Two previously undescribed cholestanol saponins from the rhizomes of Paris fargesii var. petiolata.

Two previously undescribed cholestanol saponins, parpetiosides F - G (1-2), and six known analogs (3-8) were isolated from the rhizomes of Paris fargesii var. petiolata. Their structures were elucidated by extensive spectroscopic data analysis and chemical methods. Compound 1 was a rare 6/6/6/5/5 fused-rings cholestanol saponin with disaccharide moiety linked at C-26 of aglycone which was hardly seen in genus Paris. All of these compounds were discovered in this plant for the first time. In addition, the cytotoxicities of saponins (1-8) against three human cancer cell lines (U87, HepG2 and SGC-7901) were evaluated by CCK-8 method, and saponins 5-8 displayed certain cytotoxicities. The strong interactions between saponins 5-8 and SCUBE3, an oncogene for glioma cells, were displayed by molecular docking.

Cytotoxic steroidal glycosides from the rhizomes of Paris polyphylla var. yunnanensis.

Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz. (Melanthiaceae), an important specie of the genus Paris, has long been in a traditional Chinese medicine (TCM) for a long time. This study aimed to isolate and identify the structures of bioactive saponins from the rhizomes of P. polyphylla var. yunnanensis and evaluate their cytotoxicity against BxPC-3, HepG2, U373 and SGC-7901 carcinoma cell lines. Seven previously undescribed and seven known saponins were identified, and Paris saponins VII (PSVII) showed significant cytotoxicity against the BxPC-3 cell line with IC50 values of 3.59 µM. Furthermore, flow cytometry, transmission electron microscopy and western-bolt analysis revealed that PSVII inhibited the proliferation of BxPC-3 cells and might be involved in inducing apoptosis and pyroptosis by activating caspase-3, -7 and caspase-1, respectively.

Metabonomics and 16S rRNA gene sequencing to study the therapeutic mechanism of Danggui Sini decoction on collagen-induced rheumatoid arthritis rats with Cold Bi syndrome.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent joint inflammation. The development of rheumatoid arthritis is directly correlated with the disturbance of gut microbiome and its metabolites. RA can be effectively treated with the Danggui Sini decoction (DSD), a Traditional Chinese medicine (TCM) prescription from the Treatise on Febrile Diseases. Further research is needed to clarify the precise mechanism of DSD in the treatment of RA. In this study, 1H NMR metabonomics and 16 S rRNA gene sequencing techniques were used to clarify the intervention of DSD on CIA-induced RA. The results of 1H NMR metabolomics of feces revealed that five metabolites (alanine, glucose, taurine, betaine, and xylose) were disturbed, which could be regarded as potential biomarkers of RA. The intestinal microbiome of RA rats had changed, according to the results of 16 S rRNA gene sequencing; eight microbes (g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_group, g_Dubosiell, g_Lactobacillus, g_norank_f_Desulfovibrionaceae, g_Bacteroides, g_Oscillibacter, and g_Romboutsia) occurred significantly at the genus level, and DSD significantly impacted six of them (g_Dubosiell, g_Lactobacillus, g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_grou, g_Bacteroides, and g_Romboutsia). Three of them (g_norank_f_Eubacterium_ coprostanoligenes_group, g_Romboutsia, and g_Lactobacillus) were regarded as key microbiomes for DSD to treat RA, and three common metabolic pathways (taurine and hypotaurine metabolism; alanine, aspartate, and glutamate metabolism; primary bile acid biosynthesis) were discovered based on the 1H NMR metabonomics and PICRUST2 prediction of 16 S rRNA gene sequencing. Six SCFAs in feces (acetic acid, butyric acid, propionic acid, caproic acid, isobutyric acid, and valeric acid) increased significantly in RA, according to the outcomes of targeting SCFAs, while five SCFAs (acetic acid, butyric acid, propionic acid, caproic acid, and valeric acid) had decreased significantly due to DSD treatment. In conclusion, our study indicated that DSD could regulate RA's metabolic disorder by affecting intestinal microbiome and its metabolites. It also establishes a framework for future research into exploiting gut microbes therapeutic to treat RA.

[Mechanism of Danggui Sini Decoction in improving kidney injury caused by blood stasis syndrome based on metabolomics and network pharmacology].

