Objective To develop and validate risk prediction models utilizing five machine learning algorithms for assessing postoperative pulmonary infection(PPI)risk in lung cancer patients undergoing grade Ⅳ thoracoscopic surgery.Methods A retrospective cohort study included 2,380 lung cancer patients who underwent grade Ⅳ thoracoscopic surgery at a tertiary hospital in Shanghai(January 2022 to June 2024).Patients were stratified into training(n=1,665)and validation(n=715)cohorts.Five machine learning algorithms—Logistic regression(LR),artificial neural network(ANN),support vector machine(S VM),random forest(RF),and extreme gradient boosting(XGB)—were employed to construct predictive models.A nomogram was developed for clinical utility.Results Among 2,380 patients,226(9.5％)developed PPI.The Least Absolute Shrinkage and Se-lection Operator(LASSO)regression identified eight predictive variables:daily cigarette consumption,diabetes history,preoperative diffusing capacity,maximal tumor diameter,24-hour postoperative chest drainage volume,perioperative oral nutritional supplementation(ONS),postoperative urinary cathe-terization,and intraoperative pleural adhesion severity.All models demonstrated robust discrimina-tion,with area under the curve(AUC)values ranging from 0.862 to 0.947.The XGB model a-chieved superior performance(AUC=0.947,95％CI,0.937 to 0.962),followed closely by the LR model(AUC=0.926,95％CI,0.918 to 0.933).Conclusion Machine learning-based algo-rithms models effectively stratify PPI risk in lung cancer patients following grade Ⅳ thoracoscopic surgery.The derived nomogram provides a practical tool for perioperative risk management by healthcare providers.

Objective To analyze the effect of different lateral occlusion patterns on the stress distribution of All-on-4 implanted fixed dentures.Methods A model of All-on-4 implant fixed denture was established,and lateral balanced occlusion,group functional oc-clusion,and canine protection occlusion was simulated by changing the loading method.The selected loading force was 200 N vertically and 30 N horizontally.Results The maximum stress values of each part of the simulated balanced occlusion model were the smallest,while the maximum stress values of each part of the canine protection model were the largest.The maximum stress values of each part of the group functional occlusion model were slightly larger than those of the balanced occlusion model,but significantly smaller than those of the canine protection model.Conclusion Group function occlusion could be selected for the lateral occlusion in the final restoration of All-on-4 implant prosthesis.

Objective To explore the effects of Dushu pills on cognitive ability and mitochondrial dynamics related proteins in mouse model of Alzheimer's disease(AD)based on network pharmacology.Methods The corresponding targets of Dushu pills and its related targets with AD were predicted using TCMSP database.The intersection targets of Dushu pills and AD were obtained by Venny website.The protein interaction network and drug-disease-target network were mapped using String database and Cytoscape software,respectively.GO and KEGG enrichment analysis were performed for intersection targets using David database.The mouse model of AD was established by injecting Aβ25-35 into bilateral ventricles.The learning and memory ability of the mice was detected by behavioral tests,the mitochondrial damage of neurons in the hippocampus was observed by transmission electron microscopy,and the expression of proteins related to mitochondrial dynamics was detected by Western blot.Results A total of 311 intersection targets related to drugs and diseases were screened out from the database.GO and KEGG analysis showed that the relevant targets were concentrated in mitochondria and other components,and concentrated in the pathways of ATP binding and positive regulation of MAPK activity.Compared with the normal group,the learning and memory ability of the model group was decreased(P<0.05),mitochondrial ridges appeared swelling and fracture(P<0.0001),decreased expression of MAPK,Mfn2 and OPA1 proteins in hippocampus(P<0.01),the expression of DRP1 protein increased(P<0.01).Compared with the model group,the learning and memory ability of mice in the medium and high dose groups of Dushu pills was improved(P<0.05),mitochondrial damage was significantly improved(P<0.01),increased expression of MAPK,Mfn2 and OPA1 in the hippocampus(P<0.01),DRP1 protein expression decreased(P<0.01).Conclusion Dushu pills can reduce mitochondrial damage,maintain mitochondrial homeostasis,and improve the cognitive and memory ability of AD mice.

Objective To analyze the effect of different lateral occlusion patterns on the stress distribution of All-on-4 implanted fixed dentures.Methods A model of All-on-4 implant fixed denture was established,and lateral balanced occlusion,group functional oc-clusion,and canine protection occlusion was simulated by changing the loading method.The selected loading force was 200 N vertically and 30 N horizontally.Results The maximum stress values of each part of the simulated balanced occlusion model were the smallest,while the maximum stress values of each part of the canine protection model were the largest.The maximum stress values of each part of the group functional occlusion model were slightly larger than those of the balanced occlusion model,but significantly smaller than those of the canine protection model.Conclusion Group function occlusion could be selected for the lateral occlusion in the final restoration of All-on-4 implant prosthesis.

