systemic Inflammation in COPD].

OBJECTIVE: To assess the association between chronic obstructive pulmonary disease (COPD) comorbidities and clinical characteristics, and to explore the inflammation mechanism. METHODS: 220 stable COPD patients were included. Clinical characteristics and comorbidities were recorded, and blood samples were collected. The relationship among the number and type of comorbidities, Charlson comorbidity index (CCI), clinical characteristics and the levels of plasma inflammatory markers [interleukin (IL)-6, high sensitivity C-reaction protein (hs-CRP), tumor necrosis factor-α (TNF-α), IL-8] were studied. RESULTS: The top five comorbidities were hypertension, metabolic syndrome and diabetes osteoporosis, bronchiectasis and peripheral vascular diseases. The level of plasma IL-6 was greater in higher CCI score (≥4) group compared with lower CCI score (<4) group ( P=0.011). Levels of IL-6 and IL-8 and the number of hospitalization in prior year were positively correlated with CCI and age adjusted CCI (r<0.03, P<0.05). There was a correlation between the COPD comorbidities and systemic inflammatory response (r<0.3, P<0.05). CONCLUSION: Patients with a higher CCI score had more severe symptoms, functional impairment and higher level of inflammatory factors and high frequency of hospital admission due to acute exacerbation. The mechanism by which COPD may play a role in systemic inflammatory response deserves further study.

Late-onset cobalamin C deficiency Chinese sibling patients with neuropsychiatric presentations.

The Cobalamin C deficiency (cblC), characterized with elevated methylmalonic acidemia and homocystinuria in plasma, is an inborn error of cobalamin metabolism. The late-onset cblC siblings patients were rarely reported. In this study, we analyzed the clinical presentations and treatment outcomes of late-onset cblC in Chinese sibling patients with neuropsychiatric presentations. The clinical data of four pairs of Chinese patients were retrospectively analyzed. Serum homocysteine, urine organic acids measurements, neuroimaging exams and gene analysis were carried out in all patents. Patients were reevaluated after treatments with cobalamin, folate, betaine, L-carnitine and compound vitamin B. The mean age at disease onset was 13.7 (range 2-19) years. The neuropsychiatric disturbances including cognitive decline (3/8), psychiatric disturbances (4/8), gait instability (2/8), lower extremity weakness and numbness (3/8) and thromboembolic events (1/8). Two patients suffered nephropathy. The mean serum homocysteine when patients were diagnosed was 109.4 (range 69.5-138) µM/L. The abnormal radioimaging included scoliosis by X-ray (5/6), cerebral atrophy (4/6) and spinal cord atrophy (3/6) by MRI scan. Three pairs of siblings showed heterozygous mutations of MMACHC gene including c.482G > A (4/6), c.354G > C (2/6), c.570insT (2/6), c.445_446del (2/6) and c.656_4658del (2/6). The other two siblings showed homozygous mutation with c.452A > G in MMACHC gene. After treatments, the psychiatric symptoms were obviously relieved in all the patients. In Chinese siblings with late-onset cblC, the main clinic manifestation and abnormal radioimaging were cognitive decline and cerebral atrophy respectively. The most common gene mutation was c.482G > A of MMACHC gene. The patients responded well to the treatments.

Stochastic Oscillation in Self-Organized Critical States of Small Systems: Sensitive Resting State in Neural Systems.

Self-organized critical states (SOCs) and stochastic oscillations (SOs) are simultaneously observed in neural systems, which appears to be theoretically contradictory since SOCs are characterized by scale-free avalanche sizes but oscillations indicate typical scales. Here, we show that SOs can emerge in SOCs of small size systems due to temporal correlation between large avalanches at the finite-size cutoff, resulting from the accumulation-release process in SOCs. In contrast, the critical branching process without accumulation-release dynamics cannot exhibit oscillations. The reconciliation of SOCs and SOs is demonstrated both in the sandpile model and robustly in biologically plausible neuronal networks. The oscillations can be suppressed if external inputs eliminate the prominent slow accumulation process, providing a potential explanation of the widely studied Berger effect or event-related desynchronization in neural response. The features of neural oscillations and suppression are confirmed during task processing in monkey eye-movement experiments. Our results suggest that finite-size, columnar neural circuits may play an important role in generating neural oscillations around the critical states, potentially enabling functional advantages of both SOCs and oscillations for sensitive response to transient stimuli.

