Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

OBJECTIVE To investigate the modulating effect of neotropics on form deprivation myopia(FDM)in guinea pigs.METHODS Tricolour guinea pigs were randomly divided into normal control group,FDM model group,FDM+saline group,FDM+atropine group,and FDM+neotropine group,with eight animals in each group.Except for the normal control group,the right eyes of the guinea pigs were covered for 14 d to establish a guinea pig FDM model.The drug administration groups were injected with 10 μL of saline,1%atropine,or 1%neotropine into the vitreous cavity once every other day.The changes in the refractive error and axial length of both eyes were recorded for 1 d before the intervention and for 14 d after the intervention.Then,the eyeballs of guinea pigs were taken from the right eyes.HE staining was used to evaluate the histopathological structure of the sclera while sirius red staining was used to detect the collagen protein content in the sclera.RT-qPCR was used to detect the mRNA expressions of transforming growth factor-β1(TGF-β1),matrix metalloproteinase(MMP-2)and tissue inhibitor of metalloproteinase(TIMP-2)in guinea pigs'sclera.The protein expression levels of collagen type Ⅰ(Col-Ⅰ)and TGF-β1 in guinea pig sclera were detected by Western blotting while those of MMP-2,TIMP-2 and Ki-67 were detected by immunohistochemical staining.RESULTS Compared with the nor-mal control group,eyes of guinea pig in the FDM model group showed a significantly lower refractive error(P<0.01),significant elongation of the ocular axis(P<0.01),scattered distribution of scleral fibre bundles,sparse collagen cells,reduced scleral thickness(P<0.01),and a significantly lower collagen protein content(P<0.01).The mRNA and protein expressions of TIMP-2 and TGF-β1 were lower(P<0.05,P<0.01),and MMP-2 was higher(P<0.01)in scleral tissue.The protein expression level of Col-Ⅰwas lower(P<0.05)while that of Ki-67 was elevated(P<0.01)in scleral tissue.Compared with the FDM model group,there were no significant changes in any of the indexes in the FDM+saline group.The refractive error of the right eyes of guinea pigs in the FDM+neotropium group and the FDM+atropium group were significantly higher(P<0.05),the length of the ocular axis was significantly shorter(P<0.05),the collagen fibres were arranged more tightly,the fibre bundles were distributed more orderly,the distribution of the collagen cells was more uniform,and the thickness of the sclera was significantly increased(P<0.01).Collagen protein contents were significantly higher(P<0.05,P<0.01),the mRNA and protein expressions of TIMP-2 and TGF-β1 were significantly higher(P<0.01),MMP-2 mRNA and protein expressions were significantly lower(P<0.05,P<0.01).The protein expression level of Col-Ⅰwas higher(P<0.05,P<0.01),and that of Ki-67 was lower(P<0.05,P<0.01)in scleral tissue.CONCLU-SION The muscarinic antagonist neotropine inhibits the development of myopia in guinea pigs in the FDM model by reversing both the down-regulation of TGF-β1 and the up-regulation of MMP-2 in scleral tissues and inhibiting the remodeling of the scleral extracellular matrix.

Objective To explore the imaging manifestations of ectopic pancreas based on endoscopic findings in order to find out the causes of miss diagnosis and to improve the diagnostic accuracy.Methods The clinical and CT imaging data of ectopic pancreas patients who underwent CT examination and confirmed by endoscopy and pathology microscopy at Air Force Medical Center from July 2018 to March 2023 were collected.Their im-aging characteristics were analyzed according to the endoscopic findings and the miss diagnosis was analyzed.Results There were 13 patients with ectopic pancreas and 3 of them had no obvious symptoms.Ten patients presented with gastrointestinal symptoms,including epigastric discomfort and pain,incomplete obstruction,and melena.Lesion sites:8 cases were located in the gastric antrum and 5 cases were located in the small in-testine.In this group,two patients showed apical erosions and glandular opening-like depressions on endoscop-ic results,but only one patient showed a"ductal sign"shown by CT scanning.None of the 13 patients in this group made ectopic pancreatic diagnosis on imaging,of which 4 were diagnosed as thickening of the gastroin-testinal tract wall,3 were diagnosed as gastrointestinal stromal tumor,3 were diagnosed as benign tumors and 3 had no obvious abnormalities.Conclusions The imaging diagnosis of ectopic pancreas should be made by closely combinating with the results of endoscopy to improve the accuracy of imaging diagnosis.CT is of great significance for the diagnosis of ectopic pancreas,and adequate preparation before gastrointestinal examination is an important step to avoid misdiagnosis.

