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.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14％),lower ileum 10 cases(17.86％),posterior cecum 16 cases(28.57％),lower cecum 9 cases(16.07％),lateral cecum 2 cases(3.58％),posterior ileum 6 cases(10.71％),high(subhepatic)9 cases(16.07％),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter＞6 mm in 49 cases(87.50％),appendicular wall thickening＞2 mm in 42 cases(75.00％),ppendiceal dilation lumen and effusion in 29 cases(51.79％),appendix indistinctness in 3 cases(5.36％),lppendix fecalith:27 cases(48.21％),gas in the appendix in 16 cases(28.57％).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14％),appendiceal cellulitis with peripheral abscess in 9 cases(16.07％),peritonitis and ascites in 13 cases(23.21％),ileocecal intestinal wall thickening in 22 cases(39.29％),mesenteric lymph node enlargement in 16 cases(28.57％),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93％).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.

OBJECTIVE To investigate the current status of monitoring indicators related to the"Perioperative In-fection Control"in medical institutions above the secondary level in Guizhou Province,and to delve into the imple-mentation of key measures for infection prevention and control during the perioperative period for patients under-going surgical operations.METHODS Based on the"Implementation Plan for the'Perioperative Infection Control'Initiative in Guizhou Province",a"Case Investigation Form on Key Measures for Infection Prevention and Control During the Perioperative Period for Patients Undergoing Surgical Operation"was developed.A total of 138 medi-cal institutions participated in the case investigation,and a total of 2 128 cases were investigated.RESULTS The overall monitoring indicators for the"Perioperative Infection Control"initiative in the 138 medical institutions a-bove the secondary level in Guizhou Province were at a relatively low level.The skin cleansing compliance rate was 80.32％,the hair removal compliance rate was 16.43％,the prophylactic antibacterial drug administration rate within 0.5-1 hour before surgery was 55.94％and the antibacterial drug discontinuation rate within 24 hours after prophylactic medication for type Ⅰ incision surgeries was 56.48％.The hair removal compliance rate was higher in tertiary medical institutions(19.21％)than in secondary medical institutions(14.34％)(P=0.039).The distri-bution of the four monitoring indicators varied in clinical departments and surgery types,with statistically signifi-cant differences(P＜0.05).The preferred method for surgical site skin cleansing in medical institutions across the province was local wiping,primarily with clean water(57.21％).The primary method for hair removal was razors(68.82％),and hair removal on the day of surgery was most common(61.75％).CONCLUSIONS Conduc-ting a survey on the current status of"Perioperative Infection Control"initiative monitoring indicators in medi-cal institutions in Guizhou Province helps to understand the implementation of key measures for perioperative in-fection prevention and control and set intervention targets,thus providing references for establishing a dynam-ic monitoring indicator change mechanism.

Objective To investigate the effect of tirofiban combined with oxiracetam on acute anterior circulation progressive cerebral infarction.Methods A total of 171 patients with acute anteri-or circulation progressive cerebral infarction from October 2022 to January 2024 were enrolled and ran-domly divided into three groups using a random number table.The control group of 57 patients re-ceived conventional treatment,the observation group A received tirofiban in addition to conventional treatment,and the observation group B received oxiracetam on the basis of observation group A's treat-ment.The effectiveness indicators[including the rates of neurological improvement and neurological deterioration at 14 days after treatment,the rate of good prognosis and modified Rankin Scale(MRS)scores at 90 days after treatment,as well as the National Institutes of Health Stroke Scale(NIHSS)scores at 7 and 14 days after treatment and their differences from baseline],cognitive function[as-sessed using the Montreal Cognitive Assessment(MOCA)],and safety indicators(incidence rates of symptomatic intracranial hemorrhage,fatal intracranial hemorrhage,and mortality at 90 days after treat-ment)were compared among the three groups.Results There were no statistically significant differ-ences in the rates of neurological improvement and neurological deterioration at 14 days after treatment,the rate of good prognosis,and MRS scores at 90 days after treatment among the three groups(P＞0.05).There were statistically significant differences in NIHSS scores between baseline and 7 and 14 days after treatment in all three groups(P＜0.05),and the differences in NIHSS scores from baseline at the above time points were higher in observation group B than in observation group A and the control group(P＜0.05).There were no statistically significant differences in MOCA scores among the three groups before treatment(P＞0.05);however,the MOCA scores in the observation group B were higher than those in observation group A and the control group at 14,30,and 90 days after treatment(P＜0.05).There were no statistically significant differences in the incidence rates of symptomatic intracranial hemorrhage,fatal intracranial hemorrhage,and mortality at 90 days after treatment among the three groups(P＞0.05).Conclusion Tirofiban combined with oxiracetam can improve cognitive function in patients with acute anterior circulation progressive cerebral infarc-tion without increasing the risk of hemorrhage,and has better prognosis.

