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.

Objective To establish an animal model of dampness-syndrome in mice (single model) and evaluate its characteristics of dampness-syndrome. The above-mentioned mice with dampness syndrome were used to construct mice model of ischemic stroke (double model) and observe the effect of dampness-pathogenic on the outcome of stroke. Methods Healthy C57BL/6J male mice were randomly divided into dampness-syndrome (including sham-surgery group and ischemic stroke group,with 10 mice in each group) and non dampness-syndrome groups (including sham-surgery group and ischemic stroke group,with 10 mice in each group). The dampness-syndrome group was fed with high-fat diet and the non dampness-syndrome group was fed with normal diet for 12 weeks. After the mice model of dampness-syndrome was successfully established,transient middle cerebral artery occlusion/reperfusion (tMCAO/R) surgery was used to replicate an ischemic stroke mice model. Evaluation indicators for dampness-syndrome mice model:the general status including body weight,morphology,posture,activity status,and physical characteristics,the histopathological observation of the aorta (oil red O staining,Masson-trichrome staining) and liver (HE staining,oil red O staining),electron microscopic observation of the tongue tissue (scanning electron microscopy,electron microscopy),blood lipid levels[total cholesterol(TC),triglycerides(TG)]and liver coefficient. Evaluation indicators for ischemic stroke mice model:neurological function score and the cerebral infarction volume ratio. Results Compared with the non dampness-syndrome group,the mice in the dampness-syndrome group showed an increased in body weight,poor hair color,sparse hair,fatigue and laziness,mental atrophy,anorexia and lethargy. It was observed that the aortic lumen was narrowed,the intima was significantly thickened,lipid plaque deposition was increased,and foam cells were visible. A large amount of red lipid droplets appeared in liver cells. There were obvious lipid infiltration and diffuse steatosis. Increased keratosis of the mucosal layer of tongue tissue,the thicker stratum corneum,lipofuscin,and bacteria on the tongue surface were found. Serum TG and TC levels significantly increased(P<0.01),and the liver coefficient significantly decreased (P<0.001). Compared with non dampness-syndrome group (sham-surgery group),neurological function score and the cerebral infarction volume ratio in dampness-syndrome ischemic stroke group obviously increased (P<0.001). Conclusion High-fat feeding for 12 weeks combined with tMCAO/R modeling can successfully establish a mice model with dampness-syndrome ischemic stroke,and the neurological function score and cerebral infarction volume in the dampness-syndrome ischemic stroke group was more severe than that in the non dampness-syndrome ischemic stroke group.

This video presents a case of L4–5 unstable spondylolisthesis treated with full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF), emphasizing the GUARD (Glider Used as a Rotary Device) technique for nerve root protection. This innovative approach involves controlled rotation of the cage glider before cage insertion to minimize the risk of nerve root injury, a significant complication in Endo-TLIF procedures. The GUARD technique, validated in previous cadaveric studies, provides enhanced safety during cage insertion by protecting the nerve root. A 48-year-old woman with a 3-year history of progressive low back pain and bilateral lower extremity radiculopathy (right-sided predominance) was diagnosed with L4–5 unstable spondylolisthesis and spinal stenosis. After failure of conservative management, she underwent uniportal full-endoscopic facet-resecting transforaminal lumbar interbody fusion using the GUARD technique. Postoperatively, the patient experienced significant symptomatic improvement and resolution of radiculopathy, without any intraoperative nerve root injury or postoperative neurological deficits. This case demonstrates the effectiveness of the GUARD technique in reducing neurological complications and improving patient outcomes.

Objective: Uniportal full-endoscopic transforaminal lumbar interbody fusion (FE-TLIF) carries a unique risk of nerve traction and abrasion injury during cage insertion. This study aims to evaluate the clinical efficacy of the GUARD technique and delayed ligamentum flavectomy in reducing postoperative radicular pain and neurapraxia in patients undergoing uniportal FE-TLIF. Methods: A retrospective analysis was conducted on 45 patients with an average age of 53.9±12.4 years who underwent either FE facet-sparing TLIF (FE fs-TLIF) or FE facet-resecting TLIF (FE fr-TLIF). Patients were divided into 2 groups: the sentinel group (21 patients) using traditional sentinel pin techniques, and the GUARD group (24 patients) using the GUARD technique with delayed ligamentum flavectomy. Patient-reported outcomes included the visual analogue scale (VAS) for leg and back pain, and Oswestry Disability Index. Complication rates, including incidental durotomy, postoperative neurapraxia, and hematoma, were also documented. Results: Postoperative radicular pain in the legs was significantly reduced at 6 weeks in the GUARD group compared to the sentinel group (VAS: 2.201 vs. 3.267, p=0.021). The incidence of postoperative neurapraxia was markedly lower in the GUARD group (0% vs. 19%, p=0.047). Both groups showed similar improvements in disc height, segmental lordosis, and lumbar lordosis at the 1-year follow-up, with no significant differences in endplate injury or fusion rates. Conclusion The GUARD technique and delayed ligamentum flavectomy significantly enhance patient safety by reducing postoperative radicular pain and neurapraxia without incurring additional costs. These techniques are easy to learn and integrate into existing surgical workflows, offering a valuable improvement for surgeons performing FE-TLIF procedures.