Objective To evaluate the relationship between ceftazidime-avibactam(CAZ-AVI)blood concentrations and efficacy in critically ill patients and to investigate the factors influencing blood levels.Methods The CAZ-AVI trough concentrations(Cmin)were detected in 29 patients who received CAZ-AVI treatment for at least 48 hours.The clinical materials of the patients were collected together for retrospective analysis.Results The Cmin of ceftazidime(CAZ)and avibactam(AVI)were(50.95±5.17)and(7.52±0.96)mg·L-1 in the effective group and(31.16±7.03)and(5.37±1.32)mg·L-1 in the ineffective group,respectively.The Cmin of CAZ in the effective group was significantly higher than in the ineffective group(P<0.05),and there was no significant difference in AVI Cmin between the two groups(P>0.05).Spearman's correlation analysis showed that CAZ Cmin was positively correlated with clinical efficacy(P<0.05),and no correlation between AVI Cmin and clinical efficacy(P>0.05).The optimal CAZ Cmin threshold was 24.59 mg·L-1.Multiple linear regression analysis showed that age and creatinine clearance was significantly correlated with the Cmin of CAZ,and creatinine clearance was significantly correlated with AVI Cmin(P<0.05).Conclusions The Cmin of CAZ correlates with efficacy,and it may be more beneficial for clinical treatment to keep the concentration of CAZ-AVI always greater than the minimum inhibitory concentration during the dosing interval.The creatinine clearance should be fully considered when optimizing CAZ-AVI dosage in critically ill patients.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Objective To systematically analyze influencing factors of migration stress of patients'families transferred out of intensive care unit(ICU)in China,and provide evidence-based guidance for alleviating migration stress level of families of transferred patients.Methods Computer searches were conducted on China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,VIP,China Biomedical Literature Database,Web of Science,PubMed,the Cochrane Library and Embase for observational studies such as cohort studies,case-control studies and cross-sectional studies on factors influencing migration stress among family members of ICU patients.Search deadline was from database establishment to October 2023.Literature screening,quality assessment and data extraction were conducted independently by two researchers in accordance with the inclusion and exclusion criteria.RevMan5.4 software was used to conduct a Meta-analysis of the data results.Results Fifteen studies were finally included,with a total sample size of 2558 and 12 influencing factors were extracted.Fifteen articles were divided into positive scoring group(higher scores,higher levels of migration stress,nine articles)and negative scoring group(higher scores,lower levels of migration stress,six articles)based on instruments used to measure outcome indicators.When analyzing each group,only factors mentioned in the group more than twice were included in Meta analysis.Meta analysis showed that within positive scoring group,family member education level,family member gender,patient awareness,ICU treatment time and family member uncertainty about the disease were factors affecting migration stress of ICU transfer patients'families(P<0.05);In reverse calculation group,educational level of family member,gender of family member,age of patient and ICU treatment time were influencing factors of migration stress of family members of ICU transfer patients(P<0.05).Sensitivity analysis result showed that result of each factor was relatively stable.Conclusion Educational level of family member,gender of family member,age of patient,ICU treatment time,uncertainty of family member's illness are influencing factors of migration stress of family members of patients transferred out of ICU in China.Influence of family member's religious beliefs and patient's consciousness needs further demonstration.

