Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.

[Objective]To investigate the protective effect of overexpressed miRNA-200a&c on Angiostrongylus cantonensis-induced demyelinating optic neuritis in Balb/c mice.[Methods]SPF-grade Balb/c mice(2-3 weeks old)were divided into four groups:a normal group,and three A.cantonensis-infected groups at 7,14,and 21 days post-infection(dpi).Body weight,survival status,neurobehavioral scores,and visual function scores were recorded.Visual evoked potential(VEP)was used to detect visual damage,and transmission electron microscope(TEM)was applied to observe ocular structural changes.On day 7 post-infection,mice were stereotactically injected with exogenous miRNA-200a&c mimics into the lateral ventricle,and then divided into four groups:normal control,A.cantonensis-infected(AC-21 dpi),A.cantonensis-infected+negative control(AC+NC),and A.cantonensis-infected+overexpressed miRNA-200a&c(AC+miRNA-200a&c)mimics.VEP and TEM were repeated to assess visual damage and ocular structural changes.Immunofluorescence was performed to quantify retinal ganglion cells(RGCs)and oligodendrocytes(OLs)in the optic nerve.[Results]At 21 dpi,some mice exhibited complete eyelid closure(32.52±4.67)%or ocular atrophy(15.79±3.23)%,weight loss(P＜0.05)and altered consciousness.Neurobehavioral scores significantly decreased(P＜0.01),with a 68%decline in rotarod performance;some mice even displayed hemiplegia,slowed movement,ataxia,and directional deficits.Additionally,a subset of mice showed diminished sensory responses,unilateral vision loss(83%reduction in optokinetic threshold),and impaired visual function(P＜0.05).VEP results revealed a mild prolongation of latency in infected mice at 21 dpi(P＜0.05),predominantly affecting one eye.Following overexpression of miRNA-200a&c,compared with the 21 dpi group,VEP showed significantly shortened P1 latency(P＜0.05);TEM showed alleviated cytoplasmic swelling of RGCs,and improved compactness and uniformity of myelin sheath(P＜0.05);immunofluorescence showed increased numbers of RGCs and OLs with improved cell alignment(P＜0.05).[Conclusions]A.cantonensis infection induces demyelinating optic neuritis in Balb/c mice.Overexpression of miRNA-200a&c alleviates the resulting damage and ameliorates ocular injury.

[Objective]To investigate the demyelination induced by Angiostrongylus cantonensis(AC)infection in the brain of Balb/c mice and analyze the untargeted metabolomic changes in the corpus callosum,aiming to elucidate the underlying mechanisms.[Methods]Balb/c mice were randomly assigned to a control group(n=6)and an infection group(n=6).The infection group was orally administered 30 third-stage larvae of AC,while the control group received an equal volume of saline.Body weight,visual function,and behavioral scores were measured on post-infection 3,6,9,12,15,18,and 21 days to assess neurological alterations.After 21 days,brain tissues were harvested for immunofluorescence staining,hematoxylin-eosin(HE)staining,and transmission electron microscopy to examine morphological changes in brain myelin and retina.Metabolomics analysis was performed,and differential metabolites were identified using volcano plots and heatmaps.The distribution of fold changes and bar charts were used to profile the key metabolites.These differential metabolites were then subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis and regulatory network analysis.[Results]On the 9th day after AC infection,Balb/c mice showed a decline in neurological behavioral scores(P<0.05).By day 15,visual scores decreased(P<0.05),and by day 21,significant weight loss(P＜0.001)and mortality were observed.Concurrently,transmission electron microscopy and immunofluorescence staining revealed significant myelin damage in the corpus callosum and a marked reduction in oligodendrocytes(P<0.001).HE staining showed severe retinal ganglion cell damage.Metabolomic analysis revealed that glycerophospholipids were the most abundant differential metabolites,with steroids and sphingolipids being relatively less abundant.Cholesteryl ester CE(20:2)was significantly upregulated(P<0.001),while phosphatidylmethanol(18:0_18:1)was significantly downregulated(P<0.01).KEGG enrichment and regulatory network analyses demonstrated that the differential metabolites were mainly enriched in metabolic pathways like steroid biosynthesis,bile secretion,and cholesterol metabolism,and were involved in key metabolic pathways such as sphingolipid metabolism,neural signal regulation,and glycerophospholipid metabolism.[Conclusions]AC infection affects the metabolic state of mice via multiple pathways,modifying the levels of metabolites crucial for myelination and myelin stability.Demyelination may be closely linked to the disruption of these key metabolic pathways,particularly the dysregulation of cholesterol and sphingolipid metabolism,potentially playing a central role in demyelination onset.Furthermore,alterations in phospholipid metabolism and abnormal nerve signaling regulation may exacerbate myelin damage.

Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer. Computational methods have been widely explored and have become increasingly accurate in recent years. However, the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients. We present a novel disentangled synthesis transfer network (DiSyn) for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients. DiSyn uses a domain separation network (DSN) to disentangle drug response related features, employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement. DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets, The Cancer Genome Atlas (TCGA), Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2 (I-SPY2) and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia (NIBR PDXE), achieving competitive performance with the state-of-the-art methods on cancer patients and mice. Furthermore, the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.

[Objective]To investigate the protective effect of overexpressed miRNA-200a&c on Angiostrongylus cantonensis-induced demyelinating optic neuritis in Balb/c mice.[Methods]SPF-grade Balb/c mice(2-3 weeks old)were divided into four groups:a normal group,and three A.cantonensis-infected groups at 7,14,and 21 days post-infection(dpi).Body weight,survival status,neurobehavioral scores,and visual function scores were recorded.Visual evoked potential(VEP)was used to detect visual damage,and transmission electron microscope(TEM)was applied to observe ocular structural changes.On day 7 post-infection,mice were stereotactically injected with exogenous miRNA-200a&c mimics into the lateral ventricle,and then divided into four groups:normal control,A.cantonensis-infected(AC-21 dpi),A.cantonensis-infected+negative control(AC+NC),and A.cantonensis-infected+overexpressed miRNA-200a&c(AC+miRNA-200a&c)mimics.VEP and TEM were repeated to assess visual damage and ocular structural changes.Immunofluorescence was performed to quantify retinal ganglion cells(RGCs)and oligodendrocytes(OLs)in the optic nerve.[Results]At 21 dpi,some mice exhibited complete eyelid closure(32.52±4.67)%or ocular atrophy(15.79±3.23)%,weight loss(P＜0.05)and altered consciousness.Neurobehavioral scores significantly decreased(P＜0.01),with a 68%decline in rotarod performance;some mice even displayed hemiplegia,slowed movement,ataxia,and directional deficits.Additionally,a subset of mice showed diminished sensory responses,unilateral vision loss(83%reduction in optokinetic threshold),and impaired visual function(P＜0.05).VEP results revealed a mild prolongation of latency in infected mice at 21 dpi(P＜0.05),predominantly affecting one eye.Following overexpression of miRNA-200a&c,compared with the 21 dpi group,VEP showed significantly shortened P1 latency(P＜0.05);TEM showed alleviated cytoplasmic swelling of RGCs,and improved compactness and uniformity of myelin sheath(P＜0.05);immunofluorescence showed increased numbers of RGCs and OLs with improved cell alignment(P＜0.05).[Conclusions]A.cantonensis infection induces demyelinating optic neuritis in Balb/c mice.Overexpression of miRNA-200a&c alleviates the resulting damage and ameliorates ocular injury.

