Bronze Age cheese reveals human-Lactobacillus interactions over evolutionary history.

Despite the long history of consumption of fermented dairy, little is known about how the fermented microbes were utilized and evolved over human history. Here, by retrieving ancient DNA of Bronze Age kefir cheese (∼3,500 years ago) from the Xiaohe cemetery, we explored past human-microbial interactions. Although it was previously suggested that kefir was spread from the Northern Caucasus to Europe and other regions, we found an additional spreading route of kefir from Xinjiang to inland East Asia. Over evolutionary history, the East Asian strains gained multiple gene clusters with defensive roles against environmental stressors, which can be a result of the adaptation of Lactobacillus strains to various environmental niches and human selection. Overall, our results highlight the role of past human activities in shaping the evolution of human-related microbes, and such insights can, in turn, provide a better understanding of past human behaviors.

The risk factors of neuropathic pain in neuromyelitis optica spectrum disorder: a retrospective case-cohort study.

BACKGROUND: Neuropathic pain is a common complication in neuromyelitis optica spectrum disorder (NMOSD), which seriously affects the quality of life of NMOSD patients, with no satisfactory treatment. And risk factors of neuropathic pain are still uncertain. OBJECTIVE: To investigate the risk factors of neuropathic pain in a NMOSD cohort. MATERIALS AND METHODS: Our study was a retrospective case-cohort study, the patients diagnosed with NMOSD in the Department of Neurology from the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2011 to October 2021 were screened. Inclusion criteria were: (1) patients diagnosed as NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria, (2) the aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) test was performed. Patients without AQP4-IgG antibody were excluded. Clinical data, including sex, age of the first onset, symptoms of the first episode including neuropathic pain and attack types, localization of lesions of the first episode on Magnetic Resonance Imaging (MRI), Extended disability status Scale (EDSS) of the first onset, treatment of immunosuppression in the first acute phase, disease modifying therapy (DMT), treatment of neuropathic pain and APQ4-IgG status were collected from the hospital system database. Neuropathic pain was defined according to the International Association for the Study of Pain criteria and was described as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system". RESULTS: One hundred nineteen patients were screened and finally 86 patients fulfilling the inclusion and exclusion criteria were enrolled in our study. The prevalence of neuropathic pain in patients with NMOSD was 43.0%. Univariate analysis showed that the factors associated with neuropathic pain were the age at the onset, the attack type of optic neuritis, the attack type of myelitis, length of spinal cord involvement, localization of thoracic lesion, optic lesion, upper thoracic lesions, lower thoracic lesions, extended spinal cord lesions (≥ 3 spinal lesions), extended thoracic lesions (≥ 4 thoracic lesions), intravenous immunoglobulin and mycophenolate mofetil. Multivariate regression analysis showed that extended thoracic lesions (OR 20.21 [1.18-346.05], P = 0.038) and age (OR 1.35 (1-1.81) P = 0.050) were independently associated with neuropathic pain among NMOSD patients and that gender (OR 12.11 (0.97-151.64) P = 0.053) might be associated with neuropathic pain among NMOSD patients. CONCLUSION: Extended thoracic lesions (≥ 4 thoracic lesions), age and gender might be independent risk factors of neuropathic pain among patients with NMOSD. However, with a small sample size and predominantly female, caution must be applied and these results need validating in further cohorts.

High triglyceride is an independent predictor of high on-treatment platelet reactivity in ischemic stroke patients.

BACKGROUND: Previous studies have shown high triglyceride (TG) is associated with platelet hyperactivation in metabolic syndrome patients. However, limited information is available regarding this relationship on dual anti-platelet therapy (DAPT) in ischemic stroke (IS). In this study, we attempted to evaluate the association between TG and high on-treatment platelet reactivity (HTPR) in IS patients. METHODS: Ischemic stroke patients who received maintenance doses of clopidogrel and aspirin were categorized and analyzed retrospectively in this research. The platelet reactivity was assessed by Thromboelastography (TEG). If ADP-induced platelet inhibition rate (ADPi)<30%, it was defined as HTPR, else, it would be defined as normal on-treatment platelet reactivity (NTPR). Patients were divided into high-TG-level and lower-TG-level based on a TG level of 1.7mmol/L, the cutoff point of hypertriglyceridemia. A logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 123 patients were included in this study and 24 (19.51%) patients were identified as HTPR. HTPR was observed in 36.2% of the patients in high-TG-level (TG≥1.7mmol/L) group while only 9.2% of the patients in the low-TG-level group (TG<1.7mmol/L) were HTPR (P<0.001 ). According to multivariate analysis, TG≥1.7mmol/L was independently associated with HTPR (OR=14.715, 2.445-88.549,P=0.003). CONCLUSIONS: High TG is an independent predictor of HTPR in IS patients. For IS patients with high TG level undergoing DAPT, platelet reactivity should be monitored to identify HTPR, which may proactively help to optimize the anti-platelet therapy.