【Objective】 To investigate the improvement of motor function recovery and the activation of endogenous neural stem cells (eNSCs) via voluntary exercise in mice with hyperlipidemia after intracerebral hemorrhage (ICH). 【Methods】 Four-month-old male Nestin-CreERT2: tdTomato transgenic mice were fed with high-fat diet (HFD) for eight weeks. Type Ⅳ collagenase was micro-injected into the corpus striatum to construct mouse ICH model with the help of stereotaxic apparatus. Voluntary exercise (wheel running) was initiated on the second day after ICH and monitored daily for seven days. Neurological severity score (NSS) and beam walking test were applied to evaluate motor function and coordination. Liver and brain tissues were collected at day 9 after ICH and sliced for staining. Then the Nestin-labeled cells, Ki67⁺, and doublecortin (DCX)⁺ in subventricular zone (SVZ) were counted to evaluate eNSCs activation. 【Results】 ① Compared with those of mice fed by chow diet (CD), the body weight, blood glucose level, concentration of lipid metabolism factors and the number of Nile Red positive cells in liver tissue were significantly higher in HFD-fed mice, confirming hyperlipidemia. ② Compared with the sham group, NSS score increased and the distance of cross-beam walking of ICH mice significantly decreased, showing the deficiency of motor function. It could be rescued by 7-day wheel running, as shown by a lower NSS score and a longer cross-beam walking distance. ③ Compared with the sham group, the number of Nestin⁺/Ki67⁺ cells decreased and Nestin⁺/DCX⁺ cells increased after ICH. After 7-day voluntary exercise, the number of Nestin⁺/Ki67⁺ cells decreased but that of Nestin⁺/DCX⁺ cells further increased significantly. However, compared with ICH, the increase of Nestin⁺/DCX⁺ cells in ICH+Ex was not significant. 【Conclusion】 Short-term voluntary exercise during the acute stage of ICH improved the recovery of motor function and enhance the proliferation of eNSCs in mice with hyperlipidemia. This provides a new idea for further developing ICH accelerated rehabilitation strategy based on eNSCs.

Objective:To establish and validate a predictive model for treatment failure of peritoneal dialysis-related peritonitis(PDAP)in elderly patients.Methods:Clinical data of peritoneal dialysis(PD)patients who were followed up from January 1, 2013 to December 31, 2019 at four Grade A tertiary hospitals in Jilin Province were collected.A total of 362 elderly patients with PDAP were eventually included as study subjects.Subjects recruited from 2013 to 2017 were used for model construction and the logistic regression model was used to screen risk factors for treatment failure of PDAP in elderly patients.A nomogarm was constructed to predict treatment failure of secondary PDAP using R language.The receiver operating curve(ROC)and calibration curve were used to evaluate discrimination accuracy of the model.Subjects from 2018 to 2019 were used as the cohort for validation of discrimination accuracy of the model.Results:Of 258 PDAP patients in the modeling cohort, 29 experienced treatment failure, including 15 PDAP-related deaths and 14 cases requiring catheter removal.The multivariate logistic regression model showed that types of pathogens( OR=8.849, 95% CI: 1.656-47.269, P=0.011), long dialysis age( OR=1.023, 95% CI: 1.005-1.042, P=0.013), pre-hospitalization antibiotic treatment( OR=5.123, 95% CI: 1.338-19.610, P=0.017), and dialysate white blood cell count on day 5>100×10 6/L( OR=7.085, 95% CI: 2.162-23.217, P=0.001)were independent risk factors for treatment failure of PDAP in elderly patients.For the nomogarm predictive model, the areas under the ROC curve(AUC)in the modeling cohort and the validation cohort were 0.818(95% CI: 0.735-0.902)and 0.762(95% CI: 0.656-0.889), respectively, and the calibration curves were close to a straight line with a slope of 1. Conclusions:Our nomogram predictive model based on types of pathogens, months of dialysis, pre-hospital admission antibiotic treatment, and dialysate white blood cell count on day 5 has demonstrated satisfactory discrimination accuracy for treatment failure of PDAP in elderly patients.