Global transcriptome and gene regulation network for secondary metabolite biosynthesis of tea plant (Camellia sinensis).

BACKGROUND: Major secondary metabolites, including flavonoids, caffeine, and theanine, are important components of tea products and are closely related to the taste, flavor, and health benefits of tea. Secondary metabolite biosynthesis in Camellia sinensis is differentially regulated in different tissues during growth and development. Until now, little was known about the expression patterns of genes involved in secondary metabolic pathways or their regulatory mechanisms. This study aimed to generate expression profiles for C. sinensis tissues and to build a gene regulation model of the secondary metabolic pathways. RESULTS: RNA sequencing was performed on 13 different tissue samples from various organs and developmental stages of tea plants, including buds and leaves of different ages, stems, flowers, seeds, and roots. A total of 43.7 Gbp of raw sequencing data were generated, from which 347,827 unigenes were assembled and annotated. There were 46,693, 8446, 3814, 10,206, and 4948 unigenes specifically expressed in the buds and leaves, stems, flowers, seeds, and roots, respectively. In total, 1719 unigenes were identified as being involved in the secondary metabolic pathways in C. sinensis, and the expression patterns of the genes involved in flavonoid, caffeine, and theanine biosynthesis were characterized, revealing the dynamic nature of their regulation during plant growth and development. The possible transcription factor regulation network for the biosynthesis of flavonoid, caffeine, and theanine was built, encompassing 339 transcription factors from 35 families, namely bHLH, MYB, and NAC, among others. Remarkably, not only did the data reveal the possible critical check points in the flavonoid, caffeine, and theanine biosynthesis pathways, but also implicated the key transcription factors and related mechanisms in the regulation of secondary metabolite biosynthesis. CONCLUSIONS: Our study generated gene expression profiles for different tissues at different developmental stages in tea plants. The gene network responsible for the regulation of the secondary metabolic pathways was analyzed. Our work elucidated the possible cross talk in gene regulation between the secondary metabolite biosynthetic pathways in C. sinensis. The results increase our understanding of how secondary metabolic pathways are regulated during plant development and growth cycles, and help pave the way for genetic selection and engineering for germplasm improvement.

[Determination of dimemorfan in human plasma and urine with HPLC-MS/MS].

OBJECTIVE: To develop a sensitive and reproducible HPLC-MS/MS method for analyzing dimemorfan in human plasma and urine. METHODS: Dimemorfan was extracted from plasma and urine by redistilled ether, with lidocaine serving as the internal standard (IS). The analysis was performed on a column of ultimate C18 (50 mm x 4.6 mm, 5 microm) with the mobile phase consisting of methyl alcohol-water-formic acid = 75:25 : 0.05 at a flow rate of 0. 2 mL/min. Dimemorfan was detected by API 3000 mass spectrometer, with multiple reaction monitoring after protonated with ESI in positive electron ionization mode. The ion pairs being detected were (m/z) 256.4-->155. 3 (dimemorfan) and 235.4-->86.1 (lidocaine), respectively. RESULTS: The regression equation for dimemorfan showed excellent linearity (r = 0.995 7) from 0. 025 to 5.0 ng/mL of plasma with detecting limitation of 0.025 ng/mL and perfect linearity (r = 0.9983) from 0.1 to 20.0 ng/mL of urine with detecting limitation of 0.1 ng/mL. The method recoveries of dimemorfan in plasma and urine were ranging from 103.38% to 106.88% and 90.05% to 101.40%, respectively. The maximum intra-day and inter-day relative standard deviations (RSD) of concentration of dimemorfan were 5.92% and 5. 70% (for plasma), 10.35% and 8.80% (for urine), respectively. CONCLUSION: This new method was validated to be accurate and sensitive to determinate the concentration of dimemorfan in plasma and urine samples, and can be applied for pharmacokinetic studies of dimemorfan.

Imaging and detection of sulfite in acute liver injury with a novel quinoxaline-based fluorescent probe.

