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.

ObjectiveTo explore the main mechanism of self-precipitation formed during the decoction of Sinitang（SNT）， and to provide a research basis for exploring the differences in the toxic and effective components of this compound. MethodsThe average precipitation yields of SNT， Glycyrrhizae Radix et Rhizoma（GRR）-Aconiti Lateralis Radix Praeparata（ALRP） decoction（GF）， ALRP-Zingiberis Rhizoma（ZR） decoction（FJ）， GRR-ZR decoction（GJD）， ALRP decoction（FZ）， ZR decoction（GJ） and GRR decoction（GC） were determined. The four main self-precipitation samples of SNT， GF， FZ and GC were physically characterized by particle size， scanning electron microscopy（SEM）， pH， total dissolved solids（TDS）， conductivity， and Fourier transform infrared spectroscopy（FT-IR） analysis. The chemical compositions of SNT decoction and its different phases was identified by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS） for SNT， SNT self-precipitation and SNT supernatant， and the contents of its main toxic and effective components were determined by high performance liquid chromatography（HPLC）. ResultsPrecipitation yield results of the 7 samples of SNT decoction and single decoction showed that SNT had the highest self-precipitation yield. The formation of SNT self-precipitation was mainly related to the reaction between ALRP and GRR components to form complexes， and FT-IR showed that GRR had the greatest influence on the formation of self-precipitation. A total of 110 components were identified in the SNT decoction， including 100 components in the SNT self-precipitation and 106 components in the SNT supernatant. And quantitative results of the main toxic and effective components revealed that the reaction between ALRP and GRR components formed complexes， resulting in the following content hierarchy for free components：SNT decoctionsupernatantself-precipitation， these components included free liquiritin， benzoylmesaconine， benzoylaconitine， benzoylhypacoitine， liquiritigenin， aconitine， hypoaconitine， isoliquiritigenin and ammonium glycyrrhizinate. ConclusionSNT exhibits spontaneous precipitation during compound decoction， with GRR exerting the greatest influence on its formation. This suggests GRR plays a significant role in the detoxification of SNT. The differences in the self-precipitated toxic-effective components of SNT compound decoction primarily manifest as changes in component content， reflecting the characteristics of SNT "deposition in vitro and sustained release in vivo" and the importance of "administered at draught" in the clinical application of SNT.

Evidence-based medicine (EBM) is a science that uses the best available research data to make decisions, and the core is that clinical decision-making is supported by the best research evidence. Incorporating EBM into traditional standardized residency training in hematology can foster residents' professional theoretical knowledge and clinical skills, improve the quality of standardized training, and provide ideas and methods for standardized training of hematology residents, which is worthy of further research and exploration.

Aim To evaluate the effectiveness and safety of remimazolam tosylate for administering general anesthesia in morbidly obese patients.Methods This clinical trial was conducted at a single center from De-cember 2021 to October 2023.It assessed 108 morbid-ly obese patients(body mass index,BMI≥40)who underwent laparoscopic sleeve gastrectomy.Patients were randomly assigned to either the remimazaolam group(Group R)or the propofol group(Group P)for general anesthesia induction and maintenance.The primary outcome was to compare the incidence of ad-verse events and postoperative recovery characteristics between the two groups.Results During induction pe-riod,the incidence of adverse events was higher in group P,including hypotension(P＜0.01),hypox-emia(P＜0.05),bradycardia(P＜0.01),and in-creased vasopressor requirement(P＜0.05).The time to loss of consciousness and BIS falling to 60 was shor-ter in group P than in group R(P＜0.01).There were no statistically significant differences between the two groups in terms of postoperative quality of recovery(QoR-40 score),24-hour postoperative pain visual an-alogue scale(VAS)scores and morphine consump-tion.In conclusion,remimazolam tosylate,utilized for anesthesia induction in morbidly obese patients,signif-icantly reduced hypotension and hypoxemia compared to propofol,while it could also maintain similar postop-erative recovery quality.Conclusions Remimazolam is effective in reducing the incidence of hypotension and hypoxaemia during the induction period of general anaesthesia in morbidly obese patients and it is compa-rable to propofol in terms of quality of postoperative re-covery.

