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 investigate the therapeutic efficacy， influencing factors， and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus （HCV） infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1， 2021 to May 31， 2024 were enrolled， among whom there were 86 patients with compensated liver cirrhosis （CLC group） and 167 patients with chronic hepatitis C （CHC group）. The patients were treated with coblopasvir hydrochloride capsules （60 mg）/sofosbuvir tablets （400 mg） with or without ribavirin tablets for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment （SVR12） and safety， and the secondary outcome measures were the changes in liver function， renal function， blood routine， and liver stiffness measurements （LSM） after 4 weeks of treatment， after 12 weeks of treatment， and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups， and the Friedman test was used for comparison between multiple groups， while the Bonferroni method was used for paired comparison within each group； the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years， and there were 151 male patients （59.7%）. Of all patients， 33.99% （86/253） had liver cirrhosis， 25.69% （65/253） had hypertension， 10.67% （27/253） had HIV infection， 8.70% （22/253） had diabetes， 3.95% （10/253） had liver cancer， 1.98% （5/253） had chronic hepatitis B， and 7.91% （20/253） were treatment-experienced patients. As for genotype distribution， 2.77% （7/253） had genotype 1， 12.65% （32/253） had genotype 2， 66.01% （167/253） had genotype 3， 16.60% （42/253） had genotype 6， and 1.98% （5/253） had unknown genotype. The patients had an overall SVR12 rate of 92.09%， with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.086， 95% confidence interval ［CI］： 1.007 — 1.170， P=0.032） and HCC （OR=9.178， 95%CI： 1.722 — 48.912， P=0.009） were independent influencing factors for sustained virologic response. Compared with baseline data， the CLC group had significant reductions in alanine aminotransferase （ALT） （χ²=107.103， P0.05）， aspartate aminotransferase （AST） （χ²=90.602， P0.05）， and LSM （χ²=42.235， P0.05） after 12 weeks of treatment， while the CHC group had significant reductions in total bilirubin （χ²=15.113， P0.05）， ALT （χ²=202.237， P0.05）， AST （χ²=161.193， P0.05）， and LSM （χ²=37.606， P0.05）. The incidence rate of serious adverse events was 1.58%， and none of the patients withdrew from drug therapy； the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%， among which fatigue （17.39%） and nausea （2.37%） were the most common adverse events， and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.

Objective:Analyzing the relationship between negative life events and depressive symptoms in university freshmen,and the mediating effects of neuroticism and the moderating role of exercise frequency.Meth-ods:A sampling of 8 079 university freshmen,and the Patient Health Questionnaire was used to assess depressive symptoms,the Eysenck Personality Inventory-Neuroticism subscale to assess neuroticism,the self-administered questionnaire to assess the number of negative life events that the participants had experienced and the exercise fre-quency.Model 4 in the Process plug-in was used to test the mediating effect of neuroticism,and Model 7 to test the moderating role of exercise frequency.Results:The numbers of negative life events were positively correlated with the depressive symptoms scores(r=0.16,P＜0.01),and were positively correlated with the neuroticism scores(r=0.26,P＜0.01).The neuroticism scores were positively correlated with the depressive symptoms scores(r=0.52,P＜0.01).Neuroticism score partially mediated between negative life events and depressive symptoms score,with a mediating effect of 78.4％,and exercise frequency score moderated between negative life events and neuroti-cism scores(β=-0.05,P=0.032).Conclusion:Negative life events are associated with depressive symptoms,neuroticism plays a mediating role,and exercise frequency could moderate negative life events and neuroticism.

Traumatic brain injury (TBI) can cause a series of secondary changes, such as neuronal dysfunction, blood-brain barrier destruction, secondary neurovascular injury, neuroinflammation, and even neurodegenerative diseases. In recent years, studies have found that microglia can regulate the long-term inflammation and tissue repair process after TBI through the changes of M1 phenotype and M2 phenotype, affecting the TBI progress. Therefore, this article reviews the recent advance in role of microglia, regulatory mechanisms and related therapies of microglia after TBI, in order to provide some references for TBI treatment.