Herein, a novel fluorescent probe HZY was developed for monitoring the sulfite (SO32-) dynamics. For the first time, the SO32- triggered implement was applied in the acute liver injury (ALI) model. The levulinate was selected to achieve the specific and relatively steady recognition reaction. With the addition of SO32-, the fluorescence response of HZY exhibited a large Stokes shift of 110 nm under the 380 nm excitation. The merits included high selectivity under various pH conditions. Compared with the reported fluorescent probes for sulfite, HZY indicated above-moderate performances including remarkable and rapid response (40 folds, within 15 min), and high sensitivity (limit of detection = 0.21 µM). Further, HZY could visualize the exogenous and endogenous SO32- level in living cells. Moreover, HZY could gauge the changing levels of SO32- in three types (induced by CCl4, APAP, and alcohol) of ALI models. Both in vivo imaging and depth-of-penetration fluorescence imaging demonstrated that HZY could characterize the developmental and therapeutic status during the liver injury process by measuring the dynamic of SO32-. The successful implementation of this project would promote the accurate in-situ detection of SO32- in liver injury, which was expected to guide the pre-clinical diagnosis and clinical practice.

Alternating hemiplegia of childhood in chinese following long-term treatment with flunarizine or topiramate.

OBJECTIVE: Alternating hemiplegia of childhood (AHC) is a rare and intractable disorder. The etiology and standard therapy of AHC remain unknown. The long-term effects of flunarizine or topiramate on patients with AHC are still not clear. METHODS: Fifteen patients were investigated in this study. Their neurological disturbance and mental retardation after drug therapy were evaluated. RESULTS: Nine patients treated with flunarizine therapy and three children with topimarate treatment presented with shorter duration or less frequency of the hemiplegic attacks. These drug responsive patients also showed improvements on neurological disturbance including eye movement disorder, choreoathetotic movements, dystonia, and ataxia. However, seizure episodes and cognitive impairments were not alleviated in AHC with long-term drug therapy. CONCLUSIONS: The findings from the present study support flunarizine or topitamate as the rational treatment for AHC.

Less is more: wiring-economical modular networks support self-sustained firing-economical neural avalanches for efficient processing.

The brain network is notably cost-efficient, while the fundamental physical and dynamic mechanisms underlying its economical optimization in network structure and activity have not been determined. In this study, we investigate the intricate cost-efficient interplay between structure and dynamics in biologically plausible spatial modular neuronal network models. We observe that critical avalanche states from excitation-inhibition balance under modular network topology with less wiring cost can also achieve lower costs in firing but with strongly enhanced response sensitivity to stimuli. We derive mean-field equations that govern the macroscopic network dynamics through a novel approximate theory. The mechanism of low firing cost and stronger response in the form of critical avalanches is explained as a proximity to a Hopf bifurcation of the modules when increasing their connection density. Our work reveals the generic mechanism underlying the cost-efficient modular organization and critical dynamics widely observed in neural systems, providing insights into brain-inspired efficient computational designs.

[Expression of TLR8 in human cervical cancer HeLa cells and the effect of TLR8 agonist on the cell proliferation and apoptosis].

