Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

BACKGROUND:As a common disease in middle-aged and elderly,osteoarthritis is difficult to cure,and the pathogenesis is not clear.Long non-coding RNA participates in the pathogenesis of osteoarthritis through many ways,such as regulating translation,promoting or inhibiting mRNA,and adsorbing miRNAs. OBJECTIVE:To review the types of common long non-coding RNA in osteoarthritis,and the influence of multiple long non-coding RNAs on the pathological factors related to osteoarthritis,to analyze the future application of long non-coding RNAs in osteoarthritis. METHODS:Literature retrieval was conducted in CNKI,WanFang Data,VIP database,PubMed,Web of Science and Sciencedirect databases,using the search terms of"osteoarthritis,degenerative joint disease,degenerative arthritis,OA,LncRNA,long non-coding RNA,long noncoding RNA,long intergenic non-coding RNA"in Chinese and English.All relevant literature published from 1976 and May 2024 was retrieved.After literature screening,induction,analysis and summary,93 articles were finally included for review. RESULTS AND CONCLUSION:This review collected 25 long non-coding RNAs that are well studied with osteoarthritis.Long non-coding RNAs,as a molecular sponge for miRNA,are competing endogenous RNAs to competitively adsorb miRNAs and then affect downstream targets.Long non-coding RNAs can regulate physiopathological processes such as chondrocyte apoptosis and proliferation,cartilage extracellular matrix degradation,and inflammatory responses.Long non-coding RNAs are expected to become a biomarker and potential therapeutic target for the clinical diagnosis and therapeutic prognosis of osteoarthritis,and it may become a new strategy for the clinical treatment of osteoarthritis in the future.

Objective To investigate the predictive value of combined radiomic features derived from chest CT scans with clinical characteristics for epidermal growth factor receptor(EGFR)gene mutations in non-small cell lung cancer(NSCLC).Methods A multi-center case-control study was conducted on the clinical data and CT images of 1 070 NSCLC patients from the radiology departments of the 3 medical institutions between January 2013 and October 2023.The 719 NSCLC patients from the First Affiliated Hospital of Army Medical University were randomly divided into a training set and an internal validation set in a ratio of 7∶3;The 173 patients in the Eastern Theatre General Hospital and the 178 patients in Army Medical Centre of PLA were assigned into the external validation set 1 and 2,respectively.Least absolute shrinkage and selection operator(LASSO)regression was employed to identify the optimal radiomic features,which were subsequently used to construct a radiomics model.Univariate and multivariate logistic regression analyses were applied to identify clinical features associated with EGFR mutation,thereby developing a clinical model.The radiomic and clinical features were subsequently combined to develop a comprehensive model.All the 3 classification models were built using random forest(RF)machine learning.The area under curve(AUC),accuracy,sensitivity and specificity were utilized to evaluate the predictive performance of the models.Calibration curve was plotted to assess the goodness of fit of the comprehensive model,while decision curve analysis was performed to assess the clinical utility of the model.Results The AUC value of the radiomics model was 0.762 4(95%CI:0.692 4～0.825 1),0.745 4(95%CI:0.671 1～0.814 3),and 0.724 7(95%CI:0.639 7～0.801 6),respectively,in the internal validation set,external validation set 1,and external validation set 2;The AUC value of the clinical prediction model was 0.691 7(95%CI:0.627 9～0.757 6),0.652 5(95%CI:0.576 7～0.729 1),and 0.779 2(95%CI:0.712 5～0.847 3),respectively in the above sets in turn;The comprehensive model constructed based on clinical features and radiomic features showed the best predictive efficacy,with an AUC value of 0.818 0(95%CI:0.757 7～0.874 3),0.782 4(95%CI:0.703 1～0.848 2),and 0.796 6(95%CI:0.718 1～0.868 6),respectively in the above sets.Calibration curve analysis indicated that the comprehensive model had a good fit,while decision curve analysis revealed that the model provided a favorable net benefit.Conclusion Our comprehensive model constructed based on chest CT radiomic features and clinical characteristics shows superior predictive performance for EGFR gene mutations in NSCLC across multiple center datasets,which may be helpful for clinical decision-making for treatment strategies.

