Multi-feature, Chinese-Western medicine-integrated prediction model for diabetic peripheral neuropathy based on machine learning and SHAP.

BACKGROUND: Clinical studies have shown that diabetic peripheral neuropathy (DPN) has been on the rise, with most patients presenting with severe and progressive symptoms. Currently, most of the available prediction models for DPN are derived from general clinical information and laboratory indicators. Several Traditional Chinese medicine (TCM) indicators have been utilised to construct prediction models. In this study, we established a novel machine learning-based multi-featured Chinese-Western medicine-integrated prediction model for DPN using clinical features of TCM. MATERIALS AND METHODS: The clinical data of 1581 patients with Type 2 diabetes mellitus (T2DM) treated at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine were collected. The data (including general information, laboratory parameters and TCM features) of 1142 patients with T2DM were selected after data cleaning. After baseline description analysis of the variables, the data were divided into training and validation sets. Four prediction models were established and their performance was evaluated using validation sets. Meanwhile, the accuracy, precision, recall, F1 score and area under the curve (AUC) of ROC were calculated using ten-fold cross-validation to further assess the performance of the models. An explanatory analysis of the results of the DPN prediction model was carried out using the SHAP framework based on machine learning-based prediction models. RESULTS: Of the 1142 patients with T2DM, 681 had a comorbidity of DPN, while 461 did not. There was a significant difference between the two groups in terms of age, cause of disease, systolic pressure, HbA1c, ALT, RBC, Cr, BUN, red blood cells in the urine, glucose in the urine, and protein in the urine (p < 0.05). T2DM patients with a comorbidity of DPN exhibited diverse TCM symptoms, including limb numbness, limb pain, hypodynamia, thirst with desire for drinks, dry mouth and throat, blurred vision, gloomy complexion, and unsmooth pulse, with statistically significant differences (p < 0.05). Our results showed that the proposed multi-featured Chinese-Western medicine-integrated prediction model was superior to conventional models without characteristic TCM indicators. The model showed the best performance (accuracy = 0.8109, precision = 0.8029, recall = 0.9060, F1 score = 0.8511, and AUC = 0.9002). SHAP analysis revealed that the dominant risk factors that caused DPN were TCM symptoms (limb numbness, thirst with desire for drinks, blurred vision), age, cause of disease, and glycosylated haemoglobin. These risk factors were exerted positive effects on the DPN prediction models. CONCLUSIONS: A multi-feature, Chinese-Western medicine-integrated prediction model for DPN was established and validated. The model improves early-stage identification of high-risk groups for DPN in the diagnosis and treatment of T2DM, while also providing informative support for the intelligent management of chronic conditions such as diabetes.

Studies on the humic acid structure and microbial nutrient restriction mechanism during organic-inorganic co-composting.

The effects of inorganic fertilizer addition method on the organic-inorganic co-composting process, especially the structure of humic acid and the mechanism of microbial nutrient restriction, are unclear. In this article, the effects of one-time and fractional addition of inorganic fertilizer on the structure of humic acid, extracellular enzyme activity, extracellular enzyme stoichiometry and the culturable growth-promoting bacteria during organic-inorganic co-composting were determined. The results showed that the addition of inorganic fertilizer promoted the humification degree of compost. Compared nitrogen with phosphorus, the fermentation microorganism behaved as N-restricted throughout the process. Compared one-time addition with fractional addition of inorganic treatments, the TOC, WSOC, NO3--N and humic acid content in the mature compost of the one-time addition treatment were higher. The contents of nitrogen, oxygen, the carboxyl functional groups, aromatic compounds, and the nitrogen/carbon atomic ratio in the humic acid structure increased as the composting process proceeded, while the contents of hydrogen, aliphatic substances, and the hydrogen/carbon atomic ratio decreased, and the elemental composition and structural changes of humic acids indicated that the humification degree of the one-time addition treatment was higher. The addition of inorganic fertilizer increased the relative abundances of Bacillus megaterium and Bacillus subtilis in the mature compost.

Soil Conditioner Affects Tobacco Rhizosphere Soil Microecology.

