Short-term exposure to antibiotics begets long-term disturbance in gut microbial metabolism and molecular ecological networks.

BACKGROUND: Antibiotic exposure can occur in medical settings and from environmental sources. Long-term effects of brief antibiotic exposure in early life are largely unknown. RESULTS: Post a short-term treatment by ceftriaxone to C57BL/6 mice in early life, a 14-month observation was performed using 16S rRNA gene-sequencing technique, metabolomics analysis, and metagenomics analysis on the effects of ceftriaxone exposure. Firstly, the results showed that antibiotic pre-treatment significantly disturbed gut microbial α and ß diversities (P < 0.05). Both Chao1 indices and Shannon indices manifested recovery trends over time, but they didn't entirely recover to the baseline of control throughout the experiment. Secondly, antibiotic pre-treatment reduced the complexity of gut molecular ecological networks (MENs). Various network parameters were affected and manifested recovery trends over time with different degrees, such as nodes (P < 0.001, R2 = 0.6563), links (P < 0.01, R2 = 0.4543), number of modules (P = 0.0672, R2 = 0.2523), relative modularity (P = 0.6714, R2 = 0.0155), number of keystones (P = 0.1003, R2 = 0.2090), robustness_random (P = 0.79, R2 = 0.0063), and vulnerability (P = 0.0528, R2 = 0.28). The network parameters didn't entirely recover. Antibiotic exposure obviously reduced the number of key species in gut MENs. Interestingly, new keystones appeared during the recovery process of network complexity. Changes in network stability might be caused by variations in network complexity, which supports the ecological theory that complexity begets stability. Besides, the metabolism profiles of the antibiotic group and control were significantly different. Correlation analysis showed that antibiotic-induced differences in gut microbial metabolism were related to MEN changes. Antibiotic exposure also caused long-term effects on gut microbial functional networks in mice. CONCLUSIONS: These results suggest that short-term antibiotic exposure in early life will cause long-term negative impacts on gut microbial diversity, MENs, and microbial metabolism. Therefore, great concern should be raised about children's brief exposure to antibiotics if the results observed in mice are applicable to humans. Video Abstract.

Burden of dilated perivascular spaces in patients with moyamoya disease and moyamoya syndrome is related to middle cerebral artery stenosis.

Background and objective: The correlation between intracranial large artery disease and cerebral small vessel disease (CSVD) has become a noteworthy issue. Dilated perivascular spaces (dPVS) are an important marker of CSVD, of which cerebral atrophy has been regarded as one of the pathological mechanisms. DPVS has been found to be associated with vascular stenosis in patients with moyamoya disease (MMD), but the underlying mechanism remains unclear. The purpose of our study was to explore the correlation between the middle cerebral artery (MCA) stenosis and dPVS in the centrum semiovale (CSO-dPVS) in patients with MMD/moyamoya syndrome (MMS) and to determine whether brain atrophy plays a mediating role in this relationship. Methods: A total of 177 patients were enrolled in a single-center MMD/MMS cohort. Images of their 354 cerebral hemispheres were divided into three groups according to dPVS burden: mild (dPVS 0-10), moderate (dPVS 11-20), and severe (dPVS > 20). The correlations among cerebral hemisphere volume, MCA stenosis, and CSO-dPVS were analyzed, adjusting for the confounding factors of age, gender, and hypertension. Results: After adjustment for age, gender, and hypertension, the degree of MCA stenosis was independently and positively associated with ipsilateral CSO-dPVS burden (standardized coefficient: ß = 0.247, P < 0.001). A stratified analysis found that the subgroup with a severe CSO-dPVS burden exhibited a significantly higher risk of severe stenosis of the MCA [p < 0.001, OR = 6.258, 95% CI (2.347, 16.685)]. No significant correlation between CSO-dPVS and ipsilateral hemisphere volume was found (p = 0.055). Conclusion: In our MMD/MMS cohort, there was a clear correlation between MCA stenosis and CSO-dPVS burden, which may be a direct effect of large vessel stenosis, without a mediating role of brain atrophy.

