ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

Adequate inflammation can effectively eliminate harmful substances and prevent disease as a self-protective measure to prevent further damage to the body,while abnormally activated inflammation is detrimental to the body.Nucleotide binding and oligomerization domain-like receptor protein 3(NLRP3)inflammasome that participates in inflammatory responses are closely related to many physiological and pathological processes and play an important role in the occurrence and development of pulmonary diseases.This article mainly reviewed the activation mechanism and hypothesis of NLRP3 inflammasome,as well as the research on treating respiratory diseases by interfering with NLRP3 inflammasome.

italic>Lamiophlomis rotata is an important medicinal plant species endemic to the Tibetan Plateau, which is prone to strong climate change impacts on its habitable range due to the high sensitivity of the Tibetan Plateau to climate change. Accurate quantification of species vulnerability to climate change is essential for assessing species extinction risk and developing effective conservation strategies. Therefore, we carried out the α-shape analysis to determine the habitat of L. rotata. We then carried out the climate-niche factor analysis (CNFA) to assess the vulnerability of L. rotata to climate change based on five climate variables (i.e., mean diurnal range, temperature seasonality, mean temperature of warmest quarter, precipitation of driest month and precipitation of warmest quarter) in the context of two shared socioeconomic pathways (i.e., SSP126 and SSP585) and three global climate models (CMCC-ESM2: Centro Euro-Mediterraneo sui Cambiamenti Climatici-Earth System Model version 2; HadGEM3-GC31-LL: Hadley Global Environment Model version 3-Global Coupled configuration 3.1; IPSL-CM6A-LR: Institut Pierre Simon Laplace-Climate Model version 6) during two different periods (2041-2060 and 2081-2100). The vulnerability of L. rotata to climate change was calculated by integrating the sensitivity and exposure indices of L. rotata to five climate variables. The results showed that L. rotata had the highest vulnerability to the precipitation of warmest quarter. Its vulnerability within its habitat range generally showed a spatial pattern of high value in the southern region and low in the northern region, high in the western region and low in the eastern region. In general, the vulnerability of L. rotata under the SSP585 scenario was higher than that under the SSP126 scenario. The climate data of different global climate models have some influence on the results, while the resulted uncertainty can be reduced by data integration methods. As a result of climate change, the pressure on the survival of L. rotata in the future will be intensified in the low-altitude areas such as the Yarlung Zangbo River, Yigongzangbu River, Zayu River, and Jiaomuzu River, etc., while the highly weathered scree flats or stony alpine meadows in the high-altitude zones, such as the eastern Tanggula Mountain Range, the northern part of Hengduan Mountain Range, and the western part of the Qinling Mountains, may become its refuge. It is necessary to focus on and strengthen the protection and management of L. rotata resources in these vulnerble and critical areas.

Objective:To explore the assessment value of quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and tumor markers in assessing the curative effect of neoadjuvant chemotherapy for breast cancer.Methods:A total of 75 patients with breast cancer who received neoadjuvant chemotherapy combined with surgical intervention in Jining No.1 People's Hospital from May 2019 to May 2022 were selected,and they were divided into effective group(54 cases)and ineffective group(21 cases)according to the Response Evaluation Criteria In Solid Tumour(RECIST).The Ve,Kep and Ktrans of DCE-MRI quantitative parameters and CEA,CA125 and CA15-3 levels of tumor markers between two groups were compared before and after chemotherapy,and the receiver operating characteristics(ROC)curve was adopted to analyze the predictive efficiency of each diagnostic method.Results:After chemotherapy,the differences of the Ve,Kep and Ktrans of quantitative parameters between the two groups were significant(t=7.237,51.695,16.879,P<0.05),respectively.The differences of the CEA,CA125 and CA15-3 of tumor markers between two groups were significant(t=44.201,6.736,6.885,P<0.05),respectively.The AUC value of combined prediction of 6 indicators included Ve,Kep,Ktrans,CEA,CA125 and CA15-3 was 0.979 in predicting the curative effect of neoadjuvant chemotherapy for breast cancer,which was significantly higher than the AUC value of each alone indicator,and the differences of them were statistically significant(Z=2.993,2.679,2.510,2.731,3.215,3.071,P<0.05),respectively.Conclusion:The combination of tumor markers and DCE-MRI quantitative parameters can better predict the curative effect of neoadjuvant chemotherapy for breast cancer,which can indirectly assess the prognosis.