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.

Aim To investigate the effects of SAHA on the expression of P-gp and the pharmacokinetic pa-rameters of its substrate phenytoin sodium in rats under hypoxic environments.Methods Wistar rats were randomly divided into the normioxic group,the hypoxic model group,and the low-,medium-and high-dose vorinostat(SAHA)groups.Liver tissues were col-lected,and the expression levels of P-gp and HDAC5 were detected by Real-time PCR and Western blot.The morphological changes of liver tissues were ob-served by HE staining.Following intragastric adminis-tration of 50 mg·kg-1 phenytoin sodium to each group,blood samples were collected,and the plasma concentration of phenytoin sodium was determined u-sing UFLC-MS/MS to calculate pharmacokinetic pa-rameters.Results Compared with the normoxic group,the expression of HDAC5 in the liver tissues of hypoxia model rats increased,while the expression of P-gp decreased.After SAHA treatment,HDAC5 expression decreased,and P-gp expression increased.Among the SAHA groups,the medium-dose group showed the most significant effect,and HE staining re-sults indicated that this concentration did not cause damage to rat liver tissues.Compared with the normox-ic group,the AUC,Cmax,and T1/2 of phenytoin sodium in hypoxia model rats were significantly raised.After administration of the medium dose of SAHA,the AUC,Cmax,MRT,and T1/2 were significantly reduced,while CLZ/r was significantly increased.Conclusions Un-der hypoxic environments,the expression of P-gp in rat liver tissue is significantly downregulated,leading to increased systemic exposure of phenytoin,reduced clearance,and consequently elevated blood concentra-tions,raising the risk of central nervous system toxici-ty.In contrast,SAHA suppresses HDAC5 expression,thereby activating P-gp transcription and enhancing its efflux function.This results in decreased systemic ex-posure and improved clearance of phenytoin,signifi-cantly reducing drug accumulation in body and ulti-mately lowering the risk of adverse effects.

BACKGROUND:Neurodegenerative diseases are closely related to the imbalance of mitochondrial autophagy regulation.Previous studies by the research group have shown that lycium barbarum polysaccharide has neuroprotective effects,but whether it can improve the damage of SH-SY5Y cells induced byβ-amyloid protein 1-42 by regulating mitochondrial autophagy is still unclear.OBJECTIVE:To explore the protective effect and mechanism of Lycium barbarum polysaccharide on SH-SY5Y cells induced by β-amyloid protein 1-42.METHODS:An Alzheimer's disease cell model was established by inducing SH-SY5Y cells with β-amyloid protein 1-42,and then intervening with Lycium barbarum polysaccharide.SH-SY5Y cells were divided into three groups:control group,β-amyloid protein 1-42 group(20 μmol/L β-amyloid protein 1-42 for 24 hours),and Lycium barbarum polysaccharide group(1 g/L Lycium barbarum polysaccharide was added 1 hour in advance to form a protective effect,and then 20 μmol/L β-amyloid protein 1-42 was added to intervene with Lycium barbarum polysaccharide for 24 hours).CCK8 assay was used to detect cell viability.Mitochondrial membrane potential was detected by JC-1.TUNEL staining was used to detect cell apoptosis.Immunofluorescence and western blot assay were used to detect the expression of synaptic,apoptosis,and mitophagy-related indicators.RESULTS AND CONCLUSION:(1)Compared with the control group,the cell viability of the β-amyloid protein 1-42 group decreased(P＜0.05);cell apoptosis rate increased(P＜0.05);mitochondrial membrane potential decreased(P＜0.05);the expressions of pro-apoptotic proteins Bax and Caspase3 increased(P＜0.05);the expression of anti-apoptotic protein Bcl-2 decreased(P＜0.05);the expression levels of synaptic-related proteins Syn and PSD-95 decreased(P＜0.05);the expression levels of mitochondrial autophagy-related proteins Pink1,LC3A/B,Parkin,and Beclin-1 decreased(P＜0.05);and the expression of P62 increased(P＜0.05).(2)Compared with the β-amyloid protein 1-42 group,the cell viability in the Lycium barbarum polysaccharide group was increased(P＜0.05);the apoptosis rate was decreased(P＜0.05);the mitochondrial membrane potential was increased(P＜0.05);the expression levels of Bax and Caspase3 were decreased(P＜0.05);the expression of Bcl-2 was increased(P＜0.05);the expressions of Syn and PSD-95 were increased(P＜0.05);the expression levels of Pink1,LC3A/B,Parkin,and Beclin-1 were increased(P＜0.05),and the expression of P62 was decreased(P＜0.05).These findings indicate that Lycium barbarum polysaccharide may inhibit β-amyloid protein 1-42-induced damage to SH-SY5Y cells by regulating mitophagy,reduce cell apoptosis,and increase neuronal synaptic plasticity.