Objective To explore the effects of Dushu pills on cognitive ability and mitochondrial dynamics related proteins in mouse model of Alzheimer's disease(AD)based on network pharmacology.Methods The corresponding targets of Dushu pills and its related targets with AD were predicted using TCMSP database.The intersection targets of Dushu pills and AD were obtained by Venny website.The protein interaction network and drug-disease-target network were mapped using String database and Cytoscape software,respectively.GO and KEGG enrichment analysis were performed for intersection targets using David database.The mouse model of AD was established by injecting Aβ25-35 into bilateral ventricles.The learning and memory ability of the mice was detected by behavioral tests,the mitochondrial damage of neurons in the hippocampus was observed by transmission electron microscopy,and the expression of proteins related to mitochondrial dynamics was detected by Western blot.Results A total of 311 intersection targets related to drugs and diseases were screened out from the database.GO and KEGG analysis showed that the relevant targets were concentrated in mitochondria and other components,and concentrated in the pathways of ATP binding and positive regulation of MAPK activity.Compared with the normal group,the learning and memory ability of the model group was decreased(P<0.05),mitochondrial ridges appeared swelling and fracture(P<0.0001),decreased expression of MAPK,Mfn2 and OPA1 proteins in hippocampus(P<0.01),the expression of DRP1 protein increased(P<0.01).Compared with the model group,the learning and memory ability of mice in the medium and high dose groups of Dushu pills was improved(P<0.05),mitochondrial damage was significantly improved(P<0.01),increased expression of MAPK,Mfn2 and OPA1 in the hippocampus(P<0.01),DRP1 protein expression decreased(P<0.01).Conclusion Dushu pills can reduce mitochondrial damage,maintain mitochondrial homeostasis,and improve the cognitive and memory ability of AD mice.

Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6％)were first-episode depression and 329(36.0％)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95％CI:1.00-4.44),more days out of role(OR=1.26,95％CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95％CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95％CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95％CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

【Objective】 To assess the status of HCV infection by analyzing the results of anti-HCV reactive blood samples detected by the current blood testing strategy, and discuss the viability of classified management of reactive blood donors. 【Methods】 The anti-HCV reactive samples (dual ELISA and once NAT), from May 2017 to October 2018, were divided into three groups: samples both anti-HCV and HCV RNA reactive, sole HCV RNA reactive, and sole anti-HCV reactive, and all of them were confirmed by recombinant immunoblot assay (RIBA). The positive predictive value (PPV) between groups were compared. The sensitivity, specificity and PPV for each reagent under different screening threshold (screening threshold for routine detection, optimal screening threshold, and corresponding screening threshold of the highest PPV) were analyzed. The group with low PPV were stratified by ELISA S/CO values, and PPV by different screening threshold was compared. 【Results】 There were 939 reactive samples (0.49%, 937/191 627). Confirmed by RIBA, the positive rate of anti-HCV reactive samples was 10.67%(100/937). Two samples were sole HCV RNA reactive (0.001%). Both anti-HCV+ HCV RNA reactive samples were 6.71%(63/939), with the PPV of 96.83%(61/63). Sole anti-HCV reactive samples were 93.08(874/939), with the PPV of 4.46%(39/874), among which PPV by dual and one ELISA reagent were 18.72% and 0.15%, respectively, showing statistically significant difference (P<0.05). The PPV between different S/CO values was statistically significant (P<0.05). The optimal screening thresholds of anti-HCV reagent were 9.29 and 3.97, according to the ROC curve, with significant difference noticed in PPV by different screening threshold (P<0.05). PPV in the sole anti-HCV reactive group increased from 4.46% (the routine screening threshold) to 49.35%(the optimal screening threshold), and the difference was statistically significant (P<0.05). 【Conclusion】 The blood donors with both anti-HCV and HCV RNA reactive can be determined as HCV infection and need to be permanently deferred. The S/CO value of sole anti-HCV reactive samples was positively correlated with RIBA confirmation results, and the higher the S/CO value, the greater the chances of positive confirmation are. With the current blood screening strategy, the HCV infection status of sole anti-HCV reactive blood donors can be determined by establishing a screening threshold with high PPV or adding confirmatory test.

【Objective】 To explore the viability of classification management of HIV reactive blood donors based on test results in blood screening laboratory. 【Methods】 According to the HIV test results of blood donors (including twice ELISA and once NAT), the HIV reactive blood donors were divided into three groups. Group 1 was all-test reactive (both ELISA and NAT were reactive), group 2 serological reactive (only ELISA was reactive), and group 3 NAT reactive (only NAT was reactive). The HIV test results of 191 628 blood donors from May to December 2017 were analyzed. Samples with positive RIBA results and / or the repeated reactive NAT results were determined as HIV true positive. The yielding rates of HIV true positivity in each group were analyzed. Receiver operating characteristic curve (ROC curve) was used to elevate the S/CO limit under 99% specificity as the blood donor deferral limit for ELISA. 【Results】 A total of 180 HIV reactive samples were detected out of 191 628 blood donors, including 77 positive cases in group 1, 100 in group 2 and 3 in group 3. 1) The HIV reactive results were diverse. Among the 82 true positive blood donors, 4 were early HIV infection (3 HIV antibody+ antigen window period yield, 1 HIV antibody window period yield), 2 were suspected elite controllers, and 76 cases were both serology and NAT reactive. 2) The overall yielding rate of HIV was 47.67%, with group 1 (100%) = group 3 (100%) > group 2 (2.17%), showing statistically significant (P<0.01). 3) The blood donor deferral limit for ELISA1, ELISA2 was 5.40 and 9.69 (S/CO value), respectively, with the corresponding positive expective values of 98.73% and 91.14% (P>0.05). All true positive blood donors in group 1 and group 2 could be accurately screened by using the blood donor deferral limit for ELISA1 and ELISA2 simultaneously. 【Conclusion】 The composition of HIV results among blood donors is diverse and complex. It is necessary to continuously improve the awareness of HIV prevention and control. The classification of HIV reactive blood donors is conducive to conduct fine and scientific management. The blood donors in group 1 and group 3 should be permanently deferral, and the suspected HIV elite controllers in group 2 should be paid attention to and permanently deferral.