The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

BACKGROUND: Modern acupuncture anesthesia is a combination of Chinese and Western medicine that integrates the theories of acupuncture with anesthesia. However, some clinical studies of acupuncture anesthesia lack specific descriptions of randomization, allocation concealment, and blinding processes, with subsequent systematic reviews indicating a risk of bias. OBJECTIVE: Clinical trial registration is essential for the enhancement of the quality of clinical trials. This study aims to summarize the status of clinical trial registrations for acupuncture anesthesia listed on the World Health Organization International Clinical Trials Registry Platform (ICTRP). SEARCH STRATEGY: We searched the ICTRP for clinical trials related to acupuncture anesthesia registered between January 1, 2001 and May 31, 2023. Additionally, related publications were retrieved from PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data. Registrations and publications were analyzed for consistency in trial design characteristics. INCLUSION CRITERIA: Clinical trials that utilized one of several acupuncture-related therapies in combination with pharmacological anesthesia during the perioperative period were eligible for this review. DATA EXTRACTION AND ANALYSIS: Data extracted from articles included type of surgical procedure, perioperative symptoms, study methodology, type of intervention, trial recruitment information, and publication information related to clinical enrollment. RESULTS: A total of 166 trials related to acupuncture anesthesia from 21 countries were included in the analysis. The commonly reported symptoms in the included studies were postoperative nausea and vomiting (19.9%) and postoperative pain (13.3%). The concordance between the publications and the trial protocols in the clinical registry records was poor, with only 31.7% of the studies being fully compatible. Inconsistency rates were high for sample size (39.0%, 16/41), blinding (36.6%, 15/41), and secondary outcome indicators (24.4%, 10/41). CONCLUSION The volume of acupuncture anesthesia clinical trials registered in international trial registries over the last 20 years is low, with insufficient disclosure of results. Postoperative nausea and vomiting as well as postoperative pain, are the most investigated for acupuncture intervention. Please cite this article as: Li Y, Liu YN, Guo Z, Gu ME, Wang WJ, Zhu Y, Zhuang XJ, Chen LM, Zhou J, Li J. Current situation of clinical trial registration in acupuncture anesthesia: A scoping review. J Integr Med. 2025; 23(3): 256-263.
Humans ; Acupuncture Analgesia ; Acupuncture Therapy ; Anesthesia ; Clinical Trials as Topic ; Registries

OBJECTIVES: To investigate the regulatory effects of Aurora-A in regulating proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells and the role of actin-related protein 2/3 complex subunit 4 (ARPC4) in mediating its effects. METHODS: The plasmids pCDH-NC, pCDH-Aurora-A, and shRNA-ARPC4 were used for inducing Aurora-A overexpression or ARPC4 knockdown in HeLa cells. The cells were divided into vector group, Aurora-A overexpression group, Aurora-A overexpression+ARPC4 knockdown group, and Aurora-A overexpression+NF‑κBp65 inhibitor group and transfected with the corresponding plasmids. The proliferation, colony-forming ability, migration and invasion of the treated Hela cells was evaluated using EdU immunofluorescence assay, crystal violet staining, scratch assay, Transwell assay, and Matrigel assay. Western blotting was performed to detect the changes in cellular expressions of EMT-related proteins and expression levels of NF-κBp65 and ARPC4. RESULTS: The expression of ARPC4 was significantly decreased in HeLa cells with Aurora-A knockdown and increased in Aurora-A-overexpressing cells. Aurora-A overexpression obviously promoted proliferation, migration, and invasion abilities of HeLa cells, and these effects was significantly antagonized by ARPC4 knockdown. In Aurora-A-overexpressing cells, the phosphorylation level of NF-κBp65 and the expression level of ARPC4 were increased significantly, and application of the NF‑κBp65 inhibitor obviously lowered the expression level of ARPC4. CONCLUSIONS Aurora-A overexpression upregulates the expression of ARPC4 by activating the NF-κBp65 signaling pathway, thereby promoting migration, invasion and EMT of HeLa cells.
Humans ; Uterine Cervical Neoplasms/metabolism* ; Female ; HeLa Cells ; Epithelial-Mesenchymal Transition ; Signal Transduction ; Cell Movement ; Neoplasm Invasiveness ; Cell Proliferation ; Aurora Kinase A/metabolism* ; Transcription Factor RelA/metabolism* ; Neoplasm Metastasis