Objective The causes of bleeding after endoscopic duodenal papilloma resection were analyzed and discussed,and the prediction model of nomogram was established.Methods A total of 233 patients who underwent endoscopic duodenal papilloma resection in our hospital from January 2018 to December 2023 were retrospectively analyzed,and they were divided into bleeding group(n=31 cases)and non-bleeding group(n=202 cases)according to whether postoperative bleeding occurred.The clinical data of the two groups were compared,the independent risk factors for postoperative bleeding were analyzed by multi-factor logistic regression,the risk nomogram prediction model was constructed,and the Bootstrap method was used for 1000 repeated samples to carry out internal verification.Results Anticoagulant drugs(OR=9.063,95％CI:2.132-38.525),lesion diameter ≥2 cm(OR=2.802,95％CI:1.073-7.321),intraoperative fragment resection(OR=27.653,95％CI:3.055～619.174)and pancreatic complications(OR=6.859,95％CI:1.930～24.377)were independent risk factors for postoperative bleeding after endoscopic duodenal papilloma resection(P＜0.05).A risk prediction nomogram model was constructed according to the Logistic regression analysis results.The samples were repeatedly sampled 1000 times through Bootstrap method for internal verification.The area under the ROC curve was 0.850,and the 95％CI was 0.780-0.913,indicating good differentiation ability of the model.Calibration curve analysis indicated that the prediction probability of postoperative bleeding predicted by the nomogram prediction model was in good agreement with the actual probability of postoperative bleeding,and Hosmer-Lemeshow showed good goodness of fit(x2=3.304 9,P=0.913 8).Conclusion Taking anticoagulant drugs,lesion diameter ≥2 cm,intraoperative segmentary resection,and postoperative combination of pancreas were independent risk factors for bleeding after endoscopic duodenal papilloma resection.A nomogram prediction model was established to help clinical assessment of postoperative bleeding risk in patients and improve decision-making basis for early prevention.

Objective To observe the value of 18F-FDG PET/CT semi-quantitative parameters for predicting spread through air spaces(STAS)of clinical stage Ⅰa—Ⅲa lung adenocarcinoma.Methods Data of 85 patients with clinical stage Ⅰa—Ⅲ a lung adenocarcinoma who underwent preoperative 18F-FDG PET/CT were retrospectively analyzed.The patients were divided into positive group(n=23)or negative group(n=62)according to whether pathology showed STAS or not.Clinical and PET/CT data were compared between groups,and logistic analysis was performed to explore the efficacy of each parameter for predicting STAS.Results Significant differences of gender,carcinoma embryonic antigen,clinical stage,pathological grade,micropapillary growth and proportion were found between groups(all P＜0.05).The maximum,the mean,the peak standard uptake value(SUVmax,SUVmean,SUVpeak),as well as the maximum,the mean and the peak standard uptake value normalized by lean body mass(SULmax,SULmean,SULpeak),also the total lesion glycolysis(TLG)in positive group were all significantly higher than those in negative group(all P＜0.05).Patients'gender,proportion of micropapillary growth,SUVmax and SULmax were all independent risk factors of STAS of clinical stage Ⅰa—Ⅲa lung adenocarcinoma.The area under the curve(AUC)of the above parameters for predicting STAS was 0.666,0.912,0.839 and 0.842,respectively,and of the combination was 0.957.Conclusion 18 F-FDG PET/CT semi-quantitative parameters SUVmax and SULmax were helpful for predicting STAS of clinical stage Ⅰa—Ⅲ a lung adenocarcinoma,and further combination of gender and proportion of micropapillary growth could improve diagnostic efficacy.

Objective To observe the clinical efficacy of Tongfengke Granules combined with external treatment of TCM in acute gouty arthritis(AGA)with damp-heat accumulation type.Methods A total of 96 patients with AGA were divided into the experimental group and the control group according to random number table method,with 48 patients in each group.The control group received meloxicam treatment.On this basis,the experimental group was treated with Tongfengke Granules(1 bag at a time,three times a day,orally)combined with external therapy of TCM(once a day),and mobile continuing care.The treatment for both groups lasted for 2 weeks.The clinical efficacy of both groups was observed.Before and after the treatment,pain visual analogue scale(VAS),TCM syndrome scores,major symptom scores,and levels of serum uric acid(UA),interleukin-6(IL-6),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),platelet/lymphocyte ratio(PLR),as well as engagement in self-care ability scale(ESCA),general self-efficacy scale(GSES),negative psychological condition[self-rating depression scale(SDS),self-rating anxiety scale(SAS)]were measured.The adverse reactions in both groups were monitored.Results Totally 45 and 47 patients in the experimental group and control group were finally included respectively in the analysis.The total effective rate of the experimental group was 75.6%(34/45),while that of the control group was 63.8%(30/47),with statistical significance(P<0.05).Compared with before treatment,the VAS score and TCM syndrome score in the experimental group decreased significantly(P<0.05);after treatment,the VAS score and TCM syndrome score of the experimental group were lower than those of the control group(P<0.05).Compared with before treatment,the joint pain,joint tenderness,joint swelling,and joint mobility limitation scores in both groups were significantly decreased after treatment(P<0.05,P<0.01);after treatment,the scores of joint pain,joint tenderness,and joint swelling in the experimental group were lower than those in the control group(P<0.01).Compared with before treatment,the levels of UA,ESR,CRP and PLR in both groups decreased significantly after treatment(P<0.01);after treatment,the levels of UA,ESR,CRP and PLR in the experimental group were lower than those in the control group(P<0.05,P<0.01).Compared with before treatment,the experimental group showed significant improvement in ESCA,GSES and SAS after treatment(P<0.05,P<0.01),while the control group showed significant improvement in ESCA(P<0.01);after treatment,the ESCA and GSES of the experimental group were better than those of the control group(P<0.05,P<0.01).There was no statistical significance in safety indicators and incidence of adverse reactions between the two groups(P>0.05).Conclusion Tongfengke Granules combined with external treatment of TCM can significantly improve the clinical efficacy of AGA,reduces UA levels,significantly improves inflammatory response,and has anti-inflammatory,anti-inflammatory,and analgesic effects.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