Objective To evaluate the predictive value of deep learning features from chest CT images combined with clinical and radiomics features for epidermal growth factor receptor(EGFR)mutations in non-small cell lung cancer(NSCLC).Methods This case-control study retrospectively analyzed clinical and imaging data of 1 070 NSCLC patients from radiology departments at three hospitals(January 2013 to October 2023).Patients were divided into:a training set(n=502)and internal validation set(n=217)via 7∶3 randomization of 719 cases from the First Affiliated Hospital of Army Medical University;external validation set 1(n=173)from General Hospital of Eastern Theater Command;external validation set 2(n=178)from Daping Hospital of Army Medical University.Deep learning features were extracted using a 2.5D convolutional neural network(CNN)with ResNet101 backbone,radiomics features were derived from CT images,and clinical risk factors were identified to construct models.An integrated model combined deep learning,clinical,and radiomics features.All four models were developed using random forest(RF)classifiers.Calibration curves assessed goodness-of-fit,and decision curve analysis(DCA)evaluated clinical utility.Results The deep learning model achieved AUCs of 0.833 7(95%CI:0.770 6～0.884 7),0.815 1(0.741 6～0.882 8),and 0.810 1(0.745 2～0.873 6)in the internal and two external validation sets,respectively.Clinical models yielded AUCs of 0.731 0(0.660 2～0.802 1),0.746 0(0.666 4～0.824 9),and 0.813 4(0.743 1～0.883 6);radiomics models showed AUCs of 0.762 4(0.692 4～0.825 1),0.745 4(0.671 1～0.814 3),and 0.724 7(0.639 7～0.801 6).The integrated model demonstrated optimal performance with AUCs of 0.905 5(0.857 0～0.945 4),0.832 7(0.763 3～0.896 4),and 0.889 0(0.834 4～0.934 3).DCA indicated significant net benefit for EGFR prediction at threshold probabilities of 0.15～0.85 using the integrated model.Conclusion Deep learning features from CT images effectively predict EGFR mutation status in NSCLC.The integrated model combining deep learning,clinical,and radiomics features further enhances predictive performance.

Objective:To explore the clinical application value of serum N-glycan profiles for evaluating the severity of liver tissue inflammation in patients with chronic hepatitis B (CHB).Methods:A total of 221 CHB patients who underwent liver biopsy at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2018 to December 2020 were retrospectively enrolled. The Scheuer scoring system was used to assess the histological inflammation grade of the liver tissue. Serum N-glycan levels were measured using DNA sequencer-assisted N-glycan fingerprinting (NGFP). Using the upper limit of the alanine aminotransferase (ALT) reference value (40 U/L) as a cutoff, logistic regression models were developed to construct diagnostic models under two scenarios: normal ALT or abnormal ALT. Models based on serum N-glycan levels and serum N-glycan levels combined with routine laboratory indicators, were used to non-invasively evaluation of various pathological grades of liver tissue inflammation in CHB patients. The DeLong test was used to compare the diagnostic efficacy of the models by analyzing the areas under the receiver operating characteristic curve (AUC). Glycosylation-related gene expression differences associated with varying degrees of liver inflammation were analyzed using the Gene Expression Omnibus (GEO) database.Results:In CHB patients with normal ALT level, the relative abundances of N-glycan structure peak 1 (NGA2F) and peak 2 (NGA2FB) increased with higher liver inflammation grades, while the relative abundance of peak 5 (NA2) decreased ( P<0.05). The AUCs of the HIS-G model (HIS-G A) and its enhanced version (HIS-G A Plus) for identifying significant inflammation and necrosis (≥G2, indicating the initiation of antiviral therapy) were 0.805 (95% CI 0.690-0.899) and 0.904 (95% CI 0.821-0.960), respectively. In CHB patients with ALT>40 U/L, the relative abundances of peaks 1 (NGA2F), 2 (NGA2FB), and 3 (NG1A2F) increased with higher liver inflammation grades, while the relative abundances of peaks 8 (NA3) and 11 (NA4) decreased ( P<0.05). The AUCs of the HIS-G model (HIS-G B) and its enhanced version (HIS-G B Plus) for identifying significant inflammation (≥G2) were 0.810 (95% CI 0.727-0.889) and 0.838 (95% CI 0.754-0.901), respectively. With increasing liver inflammation grades, the expression levels of four glycosyltransferase genes (CHST4, FUT8, SLC51B, and ST8SIA4) were significantly upregulated ( P<0.05). Conclusions:Serum N-glycan biomarker models can be used to assist in evaluating the severity of liver tissue inflammation in CHB patients with both normal and abnormal ALT levels.