Aim To study the effects of Taohong Siwu Tang(TSD)on serum lipid metabolites in rats with abnormal uterine bleeding(AUB),and to analyze the mechanism of action of TSD in improving lipid metabo-lism disorders in AUB.Methods The rat model of AUB was replicated by the method of incomplete abor-tion with drugs,and the lipid metabolites of serum were detected by applying UPLC-Q-Exactive Orbitrap/MS technology,and combined with the principal com-ponent analysis and orthogonal partial least squares-discriminant analysis to screen for differential lipids,the changes of lipids in serum before and after the in-tervention of TSD were clarified.Results A total of 11 differential lipids were screened,mainly phosphati-dyl inositol,phosphatidic acid,phosphatidyl ethanola-mine,phosphatidyl serine,sterol lipids,ceramide,acrylolipids and fatty acids.The screened differential lipids all tended to regress to normal after the adminis-tration of TSD intervention.Conclusion Improvement of AUB by TSD may be related to lipid metabolism such as phosphatidic acid,phosphatidyl inositol,phos-phatidyl ethanolamine,phosphatidyl serine,and ce-ramide.

This study utilized the CCK-8 assay to examine the effects of various concentrations of CoCl2(0,50,100,200,300,400 μmol/L)and different treatment durations(0,6,12,24,48 h)on the viability of adipocytes,in order to determine the most suitable treatment conditions.Western blot analysis was employed to investigate the impact of different concentrations of CoCl2(0,50,100,200,400 μmol/L)on the expression of hypoxia and its downstream key proteins in adipocytes.The results indicated that higher concentrations of CoCl2 led to lower adipocyte viability,with sig-nificant decreases in cell viability observed in the 300,400 μmol/L treatment groups(P＜0.01),while the 200 μmol/L group exhibited the highest cell viability.Compared to the control group,the 200 μmol/L CoCl2 treatment group showed a significant upregulation in the expression of hypoxia and its downstream signaling pathway key molecules:hypoxia-inducible factor 1-alpha(HIF-1α),glucose transporter type 4(GLUT4),vascular endothelial growth factor receptor 1(FLT-1),prolyl hydroxylase 2(PHD2),and vascular endothelial growth factor(VEGF)(P＜0.01).Addi-tionally,the 200 μmol/L CoCl2 treatment group exhibited higher levels of key lipolytic enzymes,including adipose triglyceride lipase(ATGL),perilipin 1(PLIN1),protein kinase A(PKA),and increased phosphorylation levels of hormone-sensitive lipase(HSL)in the 300 and 400 μmol/L groui ps(P＜0.01).CoCl2-mediated hypoxia in the 200 μmol/L treatment group also in-creased the protein expression of phosphatidylinositol 3-kinase(PI3K)and the phosphorylation level of protein kinase B(Akt).These findings suggest that adding 200 μmol/L CoCl2 can enhance the expression of hypoxia-related proteins,lipolytic enzymes,and insulin-related signaling proteins in primary bovine adipocytes.

This video presents a case of L4–5 unstable spondylolisthesis treated with full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF), emphasizing the GUARD (Glider Used as a Rotary Device) technique for nerve root protection. This innovative approach involves controlled rotation of the cage glider before cage insertion to minimize the risk of nerve root injury, a significant complication in Endo-TLIF procedures. The GUARD technique, validated in previous cadaveric studies, provides enhanced safety during cage insertion by protecting the nerve root. A 48-year-old woman with a 3-year history of progressive low back pain and bilateral lower extremity radiculopathy (right-sided predominance) was diagnosed with L4–5 unstable spondylolisthesis and spinal stenosis. After failure of conservative management, she underwent uniportal full-endoscopic facet-resecting transforaminal lumbar interbody fusion using the GUARD technique. Postoperatively, the patient experienced significant symptomatic improvement and resolution of radiculopathy, without any intraoperative nerve root injury or postoperative neurological deficits. This case demonstrates the effectiveness of the GUARD technique in reducing neurological complications and improving patient outcomes.