Objective We aimed to compare the efficacy and prognosis of percutaneous coronary intervention(PCI)in complex and high-risk patients with coronary heart disease(CHD)treated with extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)assistance,and explore the application value of combined use of mechanical circulatory support(MCS)devices in complex PCI.Methods A total of patients who met the inclusion criteria and underwent selective PCI supported by MCS at the Department of Cardiology,the First Affiliated Hospital of the Air Force Medical University from January 2018 to December 2022 were continuously enrolled.According to the mechanical circulatory support method,the patients were divided into ECMO+IABP group and IABP group.Clinical characteristics,angiographic features,in-hospital outcomes,and complications were collected.The intra-hospital outcomes and major adverse cardiovascular events(MACE)at one month and one year after the procedure were observed.The differences and independent risk factors between the two groups in the above indicators were analyzed.Results A total of 218 patients undergoing elective PCI were included,of which 66 patients were in the ECMO+IABP group and 152 patients were in the IABP group.The baseline characteristics of the two groups of patients were generally comparable,but the ECMO+IABP group had more complex lesion characteristics.The proportion of patients with atrial fibrillation(6.1％vs.0.7％,P=0.030),left main disease(43.9％vs.27.0％,P=0.018),triple vessel disease(90.9％vs.75.5％,P=0.009),and RCA chronic total occlusion disease(60.6％vs.35.5％,P＜0.001)was higher in the ECMO+IABP group compared to the IABP group.The proportion of patients with previous PCI history was higher in the IABP group(32.9％vs.16.7％,P=0.014).There was no statistically significant difference in the incidence of in-hospital complications between the two groups(P=0.176),but the incidence of hypotension after PCI was higher in the ECMO+IABP group(19.7％vs.9.2％,P=0.031).The rates of 1-month MACE(4.5％vs.2.6％,P=0.435)and 1-year MACE(7.6％vs.7.9％,P=0.936)were comparable between the two groups.Multivariate analysis showed that in-hospital cardiac arrest(OR 7.17,95％CI 1.27-40.38,P=0.025)and after procedure hypotension(OR 3.60,95％CI 1.10-11.83,P=0.035)were independent risk factors for the occurrence of 1-year MACE.Conclusions Combination use of ECMO+IABP support can provide complex and high-risk coronary heart disease patients with an opportunity to achieve coronary artery revascularization through PCI,and achieve satisfactory long-term prognosis.

Objective:To evaluate the effectiveness of oral-nasal oxygen supply mouth guard in painless gastroscopy for snoring patients.Methods:The snoring patients who underwent painless gastroscopy at two Endoscopy Centers of Shanghai East Hospital, Tongji University in July 2022 were randomly divided into the observation group (using oral-nasal oxygen supply mouth guard) and the control group (using ordinary nasal oxygen tube and mouth guard). Parameters such as the wearing time and the removal time of the mouth guard, lowest pulse oxygen saturation (SpO 2), incidence of hypoxemia, and the satisfaction of medical staff were compared between the two groups. Results:The wearing time of mouth guard was 11.63±0.84 seconds and the removal time was 5.33±0.76 seconds in the observation group ( n=40), which were lower than those in the control group ( n=47) (14.91±1.21 seconds, t=-14.463, P<0.001; 10.38±0.80 seconds, t=-30.095, P<0.001). The wearing satisfaction score was 9.80±0.61, the lowest SpO 2 was (96.70±3.42)%, the removal satisfaction score was 9.75±0.67, and the anesthesiologists' satisfaction score was 9.20±1.42 in the observation group, which were higher than those in the control group [7.70±0.93, t=12.209, P<0.001; (94.06±3.72)%, t=3.417, P=0.001; 7.96±0.98, t=9.803, P<0.001; 8.13±1.35, t=3.615, P=0.001] with significant difference. There was no significant difference in the incidence of hypoxemia [10.00% (4/40) VS 14.89% (7/47), χ2=0.130, P=0.718] and endoscopic physician satisfaction score (9.30±0.97 VS 9.02±1.31, t=1.112, P=0.269) between the two groups. Conclusion:The oral-nasal oxygen supply mouth guard is easy to wear and remove, effectively reducing SpO 2 fluctuations during painless gastroscopy for snoring patients. It can enhance medical staff satisfaction with high clinical value.