Comparing characteristics and outcomes of in-hospital stroke and community-onset stroke.

BACKGROUND: In-hospital strokes account for 4-17% of all strokes and usually lead to urgent and severe conditions. However, features of in-hospital strokes have been scarcely reported in China, and the management systems of in-hospital strokes are unestablished. The study aims to analyze the characteristics of in-hospital strokes in comparison to community-onset strokes and provides evidence for the development of national in-patient stroke care systems. METHODS: We retrospectively analyzed consecutive patients with in-hospital strokes (IHS group) and community-onset strokes (COS group) hospitalized in our hospital between June 2012, and January 2022. Clinical characteristics, care measures, and outcomes were compared between the two groups. RESULTS: A total of 1162 patients (age 61 ± 16 and 65% male) were included, of whom 193 (16.6%) had an in-hospital stroke and 969 (83.4%) had community-onset stroke. Compared with COS group, patients in IHS group had higher NIHSS at onset (7.25 vs 5.96, P = 0.054), higher use of endovascular therapy (10.4% vs 2.0%, P < 0.001), and lower use of intravascular thrombolysis (1.6% vs 7.2%, P = 0.003). Also, in-hospital strokes were associated with lower rate of mRS0-2 at discharge (OR[95%CI] = 0.674[0.49, 0.926], P = 0.015) and increased in-hospital mobility (OR[95%CI] = 3.621[1.640, 7.996], P = 0.001), after adjusting for age, sex, and cardiovascular risk factors. CONCLUSION: Compared with community-onset strokes, the patients with in-hospital stroke had insufficient urgent treatment and poorer outcomes, reflecting the need for increased awareness of in-patient stroke, and strategies to streamline in-hospital acute stroke care.

Microbial Diversity Analyses of Fertilized Thitarodes Eggs and Soil Provide New Clues About the Occurrence of Chinese Cordyceps.

Chinese cordyceps is a well-known fungus-larva complex with medicinal and economic importance. At present the occurrence of Chinese cordyceps has not been fully illuminated. In this study, the microbial diversities of fertilized Thitarodes eggs from sites A (high occurrence rates of Chinese cordyceps), B (low occurrence rates), and C (no Chinese cordyceps) were analyzed using 16S rRNA and ITS gene-sequencing technique. The previous sequencing data of soil from the same sites were conjointly analyzed. The results showed that bacterial communities among the eggs were significantly different. The bacterial diversity and evenness were much higher on site A. Wolbachia was overwhelmingly predominant in the eggs of sites B and C, while Spiroplasma showed preference on site A. The fungal between-group differences in the eggs were not as significant as that of bacteria. Purpureocillium in Cordyceps-related families showed preference on site A. Wolbachia, Spiroplasma, and Purpureocillium were inferred to be closely related to Chinese cordyceps occurrence. Intra-kingdom and inter-kingdom network analyses suggest that closer correlations of microbial communities (especially closer fungal positive correlations) in fertilized eggs might promote Chinese cordyceps occurrence. Besides, metabolic pathway analysis showed that in fertilized eggs or soil the number of bacterial metabolic pathways with significant differences in every comparison between two sites was greater than that of fungi. Collectively, this study provides novel information about the occurrence of Chinese cordyceps, contributing to the large-scale artificial cultivation of Chinese cordyceps.

Fabry Disease with Aseptic Meningitis: A Case Series and Literature Review of an Underestimated Clinical Presentation.

