Neuroinflammatory responses play an important role in the pathogenesis of various diseases, particularly those affecting the central nervous system. Inhibition of neuroinflammation is a crucial therapeutic strategy for the management of central nervous system disorders. The intestinal microbial-gut-brain axis serves as a key regulatory pathway that modulates neuroinflammatory processes. Intestinal flora metabolites such as short-chain fatty acids, indoles and their derivatives, lipopolysaccharides, trimethylamine oxide, and secondary bile acids exert direct or indirect effects on neuroinflammation. Studies have shown that electroacupuncture (EA) modulates the composition of the intestinal microbiota and its metabolites, while also suppressing neuroinflammation by targeting the TLR4/NF- κ B, NLRP3/caspase-1, and microglial cell M2-type transformation pathways. This review discusses the mechanisms by which EA regulates neuroinflammation via intestinal microbiota and its metabolites, providing information and a foundation for further investigation of the precise therapeutic mechanisms of EA in neurological disorders.
Humans ; Gastrointestinal Microbiome ; Electroacupuncture ; Neuroinflammatory Diseases/metabolism* ; Animals

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective:By analyzing the differential miRNA in seminal plasma between individuals with normal and abnormal sperm DNA fragmentation index(DFI),we aim to identify miRNA that may impact sperm DNA integrity and target genes,and attempt to analyze their potential mechanisms of action.Methods:A total of 161 study subjects were collected and divided into normal con-trol group,DFI-medium group and DFI-abnormal group based on the DFI detection values.Differential miRNA were identified through miRNA chip analysis.Through bioinformatics analysis and target gene prediction,miRNA related to DFI and specific target genes were identified.The relative expression levels of differential miRNA and target genes in each group were compared to explore the impact of their differential expression on DFI.Results:Through miRNA chip analysis,a total of 11 differential miRNA were detected.Bioin-formatics analysis suggested that miR-26a-5p may be associated with reduced sperm DNA integrity.And gene prediction indicated that PTEN was a specific target gene of miR-26a-5p.Compared to the normal control group,the relative expression levels of miR-26a-5p in both the DFI-medium group and the DFI-abnormal group showed a decrease,while the relative expression levels of PTEN showed an in-crease.The relative expression levels of miR-26a-5p in all groups were negatively correlated with DFI values,while the relative expres-sion levels of PTEN showed a positive correlation with DFI values in the DFI-medium group and the DFI-abnormal group.The AUC of miR-26a-5p in the DFI-medium group was 0.740(P＜0.05),with a sensitivity of 73.6％and a specificity of 71.5％;the AUC of PTEN was 0.797(P＜0.05),with a sensitivity of 76.5％and a specificity of 78.4％.In the DFI-abnormal group,the AUC of miR-26a-5p was 0.848(P＜0.05),with a sensitivity of 81.3％and a specificity of 78.1％.While the AUC of PTEN was 0.763(P＜0.05),with a sensitivity of 77.2％and a specificity of 80.2％.Conclusion:miR-26a-5p affects the integrity of sperm DNA by regulating the expression of PTEN negatively.The relative expression levels of seminal plasma miR-26a-5p and PTEN have good diag-nostic value for sperm DNA integrity damage,which can help in the etiological diagnosis and prognosis analysis of abnormal DFI.This provides a diagnostic and treatment approach for the study and diagnosis of DFI abnormalities without clear etiology.

Objective:To evaluate the effect of acupuncture on postoperative delirium (POD) in diabetic patients undergoing surgery under general anesthesia.Methods:In this randomized controlled trial, 92 diabetic patients of either sex, aged 30-80 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective surgery under general anesthesia, were divided into 2 groups ( n=46 each) using a table of random numbers: control group (group C) and acupuncture group (group A). Group A received acupuncture at the Baihui (GV20), Shenting (GV24) and Sishencong (EX-HN1) acupoints before anesthesia. The needles were retained for 30 min, with manual stimulation applied every 10 min for 10 s each time. After 4 stimulations, routine anesthesia was carried out. Group C received routine anesthesia only. Regional cerebral oxygen saturation was recorded on admission to the operating room (T 0), after anesthesia induction (T 1), at the start of surgery (T 2), at the end of surgery (T 3), and immediately after tracheal extubation (T 4). The POD developed within 3 days after surgery was assessed. The occurrence of needle-related adverse effects such as fainting, subcutaneous bleeding, and local paresthesia was recorded. Results:Compared with group C, the incidence of POD was significantly reduced, and the regional cerebral oxygen saturation was increased at T 1, 4 in group A ( P<0.05). Conclusions:Acupuncture can decrease the development of POD in diabetic patients undergoing surgery under general anesthesia, which is related to an increase in regional cerebral oxygen saturation.