People as third-party observers, without direct self-interest, may punish norm violators to maintain social norms. However, third-party judgment and the follow-up punishment might be susceptible to the way we frame (i.e., verbally describe) a norm violation. We conducted a behavioral and a neuroimaging experiment to investigate the above phenomenon, which we call the "third-party framing effect". In these experiments, participants observed an anonymous perpetrator deciding whether to keep her/his economic benefit while exposing a victim to a risk of physical pain (described as "harming others" in one condition and "not helping others" in the other condition), then they had a chance to punish that perpetrator at their own cost. Our results showed that the participants were more willing to execute third-party punishment under the harm frame compared to the help frame, manifesting a framing effect. Self-reported anger toward perpetrators mediated the relationship between empathy toward victims and the framing effect. Meanwhile, activation of the insula mediated the relationship between mid-cingulate cortex activation and the framing effect; the functional connectivity between these regions significantly predicted the size of the framing effect. These findings shed light on the psychological and neural mechanisms of the third-party framing effect.
Empathy ; Female ; Gyrus Cinguli ; Humans ; Neuroimaging ; Pain ; Punishment/psychology*

Objective:To investigate the incidence, drug sensitivity and drug resistance characteristies, and theraputic effect of staphylococcal peritoneal dialysis-associated peritonitis (PDAP), aim to provide clinical evidences for standardizing treatment therapy of staphylococcal PDAP. Methods:Clinical data of PDAP patients admitted to the Second Hospital of Jilin University, the First Hospital of Jilin University-the Eastern Division, Jilin Central Hospital and Jilin First Automobile Work General Hospital during January 1, 2013 and December 31, 2019 were retrospectively collected. The results of etiology, drug sensitivity and drug resistance of staphylococcal PDAP patients were collected. According to the pathogenic bacteria, patients were divided into staphylococcus aureus group ( n=48) and coagulase-negative staphylococcus group ( n=232). According to the results of methicillin resistance, patients were divided into drug-resistant group ( n=71) and drug-sensitive group ( n=30). The prognosis of antibiotic therapy in each group were compared. Poisson regression was used to test the changing trend of the incidence of staphylococcal PDAP. The changes of drug sensitivity and drug resistance of staphylococcus were compared between 2013 and 2019 by linear trend χ2 test. Results:A total of 1 085 cases of PDAP occurred in 625 patients were screened, and 280 cases of staphylococcal PDAP were finally included. The incidences of staphylococcal PDAP, staphylococcus aureus PDAP and coagulase-negative staphylococcal PDAP were 0.063 times per patient year, 0.010 times per patient year and 0.053 times per patient year respectively. In addition, the incidence of PDAP caused by staphylococcus, staphylococcus aureus and coagulase-negative staphylococcus decreased year by year (all P<0.05). With the change of years, the sensitivity rate of staphylococcus to rifampicin increased, while the sensitivity rate of staphylococcus to moxifloxacin decreased (both P<0.05). The drug resistance rate of staphylococcus to levofloxacin increased ( P<0.05). The staphylococcus aureus group was more prone to refractory PDAP and catheter removal than that in coagulase-negative staphylococcus group, and the recurrence rate was higher than that in coagulase-negative staphylococcus group (all P<0.05). The proportion of vancomycin used during the whole course of antibiotic therapy in drug-resistant group was higher than that in drug-sensitive group ( P<0.05). Conclusions:The incidence of staphylococcal PDAP decreases year by year, and the drug sensitivity characteristics of staphylococcus also change. The therapeutic outcomes of staphylococcus aureus PDAP are worse than that of coagulase-negative staphylococcus.