Objective:To assess the effectiveness and safety of beat chemotherapy in treating non-small cell lung cancer, and to investigate its anti-tumor molecular mechanism.Methods:In this study, we developed a subcutaneous tumor model of lung cancer in mice.The mice were subsequently divided into two groups: the beat chemotherapy group and the placebo group(negative control group).Throughout the treatment period, we monitored the changes in body weight and tumor size of the mice.At the conclusion of the treatment, we collected blood samples from the mice to conduct blood routine and biochemical examinations.Furthermore, we obtained tumor tissues from the mice to perform immunohistochemical staining and sequencing of the transcriptome.Results:The study found that beat chemotherapy could effectively delay the growth of lung cancer.The tumor tissues in the beat chemotherapy group were significantly smaller compared to the placebo group.The results of routine blood and blood biochemistry tests showed that the levels of red blood cells(RBCs), white blood cells(WBCs), alanine aminotransferase(ALT), aspartate aminotransferase(AST)and blood creatinine(Scr)were similar between the placebo group and the beat chemotherapy group.The values for RBCs, WBCs, ALT, AST and Scr in the placebo group were(6.97 ± 0.41)× 10 12/L, (13.26 ± 0.29)× 10 9/L, (33.33 ± 2.51)U/L, (235.33 ± 57.62)U/L and(20.67 ± 2.08)μmol/L, respectively.The corresponding values in the beat chemotherapy group were(6.87 ± 0.66)× 10 12/L, (12.59 ± 2.27)× 10 9/L, (38.67 ± 3.79)U/L, (225.33 ± 6.81)U/L and(20.33 ± 3.79)μmol/L.Statistical analysis showed no significant differences between the two groups( t=0.509, 0.209, 2.032, 0.299, 0.134, P=0.638, 0.845, 0.112, 0.780, 0.900).Furthermore, there were no signs of inflammatory infiltration or pathological changes in the liver, kidney, spleen, and lung tissues of the mice.Transcriptome analysis identified 68 differentially expressed genes, which were mainly associated with signal transduction and immunity.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis revealed the involvement of several signaling pathways, including the transforming growth factor β(TGF-β)signaling pathway, the interleukin-17(IL-17)signaling pathway, and the tumor necrosis factor(TNF)signaling pathway. Conclusions:The use of chemotherapy has been proven to be safe and effective in treating non-small cell lung cancer.It primarily functions by regulating tumor growth through various signaling pathways, including the TGF-β signaling pathway, IL-17 signaling pathway, and TNF.