Reasonable fertilization management can increase nutrient content and enzyme activity in rhizosphere soil, and even increase soil microbial richness. However, different fertilizers could raise distinct influences on the soil properties, including soil environmental factors (physicochemical properties and enzymatic activities) and microbial community. Here, the effects of two soil amendments (microbial fertilizer and woody peat) on environmental factors and microbial community structure in tobacco rhizosphere soil were evaluated, with the correlations between microbes and environmental factors explored. As the results, microbial fertilizer could effectively alleviate soil acidification, increase available potassium and organic matter contents in soil, and was also beneficial to increase nitrate reductase activity in rhizosphere soil. Fertilizers cause changes in the abundance of certain microbes in the soil. Besides, it was shown that the candidate phyla Gal15, Acidobacterota, Latescibacterota, Mortierellommycota, Basidiomycota, and Rozellomycota in tobacco rhizosphere soil had significant correlation with soil environmental factors. Through the functional analysis of these populations, it can be deduced that the changes in the abundance of certain microorganisms may be an important reason for the differences in environmental factors. All these indicated that the differences of environmental factors in different treatments are closely related to the abundance of some special soil microorganisms. Studying the life activities of these microbes would provide good guidance for exploring the interaction among crops, soil, and microorganisms and improving crop yields.

[Prescription and medication rules of traditional Chinese medicine for prevention and treatment of diabetic microangiopathy based on literature mining].

This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.

Effects of School Resumption on College Students' Mental Health During the COVID-19 Pandemic.

The current study aimed to investigate the effects of school resumption on college students' mental health during the coronavirus disease 2019 (COVID-19) pandemic. We used the Perceived Stress Scale (PSS-10), Patient Health Questionnaire-9 (PHQ-9), and Self-Rating Anxiety Scale (SAS) to assess stress, depression, and anxiety, respectively, between same-age college students returning to school and those not returning to school. Of 1,598 students who completed the baseline survey (S1), 836 students completed a follow-up survey 10 months after school resumption (S2). There were statistically significant differences in stress and mild anxiety between male and female students (p < 0.01). Comparison of PSS-10, PHQ-9, and SAS scores by perceived impact of COVID-19 showed significant differences (Welch test, p < 0.01). The correlation between PHQ-9 and SAS scores in school resumption and non-school resumption groups was relatively strong (adjusted R2 = 0.49 vs. 0.5). Multivariate linear regression showed that only PSS-10 (p < 0.01) and SAS (p < 0.05) scores significantly differed between returning and non-returning students. School resumption was an independent risk factor for PSS-10 and SAS scores. PSS-10, PHQ-9, and SAS scores were significantly higher in S1 than in S2 (p < 0.01). During the COVID-19 pandemic, stress, anxiety, and depression were prevalent among college students; however, stress and anxiety were generally lower among college students returning to school than among non-returning students. [Journal of Psychosocial Nursing and Mental Health Services, 60(5), 19-27.].

Acupuncture for functional gastrointestinal disorders: A systematic review and meta-analysis.

OBJECTIVES: The therapeutic effect of acupuncture treatments (AT) on functional gastrointestinal disorders (FGIDs) is contentious. A meta-analysis was conducted to assess the efficacy and safety of acupuncture for FGIDs. METHODS: The Cochrane Library, EMBASE, PUBMED, Web of Science, Wanfang Database, China National Knowledge Infrastructure, and VIP Database were searched through December 31, 2019 with no language restrictions. Risk ratio (RR) with 95% confidence interval (CI) was calculated to determine the improvement in symptom severity after treatment. RESULTS: A total of 61 randomized controlled trials (RCTs) on FGIDs were included. The pooled results illustrated the following: compared to pharmacotherapy (RR 1.13, 95% CI 1.09-1.17), placebo acupuncture (RR 1.69, 95% CI 1.37-2.08), no specific treatment (RR 1.86, 95% CI 1.31-2.62), and AT as an adjuvant intervention to other active treatments (RR 1.25, 95% CI 1.21-1.30), AT had more favorable improvements in symptom severity; sub-group analysis results classified according to functional dyspepsia, irritable bowel syndrome, and functional constipation also supported this finding; and the incidence of adverse events was lower in AT than in other treatments (RR 0.75, 95% CI 0.56-0.99). CONCLUSIONS: This meta-analysis found that AT was significantly associated with relief of FGIDs symptoms; however, the evidence level was moderate or low. Further data from rigorously designed and well powered RCTs are needed to verify the effectiveness and safety of AT as a FGIDs treatment. PROSPERO PROTOCOL NUMBER: CRD42020169508.

