Objective To discuss the mechanism and characteristics of clinic presentation and neuropathology in idiopathic hypereosinophilic syndrome (IHES) encephalopathy. Methods IHES encephalopathy was diagnosed by clinical presentations,lab examinations,neurologic images,marrow and brain biopsy,then treated with corticosteroids and continuous follow-up. Results The IHES patient presented progressive limbs weakness and cognitive deficit with elevated eosinophil count. Results of lab examinations and bone marrow biopsy ruled out secondary eosinophilia and clonal eosinophilia such as eosinophilic leukemia.Brain magnetic resonance imaging (MRI) study showed multiple lesions in right frontal lobe, bilateral parietal and occipital lobe, presenting hypointensity in T1 weighted images,hyperintensity in T2 and fluid-attenuated inversion recovery weighed images. Brain biopsy showed proliferation of vascular membrane,small vessels stenosis,ischemia-induced morphological change and necrosis of neurons in the lesions.The patient was continuously treated with corticosteroids,and the situation was stabilized with follow-up.Conclusions IHES encephalopathy should be paid more attention in clinical practice of neurologists for its rarity. Brain vascular damages caused by elevated eosinophil may be an important pathophysiological mechanism of IHES encephalopathy,and corticosteroids or hydroxycarbamide should be used for the treatment.

Objective To study the changes and significance of the frequencies of circulating follicular helper T cells (cTfh) and circulating regulatory follicular T cells (cTfr) as well as the cTfh/cTfr ratio in neuromyelitis optica spectrum disorder (NMOSD).Methods The frequencies of cTfh,cTfr and B cells in patients with NMOSD and health controls(HCs) were measured by flow cytometry.Enzyme-linked immunosorbent assay was used to detect the level of IL-21 and AQP4-Ab in patients and HCs.Results The frequencies of cTfh and B cells,the cTfh/cTfr ratio and the plasma level of IL-21 werc significantly higher in the relapsing patients than those in the remitting patients and HCs(P ＜ 0.05),and the cTfr level in the relapsing patients was lower than that in the remitting patients and healthy population (P ＜ 0.05).But no statistical differences were observed in the above indexes between the remitting paticnts and HCs.There was also no significant difference in AQP4-Ab level between the patients with relapse and remission (P ＞ 0.05).The frequency of cTfh in the patients wasc positively correlated with the level of B cells and IL-21(P ＜ 0.05),and the frequency of cTfr was negatively correlated with B cells and IL-21 (P ＜ 0.05).The ratio of cTfh/cTfr was positively correlated with B cell frequency and IL-21 level (P ＜ 0.05).AQP4-Ab level had no correlation with the frequencies of cTfh cells and B cells,cTfh/cTfr ratio and IL-21 concentration (P ＞ 0.05).Conclusion The changes in the frequencies of cTfh and cTfr as well as the imbalanced cTfh/cTfr ratio may promote the activation of humoral immunein NMOSD and participate in the pathogenesis of this disease.

This research adopted silt as the sample,and the five highest hydrogen production performing strains contained in the sample were isolated. The strain whose hydrogen production was the highest was identified as Enterobacter cloacae by the analysis of 16S rDNA sequencing and comparison. It is showed by Plackett-Burman Experimental Design that only glucose,citric buffer and reducing agent had significant effects on hydrogen production by Enterobacter cloacae FML-C1. The path of steepest ascent was undertaken to approach the optimal response region of those three factors. Central Composite Design(CCD) and Response Surface Methodology(RSM) were employed to investigate the interaction of the variables and to ascertain the optimal values of the factors,which finally led to the maximum hydrogen production(VH2) . The theoretical optimal medium conditions were:glucose 21.5 g/L,citric buffer 13.6 mL/L,reducing agent10.0 mL/L. The five tentative tests matched this model well. The final VH2 was up to 2347.4 mL/L,which was 127.42% enhanced in comparison to the original. The result shows that PB experiment design and RSM analytical method work well in selecting factors which have significant influences on the hydrogen production and,moreover,achieve the ideal optimal result.

Radiologically isolated syndrome (RIS) is considered as an imaging marker of the prodromal stage of multiple sclerosis (MS), and approximately one-third of patients might convert to clinically isolated syndrome or clinically definite multiple sclerosis within 5 years after diagnosis. Although it still remains inconclusive whether or not disease-modifying therapies for RIS need to be initiated, effective identification of prognostic factors for conversion would be of great benefit for early screening of high-risk patients and subsequent clinical precision management. Combined with the latest research progress at home and abroad, this review summarizes the prognostic factors for conversion of RIS to MS from the aspects of demographic characteristics, clinical presentations, imaging manifestations, cerebrospinal fluid and ophthalmological examinations. Given that disease-modifying therapies for RIS are still in clinical research stage and there are no definite recommendations to date, this article expounds the research progress on clinical monitoring, therapeutics and prevention of disease progression, which aims to provide neurologists with reference suggestions on clinical management of RIS.