Purpose::To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.Methods::This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log 2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay. Results::Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.Conclusions::Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Objective To investigate the mechanism of nootkatone(NKT)in mitigating depression-like behavior caused by blast traumatic brain injury(TBI).Methods The rat bTBI depression-like model was established by simulating the shock wave parameters of blast overpressure(BOP of 60 kPa,90 kPa,and 120 kPa)with a biological shock wave tube.After 14 days of exposure,we evaluated the depression-like behavior of rats using the tail suspension test and forced swimming test.We identified that the BOP(120 kPa)condition caused the most noticeable depressive behavior and used this condition for subsequent experiments.Thirty male SD rats were randomly divided into sham operation group,bTBI group(BOP of 120 kPa),and bTBI+NKT group[at 1 d after exposure to BOP of 120 kPa,giving NKT 10 mg/(kg·d)orally for 14 days],10 in each group.After 14 days of exposure,the depression-like behavior of rats was evaluated by tail suspension test and forced swimming test.The expression levels of protein kinase A(PKA),phosphorylated cyclic adenosine monophosphate effector binding protein(pCREB),and brain-derived neurotrophic factor(BDNF)in the hippocampus of rat were determined by Western blotting.Immunohistochemistry was used to detect the generation of proliferating cell nuclear antigen(PCNA)-labeled neurons in the hippocampal dentate gyrus(DG).Results BOP of 90 kPa can cause depression-like in rats and BOP of 120 kPa can cause the most noticeable depressive behavior(P<0.05).Therefore,we selected the BOP exposure of 120 kPa for subsequent experiments.After 14 days of BOP exposure,compared with sham operation group,the immobility time of tad suspension test in bTBI group was prolonged(P<0.05),the latency of for ced swimming test was shortened,the immobility time was prolonged(P<0.05),the expression levels of PKA,pCREB and BDNF protein in hippocampus were lowered(P<0.05),and the number of PCNA-labeled neurons in hippocampal DG area was reduced(P<0.05);compared with the bTBI group,the immobility time of tail suspension test in bTBI+NKT group was shortened(P<0.05),the latency of forced swimming test was prolonged,the immobility time was shortened(P<0.05),the expression levels of PKA,pCREB and BDNF protein in hippocampus were increased(P<0.05),and the number of PCNA-labeled neurons in hippocampal DG area was increased(P<0.05).Conclusions Early treatment with NKT can improve depression-like behavior in mild bTBI rats.The mechanism may be related to the up-regulation of the PKA-CREB-BDNF signaling pathway and increased expression levels of pCREB and BDNF in the hippocampus,which results in increased neuron numbers in the DG region of the hippocampus.

Objective To find out the social competence level of school-age children with speech sound disorders after cleft palate operation and functional speech sound disorders.Methods Thirty-four school-age children with postoperative cleft palate speech sound disorders and thirty-seven school-age children with functional speech sound disorders attending a specialty clinic for the diagnosis and treatment of childhood speech and language disorders in 2023 were selected,and 32 age-and gender-matched normal children in a local elementary school were also randomly selected as the normal group.The Achenbach Child Behavior Checklist was used to assess the so-cial competence of the three groups of children and a cross-sectional study was conducted.Results Children with cleft palate speech sound disorders and functional speech sound disorders had lower scores on activity,communication and academic ability,with specific manifestations varying in different gender groups,but there was no significant difference in scores between the two groups.In contrast,the activity and communication scores of the functional speech sound disordergroup were significantly lower than those of the normal group(P＜0.05).Conclusion School-age children with cleft palate speech sound disorders and functional speech sound disorders are at a higher risk of difficulties in social functioning,in terms of activity,communication and academic ability,whereas speech sound disorders may be one of the most important influencing factors of such difficulties and cleft palate does not have an additional impact on the social competence level of the child.

Leonurine(SCM-198)was discovered as one of the active constituents of the Herba Leonuri(HL).Now it can be artificially synthesized.Several recent researches has proven that it exhibits anti-inflammatory effect in several systems in animal models and cell culture in vitro.The key mechanism involves downgrading the activity of nuclear transcription factor-κB(NF-κB),thereby inhibiting the phosphorylation of several signal pathways such as PI3K/Akt,MAPK,ERK,and JNK,or upregulating the activity of Nrf2 related pathways,resulting in downregulated expression of inflammatory cytokines such as tumor necrosis factor-α(TNF-α),IL-1β,IL-2,IL-6,IL-8,inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),chemokines,adhesion molecules,etc.Owing to the advantages of high safety and efficiency,the ease of administration,as well as its effectiveness in many organs and systems,leonurine has a widely prospect for future research and clinical applications.This article reviews the progress in the fundamental research of leonurine in multiple inflammation-related disease,and it could be expect to offer new possibilities for the treatment of these disease.