Objective:To assess the correlation and consistency between the cancer risk-oriented endoscopic Kimura-Takemoto classification and the operative link for gastritis assessment (OLGA) in risk stratification of gastric cancer in patients with chronic gastritis after Helicobacter pylori ( H. pylori) eradication. Methods:From January 1, 2018 to October 31, 2021, 97 patients with chronic gastritis who successfully underwent H. pylori eradication at Beijing Friendship Hospital affiliated to Capital Medical University were selected. During the follow-up period, all patients underwent standardized magnifying endoscopy to assess gastric mucosal atrophy with the Kimura-Takemoto classification, which was classified as no or mild atrophy, moderate atrophy, and severe atrophy. Additionally, according to the new Sydney staging system, endoscopic biopsies were conducted at 5 sites of the patients to classify into OLGA stages 0, Ⅰ, Ⅱ, Ⅲ, or Ⅳ. Spearman rank correlation analysis and Kappa consistency test were performed to evaluate the correlation and consistency between the 2 evaluation systems, respectively. Area under the curve (AUC) of the receiver operating characteristic curve was used to calculate the predictive ability of the grading of gastric mucosal atrophy under endoscopy in high-risk histological staging. Furthermore, multivariate logistic regression analysis was used to assess factors influencing the consistency of the 2 evaluation systems. Chi-square test or Fisher′s exact test were used for statistical analysis. Results:Longitudinal follow-up was completed in 97 cases, with a follow-up time of (37.38±13.18) months after H. pylori eradication. The proportion of OLGA stage Ⅲ to Ⅳ in patients with no or mild atrophy (21.7%, 10/46) was lower than that in patients with moderate and severe atrophy (63.0%, 29/46 and 5/5, respectively), and the differences were statistically significant( χ2=16.07 and 13.30, both P<0.001). However, there was no significant difference in distribution of OLGA staging between patients with moderate atrophy and patients with severe atrophy (all P>0.05). The consistency rate of high-risk assessment for gastric cancer between the 2 evaluation systems was 73.2% (71/97). The correlation between the Kimura-Takemoto classification and OLGA staging was moderate ( r=0.47, 95% confidence interval(95% CI) 0.30 to 0.61, P<0.001). The result of consistency test indicated that the consistency of the 2 evaluation systems was moderate, and the Kappa value was 0.46 (95% CI 0.29 to 0.64, P<0.001). For patients with chronic gastritis after H. pylori eradication, the sensitivity of Kimura-Takemoto classification of moderate to severe atrophy under endoscopy in identifying high-risk of OLGA stages was 77.21% (95% CI 62.16% to 88.53%), the specificity was 69.81% (95% CI 55.66% to 81.66%), and the AUC was 0.735 (95% CI 0.636 to 0.820, P<0.01). As the time after H. pylori eradication increased (post- H. pylori eradication less than 18, 18 to 36, and more than 36 months), the consistency of atrophy assessment between the Kimura-Takemoto classification and OLGA staging reduced (7/8, 84.4% (27/32), 64.9% (37/57), respectively), and the difference was statistically significant ( χ2=4.36, P=0.037). The result of multivariate logistic regression analysis revealed that the time after H. pylori eradication more than 36 months ( OR=3.443, 95% CI 1.117 to 10.614, P=0.031) and gastric ulcer ( OR=3.928, 95% CI 1.177 to 13.110, P=0.026) were independent factors influencing the consistency between the Kimura-Takemoto classification and OLGA staging. Conclusions:The endoscopic and histological changes of chronic gastritis after eradication of H. pylori are consistent. Within short period after H. pylori eradication (no more than 36 months), the sensitivity of high-risk classification under endoscopy is high and the specificity is moderate, which can predict high-risk histological staging to a certain degree.

Objective Bioinformatics and machine learning were used to identify associations between key genes in obesity and osteoarthritis(OA)and immune infiltrating cells.Methods Three datasets GSE55235,GSE44000 and GSE151839 were screened from the gene expression omnibus(GEO)database,and differentially expressed genes(DEGs)were obtained by R software,and their potential biological functions were explored through gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)signaling pathway enrichment analysis.The minimum absolute contraction and selection operator(LASSO)regression algorithm combined with support vector machine(SVM)was used to screen characteristic genes,the diagnostic value of key genes was verified by receiver operating characteristic(ROC)curve,and the immune infiltration was assessed by CIBERSORT algorithm.The mRNA-miRNA regulatory network was constructed using NetworkAnalyst database to predict target miRNA and Cytoscape software,and the correlation between key genes and immune infiltration was analyzed.Results GO gene enrichment analysis obtained 99 DEGs.Cellular activation in the immune system and immune response is highly enriched.KEGG pathway analysis showed significant enrichment of interleukin(IL-17),nuclear factor-κB(NF-κB),B-cell receptor and chemokine signaling pathways.Two key diagnostic genes(MXRA5 and MYC)were identified based on machine learning.Immunoinfiltration analysis showed that MXRA5 was associated with resting and activated CD4 memory T cells,activated NK cells,resting and activated mast cells,and M0 macrophages.In addition,MYC is associated with resting and activated CD4 memory T cells,plasma cells,activated NK cells,resting and activated mast cells,M2 macrophages,and eosinophils.CD4+cells,NK cells and mast cells were significantly associated with these two pivot genes.Conclusion Two key immune-related genes were identified through bioinformatics analysis,which may provide new targets for the treatment of obesity-related OA.

The male patient,one day old,was admitted to the hospital due to hypoglycemia accompanied by apnea appearing six hours after birth.The patient had transient hypoglycemia early after birth,and acute heart failure suddenly occurred on the eighth day after birth.Laboratory tests showed significantly reduced levels of adrenocorticotropic hormone and cortisol,and pituitary magnetic resonance imaging was normal.Genetic testing results showed that the patient had probably pathogenic compound heterozygous mutations of the TBX19 gene(c.917-2A＞G+c.608C＞T),inherited respectively from the parents.The patient was conclusively diagnosed with congenital isolated adrenocorticotropic hormone deficiency caused by mutation of the TBX19 gene.Upon initiating hydrocortisone replacement therapy,cardiac function rapidly returned to normal.After being discharged,the patient continued with the hydrocortisone replacement therapy.By the 18-month follow-up,the patient was growing and developing well.In neonates,unexplained acute heart failure requires caution for possible endocrine hereditary metabolic diseases,and timely cortisol testing and genetic testing should be conducted.[Chinese Journal of Contemporary Pediatrics,2024,26(3):321-324,V]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.