OBJECTIVE In this study,the effects of live Lactobacillus murinus(L.m)and heat-killed L.muri-nus(H-k L.m)on DA neuronal damage in rats and the underlying mechanisms were investigated.METHODS Male SD rats were randomly divided into five groups:vehicle group,L.m/H-k L.m(1×109 cfu)group,6-OHDH group,6-OHDH + L.m/H-k L.m(1×107 cfu)group,and 6-OHDH + L.m/H-k L.m(1×109 cfu)group.Wild-type and NLRP3 knockout mice were divided into three groups:sham(vehicle),6-OHDH,and 6-OHDH + H-k L.m(1×109 cfu).The model was established after five weeks of pre-administration.Motor ability of experimental mice was assessed by rotarod,mine,and stepping experiments;the expression of dopaminergic neuron markers—tyro-sine hydroxylase(TH),microglial cell markers—ionized calnexin 1(IBA-1),and NOD-like receptor family protein 3(NLRP3)in the substantia nigra was detected by immunohistochemistry and immunofluorescence experi-ments.The expression changes of TH,IBA-1,NLRP3,apoptosis-associated microparticle protein(ASC),cas-pase 1,and inflammatory factors such as interleukin-1β(IL-1β),IL-18,and tumor necrosis factor-α(TNF-α)were detected by immunoblotting experiments.RESULTS H-k L.m ameliorated 6-OHDH-induced motor dysfunctions and loss of substantia nigra DA neurons,while no protec-tion was shown in live L.m treatment.At the same time,H-k L.m reduced the activation of NLRP3 inflammasome in microglia and the secretion of pro-inflammatory factors,thus inhibiting the development of neuroinflammation.Fur-thermore,H-k L.m failed to display its original neuropro-tective properties in NLRP3 inflammasome knockout mice.CONCLUSION H-k L.m conferred neuroprotec-tion against DA neuronal loss via the inhibition of microglial NLRP3 inflammasome activation,these findings provide a promising potential for future applications of L.m,and also beneficial strategy for PD treatment.

Panax ginseng is a traditional Chinese medicine with significant pharmaceutical effects and wide application. Through orientational modification and transformation of ginsenoside glycosyl, rare ginsenosides with high antitumor activities can be generated. Traditional chemical methods cannot be applied in clinic. because of extremely complex preparation technologies and very high cost Transformations using microorganisms and their enzymatic systems provide the most feasible methods for solving the main problems. At present, the key problems in enzymatic synthesis of ginsenosides include low specific enzyme activities, identity of enzymes involved in the enzymatic synthesis, and their catalytic mechanisms, as well as nonsystematic studies on structural bioinformatics; specificity of enzymatic hydrolysis for saponin glycosyl has been rarely studied. Many reviews have been reported on glycosidase molecular recognition, immobilization, and biotransformation in ionic liquids (ILs), whereas ginsenoside transformation and application have not been systematically studied. To evaluate theoretical and applied studies on ginsenoside-oriented biotransformation, by reviewing the latest developments in related fields and evaluating the widely applied biocatalytic strategy, this review aims to evaluate the ginsenoside-oriented transformation method with improved product specificity, increased biocatalytic efficiency, and industrial application prospect based on the designed transformations of enzyme and solvent engineering of ILs. Therefore, useful theoretical and experimental evidence can be obtained for the development of ginsenoside anticancer drugs, large-scale preparation, and clinical applications in cancer therapy.
Biocatalysis ; Ginsenosides ; Glycoside Hydrolases ; Panax ; Saponins

To improve collagen production by recombinant Pichia pastoris, we applied Placket-Burman and Box-Behnken design to optimize the fermentation medium. Through Placket-Burman design, three variables in the medium (concentration of yeast extract, peptone and glycerol) were selected for having significant effect on cell dry weight. Through Box-Behnken design regression coefficients analysis, a secondary degree polynomial equation was established, and the optimum levels of the three variables were yeast extract 1.13%, peptone 1.61% and glycerol 0.86%. During the growth period, an average cell dry weight of 4.41 g/L was obtained after 12 h fermentation, increased by 26%. Through high density fermentation, the production of recombinant human collagen (Ⅲ) was up to 4.71 g/L in 22 L fermentor. The recombinant human collagen (Ⅲ) exhibited good results to repair acetic acid induced gastric ulcer in rats.

Five new racemic N-acetyldopamine (NADA) trimers, asponchimides A-E (1-5), were isolated from Aspongopus chinensis, a prominent traditional Chinese medicinal insect employed for alleviating pain, treating indigestion, and addressing kidney ailments. Compounds 1-5 were successfully resolved by chiral high-performance liquid chromatography (HPLC), yielding five pairs of enantiomers: (+)- and (-)-asponchimides A-E (1a/1b-5a/5b). Their structural identities were discerned by extensive spectroscopic analyses, including high-resolution mass spectrometry (HRMS), ultraviolet-visible (UV-Vis) spectroscopy, infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR), and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. Compounds 1-5 are pioneering instances of NADA trimers featuring a Δ⁷ double bond. When subjected to a series of bioassays, a majority of the compounds exhibited weak inhibitory activity against nitric oxide (NO) production in LPS-induced RAW 264.7 cells.
Molecular Structure ; Magnetic Resonance Spectroscopy ; Dopamine ; Nitric Oxide