OBJECTIVE: Fabry disease (FD) is an X-linked lysosomal storage disease caused by the mutation in the α-galactosidase A gene that leads to a consequently decreased α-galactosidase A enzyme activity and a series of clinical presentations. However, FD accompanied with aseptic meningitis can be relatively scarce and rarely reported, which leads to significant clinical misdiagnosis of this disease. METHODS: Sixteen patients diagnosed with FD based on a decreased activity of α-galactosidase A enzyme and/or genetic screening were identified through a 6-year retrospective chart review of a tertiary hospital. Clinical presentations, brain magnetic resonance imaging, cerebrospinal fluid analysis, treatment and outcome data were analyzed in cases of aseptic meningitis associated with FD. RESULTS: Three out of 16 cases exhibited aseptic meningitis associated with FD. There was one female and two male patients with a mean age of 33.3 years. A family history of renal failure or hypertrophic cardiomyopathy was found in 3 cases. All cases presented with a persistent or intermittent headache and recurrent ischemic stroke. The cerebrospinal fluid analyses showed mild pleocytosis in 2 patients and an elevated level of protein in all patients. Cerebrospinal fluid cytology revealed activated lymphocytes, suggesting the existence of aseptic meningitis. In the literature review, up to 9 cases presenting with FD and aseptic meningitis were found, which bore a resemblance to our patients in demographic and clinical characteristics. CONCLUSION: Our cases suggested that aseptic meningitis in FD might be under-detected and easily misdiagnosed, and should be more thoroughly examined in further cases.

Distinct lesion features and underlying mechanisms in patients with acute multiple infarcts in multiple cerebral territories.

Objective: To determine the etiology spectrum and lesion distribution patterns of patients with acute multiple infarcts in multiple cerebral territories (AMIMCT) and provide guidance for treatment and prevention strategies in these patients. Methods: Patients with acute ischemic stroke diagnosed using diffusion-weighted imaging (DWI) were consecutively included in this study between June 2012 and Apr 2022. AMIMCT was defined as non-contiguous focal lesions located in more than one cerebral territory with acute neurological deficits. We retrospectively analyzed the clinical and imaging characteristics, etiology spectra and underlying mechanisms in patients with and without AMIMCT. Infarct lesion patterns on DWI and their relevance to etiology were further discussed. Results: A total of 1,213 patients were enrolled, of whom 145 (12%) were diagnosed with AMIMCT. Patients with AMIMCT tended to be younger (P = 0.016), more often female (P = 0.001), and exhibited less common conventional vascular risk factors (P < 0.05) compared to those without AMIMCT. The constitution of the Trial of Org 10,172 in Acute Stroke Treatment classification was significantly different between patients with and without AMIMCT (P = 0.000), with a higher proportion of stroke of other determined causes (67.6% vs. 12.4%). For detailed etiologies, autoimmune or hematologic diseases were the most common (26.2%) etiologies of AMIMCT, followed by periprocedural infarcts (15.2%), cardioembolism (12.4%), tumor (12.4%), large artery atherosclerosis (10.3%), and sudden drop in blood pressure (8.3%). Hypercoagulability and systemic hypoperfusion are common underlying mechanisms of AMIMCT. Distinctive lesion distribution patterns were found associated with stroke etiologies and mechanisms in AMIMCT. Most of patients with large artery atherosclerosis (73.3%), autoimmune/hematologic diseases (57.9%) manifested the disease as multiple infarct lesions located in bilateral supratentorial regions. However, 66.7% of cardioembolism and 83.8% of cardiovascular surgery related stroke presented with both supratentorial and infratentorial infarct lesions. Conclusion: The etiologies and mechanisms of patients with AMIMCT were more complex than those without AMIMCT. The distribution characteristics of infarct lesions might have important implications for the identification of etiology and mechanism in the future, which could further guide and optimize clinical diagnostic strategies.

Relationship Between Serum Lipid Profiles and Carotid Intraplaque Neovascularization in a High-Stroke-Risk Population: A Cross-Sectional Study in China.