Characterization of Nuclear and Mitochondrial Genomes of Two Tobacco Endophytic Fungi Leptosphaerulina chartarum and Curvularia trifolii and Their Contributions to Phylogenetic Implications in the Pleosporales.

The symbiont endophytic fungi in tobacco are highly diverse and difficult to classify. Here, we sequenced the genomes of Curvularia trifolii and Leptosphaerulina chartarum isolated from tobacco plants. Finally, 41.68 Mb and 37.95 Mb nuclear genomes were sequenced for C. trifolii and L. chartarum with the scaffold N50, accounting for 638.94 Kb and 284.12 Kb, respectively. Meanwhile, we obtained 68,926 bp and 59,100 bp for their mitochondrial genomes. To more accurately classify C. trifolii and L. chartarum, we extracted seven nuclear genes and 12 mitochondrial genes from these two genomes and their closely related species. The genes were then used for calculation of evolutionary rates and for phylogenetic analysis. Results showed that it was difficult to achieve consistent results using a single gene due to their different evolutionary rates, while the phylogenetic trees obtained by combining datasets showed stable topologies. It is, therefore, more accurate to construct phylogenetic relationships for endophytic fungi based on multi-gene datasets. This study provides new insights into the distribution and characteristics of endophytic fungi in tobacco.

Efficacy of acupuncture in the management of post-apoplectic aphasia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Aim of this study was to evaluate the effectiveness of scalp, tongue, and Jin's 3-needle acupuncture for the improvement of postapoplectic aphasia. METHOD: PubMed, Cochrane, Embase databases were searched using index words to identify qualifying randomized controlled trials (RCTs). Meta-analyses of odds ratios (OR) or standardized mean differences (SMD) were performed to evaluate the outcomes between investigational (scalp / tongue / Jin's 3-needle acupuncture) and control (traditional acupuncture; TA and/or rehabilitation training; RT) groups. RESULTS: Thirty-two RCTs (1310 participants in investigational group and 1270 in control group) were included. Compared to TA, (OR 3.05 [95% CI: 1.77, 5.28]; p<0.00001), tongue acupuncture (OR 3.49 [1.99, 6.11]; p<0.00001), and Jin's 3-needle therapy (OR 2.47 [1.10, 5.53]; p = 0.03) had significantly better total effective rate. Compared to RT, scalp acupuncture (OR 4.24 [95% CI: 1.68, 10.74]; p = 0.002) and scalp acupuncture with tongue acupuncture (OR 7.36 [3.33, 16.23]; p<0.00001) had significantly better total effective rate. In comparison with TA/RT, scalp acupuncture, tongue acupuncture, scalp acupuncture with tongue acupuncture, and Jin's three-needling significantly improved ABC, oral expression, comprehension, writing and reading scores. CONCLUSION: As treatments to postapoplectic aphasia, scalp / tongue acupuncture and Jin's Three-needling are found better than TA and/or RT in yielding total effective rate and improving ABC, oral expression, comprehension, reading and writing scores.

Composition and Genetic Diversity of the Nicotiana tabacum Microbiome in Different Topographic Areas and Growth Periods.

Fungal endophytes are the most ubiquitous plant symbionts on earth and are phylogenetically diverse. Studies on the fungal endophytes in tobacco have shown that they are widely distributed in the leaves, stems, and roots, and play important roles in the composition of the microbial ecosystem of tobacco. Herein, we analyzed and quantified the endophytic fungi of healthy tobacco leaves at the seedling stage (SS), resettling growth stage (RGS), fast-growing stage (FGS), and maturing stage (MS) at three altitudes (600, 1000, and 1300 m). We sequenced the internal transcribed spacer (ITS) region of fungal samples to delimit operational taxonomic units (OTUs) and phylogenetically characterize the communities. The results showed that the numbers of clustering OTUs at SS, RGS, FGS, and MS were 516, 709, 469, and 428, respectively. At the phylum level, species in Ascomycota and Basidiomycota had absolute predominance, representing 97.8% and 2.0% of the total number of species, respectively. We also found the number of fungi at the RGS and FGS stages was higher than those at the other two stages. Additionally, OTU richness was determined by calculating the Observed Species, Shannon, Simpson, Chao1, abundance-based coverage estimator (ACE), Good's coverage and phylogenetic distance (PD)_whole_tree indices based on the total number of species. Our results showed RGS samples had the highest diversity indices. Furthermore, we found that the diversity of fungal communities tended to decrease with increasing altitude. The results from this study indicated that tobacco harbors an abundant and diverse endophytic fungal community, which provides new opportunities for exploring their potential utilization.