ObjectiveTo investigate the effect of Tangbikang granules on oxidative stress of sciatic nerve in diabetic rats by regulating adenylate activated protein kinase/peroxisome proliferator-activated receptor γ coactivator-1α/mitochondrial Sirtuins 3 （AMPK/PGC-1α/SIRT3） signaling pathway. MethodThe spontaneous obesity type 2 diabetes model was established using ZDF rats. After modeling， they were randomly divided into high， medium， and low dose Tangbikang granule groups （2.5， 1.25， 0.625 g·kg^-1·d^-1） and lipoic acid group （0.026 8 g·kg^-1·d^-1）， and the normal group was set up. The rats were administered continuously for 12 weeks after modeling. The blood glucose of rats was detected before intervention and at 4， 8， 12 weeks after intervention. At the 12^th week， motor nerve conduction velocity （MNCV）， sensory nerve conduction velocity （SNCV）， nerve blood flow velocity， mechanical pain threshold， and thermal pain threshold were detected. The sciatic nerve was taken for hematoxylin-eosin （HE） staining to observe the tissue morphology. The ultrastructure of the sciatic nerve was observed by transmission electron microscope. The expression levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in sciatic nerve were determined by enzyme-related immunosorbent assay （ELISA）. The mRNA expressions of AMPKα， AMPKβ， PGC-1α， and SIRT3 in sciatic nerve were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， fasting blood glucose in the model group was increased at each time point （P<0.01）. The mechanical pain threshold was decreased （P<0.05）， and the incubation time of the hot plate was extended （P<0.01）. MNCV， SNCV， and nerve blood flow velocity decreased （P<0.05）. The expression level of SOD was decreased （P<0.01）. The expression levels of MDA， IL-1β， and TNF-α were increased （P<0.01）. The mRNA expression levels of AMPKα， AMPKβ， PGC-1α， and SIRT3 were decreased （P<0.01）. The structure of sciatic nerve fibers in the model group was loose， and the arrangement was disordered. The demyelination change was obvious. Compared with the model group， the fasting blood glucose of rats in the high dose Tangbikang granule group was decreased after the intervention of eight weeks and 12 weeks （P<0.01）. The mechanical pain threshold increased （P<0.05）. The incubation time of the hot plate was shortened （P<0.01）. MNCV， SNCV， and Flux increased （P<0.05）. The expression level of SOD was increased （P<0.01）. The expression levels of MDA， IL-1β， and TNF-α were decreased （P<0.01）. The mRNA expression levels of AMPKα， AMPKβ， PGC-1α， and SIRT3 were increased （P<0.01）. The sciatic nerve fibers in the high-dose Tangbikang granule group were tighter and more neatly arranged， with only a few demyelinating changes. The high， medium， and low dose Tangbikang granule groups showed a significant dose-effect trend. ConclusionTangbikang granules may improve sciatic nerve function in diabetic rats by regulating AMPK/PGC-1α/SIRT3 signaling pathway partly to inhibit oxidative stress.

Objective:To investigate the associated factors of depressive symptoms among patients with neo-plasms.Methods:Nationwide(excluding Hong Kong,Macao,and Taiwan),30 505 residents were selected by a combination of stratified sampling and quota sampling according to the proportion of the seventh national population census.Patient Health Questionnaire-9(PHQ-9),General Anxiety Disorder-7(GAD-7),self-made questionnaire,and simplified perceived social support scale used to evaluate depressive symptoms,anxiety symptoms,behaviors,and perceived social support among patients with neoplasms.Results:Totally 359(1.2％)patients with self-repor-ted clinically diagnosed neoplasms were included,of which 151(42.1％)patients with malignant neoplasms and 208(57.9％)patients with benign neoplasms.The detection rate of depressive symptoms in patients with neo-plasms was 76.6％.Less than three days of walking for more than 10 minutes per day in the past week(OR=6.63),4-6 days of walking for more than 10 minutes per day in the past week(OR=5.00),the low(OR=4.80)or medium(OR=3.06)overall sleep quality,the lower perceived friend support(OR=4.66),and anxiety symp-toms(OR=1.74)among patients with neoplasms were risk factors for depressive symptoms.Conclusion:Patients with neoplasms generally might be at a high risk of depressive symptoms,especially for those patients with less ex-ercise,poor sleep quality,and low perceived social support.