Background Evidence of the association between serum lipid profiles and intraplaque neovascularization (IPN) is still limited. We aimed to study the value of a novel Doppler method, superb microvascular imaging, in correlating serum lipid profiles and evidence of IPN in a population with a high risk of stroke. Methods and Results A community-based cross-sectional study was conducted in Beijing, China. Residents (aged ≥40 years) underwent questionnaire interviews, physical examinations, and laboratory testing in 2018 and 2019. Subjects with a high risk of stroke were then selected. Standard carotid ultrasound and carotid plaque superb microvascular imaging examinations were then performed on the high-stroke-risk participants. Logistic regression was used to evaluate the relationship between serum lipid profiles and carotid plaque IPN. Overall, a total of 250 individuals (mean age, 67.20±8.12 years; 66.4% men) met the study inclusion criteria. Superb microvascular imaging revealed carotid plaque IPN in 96 subjects (38.4%). Subjects with IPN were more likely to be current smokers (34.0% versus 46.9%, P=0.046), and their identified carotid plaques were much thicker (2.35±0.63 mm versus 2.75±0.80 mm, P=0.001). Serum lipids, including total cholesterol, non-high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were positively associated with the presence of IPN (4.33±1.00 mmol/L versus 4.79±1.12 mmol/L, P=0.001; 2.96±0.92 mmol/L versus 3.40±1.01 mmol/L, P=0.001; 2.18±0.76 mmol/L versus 2.46±0.80 mmol/L, P=0.005, respectively), and after adjustment for other confounders, the positive relationship remained significant. Furthermore, non-high-density lipoprotein cholesterol (odds ratio, 2.62 [95% CI, 1.35-5.06]) was significantly associated with the presence of carotid plaque IPN even after adjusting for low-density lipoprotein cholesterol. Conclusions Total cholesterol, non-high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were positively associated with the presence of carotid IPN in a Chinese high-stroke-risk population. Further prospective studies should be conducted to better understand how much finding IPN adds to current stroke prediction tools.

Movement disorders rounds: Atypical cases in two Chinese families with novel variants in ATP1A3.

ATP1A3-related dystonia is a disorder with high heterogeneous spectrum of clinical manifestations caused by mutations in ATP1A3 gene. Here, 2 atypical cases carring 2 de-novo ATP1A3 variants with RDP-CAPOS overlapping phenotype or continuous hemi-dystonia are described.

Assessment of Carotid Intraplaque Neovascularization Using Superb Microvascular Imaging in High Risk of Stroke Individuals: Results From a Community-Based Study.

Background: Improved stroke risk stratification may improve stroke prevention. We aimed to study the value of a novel Doppler method, superb microvascular imaging (SMI), in correlating plaque thickness and evidence of intra-plaque neovascularization with a history stroke and TIA involving any cerebrovascular territory among community residents considered at high stroke risk. Methods: We selected residents aged at least 40 years from the Donghuashi community in China who had at least three stroke risk factors (including a history of stroke or TIA) and carotid plaque thickness of at least 1.5 mm (but without heavy calcification) and no history of carotid endarterectomy or stenting. In this cross-sectional study, each subject underwent carotid plaque examination with standard ultrasound and SMI. SMI evidence of plaque neovascularization was categorized as none or mild (Grade 1) or moderate or marked (Grade 2) and correlated with past history of stroke or TIA. Results: A total of 131 individuals (mean age 69 ± 8 years, 63% male) met the study inclusion criteria. SMI revealed no or mild neovascularization in 74 subjects (56.5%) and moderate or marked neovascularization in 57 subjects (43.5%). Subjects with moderate or marked neovascularization were more likely to have a history of any territory stroke or TIA, 43.9 vs. 17.6% (P = 0.001). Multivariate logistic regression analyses showed a thicker plaque (odds ratio: 2.272, 95% CI: 1.351-3.822, P = 0.002) and a history of stroke or TIA (odds ratio: 4.017, 95% CI: 1.719-9.387, P = 0.001) significantly correlated with evidence of moderate to marked intra-plaque neovascularization. Conclusions: Moderate to marked intraplaque neovascularization detected by SMI was more likely in subjects with a history of any territory stroke or TIA or thicker plaque. This indicates a potential new role of SMI in stratifying future risk of stroke or other arterial disease complications.