Chemical Composition, Antioxidant Activity and α-Glucosidase Inhibitory Activity of Chaenomeles Speciosa from Four Production Areas in China.

Chaenomeles speciosa (Sweet) Nakai is a medicinal plant. Until date, there are no studies focusing on comparing the chemical profiles, antioxidant activity and α-glucosidase inhibitory activity of the dried fruits of C. speciosa from different production regions. In the study, we investigated the chemical components of dried fruits of C. speciosa from Yunnan, Chongqing, Zhejiang and Anhui provinces in China in relation to the antioxidant activity and α-glucosidase inhibitory activity. C. speciosa from Yunnan had higher total flavonoid (47.92 ± 3.79 mg/g), total polyphenol (29.15 ± 0.29 mg/g) and polysaccharide (27.60 ± 1.56 mg/g) contents than plants from other production areas. Samples from Yunnan, Zhejiang and Anhui (all > 3200 mg/kg) had higher free amino acid contents than those from Chongqing (2286.66 mg/kg). Oleanolic acid and ursolic acid levels were highest in samples from Zhejiang (555.98 ± 20.88 µg/g) and Anhui (321.06 ± 14.64 µg/g), respectively. C. speciosa from Chongqing had low total flavonoid, total polyphenol, polysaccharide, free amino acid, oleanolic acid and ursolic acid contents but high levels of palmitic acid (12.04 ± 0.02 mg/g) and stearic acid (2.23 ± 0.08 mg/g). Among four production areas, Yunnan represented the highest antioxidant activity and α-glucosidase inhibitory activity. In addition, correlation analysis revealed that total flavonoid, total polyphenol, polysaccharide and ursolic acid were the major components responsible for the antioxidant activity of C. speciosa, while total flavonoid and polysaccharide were the main contributors for α-glucosidase inhibitory activity of the plant. These results would be helpful for evaluating the quality of C. speciosa in the different production areas.

[Effects of Huangpu Tongqiao capsule on apoptosis of Alzheimer's disease cell model].

The loss of hippocampal neurons is one of the main pathological features of Alzheimer's disease (AD), which is related to the apoptosis of hippocampal neurons. Huangpu Tongqiao capsule is used for the treatment of AD, but the underlying mechanism is still unclear. This study is to investigate the mechanism of neuroprotective effect of Huangpu Tongqiao capsule in the treatment of AD, through observing the effect of Huangpu Tongqiao capsule containing serum on cell injury of primary cultured hippocampal neurons induced by Aß25₋35 via inhibiting the cell apoptosis. Primary cultured hippocampal neurons were cultured and identified by MAP-2 immunofluorescence staining, and cell growth state was observed by inverted microscope. The Huangpu Tongqiao capsule containing serum was prepared using the method of serum pharmacology. MTT assays were used to measure the optimum concentration range of Huangpu Tongqiao capsule containing serum, and optimum Aß concentration for establishing the AD model. After primary cultured hippocampal neurons AD cell model was induced by Aß25₋35, cell survival rate was detected by MTT, cell apoptosis rate was assayed by flow cytometry, and protein expressions of Bax, Cyt C and caspase-3 were determined by Western blot analysis. The results showed that the primary cultured hippocampal neurons were cultured successfully, and cells grew mature at seventh days; Compared with normal group, the survival rate of hippocampal neurons in AD cell model group was decreased, the apoptosis rate of hippocampal neurons was increased, and the protein expressions of Bax, Cyt C and caspase-3 were increased (P<0.05, P<0.01); Compared with AD cell model group, the survival rate of hippocampal neurons in Huangpu Tongqiao capsule containing serum group was increased, the apoptosis rate of hippocampal neurons was decreased, and the protein expressions of Bax, Cyt C and caspase-3 were decreased (P<0.05, P<0.01). These findings suggest that Huangpu Tongqiao capsule containing serum has a neuroprotective effect on cell injury of the primary cultured hippocampal neurons induced by Aß25₋35, and its effect on the treatment of AD is associated with the inhibition the apoptosis of hippocampal neurons.

[Protective effects of genistein on Aß25₋35-induced PC12 cell injury via regulating CaM-CaMKIV signaling pathway].

