ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

Objective:To evaluate the role of the CC chemokine ligand 2/CC chemokine receptor 2 (CCL2/CCR2) signaling pathway in electroacupuncture (EA)-induced reduction of spinal cord injury (SCI) in rats.Methods:Sixty clean-grade healthy adult female Sprague-Dawley rats, weighing 210-250 g, were divided into 5 groups ( n=12 each) using a random number table method: sham operation group (group S), group SCI, SCI+ Anti-CCL2 group (group SCI+ A), SCI+ EA group (group SCI+ EA), and spinal cord injury+ EA+ rCCL2 group (group SCI+ EA+ R). The SCI model was established using the Allen method in anesthetized animals. Group S only underwent spinous process and laminectomy without damaging the spinal cord. In SCI+ A group, CCL2 neutralizing antibody 50 μg/kg was intrathecally injected at 0, 3 and 6 days after successful development of the SCI model. On the 7th day after the successful development of the SCI model, Jiaji, Dazhui and Mingmen acupoints were stimulated with a depth of 2 mm, voltage of 12-15 mV and frequency of 2 Hz for 30 min once a day for 7 consecutive days in SCI+ EA group. In SCI+ EA+ R group, recombinant rat CCL2 2.5 μg/kg was intrathecally injected at the site of injury at 0, 3 and 6 days after successful development of the SCI model, and the remaining treatments were similar to those in SCI+ EA group. At 1 day before developing the model, 0, 3, 7, 14, 21 and 28 days after developing the model, the mechanical paw withdraw threshold (MWT) and thermal paw withdrawal latency (TWL) were measured, and the motor function was assessed by BBB score. The rats were sacrificed after the final behavioral testing, and their spinal cord tissues were obtained for determination of the expression of CCL2 and CCR2 protein and mRNA (by Western blot or quantitative real-time polymerase chain reaction), the expression of GFAP (by immunofluorescence), contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay) and for examination of the pathological changes (using HE staining). Results:Compared with S group, the MWT and BBB scores were significantly decreased and the TWL was shortened at each time point after developing the model, the expression of CCL2 and CCR2 protein and mRNA and GFAP was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI group ( P<0.05). Compared with SCI group, the MWT and BBB scores were significantly increased, and the TWL was prolonged at 7 days after developing the model in SCI+ A group, the MWT and BBB scores were significantly increased, and the TWL was prolonged at 14 days after developing the model in SCI+ EA group, and the expression of CCL2 and CCR2 protein and mRNA and GFAP was significantly down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in SCI+ A and SCI+ EA groups ( P<0.05). Compared with SCI+ EA group, the MWT and BBB scores were significantly decreased at 14 days after developing the model, the TWL was shortened, the expression of CCL2 and CCR2 protein and mRNA and GFAP was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI+ EA+ R group ( P<0.05). Compared with SCI+ A and SCI+ EA groups, the histopathological injury were significantly attenuated in SCI group, and the histopathological injury was aggravated in SCI+ EA+ R group. Conclusions:The CCL2/CCR2 signaling pathway is involved in the process by which EA reduces SCI, and the mechanism is related to the inhibition of astrocyte activation, thereby reducing the inflammatory response.

Objective:To evaluate the effect of electroacupuncture (EA) on ionotropic purinergic receptor 4 (P2X4R)/nuclear factor-kappa B (NF-κB) signaling pathway during spinal cord injury (SCI) in rats.Methods:Thirty-six clean-grade healthy adult female Sprague-Dawley rats, weighing 210-250 g, were divided into 3 groups ( n=12 each) using a random number table method: sham surgery group (S group), SCI group, and SCI+ EA treatment group (SCI+ EA group). The SCI model was established by the Allen′s method in anesthetized animals. In group S, only the spinous processes and vertebral laminae were resected, but the spinal cord was not injured. On the 7th day after developing the model, EA of Jiaji, Dazhui, and Mingmen lasting 30 min was performed once a day for 7 consecutive days, with a depth of 2 mm, intensity of 12-15 mV, frequency of 2 Hz, in SCI+ EA group. The mechanical paw withdraw threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before developing the model and 3, 7, 14, 21 and 28 days after developing the model, and the motor function was assessed using the Basso-Beattie-Bresnahan (BBB) score. The recovery of motor function was assessed using footprint analysis at 28 days after developing the model. After the final behavioral testing, the rats were sacrificed, and spinal cord tissues were harvested to observe the pathological changes of the spinal cord tissues using hematoxylin-eosin staining, to detect the expression of P2X4R and phosphorylated NF-κB p65 (p-NF-κB p65) (by immunohistochemical analysis and Western blot) and to determine contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with the baseline measured at 1 day before developing the model, the MWT and BBB scores were significantly decreased and the TWL was shortened at each time point after developing the model in SCI group and SCI+ EA group ( P<0.05). Compared with S group, the MWT and BBB scores were significantly decreased and the TWL was shortened at each time point after developing the model, the expression of P2X4R and p-NF-κB p65 in spinal cord tissues was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI group ( P<0.05). Compared with SCI group, the MWT and BBB scores were significantly increased and the TWL was prolonged at 14, 21 and 28 days after developing the model, the expression of P2X4R and p-NF-κB p65 in spinal cord tissues was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased ( P<0.05), and the pathological damage of spinal cord tissues was alleviated and footprints were reduced in SCI+ EA group. Conclusions:The mechanism by which EA alleviates SCI may be related to the inhibition of the activation of the P2X4R/NF-κB signaling pathway and the reduction in the inflammatory response in rats.