This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.

Discussion on Collection of Clinical Questions in International Clinical Practice Guidelines of Acupuncture-Moxibustion / 中国结合医学杂志

The clinical questions of acupuncture-moxibustion (Acup-Mox) guidelines are complicated, including not only the curative effect of Acup-Mox intervention measures, but also the operational elements of Acup-Mox. This paper aimed to put forward the idea and process of collecting clinical questions in developing international acupuncture clinical practice guidelines. The experience was collected and the idea of collecting clinical questions of Acup-Mox was formed through expert consultation and discussion in combination with expert opinions. Based on the characteristics of Acup-Mox discipline. This paper put forward the thinking of collecting elements of clinical questions following the intervention-population-outcome-control (I-P-O-C) inquiry process, according to the discipline of Acup-Mox. It was emphasized that in the process of collecting clinical questions, "treatable population" and "alleviable outcome indicators" for a specific Acup-Mox intervention with certain therapeutic effect should be focused on, so as to highlight the pertinence of clinical questions of Acup-Mox guidelines in terms of population and outcome elements.

Ilex rotunda Thunb Protects Against Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Restoring the Intestinal Mucosal Barrier and Modulating the Oncostatin M/Oncostatin M Receptor Pathway.

Ilex rotunda Thunb (IR) is a traditional Chinese medicine used for the clinical treatment of gastric ulcers and duodenal ulcers; however, the effect of IR on ulcerative colitis (UC) and its underlying mechanism remains unclear. This study investigated the therapeutic effect of IR on UC mice induced by dextran sulfate sodium (DSS) as well as the potential underlying mechanism. The main components of IR were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Then we established a model of UC mice by administering 2.0% DSS for 7 days followed by 2 weeks of tap water for three cycles and administered IR. On day 56, the disease activity index (DAI), colon length, pathological changes, and inflammatory response of the colon tissue of mice were assessed. The oxidative stress and apoptosis of colon tissue were detected, and the integrity of the intestinal mucosal barrier was evaluated to assess the effect of IR. Furthermore, the relationship between oncostatin M (OSM) and its receptor (OSMR) in addition to the IR treatment of UC were evaluated using a mouse model and Caco2 cell model. The results showed that IR significantly alleviated the symptoms of UC including rescuing the shortened colon length; reducing DAI scores, serum myeloperoxidase and lipopolysaccharide levels, pathological damage, inflammatory cell infiltration and mRNA levels of interleukin one beta, tumor necrosis factor alpha, and interleukin six in colon tissue; alleviating oxidative stress and apoptosis by decreasing kelch-like ECH-associated protein 1 expression and increasing nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase-1 protein expression; and promoting the regeneration of epithelial cells. IR also promoted the restoration of the intestinal mucosal barrier and modulated the OSM/OSMR pathway to alleviate UC. It was found that IR exerted therapeutic effects on UC by restoring the intestinal mucosal barrier and regulating the OSM/OSMR pathway.

Deep mining decreases the microbial taxonomic and functional diversity of subsurface oil reservoirs.

Microbes in subsurface oil reservoirs play important roles in elemental cycles and biogeochemical processes. However, the community assembly pattern of indigenous microbiome and their succession under long-term human activity remain poorly understood. Here we studied the microbial community assembly in underground sandstone cores from 190 to 2050 m in northeast China and their response to long-term oil recovery (10-50 years). Indigenous microbiome in subsurface petroleum reservoirs were dominated by Gammaproteobacteria, Firmicutes, Alphaproteobacteria, Bacteroidetes, and Actinobacteria, which exhibited a higher contribution of homogenizing dispersal assembly and different taxonomy distinct ecological modules when compared with perturbed samples. Specifically, the long-term oil recovery reduced the bacterial taxonomic- and functional-diversity, and increased the community co-occurrence associations in subsurface oil reservoirs. Moreover, distinguished from the perturbed samples, both variation partition analysis and structural equation model revealed that the contents of quartz, NO3- and Cl- significantly structured the α- and ß-diversity in indigenous subsurface bacterial communities. These findings first provide the holistic picture of microbiome in the deep oil reservoirs, which demonstrate the significant impact of human activity on microbiome in deep continental subsurface.

