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.

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

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

Objective:To investigate the correlation between early energy supplement and bronchopulmonary dysplasia (BPD) in very preterm and very low birth weight infants.Methods:A retrospective cohort study design was used. A total of 939 preterm infants who were admitted to the Department of Neonatology of the West China Second Hospital of Sichuan University within 24 h after birth from January 2019 to December 2021 were enrolled in the study. They were born with a gestational age of <32 weeks and (or) a birth weight of <1 500 g. Of them, 250 preterm infants who developed BPD were enrolled in the BPD group, and each of them was matched to a preterm infant who did not develop BPD (matched for gestational age and birth weight) in the order of priority after calculating propensity score. Their total energy, enteral energy, parenteral energy, total fluid intake and energy per unit of fluid per week were collected within the first 2 weeks of life. The independent sample t-test or Mann Whitney U test was used for continuous variables, and the χ2 test for between-group comparisons of categorical variables. Univariate and multivariate Logistic regression analyses were used to explore the association between total energy and total fluid and BPD incidence, respectively. The dose-response relationship between parenteral energy and BPD was investigated by a generalized additive model, and the threshold effect of parenteral energy on BPD used a two-piecewise linear regression model. Results:The gestational age was (28.4±1.9) weeks in the BPD group and (29.5±1.3) weeks in the control group; the birth weight was (1 107±258) g in the BPD group and (1 324±261) g in the control group; and there were 140 males (56.0%) and 131 males (52.4%) in each group, respectively. An increase in energy per unit of fluid in the second week of life was associated with a reduced risk of BPD ( OR=0.32, 95% CI 0.12-0.84, P=0.021), and an increase in total energy in the second week of life was also associated with a reduced risk of BPD, with total energy of >418-502 kJ/(kg·d) was significantly lower than when total energy was ≤334 kJ/(kg·d) ( OR=0.15, 95% CI 0.03-0.85, P=0.033). There was no association between the average total fluid intake and BPD incidence (both P>0.05) in the first and second week. The increase in the proportion of parenteral energy to total energy in the second week of life was associated with an increased incidence of BPD ( OR=8.45, 95% CI 2.14-33.32, P=0.003); specifically, the risk of BPD significantly increased when the parenteral energy was ≥305 kJ/(kg·d) ( OR=1.02, 95% CI 1.01-1.03, P=0.003). Conclusions:Maintaining a high total energy supply in the early postnatal period in preterm infants may reduce the risk of BPD, but continued reliance on high parenteral energy to meet total energy requirements increases the risk of BPD, so enteral feeds should be initiated as early as possible and maximized as tolerated.

AIM To analyze the component composition of Xeriga-4 Powder,and to determine the contents of phellodendrine,chlorogenic acid,gardenoside,berberine,rutin and curcumin.METHODS The high performance liquid chromatography-Q-exactive orbitrap mass spectrometry(HPLC-Q-Exactive-MS)qualitative analysis was performed on a 35℃thermostatic Agilent ZORBAX SB-Aq column(4.6 mm×150 mm,5 &mu;m),with the mobile phase comprising of methanol-0.1%formic acid flowing at 0.35 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning.High performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS)quantitative analysis was performed on a 35℃thermostatic Shim-pack GIST-HP C18 column(2.1 mm×100 mm,3 &mu;m),with the mobile phase comprising of methanol-0.1%formic acid flowing at 0.25 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Total 65 constituents were identified,containing 19 alkaloids,13 organic acids,13 flavonoids,7 curcumins,6 iridoids,4 fatty acids,2 aldehydes,and 1 amino acid.Six constituents showed good linear relationships within their own ranges(r≥0.999 1),whose average recoveries were 96.44%-102.37%with the RSDs of 2.05%-3.74%.CONCLUSION This study can provide a reference for the quality control for Xieriga-4 Powder.