The C 2-C 7 sagittal vertical axis (SVA) is an essential biomechanical parameter for evaluating cervical spine alignment, and it is integral to the pathogenesis, progression, and prognosis of cervical spine disorders. This parameter is widely used in evaluating cervical sagittal balance and functional status. Internationally, a C 2-C 7 SVA of less than 25 mm is considered within the cervical range for sagittal balance, while values exceeding 40 mm indicate cervical sagittal imbalance or deformity. An increased C 2-C 7 SVA disrupts cervical spine biomechanics, leading to heightened static and dynamic loads on the cervical musculature. This, in turn, results in muscle fatigue and discomfort. In the short term, patients may experience axial neck symptoms, while a sustained elevation in SVA over time significantly raises the risk of cervical disc degeneration, radiculopathy, and myelopathy. Additionally, a higher C 2-C 7 SVA postoperatively places excessive stress on adjacent spinal segments, which can accelerate degeneration of intervertebral discs and facet joints, contributing to adjacent segment degeneration. Both short-term and long-term postoperative evaluations have shown that an increase in C 2-C 7 SVA is typically associated with poorer surgical outcomes, whereas effective control of SVA values is closely linked to better functional recovery. Therefore, in clinical practice, maintaining C 2-C 7 SVA within the normal range (<25 mm) is critical not only for optimizing treatment results but also for significantly reducing postoperative complications and improving overall patient quality of life.

Objective To compare imaging quality and semi-quantitative parameters of 18F-FDG whole-body images obtained with domestic NeuWise and Philips Ingenuity TF PET/CT scanners.Methods Thirty-four patients who underwent 18F-FDG whole-body scanning using NeuWise and Philips Ingenuity TF PET/CT systems respectively on the same day were enrolled.The imaging quality and semi-quantitative parameters of 2 kind images,also the mean standard uptake value(SUVmean)of normal tissue,the maximum standard uptake value(SUVmax),peak standard uptake value(SUVpeak),SUVmean of lesions,total lesion glycolysis(TLG)and metabolic tumor volume(MTV)were compared.Results No significant difference of imaging quality nor semi-quantitative parameters of lesions(all P＞0.05),while significant differences of SUVmean of aortic arch,liver,lumbar vertebra and spinal cord were found between 2 kind images(all P＜0.05).Strong correlations of SUVmax,SUVmean,MTV and TLG of lesions(r,=0.734-0.890,P＜0.001),and high correlation of SUVpeak(rs=0.919,P＜0.001)were found between 2 kind images.The consistency of SUVmax,SUVpeak,SUVmean,TLG and MTV at the lesion site between 2 kind images were very good to extremely good(ICC=0.891-0.986,all P＜0.001),and the differences of all above semi-quantitative parameters were within 95％confidence interval.Conclusion Imaging quality of 18F-FDG whole-body images obtained with domestic NeuWise and Philips Ingenuity TF PET/CT scanners could meet the requirements of clinical diagnosis and treatment,and semi-quantitative parameters obtained based on both images had good consistencies.