Internal and External Microbial Community of the Thitarodes Moth, the Host of Ophiocordyceps sinensis.

Ophiocordyceps sinensis is a widely known medicinal entomogenous fungus, which parasitizes the soil-borne larva of Thitarodes (Hepialidae, Lepidoptera) distributed in the Qinghai-Tibetan Plateau and its adjacent areas. Previous research has involved artificial cultivation of Chinese cordyceps (the fungus-caterpillar complex), but it is difficult to achieve large-scale cultivation because the coupling relation between the crucial microbes and their hosts is not quite clear. To clarify the influence of the internal microbial community on the occurrence of Chinese cordyceps, in this study, the unfertilized eggs of Thitarodes of different sampling sites were chosen to analyze the bacterial and fungal communities via 16S rRNA and ITS sequencing for the first time. The results showed that for bacteria, 348 genera (dominant genera include Wolbachia, Spiroplasma, Carnobacterium, Sphingobium, and Acinetobacter) belonging to 26 phyla (dominant phyla include Proteobacteria, Firmicutes, Tenericutes, Actinobacteria, Acidobacteria, and Bacteroidetes), 58 classes, 84 orders, and 120 families were identified from 1294 operational taxonomic units (OTUs). The dominant bacterial genus (Spiroplasma) may be an important bacterial factor promoting the occurrence of Chinese cordyceps. For fungi, 289 genera, mainly including Aureobasidium, Candida, and Cryptococcus, were identified, and they belonged to 5 phyla (Ascomycota, Basidiomycota, Chytridiomycota, Glomeromycota, and Zygomycota), 26 classes, 82 orders, and 165 families. Eight bacterial OTUs and 12 fungal OTUs were shared among all of the detected samples and were considered as core species. Among them, Wolbachia, Spiroplasma, Carnobacterium, Aureobasidium, and Phoma may play important roles in helping the host larva to digest foods, adapt to extreme environments, or resist pathogens. On the other hand, the external (soil) microbial community was synchronously and comparatively analyzed. Comparative analysis revealed that external microbial factors might play a more significant role in the occurrence of Chinese cordyceps, owing to the significant differences revealed by α-diversity and ß-diversity analyses among different groups. In summary, the results of this study may contribute to the large-scale cultivation of Chinese cordyceps.

Diversity and Co-Occurrence Patterns of Soil Bacterial and Fungal Communities of Chinese Cordyceps Habitats at Shergyla Mountain, Tibet: Implications for the Occurrence.

Chinese Cordyceps is a well-known medicinal larva-fungus symbiote distributed in the Qinghai-Tibetan Plateau and adjacent areas. Previous studies have involved its artificial cultivation but commercial cultivation is difficult to perform because the crucial factors triggering the occurrence of Chinese Cordyceps are not quite clear. The occurrence of Chinese Cordyceps is greatly affected by the soil environment, including the soil's physicochemical and microecological properties. In this study, the effects of these soil properties on the occurrence of Chinese Cordyceps were investigated. The results show that the physicochemical properties, including easily oxidizable organic carbon (EOC), soil organic carbon (SOC), humic acid carbon (HAC), humin carbon (HMC), and pH, might be negatively related to the occurrence of Chinese Cordyceps, and soil water content (SWC) might be positively related. Several soil physicochemical parameters (pH, SOC, HMC, HAC, available potassium (APO), available phosphorus (APH), microbial biomass carbon (MBC), and the ratio of NH4+ to NO3- (NH4+/NO3-)) and microbial properties interact and mix together, which might affect the occurrence of Chinese Cordyceps. Soil microbial community structure was also a possible factor, and a low level of bacterial and fungal diversity was suitable for the occurrence of Chinese Cordyceps. The intra-kingdom network revealed that a closer correlation of the bacterial community might help the occurrence of Chinese Cordyceps, while a closer correlation of the fungal community might suppress it. The inter-kingdom network revealed that the occurrence rate of Chinese Cordyceps might be negatively correlated with the stability of the correlation state of the soil habitat. In conclusion, this study shows that soil physicochemical properties and microbial communities could be greatly related with the occurrence of Chinese Cordyceps. In addition, soil physicochemical properties, the level of bacterial and fungal diversity, and correlations of bacterial and fungal communities should be controlled to a certain level to increase the production of Chinese Cordyceps in artificial cultivation.

