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.

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.

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.

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 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.

ObjectiveTo assess the level of internal exposure to PCP in a community population in Shanghai， to investigate the factors affecting the level of PCP， and to analyze the correlation between the exposure and thyroid hormone levels. MethodsA total of 464 residents of a community in Shanghai were selected as the study subjects. A questionnaire survey was conducted to obtain the demographic information， dietary situation， lifestyle and behavioral habits， and disease history of the individuals， and blood samples were collected. Gas chromatography-electron trap was applied to determine the PCP levels in serum. Multicategorical logistic regression analysis was used to analyze the possible influencing factors of PCP exposure in humans. Thyroid hormone levels were used as the dependent variable and serum PCP as the independent variable. Multiple linear regression analysis was used to assess the association between PCP and thyroid hormones in the community population after controlling the confounding factors such as age， gender， literacy， annual personal income， and chronic diseases. ResultsThe detection rate of serum PCP in 464 subjects was 90.3%， and the median serum PCP level was 0.43 μg·L^-1. The differences in PCP levels among different age groups were statistically significant. There were no significant differences in PCP levels among different gender and BMI groups. The study of PCP exposure factors showed that age， frequency of using plastic products， consumption of freshwater fish， type of occupation， annual income， and consumption of tea or coffee were the potential influencing factors for PCP exposure. Among them， age， frequency of using plastic products， consumption of tea or coffee， and consumption of freshwater fish were positively associated with PCP levels， and annual personal income was negatively associated with it. The results of multiple linear regression analysis showed that among men， PCP levels were positively correlated with TSH （b=0.105， 95%CI：0.017‒0.313） and negatively correlated with FT4 （b=-0.026， 95%CI：-0.057‒0.004）， and among women， PCP levels were positively correlated with TSH （b=0.092， 95%CI：-0.211‒0.904） and FT3 （b=0.017， 95%CI：-0.058‒0.230） and negatively correlated with FT4 （b=-0.013， 95%CI：-0.011‒0.037）. ConclusionSerum PCP detection is common among community residents in Shanghai. Different demographic characteristics or behavioral habits may increase or decrease PCP exposure. PCP exposure then affects human thyroid hormone levels.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.