Analysis and thought on reaching the consensus during the development of acupuncture and moxibustion clinical practice guidelines in China / 中国针灸

Based on the 28 Chinese clinical practice guidelines of acupuncture and moxibustion, this study summarized and analyzed the contents related to reaching consensus during the development process. The results indicated that all the 28 guidelines reported they have used consensus in the "recommendations" section, and provided details on consensus personnel, consensus methods, consensus process and consensus materials. However, it was found that the reporting of consensus was in need of further improvement. The limitations included unclear definition and responsibilities of "expert group", obscure concept between "consensus meeting" and "expert discussion", non-rigorous process of reaching consensus when generating recommendations and lacking of detailed reporting of the consensus reaching process. As such, we suggested that future researchers should conduct researches to further standardized the consensus process when developing acupuncture and moxibustion clinical practice guidelines, so as to improve the quality and clinical applicability of guidelines．.

Stochastic assembly process dominates bacterial succession during a long-term microbial enhanced oil recovery.

Microbial enhanced oil recovery (MEOR) has been successfully used in oil exploitation to increase oil production. However, the mechanisms of microbial interactions and community assembly related to oil production performance along MEOR process are poorly understood. Here, we investigated the microbiome of an oil reservoir for a period of 5 years under three phases of different treatments with the injection of a mixture of microbes, nutrients, and air at different intensity. During the MEOR process, amplification of functional genes revealed an increase of genes related to hydrocarbon degradation linked to methanogenesis, supported by stable isotope analysis for confirmation of the methanogenesis activity. Meanwhile, a lower contribution of the ubiquitous/common taxa, closer and more positive associations, and lower modularity were observed in bacterial co-occurrence networks, with the rare taxa being the keystone taxa. The null model analysis and structural equation modeling revealed that the contribution of stochastic processes affected by functional groups and co-occurrence patterns to bacterial community increased significantly with the increase of oil production. This provides new insight that stochastic assembly in bacterial community increased along with MEOR process, and it is worthwhile paying attention to the uncertain consequences caused by random evolution since the treatment effect of MEOR is closely related to the in-situ community in oil reservoir.

Consideration on existing problems in development of clinical practice guidelines for acupuncture and moxibustion in China / 中国针灸

To sort out the existing problems within the published 35 evidence-based acupuncture-moxibustion clinical practice guidelines (group standards) in Chinese: the development methods and the development process are not clear and strict enough; the evidence evaluation system fails to fully reflect the characteristics of acupuncture and moxibustion. Therefore,

Investigation and analysis on the current situation of clinical practice guidelines for acupuncture and moxibustion at home and abroad / 中国针灸

To provide directional suggestions for the establishment of international clinical practice guidelines for acupuncture and moxibustion by investigating the current situation of clinical practice guidelines for acupuncture and moxibustion at home and abroad. The clinical practice guidelines were obtained by questionnaire survey, database retrieval and experts consulting. The guidelines were read carefully, and the content was analyzed. A total of 27 acupuncture-moxibustion clinical practice guidelines were retrieved, of which most of the guidelines came from China. The definition and scope of "acupuncture and moxibustion "vary according to different guidelines; and the focus of the content and the method of establishing the guidelines are quite different, so it is very necessary to unify the formulation methods of acupuncture-moxibustion clinical practice guidelines. Chinese clinical practice guidelines for acupuncture and moxibustion were characterized by taking the ancient literature as the evidence. Excavating the value of ancient literature and clinical experience of acupuncture-moxibustion experts are the key points and difficulties in the developing of clinical practice guidelines of acupuncture and moxibustion in the future.

Halomonas plays a central role in the syntrophic community of an alkaline oil reservoir with alkali-surfactant-polymer (ASP) flooding.