Objective:To investigate the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage in Chinese population from childhood to middle age.Methods:This study is a population-based, long-term follow-up cohort study. Participants who had their blood pressure measured at least 5 times in the Hanzhong Adolescent hypertension cohort from 1987 to 2023 were included in this study. Group-based trajectory modeling was used to identify different systolic and diastolic blood pressure trajectories, and the subjects were divided into low-increasing group, moderate-increasing group and high-increasing group according to blood pressure trajectories. Blood pressure variability was assessed using standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Target organ damage was evaluated during the final follow-up in 2023 (middle age). Logistic regression models were used to analyze the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage.Results:A total of 2 447 subjects were included, with a median age of 48 years, of whom 1 373 were male (56.1%). Based on systolic blood pressure, 868 were in the low-increasing group, 1 238 in the moderate-increasing group, and 341 in the high-increasing group. For diastolic blood pressure, the distribution was 894, 1 263 and 290, respectively. Compared with the low-increasing group of systolic blood pressure, the moderate-increasing group (arteriosclerosis: OR=4.14, 95% CI 2.96-5.79; proteinuria: OR=2.06, 95% CI 1.38-3.07; left ventricular hypertrophy: OR=1.68, 95% CI 1.00-2.82) and high-increasing group (arterial stiffness: OR=15.44, 95% CI 10.14-23.50; proteinuria: OR=5.80, 95% CI 3.63-9.29; left ventricular hypertrophy: OR=2.93, 95% CI 1.55-5.53) had a higher risk of target organ damage (all P<0.005). The moderate-increasing group of diastolic blood pressure had a higher incidence of arterial stiffness ( OR=3.72, 95% CI 2.69-5.12) and proteinuria ( OR=1.67, 95% CI 1.15-2.42) than the low-increasing group (all P<0.005), while the high-increasing group had a significantly higher risk of all type of target organ damage compared to the low-increasing group (arterial stiffness: OR=10.84, 95% CI 7.08-16.61; proteinuria: OR=3.72, 95% CI 2.31-5.99; left ventricular hypertrophy: OR=2.38, 95% CI 1.23-4.59; all P<0.005). Additionally, higher systolic blood pressure variability was associated with an increased incidence of arterial stiffness (SD: OR=2.25, 95% CI 1.96-2.57; VIM: OR=1.64, 95% CI 1.45-1.86; ARV: OR=1.70, 95% CI 1.50-1.93) and proteinuria (SD: OR=1.65, 95% CI 1.44-1.89; VIM: OR=1.41, 95% CI 1.22-1.63; ARV: OR=1.45, 95% CI 1.26-1.67; all P<0.005). The results for diastolic blood pressure variability indicators were similar to those for systolic blood pressure. Conclusion:Early-life blood pressure trajectories are predictive of target organ damage risk in middle age. Higher blood pressure variability is related to an increased risk of arterial stiffness and proteinuria, but was less associated with left ventricular hypertrophy. Focusing on the risk of high blood pressure early in life can help prevent the occurrence of target organ damage in middle age.