Public Awareness of Stroke and the Appropriate Responses in China: A Cross-Sectional Community-Based Study (FAST-RIGHT)

Background and Purpose­Early presentation is critical for receiving effective reperfusion therapy for acute ischemic stroke, therefore, we undertook a national survey of awareness and responses to acute stroke symptoms in China. Methods­We undertook a cross-sectional community-based study of 187 723 adults (age ≥40 years) presenting to 69 administrative areas across China between January 2017 and May 2017 to determine the national stroke recognition rate and the correct action rate. Multivariable logistic regression models were used to identify factors associated with stroke recognition and intention-to-avail emergency medical services. Results­Estimates of stroke recognition rate and correct action rate were 81.9% (153 675/187723) and 60.9% (114 380/187723), respectively, but these rates varied widely by sociodemographic status, region, and stroke risk. Approximately one-third of participants who recognized a stroke failed to call emergency medical service. Low likelihood of emergency medical service use was associated with younger age (40­59 years), being male, rural location, (regions of east, south, and northwest China), high body mass index (≥24), low education (primary school or below), low personal income (

Lesion Topography and Its Correlation With Etiology in Medullary Infarction: Analysis From a Multi-Center Stroke Study in China.

Objectives: The lesion topography of medullary infarction (MI) is heterogeneous and its correlation with stroke etiology remains elusive. We aim to clarify the lesion pattern of MI and to assess its correlation with stroke etiology. Material and Methods: Of 1129 subjects with available DWI in SMART study (a multi-center trial concerning secondary stroke prevention in China) between April 2008 and December 2010, 43 patients with DWI confirmed MI (3.8%) were retrospectively evaluated. Lesions were categorized as lateral and medial medullary infarction (LMI and MMI, 33 and 10 subjects respectively) at 3 levels rostro-caudally and correlated with the stroke etiology. Clinical profiles and long-term prognosis were analyzed. Results: Large artery atherosclerosis, small vessel occlusion, cardiogenic embolism and artery dissection accounted for 29, 11, 1, and 2 infarcts, respectively. Large artery disease was the most common cause in LMI (24 of 33, 72.7%) whereas small vessel occlusion was not uncommon in MMI (5 of 10, 50.0%). Though the difference of infarct pattern between large artery atherosclerosis and small vessel occlusion was insignificant, two distinct lesion patterns were considered to be relevant: (1) Rostral MMI with continuous medial pontine infarctions were more likely attributed to small vessel occlusion than large artery atherosclerosis. Kameda et al. (2) MMI with ventral to dorsal extension were more often caused by large artery disease than small vessel occlusion. Median NIHSS at admission was 4. During a median follow-up of 17 months, 2 patients died and 2 experienced recurrent ischemic events, 39 of 41 subjects (95.1%) were functional independent (mRS 0-2). Conclusions: This multi-center study demonstrates that MI has distinct lesion pattern depending on various stroke etiologies and mechanisms. Future investigations with larger sample size should establish the lesion pattern of MI and validate its correlation with the stroke etiology and mechanisms, which might improve stroke management.

Molecular cloning and functional characterization of cathepsin B from Nile tilapia (Oreochromis niloticus).