According to the principle and current domestic and international construction processes of core outcome set(COS) and the characteristics of post-stroke aphasia, this study built COS with evidence-based support for traditional Chinese medicine(TCM) treatment of post-stroke aphasia. Firstly, a comprehensive review was conducted on the articles about the TCM treatment of post-stroke aphasia that were published in the four major Chinese databases, three major English databases, and three clinical registration centers over the past five years. The articles were analyzed and summarized, on the basis of which the main part of the COS for clinical research on the TCM treatment of post-stroke aphasia was formed. Secondly, clinical doctors and related nursing personnel were interviewed, and important outcome indicators in the clinical diagnosis and treatment process were supplemented to form a pool of core outcome indicators. Two rounds of Delphi surveys were carried out to score the importance of the core outcome indicators in the pool. Finally, a consensus meeting of experts was held to establish the COS for clinical research on the TCM treatment of post-stroke aphasia. The final COS included a total of 268 studies [236 randomized controlled trials(RCTs), 21 Meta-analysis, and 11 clinical registration protocols] and 20 open questionnaire survey results. After two rounds of Delphi surveys, a total of 14 outcome indicators and their corresponding measurement tools were included in the expert consensus meeting. The final expert consensus meeting determined the COS for post-stroke aphasia, which included 9 indicator domains and 12 outcome indicators.
Humans ; Aphasia/therapy* ; Stroke/complications* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Treatment Outcome

Objective To preliminarily explore the safety of collecting colostrum in the third trimester,and to evaluate postpartum breastfeeding in pregnant women with hyperglycemia during pregnancy.Methods Pregnant women with hyperglycemia during pregnancy who had prenatal examinations in Obstetrics and Gynecology Hospital,Fudan University from Jul to Nov 2022 were prospectively divided into the colostrum collection group(n=52)in the third trimester and the control group(n=55)by randomized controlled grouping method.The t-test,χ2 test,Fisher's exact probability method and rank sum test were used for statistical analysis of the data to compare the delivery outcomes,neonatal outcomes and postpartum breastfeeding status between the two groups.Results There were no significant differences in the gestational weeks at delivery,delivery methods,breastfeeding rates at 42 days postpartum and 4 months postpartum between the two groups of pregnant women with hyperglycemia during pregnancy.There were also no significant differences in the Apgar scores at 1 minute and 5 minutes after birth and the neonatal hospitalization rate.The proportion of formula milk as the first supplementary feeding after delivery and the delayed lactation rate at 3 days postpartum in the colostrum collection group were significantly lower than those in the control group(P<0.05).The exclusive breastfeeding rates at 24 hours postpartum and 3 days postpartum in the colostrum collection group were significantly higher than those in the control group(P<0.05).Conclusion Collecting colostrum in the third trimester among pregnant women with hyperglycemia during pregnancy is safe,and it can reduce the rate of supplementary feeding with formula milk after delivery,and increase the exclusive breastfeeding rates at 24 hours postpartum and 3 days postpartum.