Objective: Uniportal full-endoscopic transforaminal lumbar interbody fusion (FE-TLIF) carries a unique risk of nerve traction and abrasion injury during cage insertion. This study aims to evaluate the clinical efficacy of the GUARD technique and delayed ligamentum flavectomy in reducing postoperative radicular pain and neurapraxia in patients undergoing uniportal FE-TLIF. Methods: A retrospective analysis was conducted on 45 patients with an average age of 53.9±12.4 years who underwent either FE facet-sparing TLIF (FE fs-TLIF) or FE facet-resecting TLIF (FE fr-TLIF). Patients were divided into 2 groups: the sentinel group (21 patients) using traditional sentinel pin techniques, and the GUARD group (24 patients) using the GUARD technique with delayed ligamentum flavectomy. Patient-reported outcomes included the visual analogue scale (VAS) for leg and back pain, and Oswestry Disability Index. Complication rates, including incidental durotomy, postoperative neurapraxia, and hematoma, were also documented. Results: Postoperative radicular pain in the legs was significantly reduced at 6 weeks in the GUARD group compared to the sentinel group (VAS: 2.201 vs. 3.267, p=0.021). The incidence of postoperative neurapraxia was markedly lower in the GUARD group (0% vs. 19%, p=0.047). Both groups showed similar improvements in disc height, segmental lordosis, and lumbar lordosis at the 1-year follow-up, with no significant differences in endplate injury or fusion rates. Conclusion The GUARD technique and delayed ligamentum flavectomy significantly enhance patient safety by reducing postoperative radicular pain and neurapraxia without incurring additional costs. These techniques are easy to learn and integrate into existing surgical workflows, offering a valuable improvement for surgeons performing FE-TLIF procedures.

This video presents a case of L4–5 unstable spondylolisthesis treated with full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF), emphasizing the GUARD (Glider Used as a Rotary Device) technique for nerve root protection. This innovative approach involves controlled rotation of the cage glider before cage insertion to minimize the risk of nerve root injury, a significant complication in Endo-TLIF procedures. The GUARD technique, validated in previous cadaveric studies, provides enhanced safety during cage insertion by protecting the nerve root. A 48-year-old woman with a 3-year history of progressive low back pain and bilateral lower extremity radiculopathy (right-sided predominance) was diagnosed with L4–5 unstable spondylolisthesis and spinal stenosis. After failure of conservative management, she underwent uniportal full-endoscopic facet-resecting transforaminal lumbar interbody fusion using the GUARD technique. Postoperatively, the patient experienced significant symptomatic improvement and resolution of radiculopathy, without any intraoperative nerve root injury or postoperative neurological deficits. This case demonstrates the effectiveness of the GUARD technique in reducing neurological complications and improving patient outcomes.

Objective: Uniportal full-endoscopic transforaminal lumbar interbody fusion (FE-TLIF) carries a unique risk of nerve traction and abrasion injury during cage insertion. This study aims to evaluate the clinical efficacy of the GUARD technique and delayed ligamentum flavectomy in reducing postoperative radicular pain and neurapraxia in patients undergoing uniportal FE-TLIF. Methods: A retrospective analysis was conducted on 45 patients with an average age of 53.9±12.4 years who underwent either FE facet-sparing TLIF (FE fs-TLIF) or FE facet-resecting TLIF (FE fr-TLIF). Patients were divided into 2 groups: the sentinel group (21 patients) using traditional sentinel pin techniques, and the GUARD group (24 patients) using the GUARD technique with delayed ligamentum flavectomy. Patient-reported outcomes included the visual analogue scale (VAS) for leg and back pain, and Oswestry Disability Index. Complication rates, including incidental durotomy, postoperative neurapraxia, and hematoma, were also documented. Results: Postoperative radicular pain in the legs was significantly reduced at 6 weeks in the GUARD group compared to the sentinel group (VAS: 2.201 vs. 3.267, p=0.021). The incidence of postoperative neurapraxia was markedly lower in the GUARD group (0% vs. 19%, p=0.047). Both groups showed similar improvements in disc height, segmental lordosis, and lumbar lordosis at the 1-year follow-up, with no significant differences in endplate injury or fusion rates. Conclusion The GUARD technique and delayed ligamentum flavectomy significantly enhance patient safety by reducing postoperative radicular pain and neurapraxia without incurring additional costs. These techniques are easy to learn and integrate into existing surgical workflows, offering a valuable improvement for surgeons performing FE-TLIF procedures.