OBJECTIVE: To observe the expression of Toll-like receptor 8 (TLR8) in human cervical cancer cell-line HeLa cells, and the effects of TLR8 agonist CL075 on the survival and proliferation of HeLa cells. METHODS: PCR and RT-PCR were used to detect the expression of TLR8 in 13 cancer cell lines, and the expression of COX-2, Bcl-2, VEGF mRNA in the HeLa cells stimulated by TLR8 agonist CL075 were also measured by RT-PCR. Immunofluorescence technique was used to determine the exact location of TLR8 in the cells. The percentage of viable cells was determined by trypan blue exclusion after the HeLa cells were stimulated with TLR8 agonist CL075 (0.1 µg/ml, 0.5 µg/ml, 1.0 µg/ml, 2.5 µg/ml), and cell cycle and apoptosis were analyzed by flow cytometry, and the proliferation was measured by MTT. RESULTS: Compared with the other cancer cell lines, the expression of TLR8 in HeLa cells was the highest (703.7 ± 20.6). After stimulation by CL075, the cells had a remarkable increase of the percentage of cells in G(2)/M + S phases. In the control group, the percentage of cells in G(2)/M +S phases was (39.02 ± 2.33)%, whereas after stimulated with 1.0 µg/ml CL075, the percentage of cells in G(2)/M + S phases reached the highest ratio (57.67 ± 1.73)%, and the percentage of cells in G(2)/M + S phases had a less decrease after 2.5 µg/ml CL075 stimulation and the percentage was (56.14 ± 3.73)%. After the CL075 treatment, there was no significant changes of apoptosis compared with that of the control cells (P > 0.05), but after DDP treatment the apoptosis had a significant change (P < 0.01). After stimulation by 1.0 µg/ml CL075 for 24 h, no significant difference (P > 0.05) was found by MTT test, but a significant difference was found at 48 h and 72 h (P < 0.01). An increased expression of COX-2, Bcl-2 and VEGF mRNA was observed in HeLa cells after stimulation by TLR8 agonist CL075 for 24 h and 48 h (P < 0.05). CONCLUSIONS: Expression of TLR8 is significantly increased in HeLa cells. The proportion of cells at different phases has a significant change after CL075 stimulation, which may up-regulate the proliferation of HeLa cells. These data suggested that TLR8 agonist may influence the tumor development and TLR8 may become a potential target in the treatment for cervical cancer.

The Clinical Features of FLAIR-Hyperintense Lesions in Anti-MOG Antibody Associated Cerebral Cortical Encephalitis with Seizures: Case Reports and Literature Review.

Background: The presence of fluid attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated cerebral cortical encephalitis with seizures (FLAMCES) was recently reported. However, the clinical characteristics and outcome of this rare clinico-radiographic syndrome remain unclear. Methods: The present study reported two new cases. In addition, cases in the literature were systematically reviewed to investigate the clinical symptoms, magnetic resonance imaging (MRI) abnormalities, treatments and prognosis for this rare clinico-radiographic syndrome. Results: A total of 21 cases were identified during a literature review, with a mean patient age at onset of 26.8 years. The primary clinicopathological characteristics included seizures (100%), headache (71.4%), fever (52.3%) and other cortical symptoms associated with the encephalitis location (61.9%). The common seizure types were focal to bilateral tonic-clonic seizures (28.6%) and unknown-onset tonic-clonic seizures (38.1%). The cortical abnormalities on MRI FLAIR imaging were commonly located in the frontal (58.8%), parietal (70.6%) and temporal (64.7%) lobes. In addition, pleocytosis in the cerebrospinal fluid was reported in the majority of the patients (95.2%). All patients received a treatment regimen of corticosteroids and 9 patients received anti-epileptic drugs. Clinical improvement was achieved in all patients; however, one-third of the patients reported relapse following recovery from cortical encephalitis. Conclusions: FLAMCES is a rare phenotype of MOG-associated disease. Thus, the wider recognition of this rare syndrome may enable timely diagnosis and the development of suitable treatment regimens.

[Detection and significance of transcription factors and cytokines of Th17/Treg cells in peripheral blood in the gastric cancer patients].

OBJECTIVE: To detect the expression levels of transcription factors and associated cytokines of Th17 and Treg cells in peripheral blood mononuclear cells (PBMC) of patients with gastric cancer, and explore the possible pathological mechanism of these cells involved in the development of gastric cancer. METHODS: The mRNA levels of RORgammat, FoxP3 in PBMC were determined by quantitative real-time PCR (QRT-PCR) from 57 patients with gastric cancer, 31 patients with benign gastric illness and 40 healthy people. The concentration of IL-17, IL-23, TGF-beta, IL-10 in plasma were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with healthy volunteers, patients with gastric cancer showed higher levels of RORgammat and FoxP3 in PBMC (P < 0.05). The ratio of FoxP3/RORgammat in gastric cancer group was higher than that in the volunteer group and benign gastric illness group (P < 0.05). The ratio of FoxP3/RORgammat was higher in advanced disease than early disease (P < 0.05). The expressions of IL-17, IL-23, TGF-beta and IL-10 were higher in patients with gastric cancer than that in healthy volunteers (P < 0.05). In addition, The expression of TGF-beta and IL-10 were significantly increased in the advanced disease group than that in the early group (P < 0.05), but IL-17 and IL-23 was not significantly changed between the two groups (P > 0.05). CONCLUSION: There are higher levels of Th17 and Treg cells in gastric cancer patients, and it also shows a persistent predominant tendency of Treg cells and a reduced tendency of Th17 cells in advanced disease. Detecting the expression of Th17/Treg transcription factor and related cytokines would contribute to the diagnosis and prediction of the disease development and prognosis.