This study was analyzed the spatial-temporal distribution and aggregation characteristics of Yersinia pestispositive host animals and vector pathogens in marmot natural foci in the Qilian-Altun mountains,Gansu Province,to provide a scientific basis for precise plague prevention and control.Y.pestissurveillance data for marmot natural foci in Qilian-Altun Mountains of Gansu Province from 2014 to 2023 were obtained from the Disease Control and Prevention Center of Gansu Province.Origin 2024 software was used for data visualization and presentation.Global and local spatial autocorrelation analyses and trend analyses were conducted in ArcGIS 10.8 software,with townships as the spatial scale.Cumulatively,440 strains of Y.pestis were isolated from the natural marmot foci in the Qilian-Altun mountainsof Gansu Province from 2014 to 2023.Most strains was isolated from marmots(345 strains,78.41%),and the remainder were isolated from vectors.Temporal distribution analysis indicated that the highest number of detected bacteria was reported in July and August(both 121 strains,27.50%).Regional distribution analysis revealed that Aksai County reported the highest number of detected bacteria(255 strains,57.95%).Global spatial autocorrelation analysis showed a spatially clustered distribution of the number of bacteria detected annually in the townships containing natural foci,except in2014,2016,and 2021-2023.The strongest spatial clustering was observed in 2020(Moran's I=0.521 2,Z=14.397 0,P<0.001).Local spatial autocorrelation analysis indicated a"high-high"aggregation area in the natural foci every year from 2014 to 2023,primarily in Hongliuwan Town of Aksai County and Dangchengwan Town of Subei County.The distribution of the"low-low"aggregation area was essentially consistent with the low activity area of the Yersinia pestisepidemic.The trend in annual total bacterial count gradually increased from east to west,and peaked in the western part of the epidemic focus.Clear spatial aggregation characteristics of the number of Y.pestis were detected in the marmot natural foci in the Qilian-Altun mountains at the townshiplevel as a whole in Gansu Province from 2014 to 2023.The aggregation area was mainly in the western section of Qilian Mountain to the Altun mountain section of the epidemic source area.Monitoring and prevention and control efforts should be focused in this key area,with prevention and control measures tailored to the local conditions,and classified guidance to decrease the risk of plague occurrence and spread.

Objective:To evaluate the role of the CC chemokine ligand 2/CC chemokine receptor 2 (CCL2/CCR2) signaling pathway in electroacupuncture (EA)-induced reduction of spinal cord injury (SCI) in rats.Methods:Sixty clean-grade healthy adult female Sprague-Dawley rats, weighing 210-250 g, were divided into 5 groups ( n=12 each) using a random number table method: sham operation group (group S), group SCI, SCI+ Anti-CCL2 group (group SCI+ A), SCI+ EA group (group SCI+ EA), and spinal cord injury+ EA+ rCCL2 group (group SCI+ EA+ R). The SCI model was established using the Allen method in anesthetized animals. Group S only underwent spinous process and laminectomy without damaging the spinal cord. In SCI+ A group, CCL2 neutralizing antibody 50 μg/kg was intrathecally injected at 0, 3 and 6 days after successful development of the SCI model. On the 7th day after the successful development of the SCI model, Jiaji, Dazhui and Mingmen acupoints were stimulated with a depth of 2 mm, voltage of 12-15 mV and frequency of 2 Hz for 30 min once a day for 7 consecutive days in SCI+ EA group. In SCI+ EA+ R group, recombinant rat CCL2 2.5 μg/kg was intrathecally injected at the site of injury at 0, 3 and 6 days after successful development of the SCI model, and the remaining treatments were similar to those in SCI+ EA group. At 1 day before developing the model, 0, 3, 7, 14, 21 and 28 days after developing the model, the mechanical paw withdraw threshold (MWT) and thermal paw withdrawal latency (TWL) were measured, and the motor function was assessed by BBB score. The rats were sacrificed after the final behavioral testing, and their spinal cord tissues were obtained for determination of the expression of CCL2 and CCR2 protein and mRNA (by Western blot or quantitative real-time polymerase chain reaction), the expression of GFAP (by immunofluorescence), contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay) and for examination of the pathological changes (using HE staining). Results:Compared with S group, the MWT and BBB scores were significantly decreased and the TWL was shortened at each time point after developing the model, the expression of CCL2 and CCR2 protein and mRNA and GFAP was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI group ( P<0.05). Compared with SCI group, the MWT and BBB scores were significantly increased, and the TWL was prolonged at 7 days after developing the model in SCI+ A group, the MWT and BBB scores were significantly increased, and the TWL was prolonged at 14 days after developing the model in SCI+ EA group, and the expression of CCL2 and CCR2 protein and mRNA and GFAP was significantly down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in SCI+ A and SCI+ EA groups ( P<0.05). Compared with SCI+ EA group, the MWT and BBB scores were significantly decreased at 14 days after developing the model, the TWL was shortened, the expression of CCL2 and CCR2 protein and mRNA and GFAP was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI+ EA+ R group ( P<0.05). Compared with SCI+ A and SCI+ EA groups, the histopathological injury were significantly attenuated in SCI group, and the histopathological injury was aggravated in SCI+ EA+ R group. Conclusions:The CCL2/CCR2 signaling pathway is involved in the process by which EA reduces SCI, and the mechanism is related to the inhibition of astrocyte activation, thereby reducing the inflammatory response.