Exploration of adaptation, evolution and domestication of fermentation microorganisms by applying ancient DNA technology.

Fermentation production is the most primitive application of microorganisms by humans, which is of great significance in human history. However, due to the lack of molecular evidence, the history of human fermentation production and the evolution and domestication of fermentation microorganisms remain to be further investigated. Taking wine and fermented dairy, the two most common types of fermented foods as examples, we introduce the archaeology evidence of fermented foods and the evolution and domestication of fermented microorganisms, introduce the research status of paleomicrobiology and fermented paleomicroorganisms, and explore the feasibility and challenges of the research of ancient fermented microorganisms applying microbial ancient DNA technology, as well as the application potential of ancient DNA capture technology in this field.

[Therapeutic effect of Shengjiang Powder on experimental autoimmune encephalomyelitis mice through IL-6/JAK2/STAT3 signaling pathway:based on HPLC].

A high performance liquid chromatography(HPLC) method was established to analyze the components in Shengjiang Powder(SJP) such as emodin and curcumin and explore its therapeutic effect on experimental autoimmune encephalomyelitis(EAE) mice. To be specific, HPLC was performed to determine the content of compounds in SJP such as emodin and curcumin. A total of 72 female SPF C57 BL/6 mice were randomized into control group(equivalent volume of ultrapure water, ig), model group(equivalent volume of ultrapure water, ig), low-, medium-, and high-dose SJP groups(SJP, ig), and positive control group(prednisone acetate, ig), 12 each group. EAE was induced in mice except the control group. Administration began from the first day after immunization. The general conditions, symptom score, and body weight of the mice were recorded. On the 21 st day, mouse brain tissues were separrated. Then hematoxylin-eosin(HE) staining and Luxol Fast Blue(LFB) staining were used to detect the pathological changes of brain tissues. Immunohistochemistry(IHC) was employed to determine the myelin basic protein(MBP) level, and Western blot the expression of occludin and claudin-5, as well as the levels of interleukin-6(IL-6) and proteins in the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) pathway and their phosphorylation levels. The mRNA expression of IL-6, JAK2, and STAT3 was detected by real-time quantitative polymerase chain reaction(qPCR). Finally, molecular docking of six main active components in SJP, including emodin and curcumin, with IL-6, JAK2 and STAT3 was performed, and the binding affinity was evaluated. The results showed that the established HPLC method demonstrated high precision, reproducibility, stability, and high recovery of samples. Compared with the model group, SJP reduced the clinical symptom score and alleviate the inflammatory infiltration of brain white matter and demyelination of EAE mice. At the same time, SJP increased the expression of occludin and claudin-5, down-regulated the mRNA expression of IL-6, JAK2, and STAT3, as well as the levels of IL-6/JAK/STAT3 proteins and the phosphorylation levels, with significant difference. Molecular docking suggested that the six active components in SJP had high binding energy with IL-6, JAK2, and STAT3 proteins. The established HPLC method is simple, accurate, and highly sensitive, which can simultaneously determine the content of emodin and curcumin in SJP. SJP may alleviate the clinical symptoms of EAE by inhibiting IL-6/JAK2/STAT3 signaling pathway, protecting the blood-brain barrier, and relieving the inflammatory response and demyelinization of brain tissue.

Health Communication Through News Media During the Early Stage of the COVID-19 Outbreak in China: Digital Topic Modeling Approach.