Little is known about the microbial characteristics in oil reservoirs under alkali-surfactant-polymer (ASP)-flooding. In the present study, we collected two ASP-flooding samples and two nearby water-flooding samples from the Daqing oil field and performed 16S rRNA gene sequencing and metagenomic sequencing to fill this knowledge gap. The results indicated that the highly elevated pH resulted in a simple Euryarchaeotal community and a Halomonas &Nitrincola-dominated bacterial community in the production water of the alkaline oil reservoir. In addition, we hypothesized that multiple copies of genes encoding monovalent cation/proton antiporters in Halomonas and Nitrincola, and their facultative anaerobic and movable traits, were the adaptive mechanisms responsible for their competitive growth in the alkaline oil reservoir. We also revealed a unique syntrophic community in the alkaline oil reservoir and identified the central role of Halomonas within it. The present study revealed the microbial characteristics in an alkaline oil reservoir environment formed by ASP-flooding and indicated the application potential of Halomonas in AMP-flooding and microbial enhanced oil recovery (MEOR) technology to elevate the oil recovery rate from ASP-flooded oil reservoirs.

Observation on Effect of Atractylodesin Ⅱ on Gastric Cancer Cells Based on Macrophage Polarization / 中国实验方剂学杂志

Objective:To investigate the anti-tumor effect mechanism of atractylenolide Ⅱ by studying its effect on macrophage polarization. Method:Phorbol myristate acetate （PMA） was used to induce THP-1 cells differentiation into macrophages， and methylthiazolyldiphenyl-tetrazolium bromide（MTT）colorimetric assay was used to detect the effect of different concentrations of atractylenolide Ⅱ on macrophage growth at different time points to screen out the safe concentration of atractylenolide Ⅱ. The macrophages were treated with different concentrations of atractylenolide Ⅱ for 24 hours and then were co-cultured with gastric cancer cells. The survival of the two types of cells was observed under light microscope. The proliferation of gastric cancer cells was detected by MTT assay to determine the effective administration concentrations of atractylenolide Ⅱ. Cells were divided into blank group， model group， atractylenolide Ⅱ high dose group （200 mg·L-1）， atractylenolide Ⅱ medium dose group （100 mg·L-1）， and atractylenolide Ⅱ low dose group（50 mg·L-1）. Wound healing assay was carried out to observe the effects of different concentrations of atractylenolide Ⅱ on the migration and morphology of gastric cancer cells. The expression levels of M1 and M2 macrophage surface markers CD86 and CD206 were detected by flow cytometry analysis（FCM）. Quantitative polymerase chain reaction（Real-time PCR）and Western blot were used to detect M1， M2 macrophage-associated tumor necrosis factor （TNF） -α， human leukocyte antigen 2 （HLA-DRA）， CD80， transforming growth factor （TGF）-β， interleukin （IL） -10 and IL-6 genes and protein expression. Western blot was used to detect intracellular phosphatidyl inositol kinase （PI3K） and p-PI3K protein expression in macrophages. Result:When the concentration of atractylenolide Ⅱ was 1， 10， 50， 100， 200 mg·L-1， it showed no inhibition on macrophage growth. As compared with the model group， macrophages treated with 50， 100， 200 mg·L-1 atractylenolide Ⅱ significantly inhibited tumor cell proliferation （P<0.01）. As compared with the model group， the migration rate of tumor cells in the atractylenolide Ⅱ （200，100 mg·L-1） groups decreased （P<0.05）. The expression levels of CD86 on M1 macrophage surfacen in the atractylenolide Ⅱ （200，100，50 mg·L-1） groups were increased（P<0.05，P<0.01）， and the expression levels of CD206 on M2 macrophagen in the atractylenolide Ⅱ （200 mg·L-1） group were decreased （P<0.05）. The expression levels of M1 macrophage-associated cytokines TNF-α， HLA-DRA， CD80 mRNA in the atractylenolide Ⅱ （200，100 mg·L-1） groups were increased（P<0.05，P<0.01）， and TNF-α protein expression in the atractylenolide Ⅱ （200 mg·L-1） group was increased （P<0.05）， M2 type macrophage-associated cytokine TGF-β mRNA expression levels in the atractylenolide Ⅱ （50 mg·L-1） group were decreased， and IL-10， IL-6 protein expression levels in the atractylenolide Ⅱ （200 mg·L-1） group were decreased （P<0.05，P<0.01）. The expression levels of p-PI3K protein in the atractylenolide Ⅱ （200，100 mg·L-1） groups were also decreased（P<0.05，P<0.01）. Conclusion:Atractylenolide Ⅱ could induce the polarization of macrophages to M1 type by reducing the expression of p-PI3K in macrophages and inhibiting the proliferation and migration of gastric cancer cells.