Objective:To evaluate the effect of acupuncture on postoperative delirium (POD) in diabetic patients undergoing surgery under general anesthesia.Methods:In this randomized controlled trial, 92 diabetic patients of either sex, aged 30-80 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective surgery under general anesthesia, were divided into 2 groups ( n=46 each) using a table of random numbers: control group (group C) and acupuncture group (group A). Group A received acupuncture at the Baihui (GV20), Shenting (GV24) and Sishencong (EX-HN1) acupoints before anesthesia. The needles were retained for 30 min, with manual stimulation applied every 10 min for 10 s each time. After 4 stimulations, routine anesthesia was carried out. Group C received routine anesthesia only. Regional cerebral oxygen saturation was recorded on admission to the operating room (T 0), after anesthesia induction (T 1), at the start of surgery (T 2), at the end of surgery (T 3), and immediately after tracheal extubation (T 4). The POD developed within 3 days after surgery was assessed. The occurrence of needle-related adverse effects such as fainting, subcutaneous bleeding, and local paresthesia was recorded. Results:Compared with group C, the incidence of POD was significantly reduced, and the regional cerebral oxygen saturation was increased at T 1, 4 in group A ( P<0.05). Conclusions:Acupuncture can decrease the development of POD in diabetic patients undergoing surgery under general anesthesia, which is related to an increase in regional cerebral oxygen saturation.

Objective This study aimed to comprehensively survey the tick distribution in the natural scenic belts of various counties and districts in Huai'an City, Jiangsu Province, and to provide guidance on tick control measures. Methods From 2023 to 2024, questing ticks in 29 natural scenic belts spanning seven counties and districts of Huai'an City were collected using hand-scratching method. Further, parasitic ticks in the surrounding areas were collected using the animal search method. Collected ticks were subsequently identified to the species level in the laboratory. Results In total, 288 questing ticks were collected, all belonging to the genus Haemaphysalis of family Ixodidae. Hae. longicornis was the dominant species, accounting for 98.61%, followed by Hae. flava(1.04%)and Hae. phasiana(0.35%). The average tick density index in Lotus Lake Scenic Area(Jinhu County), All-People Fitness Theme Park(Lianshui County), Peach Blossom Valley(Qingjiangpu District), Huai'an Forest Park(Huai'an District), Qizu of Gaozhuang Village(Hongze District), Ancient Yellow River Sports Park(Huaiyin District), Putao Trench and(Xuyi County)was 0.022, 0.025, 0.01, 0.10,0.22,0.28, and 0.79 ticks/flag·100 m, respectively. In total,114 parasitic ticks were collected at the monitoring sites, with an average tick infestation rate of 69.25% in sheep and 100% in dogs at Tianquanhu Town in Xuyi County; all of these were Hae. longicornis. All parasitic ticks were from Xuyi County, and no parasitic ticks were found at the monitoring sites in Huai'an District, Hongze District, and Lianshui County. Conclusions Overall, with the advancement of eco-tourism resorts and urban greening construction in Huai'an City, the presence of ticks was confirmed by this study in previously unsurveyed areas. As the frequency of human-animal interactions increases in these areas, the potential risk of tick-borne diseases also rises. Furthermore, this study provides important clues for subsequent investigations into local tick-borne pathogens.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To investigate the protective effect of butyrolphthalein on nerve injury in rats with acute cerebral infarction(ACI)by regulating Toll-like receptor 4(TLR4)/nuclear transcription factor-κB(NF-κB)pathway.Methods SD rats were randomly divided into model group and experimental-L,-M,-H groups;ACI models were established in vivo except sham operation group.The experimental-L,-M,-H groups were given 20,40,80 mg·kg-1 butylphthalide,qd,for 7 days;the sham operation group and the model group were given the same amount of 0.9％NaCl,for 7 days.Neural function score,bilateral sticker removal time,balance beam crossing score,cerebral water content and cerebral infarction volume of rats in each group were measured.The expression of axonal growth inhibitory factor A(Nogo-A)and serum inflammatory factor in hippocampus were detected by enzyme-linked immunosorbent assay(ELISA).The expression of TLR4/NF-κB pathway related proteins was detected by Western blot.Results The neural function scores of sham operation group,model group,and experimental-L,-M,-H groups were 0,3.55±0.52,2.55±0.52,1.82±0.60,0.91±0.30,respectively;the Nogo-A in hippocampus were(0.93±0.23),(6.32±0.53),(5.10±0.55),(3.54±0.57),(1.58±0.30)ng·L-1,respectively;serum Nogo-A were(0.49±0.12),(5.09±0.82),(3.83±0.54),(2.23±0.64),(1.13±0.25)ng·L-1,respectively;TLR4 protein expression were 0.44±0.05,1.23±0.14,0.93±0.07,0.75±0.06,0.55±0.07,respectively;the expressions of p-p65 NF-κB protein were 0.32±0.05,0.82±0.06,0.68±0.08,0.57±0.07,0.44±0.05,respectively.There were statistically significant differences between sham operation group and model group(all P＜0.05).There were significant differences in the above indexes between the model group and the experimental-L,-M,-H groups(P＜0.05).Conclusion Butylphthalein can play a neuroprotective role in ACI rats by regulating TLR4/NF-κB pathway to improve nerve function and reduce inflammatory damage.