Genistein is a kind of isoflavone compounds， also called phytoestrogens， with clinical effects on cardiovascular disease， cancer and postmenopausal-related gynecological diseases， and also has the potentiality in the prevention and treatment of Alzheimer's disease(AD). In this study， the protective effect of genistein on Aß25₋35-induced PC12 cell injury and effect on CaM-CaMKIV signaling pathway were observed to investigate its mechanism for AD. PC12 cells were cultured in vitro and then the safe concentration of genistein and the modeling concentration and optimal time point of administration of Aß25₋35 were screened by MTT assay. After being pretreated with different concentrations of genistein(25， 50， 100 µmol·L⁻¹) on PC12 cells， the AD model of PC12 cells was induced by Aß25₋35. Then the survival rate of cells was detected by MTT assay; morphological change of cells was observed under the inverted microscope， and apoptosis of cells was assessed by AO/EB fluorescence staining; the neuroprotective effects of genistein on AD cell model were observed and the optimal concentration of genistein was determined. Expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau were detected by qRT-PCR and Western blot assay， respectively. The results showed that as compared with the blank group， the cell survival rate was decreased; the cell damage and apoptosis were increased; and the expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau were increased in AD model group. Genistein could significantly improve the cell survival rate， reduce the cell damage and apoptosis of AD cell model， and significantly down-regulate the expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau of AD cell model. These results indicated that genistein has obviously neuroprotective effect on the AD cell model induced by Aß25₋35， and the mechanism may be related to the down-regulation of CaM-CaMKIV signaling pathway and Tau protein expression.

[Research advances on astragaloside-IV in treatment of diabetes mellitus and its complications pharmacological effects].

Diabetes has become a global public health problem that seriously threatens human health. Traditional Chinese medicine, the characteristics of the role of multiple targets, has a unique advantage in the prevention and treatment of diabetes mellitus and its complications. Astragaloside-Ⅳ (AS-Ⅳ), one of the main activities of Astragalus membranaceus, has a series of pharmacological effects including improvement in the function of endothelial cells and neovascularization, anti-inflammatory, antioxidant, regulating energy metabolism, protectionnervous, anti-cancer and so on. In this paper, AS-Ⅳ to prevent and treat diabetes and its complications has been reviewed, which has effect on lowering blood sugar, lowering blood pressure, improving insulin resistance, inhibiting inflammatory reaction and oxidative stress. Additionally, it also can improve the diabetic animal and cell model of diabetic vascular disease, diabetic nephropathy, diabetic retinopathy, diabetic peripheral neuropathy, diabetic cardiomyopathy and other pathological damages. AS-Ⅳ may be a potential active substance for the treatment of diabetes and its complications.

Characterization of the neural circuitry of the auditory thalamic reticular nucleus and its potential role in salicylate-induced tinnitus.

Introduction: Subjective tinnitus, the perception of sound without an external acoustic source, is often subsequent to noise-induced hearing loss or ototoxic medications. The condition is believed to result from neuroplastic alterations in the auditory centers, characterized by heightened spontaneous neural activities and increased synchrony due to an imbalance between excitation and inhibition. However, the role of the thalamic reticular nucleus (TRN), a structure composed exclusively of GABAergic neurons involved in thalamocortical oscillations, in the pathogenesis of tinnitus remains largely unexplored. Methods: We induced tinnitus in mice using sodium salicylate and assessed tinnitus-like behaviors using the Gap Pre-Pulse Inhibition of the Acoustic Startle (GPIAS) paradigm. We utilized combined viral tracing techniques to identify the neural circuitry involved and employed immunofluorescence and confocal imaging to determine cell types and activated neurons. Results: Salicylate-treated mice exhibited tinnitus-like behaviors. Our tracing clearly delineated the inputs and outputs of the auditory-specific TRN. We discovered that chemogenetic activation of the auditory TRN significantly reduced the salicylate-evoked rise in c-Fos expression in the auditory cortex. Discussion: This finding posits the TRN as a potential modulatory target for tinnitus treatment. Furthermore, the mapped sensory inputs to the auditory TRN suggest possibilities for employing optogenetic or sensory stimulations to manipulate thalamocortical activities. The precise mapping of the auditory TRN-mediated neural pathways offers a promising avenue for designing targeted interventions to alleviate tinnitus symptoms.