【Objective】 To investigate the association between genetic variations in the glucagon-like peptide-1 receptor (GLP-1R) gene and BP responses to sodium and potassium intake. 【Methods】 A total of 514 subjects from 124 families were recruited in Meixian County, Shaanxi Province, in 2004, resulting in the establishment of a "salt-sensitive hypertension study cohort" . The subjects followed a dietary regimen which involved a normal diet for 3 days, a low-salt diet for 7 days, a high-salt diet for 7 days, and a high-salt potassium-supplemented diet for 7 days. BP measurement was conducted at different intervention periods, and peripheral blood samples were collected. Additionally, eight single nucleotide polymorphisms (SNPs) of the GLP-1R gene were genotyped using the MassARRAY detection platform. 【Results】 The GLP-1R gene SNP rs9462472 exhibited a significant association with systolic BP, diastolic BP, and mean arterial pressure response to high-salt intervention. Similarly, SNP rs2268637 showed a significant association with systolic BP response to high-salt intervention. Furthermore, SNP rs2268637 was significantly associated with systolic BP and mean arterial pressure responses to high-salt plus potassium supplementation intervention. 【Conclusion】 Our findings indicate a significant association of genetic variations in the GLP-1R gene with BP responses to sodium and potassium intake. This suggests that the GLP-1R gene plays a role in the regulation of BP salt sensitivity and potassium sensitivity.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Objective To explore the protective effect of Lycium barbanun glycopeptide(LbGP)against osteogenic inhibition induced by exosomes derived from human gingival fibroblasts(HGFs)exposed to radiation.Methods Cultured HGFs with or without LbGP pretreatment were exposed to 8 Gy X-ray radiation,and the changes in cell apoptosis,senescence and α-SMA level were detected using RT-qPCR,Western blotting and β-galactosidase staining.The exosomes secreted by the treated cells were extracted,and after identification by electron microscopy,particle size analysis and Western blotting,the exosomes were added into primary cultured bone mesenchymal stem cells(BMSCs),and osteoclast activity and osteogenesis in the cell cultures were detected by Trap staining,Alizarin red staining,ALP staining,RT-qPCR and Western blotting.Results In cultured HGFs,X-ray radiation significantly increased the percentage of senescent cells,which was obviously lowered by LbGP treatment.X-ray radiation significantly reduced Bcl-2/Bax ratio and increased α-SMA expression in HGFs,and these changes were significantly suppressed by LbGP pretreatment.In rat BMSCs,incubation with the exosomes derived from HGFs with radiation exposure caused a significant increase of osteoclasts,reduced calcium nodules and lowered alkaline phosphatase expression in the cells;The opposite changes were observed in the cells treated with exosomes from LbGP-pretreated HGFs,which also significantly increased the cellular expressions of the osteogenic genes(BMP2,ALP,and RUNX2)and proteins(ALP and RUNX2)as compared with the exosomes from irradiated HGFs.Conclusion LbGP can effectively inhibit osteoclast activity and promote osteogenesis by acting on exosomes secreted by irradiated HGFs,suggesting its potential value for treatment of osteoradionecrosis of the jaw.

Lung cancer is the malignant tumor with the highest incidence and mortality rate worldwide.For lung adenocarcinoma,identifying specific gene mutations,fusions,and giving corresponding targeted drugs can greatly improve the survival time of the patients.Among them,anaplastic lymphoma kinase(ALK)fusion occurs in 3％-7％of non-small cell lung cancer(NSCLC).In clinical practice,a variety of detection methods can be used to determine the ALK fusion status,but false negative test results are possible.This paper retrospectively analyzed the diagnosis and treatment of a patient with lung adeno-carcinoma,judged the ALK fusion status by various detection methods.Among them,immunohistochemistry(IHC)(Ventana D5F3),RNA based next-generation sequencing(RNA-based NGS)confirmed positive echinoderm microtubule associated protein like 4(EML4)-ALK fusion,while DNA-based NGS was negative.This paper analyzed the detection methods of ALK fusion,in order to clarify which detection method is the most accurate and simple to choose in different clinical cases and guide the subsequent treatment.

Objective To analyze the clinical efficacy and safety of photodynamic therapy(PDT)com-bined with CO2 laser in treating vaginal intraepithelial neoplasia(VaIN)to provide reference for the treatment scheme of the patients with VaIN.Methods A total of 80 patients with definitely diagnosed VaIN by colpo-scopic biopsy in Henan University People's Hospital from June 2022 to February 2023 were selected and di-vided into the PDT combined CO2 laser group and CO2 laser group by the random number table method,40 cases in each group.The follow up lasted for 6 months.The cure rate,negative conversion rate of human papillomavir-us(HPV),adverse reactions,recurrence and progression were compared between the two groups.Results After 3,6 months of treatment,the cure rates of VaIN in the PDT combined CO2 laser group were 77.50％and 82.50％,respectively,which in the CO2 laser group were 75.00％and 70.00％respectively,and the differ-ences between the two groups were not statistically significant(P＞0.05).There was no statistically signifi-cant difference in the cure rates of low-grade squamous intraepithelial lesion(LSIL)and high-grade squamous intraepithelial lesion(HSIL)after 3,6 months of treatment between the two groups(P＞0.05).There was no statistically significant difference in the negative conversion rate of HPV after 3 months of treatment be-tween the PDT combined with CO2 laser group and CO2 laser group(71.79％vs.56.41％,P＞0.05).How-ever,after 6 months of treatment,the negative conversion rate of HPV in the PDT combined CO2 laser group was significantly higher than that in the CO2 laser group(82.05％vs.58.97％,P＜0.05).In the CO2 laser group,one case experienced vaginal bleeding during treatment process,two cases appeared mild vaginal wall adhesion.No obvious adverse reaction was observed in the PDT combined with CO2 laser group.After 6 months of treatment,there was no case with progression of lesion in both groups;there were one case(3.23％)of relapse in the PDT combined CO2 laser group and three cases(10.00％)of relapse in the CO2 laser group,and the difference was not statistically significant(P＞0.05).Conclusion PDT combined with CO2 laser for treating VaIN has a high cure rate and HPV clearance rate,which is a safe and effective method for treating VaIN.