BACKGROUND: In December 2019, a few coronavirus disease (COVID-19) cases were first reported in Wuhan, Hubei, China. Soon after, increasing numbers of cases were detected in other parts of China, eventually leading to a disease outbreak in China. As this dreadful disease spreads rapidly, the mass media has been active in community education on COVID-19 by delivering health information about this novel coronavirus, such as its pathogenesis, spread, prevention, and containment. OBJECTIVE: The aim of this study was to collect media reports on COVID-19 and investigate the patterns of media-directed health communications as well as the role of the media in this ongoing COVID-19 crisis in China. METHODS: We adopted the WiseSearch database to extract related news articles about the coronavirus from major press media between January 1, 2020, and February 20, 2020. We then sorted and analyzed the data using Python software and Python package Jieba. We sought a suitable topic number with evidence of the coherence number. We operated latent Dirichlet allocation topic modeling with a suitable topic number and generated corresponding keywords and topic names. We then divided these topics into different themes by plotting them into a 2D plane via multidimensional scaling. RESULTS: After removing duplications and irrelevant reports, our search identified 7791 relevant news reports. We listed the number of articles published per day. According to the coherence value, we chose 20 as the number of topics and generated the topics' themes and keywords. These topics were categorized into nine main primary themes based on the topic visualization figure. The top three most popular themes were prevention and control procedures, medical treatment and research, and global or local social and economic influences, accounting for 32.57% (n=2538), 16.08% (n=1258), and 11.79% (n=919) of the collected reports, respectively. CONCLUSIONS: Topic modeling of news articles can produce useful information about the significance of mass media for early health communication. Comparing the number of articles for each day and the outbreak development, we noted that mass media news reports in China lagged behind the development of COVID-19. The major themes accounted for around half the content and tended to focus on the larger society rather than on individuals. The COVID-19 crisis has become a worldwide issue, and society has become concerned about donations and support as well as mental health among others. We recommend that future work addresses the mass media's actual impact on readers during the COVID-19 crisis through sentiment analysis of news data.

An Innovative Artificial Intelligence-Based App for the Diagnosis of Gestational Diabetes Mellitus (GDM-AI): Development Study.

BACKGROUND: Gestational diabetes mellitus (GDM) can cause adverse consequences to both mothers and their newborns. However, pregnant women living in low- and middle-income areas or countries often fail to receive early clinical interventions at local medical facilities due to restricted availability of GDM diagnosis. The outstanding performance of artificial intelligence (AI) in disease diagnosis in previous studies demonstrates its promising applications in GDM diagnosis. OBJECTIVE: This study aims to investigate the implementation of a well-performing AI algorithm in GDM diagnosis in a setting, which requires fewer medical equipment and staff and to establish an app based on the AI algorithm. This study also explores possible progress if our app is widely used. METHODS: An AI model that included 9 algorithms was trained on 12,304 pregnant outpatients with their consent who received a test for GDM in the obstetrics and gynecology department of the First Affiliated Hospital of Jinan University, a local hospital in South China, between November 2010 and October 2017. GDM was diagnosed according to American Diabetes Association (ADA) 2011 diagnostic criteria. Age and fasting blood glucose were chosen as critical parameters. For validation, we performed k-fold cross-validation (k=5) for the internal dataset and an external validation dataset that included 1655 cases from the Prince of Wales Hospital, the affiliated teaching hospital of the Chinese University of Hong Kong, a non-local hospital. Accuracy, sensitivity, and other criteria were calculated for each algorithm. RESULTS: The areas under the receiver operating characteristic curve (AUROC) of external validation dataset for support vector machine (SVM), random forest, AdaBoost, k-nearest neighbors (kNN), naive Bayes (NB), decision tree, logistic regression (LR), eXtreme gradient boosting (XGBoost), and gradient boosting decision tree (GBDT) were 0.780, 0.657, 0.736, 0.669, 0.774, 0.614, 0.769, 0.742, and 0.757, respectively. SVM also retained high performance in other criteria. The specificity for SVM retained 100% in the external validation set with an accuracy of 88.7%. CONCLUSIONS: Our prospective and multicenter study is the first clinical study that supports the GDM diagnosis for pregnant women in resource-limited areas, using only fasting blood glucose value, patients' age, and a smartphone connected to the internet. Our study proved that SVM can achieve accurate diagnosis with less operation cost and higher efficacy. Our study (referred to as GDM-AI study, ie, the study of AI-based diagnosis of GDM) also shows our app has a promising future in improving the quality of maternal health for pregnant women, precision medicine, and long-distance medical care. We recommend future work should expand the dataset scope and replicate the process to validate the performance of the AI algorithms.

Risk factors of neuropathic pain in multiple sclerosis: a retrospective case-cohort study.