Progress of the application of PET technology in acupuncture research / 中国针灸

To further investigate the application of positron emission tomography (PET) technology in acupuncture research field, with "PET" and "acupuncture" as keywords, the related literature published from 1997 to 2018 was searched in PubMed, CNKI and WANFANG database; then the literature was classified and analyzed. The results showed that in clinical and experimental studies, whether in physiological or pathological conditions, PET technology has verified the specificity of acupoints, bidirectional regulation of acupoints, and the clinical effect of -arrival from the level of brain functional activity. It has deeply revealed the central mechanism underlying that acupuncture has multi-target, multi-channel and multi-level overall effects. The purpose of this study is to provide objective scientific basis for acupuncture research, and then potentially guide the clinical practice.

The pharmacological mechanism of gastrodin on calcitonin gene-related peptide of cultured rat trigeminal ganglion / 药学学报

The Chinese herbal medicine Tianma (Gastrodia elata) has been used for treating and preventing primary headache over thousands of years, but the exact pharmacological mechanism of the main bioactive ingredient gastrodin remains unclear. In present study, the effects of gastrodin on calcitonin gene-related peptide (CGRP) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) expression were observed in rat trigeminal ganglion (TG) after in vitro organ culture to explore the underlying intracellular mechanism of gastrodin on primary vascular-associated headache. CGRP-immunoreactivity (CGRP-ir) positive neurons count, positive area, mean optical density and integrated optical density by means of immunohistochemistry stain were compared at different concentrations of gastrodin, which was separately co-incubated with DMEM in SD rat TG for 24 hours. Only at 5 or 10 mmol L(-1) concentration, gastrodin demonstrated significantly concentration-dependent reduction of CGRP-ir (+) expression and its action closed to 1.2 mmol L(-1) sumatriptan succinate. While at 2.5, 20, and 40 mmol L(-1) concentration, gastrodin did not show remarkable effects on CGRP-ir (+) expression. The optimal concentration of gastrodin (5 and 10 mmol L(-1)) similarly inhibited CGRP-mRNA expression level separately compared with 1.2 mmol L(-1) sumatriptan succinate and 10 micromol L(-1) flunarizine hydrochloride, which was quantitatively analyzed by real-time PCR (RT-PCR). pERK1/2 level was examined by Western blotting after co-cultured with optimal concentration of gastrodin and effective specific ERK1/2 pathway inhibitors PD98059, U0126. The result indicated that gastrodin significantly reduced pERK1/2 protein actions similarly to ERK1/2 pathway specific blockade. It suggests ERK1/2 signaling transduction pathway may be involved in gastrodin intracellular mechanism. This study indicates gastrodin (5 and 10 mmol L(-1)) can remarkably reduce CGRP-ir (+) neuron, CGRP-mRNA and pERK1/2 expression level in cultured rat TG, with its actions similar to the effective concentration of sumatriptan succinate, flunarizine hydrochloride and specific ERK1/2 pathway blocker. The intracellular signaling transduction ERK1/2 pathway may be involved in the gastrodin reducing CGRP up-regulation in rat TG after organ culture.

Effects of injection of Huangqi injectio into Zusanli (ST 36) on immune function in the patient of schizophrenia / 中国针灸

<p><b>OBJECTIVE</b>To study on effects of injection of Huangqi Injectio into Zusanli (ST 36) on the hospital infection and immune function in the patient of schizophrenia.</p><p><b>METHODS</b>Thirty inpatients of chronic schizophrenia were treated with injection of Huangqi Injectio into bilateral Zusanli (ST 36), 2 mL each point, thrice each week, for 8 weeks. Relative immune indexes and the hospital infection were investigated.</p><p><b>RESULTS</b>The hospital infection and the sub-infection were 4 cases (13.3%), 7 cases-times (23.3%) in the injection group; and 9 cases (15.0%), 19 cases-times (31.7%) in the control group, respectively, with no significant difference between the two groups (P>0.05). The drug-administration duration was 7.77 days/case and 11.87 days/case in the two groups, respectively (P<0.01). In the injection group, as compared with that of last 3 years the duration was 7.77 days/case and 14.08 days/case (P<0.01). IgG, IgA, IgM and T-cell subgroups did not have significant changes, but there was the most different value before and after injection in SIL-2R of the no-infection group, and the longer the drug administration duration, the smaller the different values.</p><p><b>CONCLUSION</b>Injection of Huangqi Injectio into Zusanli (ST 36) has definite effect for prevention of the hospital infection in inpatients of chronic schizophrenia, and SIL-2R is a valuable index for investigation of the hospital of infection.</p>

Docosahexaenoic acid is superior to eicosapentaenoic acid as the essential fatty acid for growth of grouper, Epinephelus malabaricus.