Microglial activation in the lateral amygdala promotes anxiety-like behaviors in mice with chronic moderate noise exposure.

BACKGROUND: Long-term non-traumatic noise exposure, such as heavy traffic noise, can elicit emotional disorders in humans. However, the underlying neural substrate is still poorly understood. METHODS: We exposed mice to moderate white noise for 28 days to induce anxiety-like behaviors, measured by open-field, elevated plus maze, and light-dark box tests. In vivo multi-electrode recordings in awake mice were used to examine neuronal activity. Chemogenetics were used to silence specific brain regions. Viral tracing, immunofluorescence, and confocal imaging were applied to define the neural circuit and characterize the morphology of microglia. RESULTS: Exposure to moderate noise for 28 days at an 85-dB sound pressure level resulted in anxiety-like behaviors in open-field, elevated plus maze, and light-dark box tests. Viral tracing revealed that fibers projecting from the auditory cortex and auditory thalamus terminate in the lateral amygdala (LA). A noise-induced increase in spontaneous firing rates of the LA and blockade of noise-evoked anxiety-like behaviors by chemogenetic inhibition of LA glutamatergic neurons together confirmed that the LA plays a critical role in noise-induced anxiety. Noise-exposed animals were more vulnerable to anxiety induced by acute noise stressors than control mice. In addition to these behavioral abnormalities, ionized calcium-binding adaptor molecule 1 (Iba-1)-positive microglia in the LA underwent corresponding morphological modifications, including reduced process length and branching and increased soma size following noise exposure. Treatment with minocycline to suppress microglia inhibited noise-associated changes in microglial morphology, neuronal electrophysiological activity, and behavioral changes. Furthermore, microglia-mediated synaptic phagocytosis favored inhibitory synapses, which can cause an imbalance between excitation and inhibition, leading to anxiety-like behaviors. CONCLUSIONS: Our study identifies LA microglial activation as a critical mediator of noise-induced anxiety-like behaviors, leading to neuronal and behavioral changes through selective synapse phagocytosis. Our results highlight the pivotal but previously unrecognized roles of LA microglia in chronic moderate noise-induced behavioral changes.

Targeting the gut-microbiota-brain axis in irritable bowel disease to improve cognitive function - recent knowledge and emerging therapeutic opportunities.

The brain-gut axis forms a bidirectional communication system between the gastrointestinal (GI) tract and cognitive brain areas. Disturbances to this system in disease states such as inflammatory bowel disease have consequences for neuronal activity and subsequent cognitive function. The gut-microbiota-brain axis refers to the communication between gut-resident bacteria and the brain. This circuits exists to detect gut microorganisms and relay information to specific areas of the central nervous system (CNS) that in turn, regulate gut physiology. Changes in both the stability and diversity of the gut microbiota have been implicated in several neuronal disorders, including depression, autism spectrum disorder Parkinson's disease, Alzheimer's disease and multiple sclerosis. Correcting this imbalance with medicinal herbs, the metabolic products of dysregulated bacteria and probiotics have shown hope for the treatment of these neuronal disorders. In this review, we focus on recent advances in our understanding of the intricate connections between the gut-microbiota and the brain. We discuss the contribution of gut microbiota to neuronal disorders and the tangible links between diseases of the GI tract with cognitive function and behaviour. In this regard, we focus on irritable bowel syndrome (IBS) given its strong links to brain function and anxiety disorders. This adds to the growing body of evidence supporting targeted therapeutic strategies to modulate the gut microbiota for the treatment of brain/mental-health-related disease.

Low-level inflammation, immunity, and brain-gut axis in IBS: unraveling the complex relationships.

Irritable bowel syndrome is a common functional gastrointestinal disorder, and it has been shown that the etiology of irritable bowel syndrome is a multifactorial complex of neurological, inflammatory, and immunological changes. There is growing evidence of low-grade chronic inflammation in irritable bowel patients. The peripheral action response of their intestinal immune factors is integrated into the central nervous system, while the microbiota interacts with the brain-gut axis contributing to the development of low-grade chronic inflammation. The objective of this review is to present a discussion about the impact of immune-brain-gut axis-inflammation interactions on irritable bowel syndrome, its clinical relevance in the course of irritable bowel syndrome disease, and possible therapeutic modalities.

Effect on Satisfactory Seizure Control and Heart Rate Variability of Thread-Embedding Acupuncture for Drug-Resistant Epilepsy: A Patient-Assessor Blinded, Randomized Controlled Trial.