Objective To investigate the abnormal changes characteristics of the degree centrality(DC)of the brain functional network in patients with benign paroxysmal positional vertigo(BPPV)in the classical frequency band(0.010-0.080 Hz),the slow-4 frequency band(0.027-0.073 Hz),and the slow-5 frequency band(0.010-0.027 Hz).Methods Twenty patients with BPPV(BPPV group)and 14 healthy controls(HC)(HC group)were selected.Resting-state functional magnetic resonance imaging(rs-fMRI)scans were performed,and the clinical data were analyzed.The DC method was used to analyze the changes of centrality of resting state network in patients with BPPV.Results Compared with the HC group,the BPPV group showed an increase in DC in the left caudate nucleus in the classical frequency band(P＜0.05),and a decrease in DC in the right auxiliary motor region in the classical frequency band(P＜0.05);within the slow-4 frequency band,no significant differences were observed in brain regions(P＞0.05);within the slow-5 frequency band,the BPPV group showed an increase in DC in the left thalamus(P＜0.05),while the left anterior cingulate and paracingulate gyrus showed a decrease in DC(P＜0.05).Conclusion Patients with BPPV have spontaneous activity disorders in multiple brain regions at resting states,and these changes show frequency band specificity.

Objective To analyze the CT manifestations of high altitude pulmonary edema(HAPE)to provide radiological evidence for its early and accurate diagnosis.Methods Totally 200 HAPE patients clinically confirmed at some hospital from April 2021 to April 2024 were enrolled into a study group,and 56 individuals undergoing health examinations at the hospital's physical examination center between January and June 2023 were included into a control group.Examinations were carried out with a United Imaging uCT528 40-slice spiral CT scanner.The patients in the study group were observed in terms of HAPE staging,the extent of pulmonary involvement,CT manifestations of different stages including location,distribution,density and morphology of pulmonary lesion.The diameters of the main pulmonary arteries and ascending aortas of the subjects in the two groups were measured,and the ratios of the two diameters were calculated.SPSS 25.0 software was used for statistical analysis.Results In the study group,there were 26 cases(13.0%)at early stage,105 ones at progression stage(52.5%),32 ones at critical outbreak stage(16.0%)and 37 ones at resolution and absorption stage(18.5%),and there were 35.5%with unilateral lung involvement and 64.5%with bilateral involvement.At early stage,HAPE chest CT manifestations included increased and thickened bilateral bronchovascular bundles,widened main pulmonary artery lumen and faint ground-glass opacity in lungs;at progression stage,HAPE chest CT manifestations revealed multiple cloud-like or patchy areas of increased density within lungs;at critical outbreak stage,CT scanning indicated diffuse patchy opacities and consolidation in lungs,white lung-like changes could be found in some severe cases,and bronchial air signs were shown within affected segments in some ones with severer signs in the right lung than in the left lung;at resolution and absorption stage the CT manifestations were similar to those at early stage,with lesions completely resolving after treatment.The study group had the diameters of the main pulmonary arteries greater while the diameters of the ascending aortas less than those of the control group,and the ratios of the diameters of the two diameters in the study group were higher than those in the control group,with the differences being statistically significant(all P<0.05).Conclusion Chest CT is an important examination method for the early diagnosis of HAPE and clarification of its clinical staging,which directly reflects the pulmonary pathological changes in HAPE patients and helps doctors fully understand the disease progression.