Background: Pain is a common symptom in multiple sclerosis (MS), especially neuropathic pain, which has a significant impact on patients' mental and physical health and quality of life. However, risk factors that related to neuropathic pain, still remain unclear. Objective: The study aimed to explore the risk factors of neuropathic pain among MS patients. Materials and methods: This retrospective study examined the consecutive patients diagnosed with MS in the Department of Neurology of Guangdong Provincial Hospital of Chinese Medicine between August 2011 and October 2022. Neuropathic pain was defined as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system". Demographic and clinical features were obtained from the electronic system of the hospital. Results: Our cohort revealed that the prevalence of patients with neuropathic pain in MS was 34.1%. The results indicated that the longer the spinal lesions, the greater the neuropathic pain risks (2-4: OR, 13.3(2.1-82), >5: OR, 15.2(2.7-86.8), p for tread: 0.037). Meanwhile, multivariate regression analysis showed that cervical and thoracic lesions (OR 4.276, 95% CI 1.366-13.382, P = 0.013), upper thoracic lesions (T1-T6) (OR 3.047, 95% CI 1.018-9.124, P = 0.046) were positively correlated with neuropathic pain, while basal ganglia lesions (OR 0.188, 95% CI 0.044-0.809, P = 0.025) were negatively correlated with neuropathic pain among MS patients. Conclusion: Extended spinal lesions (≥3 spinal lesions), cervical and thoracic lesions, upper thoracic lesions were independent risk factors of neuropathic pain among MS patients. Furthermore, our study found that the longer the spinal lesions, the greater the neuropathic pain risks.

Gut microbiota as predictors of the occurrence of high on-treatment platelet reactivity in acute ischemic stroke patients.

Introduction: In this study, we aimed to investigate the association between gut microbiota and high on-treatment platelet reactivity (HTPR) in patients with acute ischemic stroke (AIS). Methods: We enrolled a total of 48 AIS patients, including 19 HTPR patients and 29 non-high on-treatment platelet reactivity (NHTPR) patients, along with 10 healthy controls. Clinical and laboratory data, as well as stool samples, were collected from all participants. The composition and function of gut microbiota were assessed using 16S rRNA sequencing. Differences in the gut microbiota between the two groups were analyzed, and a diagnostic model based on the gut microbiota was established using random forest model. Results: HTPR patients exhibited a decreased microbial richness compared to NHTPR patients. Additionally, the relative abundance of unidentified_Clostridia and Ralstonia was lower in HTPR patients. Significant differences in biological functions, such as toxoplasmosis, were observed between the two groups. The combination of Ralstonia, unidentified-Clostridia, Mailhella, Anaerofustis, and Aggregatibacter showed excellent predictive ability for HTPR occurrence (AUC=0.896). When comparing AIS patients with healthy controls, alterations in the microbiota structure were observed in AIS patients, with imbalances in short-chain fatty acid-producing bacteria and pathogenic bacteria. Significant differences in biological functions, such as oxidative phosphorylation, were noted between the two groups. The combination of Alloprevotella, Terrisporobacter, Streptococcus, Proteus, and unidentified_Bacteria exhibited strong predictive power for AIS occurrence (AUC=0.994). Conclusions: This study is the first to uncover the microbial characteristics of HTPR in AIS patients and demonstrate the predictive potential of specific bacterial combinations for HTPR occurrence.

Network Pharmacology Experiments Show That Emodin Can Exert a Protective Effect on MCAO Rats by Regulating Hif-1α/VEGF-A Signaling.

Modern pharmacological studies have shown that emodin, the main effective component of rhubarb, has good anti-inflammatory and antioxidant effects, but its pharmacodynamic mechanism remains unclear yet. This study aims to elucidate the multitarget action mechanism of emodin in ischemic stroke through network pharmacology and in vivo experiments. Sprague-Dawley rats were randomly divided into control (normal saline), sham (normal saline), model (normal saline), and emodin groups (n = 9 per group). Emodin was administered at 40 mg/kg/d for 3 consecutive days. The rats were subjected to middle cerebral artery occlusion for 2 h, followed by reperfusion for 24 h to establish the cerebral ischemia-reperfusion injury. To search for relevant studies in databases, emodin, ischemic stroke, and stroke were used as keywords. Subsequently, protein-protein interaction networks and complex disease target networks were established, and an enrichment analysis and molecular docking of core targets were performed. Gene expression was detected through western blotting and reverse-transcription polymerase chain reaction. Localization and expression of proteins were detected through immunohistochemistry. Furthermore, the neurological function, 2,3,5-triphenyltetrazolium chloride staining, levels of brain tissue inflammatory factors, the role of the blood-brain barrier (BBB), and relevant signaling pathways were assessed in vivo. The molecular docking of core targets revealed that the docking between vascular endothelial growth factor A (VEGF-A) and emodin was the most efficient. Emodin pretreatment decreased the neurological score from 2.875 to 1.125. Moreover, emodin inhibited the degradation of occludin and claudin-5 caused by matrix metalloprotein kinase (MMP)-2/MMP-9, thereby protecting the BBB. Additionally, related proteins such as hypoxia-inducible factor-1α/VEGF-A and nuclear factor kappa B were down-regulated. Thus, emodin may play a protective role during cerebral ischemia reperfusion through mediation of the Hif-1α/VEGF-A signaling pathway to inhibit the expression of inflammatory factors.