[Protective efficacy induced by dendritic cells pulsed with GST in combination with CpG oligodeoxynucleotide against Schistosoma japonicum infection].

OBJECTIVE: To study the protective effects on the infection of Schistosoma japonicum in C57BL/6 mice induced by dendritic cells DCs pulsed with GST in combination with CpG oligodeoxynucleotide. METHODS: GST was purified and used to stimulate DC2.4 cell line. Antigen loading was analyzed by immunofluorescence method. Thirty-five C57BL/6 mice were divided into seven groups(5 mice per group). Mice in groups A, B, C, D and E were immunized subcutaneously with DCs, DCs treated with PSA, DCs pulsed with GST, DCs stimulated with GST+CpG ODN, DCs stimulated with CpG ODN, respectively. For the above five groups, each mouse received 100 microl cell suspension at the density of 10(7)/ml subcutaneously for three times at 2-week intervals. Each mouse of group F was immunized subcutaneously with 50 microg GST formulated in complete Freund's adjuvant first, and 50 microg, 10 microg GST respectively in incomplete Freund's adjuvant for the last two doses. Group G received PBS and served as control. Serum samples were collected 10 days after the final immunization, and were analyzed for specific antibodies by ELISA. At two weeks after the final immunization, each mouse were challenged by 30 +/- 1 cercariae of S. japonicum. Six weeks after infection the mice were sacrificed, and number of worms was counted. RESULTS: Light green fluorescence was observed in dendritic cells under the fluoroscope after pulsing with GST which indicated the protein loaded dendritic cells. The IgG level in groups C, D and F was 0.555 2 +/- 0.078 9, 0.715 0 +/- 0.052 3, and 2.127 0 +/- 0.411 5, respectively, all higher than that of group G (P < 0.05). The worm reduction rate of group D was 53.3%, followed by group F (24.0%) and group C (21.3%). There was no significantly difference in the worm reduction rate between group D and groups F and C (P > 0.05). CONCLUSION: Dendritic cells pulsed with GST in combination with CpG oligodeoxynucleotide induce significant immunoprotection against the infection of Schistosoma japonicum.

Clinical features and outcomes of Chinese patients with anti-γ-aminobutyric acid B receptor encephalitis.

Antibodies against γ-aminobutyric acid B (GABAB) receptor are associated with limbic encephalitis (LE). It is estimated that ~1/2 of patients with LE have small-cell lung cancer. The present study analyzed the specific GABAB receptor antibodies in serum and cerebrospinal fluid (CSF) samples of 12 patients. The clinical manifestations, therapy and outcome were retrospectively compared. The median onset age was 65.1 years and all patients presented with new-onset seizures. In total, 11 (91.6%) patients had memory deficits, 7 (58.3%) patients had psychiatric problems and 4 (33.3%) patients had a disturbance of consciousness. Furthermore, lung cancer was detected in 7 patients (58.3%) by CT scan. Lymphocytic pleocytosis and protein concentration elevation in CSF were detected in 3 (25%) and 4 (33.3%) patients, respectively. Furthermore, MRI scan results identified 4 (33.3%) patients with abnormalities in the mesial temporal region. The lung cancer tissues of 3 patients were positively stained for anti-GABAB receptor on immunohistochemistry. All patients received antiepileptic drugs and immunotherapy. In total, 3 patients with lung cancer were subjected to tumor resection. Those patients without cancer exhibited neurological improvement at the follow-up. The present results suggested that seizures and memory deficits were the major manifestations in Chinese patients with anti-GABAB receptor antibodies who were responsive to immunotherapy. The lung cancer tissues from patients with anti-GABAB receptor antibodies were positively stained for anti-GABAB receptor. Collectively, the present results suggested that patients with underlying lung cancer have a relatively poor prognosis.