This randomized controlled trial investigates the efficacy of thread-embedding acupuncture (TEA) compared to sham TEA in treating drug-resistant epilepsy (DRE). Fifty-four DRE outpatients were randomly divided into two groups: TEA (27 patients) and sham TEA (27 patients). Both groups received four sessions of TEA or sham TEA, spaced four weeks apart, targeting GV20, GV14, BL15, BL18, ST40, and GB34 acupoints. Antiseizure medications were maintained at consistent doses throughout the study. Outcome measures included satisfactory seizure control, seizure freedom, and heart rate (HR) and heart rate variability (HRV) measurements. TEA demonstrated a significantly higher rate of satisfactory seizure control at follow-up compared to the sham TEA group (37% vs. 3.7%, p = 0.003). While no significant intergroup differences were observed in HR, HRV, and HRV components at each stage, the TEA group experienced a significant decrease in HR and a significant increase in HRV posttreatment. This study demonstrates TEA's effectiveness in managing DRE and suggests its impact may relate to heightened parasympathetic nerve activity. Further research with extended follow-up periods is necessary to validate these findings.

A neural circuit for gastric motility disorders driven by gastric dilation in mice.

Introduction: Symptoms of gastric motility disorders are common clinical manifestations of functional gastrointestinal disorders (FGIDs), and are triggered and exacerbated by stress, but the neural pathways underpinning them remain unclear. Methods: We set-up a mouse model by gastric dilation (GD) in which the gastric dynamics were assessed by installing strain gauges on the surface of the stomach. The neural pathway associated with gastric motility disorders was investigated by behavioral tests, electrophysiology, neural circuit tracing, and optogenetics and chemogenetics involving projections of the corticotropin-releasing hormone (CRH) from the paraventricular nucleus of the hypothalamus (PVN) to acetylcholine (ChAT) neurons in the dorsal motor nucleus of the vagus (DMV). Results: We found that GD induced gastric motility disorders were accompanied by activation of PVN CRH neurons, which could be alleviated by strategies that inhibits the activity of PVN CRH neurons. In addition, we identified a neural pathway in which PVN CRH neurons project into DMV ChAT neurons, modulated activity of the PVN CRH →DMV ChAT pathway to alleviate gastric motility disorders induced by GD. Discussion: These findings indicate that the PVN CRH →DMV ChAT pathway may mediate at least some aspects of GD related gastric motility, and provide new insights into the mechanisms by which somatic stimulation modulates the physiological functions of internal organs and systems.

A central amygdala input to the dorsal vagal complex controls gastric motility in mice under restraint stress.

Background/aims: Psychological and physiological stress can cause gastrointestinal motility disorders. Acupuncture has a benign regulatory effect on gastrointestinal motility. However, the mechanisms underlying these processes remain unclear. Methods: Herein, we established a gastric motility disorder (GMD) model in the context of restraint stress (RS) and irregular feeding. The activity of emotional center-central amygdala (CeA) GABAergic neurons and gastrointestinal center-dorsal vagal complex (DVC) neurons were recorded by electrophysiology. Virus tracing and patch clamp analysis of the anatomical and functional connection between the CeAGABA → dorsal vagal complex pathways were performed. Optogenetics inhibiting or activating CeAGABA neurons or the CeAGABA → dorsal vagal complex pathway were used to detect changes in gastric function. Results: We found that restraint stress induced delayed gastric emptying and decreased gastric motility and food intake. Simultaneously, restraint stress activated CeA GABAergic neurons, inhibiting dorsal vagal complex neurons, with electroacupuncture (EA) reversing this phenomenon. In addition, we identified an inhibitory pathway in which CeA GABAergic neurons project into the dorsal vagal complex. Furthermore, the use of optogenetic approaches inhibited CeAGABA neurons and the CeAGABA → dorsal vagal complex pathway in gastric motility disorder mice, which enhanced gastric movement and gastric emptying, whereas activation of the CeAGABA and CeAGABA → dorsal vagal complex pathway mimicked the symptoms of weakened gastric movement and delayed gastric emptying in naïve mice. Conclusion: Our findings indicate that the CeAGABA → dorsal vagal complex pathway may be involved in regulating gastric dysmotility under restraint stress conditions, and partially reveals the mechanism of electroacupuncture.