Cathepsin B (CatB) has been widely known for its hydrolytic ability and involvement in the innate immunity. However, the mechanism of CatB from teleosts participating in immunoregulation remains poorly understood; and the sequence of CatB from Nile tilapia (NtCatB) has not been cloned and characterized. In this study, the coding sequence of NtCatB was cloned, and then characterized by bioinformatic analysis and heterologous expression. The deduced amino acid sequence (330-aa) of NtCatB contains the representative features of CatB. Quantitative real-time PCR revealed the extensive mRNA expression of NtCatB in six tissues of healthy Nile tilapia, and its transcription level was significantly up-regulated after Streptococcus agalactiae challenge. NtCatB may interact with some immunological function proteins and take part in the regulatory pathway. These results suggest that NtCatB is likely to be involved in the immune reaction. The mature region (residues 79-328, mNtCatB) of NtCatB was cloned and transferred to pET-28a for expressing the recombinant protein. The purified recombinant mNtCatB was verified with the activity of 992.34 U mg-1 min-1 under the optimal condition using a substrate hydrolyzing assay. The recombinant cystatin-A1-like can effectively inhibit the activity of the recombinant mNtCatB, and their binding form was predicted by molecular docking. Our results contribute to elucidating the immunological functions of NtCatB.

Publisher Correction: Fungus-larva relation in the formation of Cordyceps sinensis as revealed by stable carbon isotope analysis.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Stable Carbon Isotope Composition of the Lipids in Natural Ophiocordyceps sinensis from Major Habitats in China and Its Substitutes.

Ophiocordyceps sinensis is one rare medicinal fungus produced in the Qinghai-Tibetan Plateau. Its quality and price varies hugely with different habitat, and its numerous substitutes have sprung up in functional food markets. This paper aims to discriminate the geographic origin of wild O. sinensis and its substitutes via element analyzer-isotope ratio mass spectrometry and gas chromatography-isotope ratio mass spectrometry. The δ13C values of major fatty acids in the lipids of O. sinensis are characterized unanimously by the variation relation C18:0 < C18:2 ≈ C16:0 < C18:1, while their fluctuation intervals are notably different between those of neutral and polar lipids. The comparative analysis of the δ13C ratios of major fatty acids in lipids of O. sinensis suggests that the δ13C patterns may be sensitive potential indicators to discriminate its geographical origin. The δ13C values of individual major fatty acids of lipids from the cultivated stromata of Cordyceps militaris (SCM), the fermented mycelia of Hirsurella sinensis (FMH) and Paecilomyces epiali (FMP) range from -31.2‰ to -29.7‰, -16.9‰ to -14.3‰, and -26.5‰ to -23.9‰, respectively. Their δ13C pattern of individual major fatty acids may be used as a potential indicator to discriminate the products of natural O. sinensis and its substitutes.

Association between large artery atherosclerosis and cerebral microbleeds: a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to provide evidence that biomarkers of large artery atherosclerosis, including arterial stenosis and greater carotid intima-media thickness (cIMT), may serve as clinical markers of subclinical haemorrhage-prone cerebral small vessel disease, reflected by cerebral microbleeds (CMBs). METHODS: We searched PubMed, MEDLINE, Web of Science, EMBASE and the Cochrane Library to identify relevant studies published before 1 July 2016. The association between arterial stenosis and CMBs was estimated by the OR and 95% CI. The association of cIMT and CMBs was calculated using the standardised mean difference (SMD). Heterogeneity and publication bias were explored. RESULTS: 8 studies including a total of 7160 participants were pooled in the meta-analysis. 6 of the included studies were cross-sectional, except that 2 were prospective. We found a significant association between arterial stenosis >50% and the presence of CMBs (OR 1.95, 95% CI 1.13 to 3.36, I2=56.1%). A fixed-effects model suggested that patients with CMBs were more likely to have a greater cIMT (SMD 0.20, 95% CI 0.11 to 0.28, I2=24.7%). CONCLUSIONS: This systematic review and meta-analysis found that there is a relationship between large artery atherosclerosis and CMBs. Future studies are needed to confirm the impact of atherosclerosis on the CMBs, which may have potential therapeutic implications.