The compound (E)-1-(4-(3-(5-chloro-6-oxo-3,6-dihydropyridin-1(2H)-yl)-3-oxo-propyl-1-ene-1-yl) phenyl)-3-(4-fluorophenyl) urea (C12), a novel derivative of piperlongumine previously synthesized by our research group, was investigated in this study to examine its effects on human non-small cell lung cancer cell line H1299 in vitro and elucidate its potential mechanism of action. The impact of C12 on the proliferation, migration, and invasion abilities of H1299 cells were assessed using methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, cloning formation assay, and Transwell assay. Flow cytometry was employed to evaluate the influence of C12 on cell cycle progression, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis induction in H1299 cells. Western blot analysis was conducted to investigate the expression levels of p21, Cyclin B1, CDK1, Bax, Bcl-2, JNK, p-JNK, Erk1/2, p-Erk1/2, p38 and p-p38 proteins for exploring the anti-tumor mechanism underlying C12's actions. The results demonstrated that C12 exerted inhibitory effects on the proliferation, migration, and invasion capacities of H1299 cells in a time-dependent and concentration-dependent manner. Moreover, C12 induced G2/M phase arrest in the cell cycle, reduced MMP levels, elevated ROS production, and triggered apoptotic processes. Flow cytometry analysis revealed that C12 downregulated Cyclin B1 and CDK1 protein expressions, resulting in G2/M phase arrest. C12 also upregulated Bax/Bcl-2 ratio, promoting apoptosis. Furthermore, C12 activated MAPK signaling pathway by enhancing phosphorylation levels of JNK, Erk1/2, and p38 proteins. In conclusion, C12 significantly suppressed proliferation, migration, and invasion capabilities while inducing cell cycle arrest and apoptosis in H1299 cells. These effects may be attributed to activation of the MAPK signaling pathway.

OBJECTIVE: To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms. METHODS: Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05). CONCLUSION EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.
Rats ; Animals ; Electroacupuncture ; Rats, Sprague-Dawley ; Serotonin ; Acupuncture Points ; Pain, Referred ; Calcitonin Gene-Related Peptide ; Signal Transduction ; Colitis/therapy* ; Indoles ; Sulfonamides