Juvenile grouper (Epinephelus malabaricus) were fed seven experimental diets, one control diet and one reference diet for 12 wk to determine the dietary requirement of grouper for docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. Each of the seven diets contained 1 g/100 g DHA and EPA in various combinations and 9 g/100 g tristearin. The control diet contained 1 g/100 g trilinolenin and trilinolein (3:1, wt/wt), and no supplemental EPA or DHA. The reference diet contained only natural oils from a mixture of cod liver oil, linseed oil and safflower oil at a ratio of 2:1:1 (wt/wt/wt). Significant differences (P < 0.05) in growth were observed among the dietary treatments but not in survival rate or relative liver weight. Only the diet with the highest DHA/EPA ratio (3:1) promoted significantly greater growth than the control diet. Purified EPA and DHA did not perform better in promoting growth than did the impure EPA and DHA oils. Enhanced growth was observed when the dietary DHA/EPA ratio was greater than 1, indicating that DHA was superior to EPA in promoting fish growth. Neutral lipid (NL) was the predominant lipid fraction (>70%) in both liver and muscle. Tissue NL/polar lipid did not differ among groups except the reference diet group that had a higher ratio (P < 0.05). DHA and EPA levels in the grouper tissues, especially muscle, were highly reflective of dietary levels of DHA and EPA, indicating that direct incorporation was likely. In addition, the 20:1(n-9), concentration in NL fractions seems to be an appropriate indicator of dietary essential fatty acid deficiency in grouper.

inical and radiological features of the late-onset methylmalonic aciduria: a review of three cases / 中华神经科杂志

jective To study the clinical and radiological features of the patients with late-onset methylmalonic aciduria ( MMA). Methods Two men and one woman with MMA were screened and confirmed by urinary organic acid analysis with gas chromatograph/mass spectrometer (GC/MS) at their 26, 18 and 34 years old, respectively. Their clinical features, laboratory findings, radiological manifestations, treatment and outcome were reviewed. Results The clinical features of 3 patients were varied with neurological abnormalities. Case 1 had periodic enuresis for 16 months, progressive dementia and movement disorder for 3 months. Physical examination showed an apparent cognitive decline with psychiatric symptoms. Dysarthria, bilateral weakness and pyramidal signs, rigidity and mild tremor of limbs were observed. Case 2 had a progressive memory deterioration, learning difficulty, walking unstably and decreased vision when he was 13 years old, and a general seizure at an age of 16 years. Diffused abnormalities of EEG and rnild renal defects were found in the above two patients. General white matter hyperintensity and cerebral atrophy on T2-weighted MR images were evident. Additionally, these two patients had hyperhomocystinemia and carnitine deficiency. Case 3 had complained about walking unstably and fatigue over 2 months. Reduced facial movements, deep sensation loss and muscle weakness in lower extremities, marked rigidity and diminished tendon reflexes were detected. Megaloblastic anemia and cobalamin deficiency were found. MRJ performed revealed bilateral symmetric areas having high density involving the globi pallidi, posterior limbs of internal capsule and the cerebral peduncles. Remarkable elevations of urinary methylmalonic and methylcitric acid were confirmed in all 3 patients. After vitamin B12 supplementation, significant improvement was observed. Conclusion Three cases with vitamin BI2 responsive type of late-onset MMA were reported. Two patients were combined with hyperhomocystinemia and the other had only isolated MMA. There might remain prominent differences among MMA subgroups in clinical presentations and neuroradiologic findings. VitaminB12 might be very effective to improve the prognosis of the patients. MMA should be considered as a differential diagnosis for the etiological investigation of adult cerebral metabolic or degenerative diseases.