Diversity of rationality affects the evolution of cooperation.

By modifying the Fermi updating rule, we present the diversity of individual rationality to the evolutionary prisoner's dilemma game, and our results shows that this diversity heavily influences the evolution of cooperation. Cluster-forming mechanism of cooperators can either be highly enhanced or severely deteriorated by different distributions of rationality. Slight change in the rationality distribution may transfer the whole system from the global absorbing state of cooperators to that of defectors. Based on mean-field argument, quantitative analysis of the stability of cooperative clusters reveals the critical role played by agents with moderate degree values in the evolution of the whole system. The inspiration from our work may provide us a deeper comprehension toward some social phenomena.

Clinical feature and outcome of late-onset cobalamin C disease patients with neuropsychiatric presentations: a Chinese case series.

OBJECTIVE: The Cobalamin C (cblC) disease is an inborn error of cobalamin metabolism. Late-onset cblC disease was diagnosed in patients having overt symptoms after 4 years of age. The late-onset cblC disease patients were rare and easily misdiagnosed. This study analyzed the clinical presentations, gene mutations, and treatments of Chinese patients with late-onset cblC disease. METHODS: The clinical data of 26 Han Chinese patients diagnosed with late-onset cblC disease were retrospectively analyzed. All patients underwent serum homocysteine level exam, urine concentrations of organic acids measurement, neuroimaging scans, gene analysis, and treatments evaluations. RESULTS: The mean age at disease onset and diagnosis was 17.8±7.0 years. The most frequent neuropsychiatric disturbances were lower limb weakness (50%), psychiatric disturbances (46.2%), and gait instability (42.3%). The mean methylmalonic acid level in urine was 107.4±56.6 µmol/L, and mean serum total homocysteine was 105.4±41.0 µmol/L. The most common abnormal radioimaging changes were observed in the spinal cord (88%) and brain (32%). Scoliosis was detected in 85.7% of patients. The methylmalonic aciduria and homocystinuria type C protein gene analysis showed that c.482G>A (57.7%) and c.609G>A (34.6%) mutations were the most frequent genotypes. After treatments with hydroxycobalamin, betaine, folic acid, L-carnitine, and compound vitamin B, the clinical features and biochemical parameters of patients with late-onset cblC disease were found to be alleviated. CONCLUSION: In our late-onset cblC disease cases, lower limb weakness, psychiatric disturbances, and gait instability were the most frequent manifestations. Patients responded well to the drug treatments with hydrocobalamin and betaine. When juvenile or adult patients with hyperhomocysteinemia present with neurological symptoms, cblC disease needs to be considered.

CXCL13 Is A Biomarker Of Anti-Leucine-Rich Glioma-Inactivated Protein 1 Encephalitis Patients.

BACKGROUND: Although antibody-mediated immune responses are considered pathogenic and responsible for neural injury in anti-leucine-rich glioma-inactivated protein 1 (anti-LGI1) encephalitis, previous studies have indicated that cytokines and chemokines might play roles in the pathogenic process by serving as B cell enhancers. In this study, we detected the profiles of cytokines and chemokines in the cerebral fluid (CSF) and serum of patients with anti-LGI1 encephalitis to identify potential biomarkers. METHODS: Sixteen patients diagnosed with anti-LGI1 encephalitis and nine patients diagnosed with noninflammatory neurologic disorders were included in the study. Cytokines and chemokines including IL-6, IL-10, IL-17, CXCL12, CXCL13, BAFF and HMGB1 in serum and CSF were measured. RESULTS: The serum and CSF levels of CXCL13 were significantly higher in patients with anti-LGI1 encephalitis (36.32±34.71 pg/mL and 2.23±2.41 pg/mL, respectively) than in controls (10.84±5.02 pg/mL and 0.34±0.21 pg/mL, respectively). There was no significant difference in serum or CSF levels of IL-6, IL-10, IL-17, CXCL12, BAFF and HMGB1 between the two groups. CONCLUSION: CXCL13 is a potential biomarker of active inflammation in anti-LGI1 encephalitis. The distinctive response of cytokines and chemokines might be closely linked to the mechanisms underlying this condition.