Protecting effect of emodin in experimental autoimmune encephalomyelitis mice by inhibiting microglia activation and inflammation via Myd88/PI3K/Akt/NF-κB signalling pathway.

Experimental autoimmune encephalomyelitis (EAE) is characterized by demyelination of the central nervous system. Emodin is an anthraquinone derivative with comprehensive anti-inflammatory, anti-cancer, and immunomodulatory effects and is widely used in the treatment of inflammatory, tumor, and immune system diseases. However, none of the clinical or experimental studies have explored the therapeutic efficacy of emodin in EAE/multiple sclerosis (MS). Thus, we evaluated the protective effect of emodin on EAE mediated via inhibition of microglia activation and inflammation. Wild-type mice were randomly divided into the normal control, EAE, low-dose emodin, and high-dose emodin groups. Clinical scores and pathological changes were assessed 21 days after immunization. The network pharmacology approach was used to elucidate the underlying mechanisms by using an online database. Molecular docking, polymerase-chain reaction tests, western blotting, and immunofluorescence were performed to verify the network pharmacology results. An in vivo experiment showed that high-dose emodin ameliorated clinical symptoms, inflammatory cell infiltration, and myelination. Pharmacological network analysis showed AKT1 was the main target and that emodin played a key role in MS treatment mainly via the PI3K-Akt pathway. Molecular docking showed that emodin bound well with PI3K, AKT1, and NFKB1. Emodin decreased the expression of phosphorylated(p)-PI3K, p-Akt, NF-κB, and myeloid differentiation factor 88 and the levels of markers (CD86 and CD206) in M1- and M2-phenotype microglia in EAE. Thus, the emodin inhibited microglial activation and exhibited anti-inflammatory and neuroprotective effects against EAE via the Myd88/PI3K/Akt/NF-κB signalling pathway. In conclusion, emodin has a promising role in EAE/MS treatment, warranting further detailed studies.

Health Communication About Hospice Care in Chinese Media: Digital Topic Modeling Study.

BACKGROUND: Hospice care, a type of end-of-life care provided for dying patients and their families, has been rooted in China since the 1980s. It can improve receivers' quality of life as well as ease their economic burden. The Chinese mass media have continued to actively dispel misconceptions surrounding hospice care and deliver the latest information to citizens. OBJECTIVE: This study aims to retrieve and analyze news reports on hospice care in order to gain insight into whether any differences existed in heath information delivered over time and to evaluate the role of mass media in health communication in recent years. METHODS: We searched the Huike (WiseSearch) news database for relevant news reports from Chinese mass media released between 2014 and 2019. We defined two time periods for this study: (1) January 1, 2014, to December 31, 2016, and (2) January 1, 2017, to December 31, 2019. The data cleaning process was completed using Python. We determined appropriate topic numbers for these two periods based on the coherence score and applied latent Dirichlet allocation topic modeling. Keywords for each topic and corresponding topics' names were then generated. The topics were plotted into different circles, and their distances on the 2D plane was represented by multidimensional scaling. RESULTS: After removing duplicated and irrelevant news articles, we obtained a total of 2227 articles. We chose 8 as the suitable topic number for both study periods and generated topic names and associated keywords. The top 3 most reported topics in the first period were patient treatment, hospice care stories, and development of health care services and health insurance, accounting for 18.68% (178/953), 16.58% (158/953), and 14.17% (135/953) of the collected reports, respectively. The top 3 most reported topics in the second period were hospice care stories, patient treatment, and development of health care services, accounting for 15.62% (199/953), 15.38% (15.38/953), and 14.27% (182/953), respectively. CONCLUSIONS: Topic modeling of news reports gives us a better understanding of the patterns of health communication about hospice care by mass media. Chinese mass media frequently reported on hospice care in April of every year on account of a traditional Chinese festival. Moreover, an increase in coverage was observed in the second period. The two periods shared 6 similar topics, of which patient treatment outstrips hospice care stories was the most reported topic in the second period, implying the humanistic spirit behind the reports. Based on the findings of this study, we suggest stakeholders cooperate with the mass media when planning to update policies.