Objective:To investigate the epidemiological dynamics and spatiotemporal diffusion trend of brucellosis in China from 2010 to 2024.Methods:Data on reported human brucellosis cases in mainland China from January 1, 2010, to December 31, 2024, were collected via the"China Information System for Disease Control and Prevention", including detailed information on the date of onset, gender, age, occupation, and residential address of the cases. The Joinpoint regression and spatial interpolation techniques were used to investigate the spatiotemporal dynamics and population distribution characteristics of human brucellosis in pastoral/semi-pastoral areas and other regions, as well as urban and rural areas, and explore the epidemic trends of the disease.Results:From 2010 to 2024, pastoral/semi-pastoral regions reported 252 094 brucellosis cases, with a mean annual incidence rate of 36.57±7.28 per 100 000. In contrast, other regions cumulatively recorded 519 748 cases during the same period, demonstrating a significantly lower mean annual incidence rate of 2.54±0.74 per 100 000. The incidence rate of human brucellosis in pastoral/semi-pastoral regions exhibited a declining-rebounding-declining trend. Specifically, the incidence rate decreased significantly from 2010 to 2017 (APC=-7.20; P<0.001) and increased notably from 2017 to 2021 (APC=18.00; P=0.015) with a decline again from 2021 to 2024 (APC=-7.53; P=0.027). In other regions, the incidence rate showed a fluctuating upward trend. Specifically, the incidence rate increased significantly from 2010 to 2015 (APC=20.37; P<0.001) and decreased notably from 2015 to 2018 (APC=-21.78; P<0.001), followed by an increase again from 2018 to 2024, a significant upward trend in incidence rate from 2018 to 2021 (APC=26.73; P<0.001) and a non-significant decline from 2021 to 2024 (APC=-0.99; P=0.735), resulting in the maintenance of a relatively high incidence level. Rural areas demonstrated significantly higher brucellosis incidence rates than urban settings (all P<0.001). Brucellosis exhibited a diffusion trend from the northern epidemic areas of China to neighboring regions, along with sporadic diffusion in southern regions between 2010 and 2024. The age structure of patients in pastoral/semi-pastoral areas differed significantly from that in other regions. Specifically, in pastoral/semi-pastoral areas, the incidence rate was higher among the 35-49 age groups, while in other regions, the incidence rate was higher among those aged 55-64. Conclusion:There are notable disparities in the incidence of human brucellosis between pastoral/semi-pastoral areas and other regions in China. Human brucellosis exhibits a diffusion trend from the northern epidemic areas of China to neighboring regions, along with sporadic diffusion in southern regions.

Objective:To investigate the interventional effects of the Fuzheng Huayu (FZHY) formula and its partial mechanistic role on cholestatic liver fibrosis in mice.Methods:Mdr2 gene knockout (Mdr2－/ －) mice were randomly divided into a model group, FZHY group, and Obeticholic acid group. Wild-type C57BL/6J mice of the same age served as the control group. Mdr2－/ －mice were given the corresponding drugs starting from the first day of 9 weeks of age by oral gavage in each group. The control and model groups were administered 0.3% sodium carboxymethylcellulose by oral gavage and were sacrificed at 12 weeks of age for specimen collection. High-speed biochemistry analyzer was used to detect serum alkaline phosphatase and alanine aminotransferase activity in mice. Hematoxylin-eosin staining and Sirius red staining were used to observe pathological changes in liver tissues. Hydroxyproline content was measured to assess collagen in liver tissues. Immunohistochemical staining, Western blotting, and real-time fluorescence quantitative PCR were used to detect the expression of fibrosis markers Col-I and alpha-smooth muscle actin in liver tissues. The expressional condition of cholangiocyte response markers Epcam, CK7, CK19, as well as Pcna, Mki67, and Ccnd1, inflammatory related factors Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4, phosphorylated peroxisome proliferator-activated receptor alpha (PPARα) and nuclear factor kappa-B (NF-κB) were determined. Comparative analysis among multiple groups was performed using one-way ANOVA. The LSD method was used for comparisons between groups. Two-tailed statistical tests were used.Results:Compared with wild-type mice, Mdr2 －/ － mice had a significant increase in serum alanine aminotransferase and alkaline phosphatase activity ( P<0.001). The percentage of Sirius red-positive staining areas and hydroxyproline content in liver tissues was significantly increased ( P<0.01). The expression of Col-I, α-smooth muscle actin, Epcam, CK7, CK19, Pcna, Mki67, and Ccnd1, and the expression of Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4 were significantly increased ( P<0.01); however, both FZHY and Obeticholic acid significantly reversed the increases in these indicators ( P<0.05; P<0.01). Further results showed that compared to wild-type mice, the expression of PPARα was significantly reduced in liver tissues of Mdr2 －/ － mice, while NF-κB was significantly enhanced ( P<0.01). In contrast, compared to Mdr2-/- mice, the expression of PPARα in the liver tissues of FZHY group mice was significantly increased ( P<0.05), while NF-κB was significantly inhibited ( P<0.05). Conclusion:FZHY can significantly improve liver fibrosis, cholangiocyte response, and inflammation in Mdr2 －/ － mice with spontaneously occurring cholestatic liver fibrosis, and its mechanistic role is related to the regulation of the PPARα/NF-κB pathway.