Objective To design and synthesize dual-target antidepressant compounds possessing high-affinity binding to the serotonin 1A receptor(5-HT1A)and dual-site synergistic inhibition of the serotonin transporter(SERT).Methods Based on a dual-target synergistic mechanism,benzodioxolane derivatives were designed via scaffold hopping strategy before being synthesized.Their binding affinities to both targets were determined via competitive radioligand binding assays,and their binding modes were investigated using molecular docking.Results Eleven structurally novel target compounds were synthesized and structurally characterized by electrospray ionization mass spectrometry(ESI-MS)and nuclear magnetic resonance(NMR)spectroscopy.Compound 18b demonstrated dual nanomolar affinity for both the 5-HT1A receptor(Ki=2.72 nmol/L)and SERT(Ki=8.85 nmol/L).Molecular docking revealed that its inhibitory effect on SERT resulted from simultaneous occupation of the orthosteric site S1(Asp98 salt bridge)and the allosteric site S2(Arg104 rr-cation interaction),while its high affinity for 5-HT1A depended on the Asp116332 salt bridge anchor and π-π stacking with Phe362652.Conclusion The benzodioxolane-scaffold compounds designed and synthesized in this study exhibited functional synergy between simultaneous occupation of both the S1 and S2 sites of SERT and high-affinity binding to the 5-HT1Areceptor.Among them,compound 18b demonstrates superior activity and promises to be a lead compound for more investigation.

Objective:To evaluate the accuracy and safety profile of a novel cuboid orientation-guided frontal horn ventriculostomy technique in patients with large hemispheric infarction (LHI).Methods:It was conducted a retrospective cohort study of 48 consecutive LHI patients who underwent the innovative ventriculostomy procedure between time period. Primary outcomes included procedural accuracy (success rates, catheter positioning) and safety indicators (complication rates).Results:All the punctured ventricles were small or of normal size. The success rate of puncture was 100%, the success rate of one-time puncture was 87% (42/48), and the average number of puncture was 1.13 times per case. The ratio of well-positioned tube heads was 87.5% (42/48). The actual angle of the inward deviation of the puncture ranged from -2o to 5o, with an average of 0o±0.3o. The depth of puncture was 7.0-8.0 cm ( 7.3±0.3) cm. The incidence of bleeding around the puncture path was 1.3% (2/48 ) and no massive bleeding occurred. At the 6-month follow-up, one case (2.94%) among the 34 survivors had epilepsy.Conclusions:The cuboid orientation-guided frontal horn ventriculostomy technique demonstrates exceptional procedural accuracy and an excellent safety profile in LHI patients, with high first-pass success rates (87.5%) and minimal complications (4.2% minor hemorrhage). These findings support its clinical adoption for this patient population.

OBJECTIVE To explore the clinical efficacy and possible mechanism of the classic prescription Xinyi Powder in the treatment of allergic rhinitis with lung deficiency related cold.METHODS A total of 189 patients who met the inclusion criteria of al-lergic rhinitis with lung deficiency related cold in the otolaryngology clinic of Jiangsu Province Hospital of Chinese Medicine from Janu-ary 2023 to July 2024 were selected and randomly divided into the experimental group(n=126)and the control group(n=63).The control group was treated with oral loratadine,and the experimental group took Xinyi Powder.Before and after treatment,the TNSS,TNNSS scores and TCM syndrome scores of the two groups of patients were compared to comprehensively evaluate the clinical efficacy.The changes in the patients'quality of life were evaluated in multiple dimensions using nasal VAS and RQLQ scores.The changes in serum IL-4,IL-5,IgE,SP and CGRP expression levels were detected by ELISA.RESULTS After 14 days of treatment,the TNSS,TNNSS,VAS,RQLQ scores and TCM syndrome scores of the two groups of patients were reduced(P<0.01);the experi-mental group was better than the control group in improving the concomitant symptoms such as nasal congestion,runny nose,postnasal drip,and itchy eyes(P<0.05,P<0.01),and it could also significantly improve the symptoms of fear of wind and cold,spontaneous sweating,shortness of breath,and cough with thin sputum(P<0.01),and the total RQLQ score was significantly better than the con-trol group(P<0.01).After treatment,the serum IL-4,IL-5,IgE,SP,and CGRP levels of the two groups of patients were signifi-cantly reduced(P<0.01),and there was no statistical difference between the two groups.CONCLUSION Xinyi Powder can signifi-cantly alleviate the nasal symptoms and systemic concomitant symptoms of patients with allergic rhinitis of lung deficiency and cold type,and significantly improve the quality of life of patients.It may play a therapeutic role by inhibiting the expression of inflammatory factors and neuropeptides and regulating neuroimmunity.