Objective:To evaluate the effect of electroacupuncture (EA) on ionotropic purinergic receptor 4 (P2X4R)/nuclear factor-kappa B (NF-κB) signaling pathway during spinal cord injury (SCI) in rats.Methods:Thirty-six clean-grade healthy adult female Sprague-Dawley rats, weighing 210-250 g, were divided into 3 groups ( n=12 each) using a random number table method: sham surgery group (S group), SCI group, and SCI+ EA treatment group (SCI+ EA group). The SCI model was established by the Allen′s method in anesthetized animals. In group S, only the spinous processes and vertebral laminae were resected, but the spinal cord was not injured. On the 7th day after developing the model, EA of Jiaji, Dazhui, and Mingmen lasting 30 min was performed once a day for 7 consecutive days, with a depth of 2 mm, intensity of 12-15 mV, frequency of 2 Hz, in SCI+ EA group. The mechanical paw withdraw threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before developing the model and 3, 7, 14, 21 and 28 days after developing the model, and the motor function was assessed using the Basso-Beattie-Bresnahan (BBB) score. The recovery of motor function was assessed using footprint analysis at 28 days after developing the model. After the final behavioral testing, the rats were sacrificed, and spinal cord tissues were harvested to observe the pathological changes of the spinal cord tissues using hematoxylin-eosin staining, to detect the expression of P2X4R and phosphorylated NF-κB p65 (p-NF-κB p65) (by immunohistochemical analysis and Western blot) and to determine contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with the baseline measured at 1 day before developing the model, the MWT and BBB scores were significantly decreased and the TWL was shortened at each time point after developing the model in SCI group and SCI+ EA group ( P<0.05). Compared with S group, the MWT and BBB scores were significantly decreased and the TWL was shortened at each time point after developing the model, the expression of P2X4R and p-NF-κB p65 in spinal cord tissues was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI group ( P<0.05). Compared with SCI group, the MWT and BBB scores were significantly increased and the TWL was prolonged at 14, 21 and 28 days after developing the model, the expression of P2X4R and p-NF-κB p65 in spinal cord tissues was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased ( P<0.05), and the pathological damage of spinal cord tissues was alleviated and footprints were reduced in SCI+ EA group. Conclusions:The mechanism by which EA alleviates SCI may be related to the inhibition of the activation of the P2X4R/NF-κB signaling pathway and the reduction in the inflammatory response in rats.

This study was analyzed the spatial-temporal distribution and aggregation characteristics of Yersinia pestispositive host animals and vector pathogens in marmot natural foci in the Qilian-Altun mountains,Gansu Province,to provide a scientific basis for precise plague prevention and control.Y.pestissurveillance data for marmot natural foci in Qilian-Altun Mountains of Gansu Province from 2014 to 2023 were obtained from the Disease Control and Prevention Center of Gansu Province.Origin 2024 software was used for data visualization and presentation.Global and local spatial autocorrelation analyses and trend analyses were conducted in ArcGIS 10.8 software,with townships as the spatial scale.Cumulatively,440 strains of Y.pestis were isolated from the natural marmot foci in the Qilian-Altun mountainsof Gansu Province from 2014 to 2023.Most strains was isolated from marmots(345 strains,78.41%),and the remainder were isolated from vectors.Temporal distribution analysis indicated that the highest number of detected bacteria was reported in July and August(both 121 strains,27.50%).Regional distribution analysis revealed that Aksai County reported the highest number of detected bacteria(255 strains,57.95%).Global spatial autocorrelation analysis showed a spatially clustered distribution of the number of bacteria detected annually in the townships containing natural foci,except in2014,2016,and 2021-2023.The strongest spatial clustering was observed in 2020(Moran's I=0.521 2,Z=14.397 0,P<0.001).Local spatial autocorrelation analysis indicated a"high-high"aggregation area in the natural foci every year from 2014 to 2023,primarily in Hongliuwan Town of Aksai County and Dangchengwan Town of Subei County.The distribution of the"low-low"aggregation area was essentially consistent with the low activity area of the Yersinia pestisepidemic.The trend in annual total bacterial count gradually increased from east to west,and peaked in the western part of the epidemic focus.Clear spatial aggregation characteristics of the number of Y.pestis were detected in the marmot natural foci in the Qilian-Altun mountains at the townshiplevel as a whole in Gansu Province from 2014 to 2023.The aggregation area was mainly in the western section of Qilian Mountain to the Altun mountain section of the epidemic source area.Monitoring and prevention and control efforts should be focused in this key area,with prevention and control measures tailored to the local conditions,and classified guidance to decrease the risk of plague occurrence and spread.