Objective To explore the correlation between serum vitamin D(VD3)level differences and immune inflammatory markers in elderly sepsis patients.Methods A total of 103 elderly patients with sepsis(aged 65-99 years)in the ICU of the First Affiliated Hospital of Kunming Medical University from January 2020 to December 2022 were collected and divided into two groups according to the diagnostic criteria for VD3 deficiency:VD3 deficiency group(n=32)and VD3 severe deficiency group(n=71).Correlation analysis was conducted by comparing the differences in serum 25-(OH)-D3(VD3)levels,immune function-related indicators upon admission(blood routine,infection-related proteins,combined detection of 12 cytokines,absolute count analysis of lymphocytes and subgroups,quantitative determination of infection-related immune cells,immunoglobulin,and complement),illness severity,and prognostic indicators(APACHE-II score,SOFA score,duration of ICU stay,and 28-day mortality rate).Result(1)Serum VD3 levels were lower in elderly patients with sepsis.No patient was in the VD3 normal or insufficient group.Patients with severe VD3 deficiency had higher APACHE-II scores,SOFA scores,and 28-day mortality rates than those with VD3 deficiency,and these scores were negatively correlated with serum VD3 levels(P<0.001),while the difference in ICU stay duration between the two groups was not statistically significant(P>0.05);(2)WBC,PCT,CRP,and CD4/CD8 in the VD3 deficiency group were all lower than those in the VD3 severe deficiency group(P<0.05),while IL-6,IL-10,CD45+,CD3+/CD45+,and CD19+Abs were all higher than those in the VD3 severe deficiency group(P<0.05);In the VD3 deficiency group,VD3 levels were positively correlated with CD45+(P<0.05 for all),while negatively correlated with IL-6,IL-10,PCT,and CRP(P<0.05 for all);In the VD3 severe deficiency group,there were fewer corre-lation indicators and the correlation strength was not as strong as that in the VD3 deficiency group.Conclusion(1)Elderly patients with sepsis generally have lower levels of VD3,with lower levels associated with more severe illness and poorer prognosis;(2)In elderly sepsis patients,compared to patients with severe VD3 deficiency,patients with VD3 deficiency have lower levels of inflammation,stronger cellular immune response,and stronger correlation,suggesting that the effects of different VD3 levels on immune inflammatory responses may vary in elderly sepsis patients.

Objective To investigate the abnormal changes characteristics of the degree centrality(DC)of the brain functional network in patients with benign paroxysmal positional vertigo(BPPV)in the classical frequency band(0.010-0.080 Hz),the slow-4 frequency band(0.027-0.073 Hz),and the slow-5 frequency band(0.010-0.027 Hz).Methods Twenty patients with BPPV(BPPV group)and 14 healthy controls(HC)(HC group)were selected.Resting-state functional magnetic resonance imaging(rs-fMRI)scans were performed,and the clinical data were analyzed.The DC method was used to analyze the changes of centrality of resting state network in patients with BPPV.Results Compared with the HC group,the BPPV group showed an increase in DC in the left caudate nucleus in the classical frequency band(P＜0.05),and a decrease in DC in the right auxiliary motor region in the classical frequency band(P＜0.05);within the slow-4 frequency band,no significant differences were observed in brain regions(P＞0.05);within the slow-5 frequency band,the BPPV group showed an increase in DC in the left thalamus(P＜0.05),while the left anterior cingulate and paracingulate gyrus showed a decrease in DC(P＜0.05).Conclusion Patients with BPPV have spontaneous activity disorders in multiple brain regions at resting states,and these changes show frequency band specificity.