Objective　Establishing an animal model of demyelinating optic neuritis (DON) to provide reference for the study of DON. Methods Balb/c mice were firstly infected with Angiostrongylus cantonensis (A. cantonensis) larvae by oral gavage. Then, neurobehavioral and visual scores were used to evaluate the neurofunctional changes in mice. Visual action potential and electroretinogram were used to detect the changes of visual pathways in mice. Histopathological staining and transmission electron microscopy were used to observe the morphological and functional changes of the retina and optic nerve myelin sheath in mice. RT-qPCR and Western Blotting were used to detect the changes of retinal ganglion cell marker Brn-3a and optic nerve myelin marker MBP. Results On the 21st day after infection with A. cantonensis, the body weight of Balb/c mice decreased significantly, and both neurobehavioral scores and visual scores were significantly reduced. At the same time, the visual action potential and electroretinogram test results showed that the visual path conduction function of the optic nerve and retina was damaged; additionally, HE staining, LFB staining, and transmission electron microscopy observed significant damage to retinal ganglion cells and optic nerve myelin; finally, RT-qPCR and Western Blotting results showed s in protein levels and mRNA levels of retinal ganglion cell marker Brn-3a and myelin oligodendrocyte marker MBP. Conclusions A. cantonensis infection in Balb/c mice can damage the retina and optic nerve, leading to demyelinating optic neuritis, which can be used as a new and ideal animal model of DON.

Objective:To observe the clinical efficacy of intra-articular injection with Triamcinolone acetonide on the treatment of juvenile idiopathic arthritis (JIA).Methods:The clinical data of 26 children diagnosed with JIA undergoing the intra-articular injection of Triamcinolone acetonide for the joints with obvious swelling and pain at the Children′s Hospital Affiliated to Capital Institute of Pediatrics from October 2018 to December 2019 who were retrospectively analyzed.Erythrocyte sedimentation rate (ESR) and C-reactive protein(CRP) were tested before and after the application of Triamcinolone acetonide.Detailed clinical manifestations were recorded.The nonparametric Kruskal- Wallis test was used to compare the differences in clinical evaluation indicators and changes in laboratory tests at diffe-rent treatment times. Results:Among the 26 children, 8 were boys and 18 were girls.After the intra-articular injection of Triamcinolone acetonide, 9 cases (34.62%) achieved complete remission, 15 cases(57.69%) achieved partial remission, and 2 cases (7.69%) were not responsive to the intra-articular injection.The overall therapeutic efficacy was 92.31%.Compared with pre-treatment period, from 4 weeks after treatment, assessment of disease activity by the physicians and parents of the children was significantly improved after 4-week treatment, and the number of active joints, ESR and CRP and the Juvenile Arthritis Disease Activity Score with 27 joints (JADAS 27) gradually decreased, and the differences were statistically significant (all P<0.05). No adverse drug reactions were seen during the treatment and follow-up period. Conclusions:Intra-articular injection of Triamcinolone acetonide is effective in contro-lling joint symptoms of JIA with less adverse events.

Objective    To investigate the feasibility of using magnetic beads to locate small pulmonary nodules. Methods    Twelve rabbits were randomly divided into two groups, 6 in each group. One group underwent thoracotomy after anesthesia and the other group underwent percutaneous puncture under the guidance of X-ray. One and two cylindrical tracer magnets (magnetic beads) with a diameter of 1 mm and a height of 3 mm were injected adjacent to the imaginary pulmonary nodules in left lung in each group. The magnetic beads beside the imaginary nodules were attracted by a pursuit magnet with a diameter of 9 mm and a height of 19 mm. The effectiveness of localization by magnetic beads were determined by attraction between tracer and pursuit magnets. Results    All processes were uneven in 12 rabbits. There was micro hemorrhage and no hematoma in the lung tissue at the injection site of the magnetic beads. When tracked with the pursuit magnets, there was one bead divorce in cases that one bead was injected, but no migration or divorce of the magnetic beads in cases that two magnetic beads were simultaneously injected to localize the small pulmonary nodules. Conclusion    The feasibility of using magnetic beads to locate small pulmonary nodules has been  preliminarily verified.

With the development of CT and the popularization of health examination, the detection rate of small pulmonary nodules has been improved. Some small pulmonary nodules could be malignant nodules. Surgical resection is the preferred treatment. Therefore, it is an important task for thoracic surgeons to accurately locate pulmonary nodules during surgery and remove nodules accurately on the premise of maximum protection of lung function. At present, the core of preoperative auxiliary localization of pulmonary nodules is the implantation of markers. The commonly used clinical localization methods include hook wire localization, microcoil localization, methylene blue puncture injection localization and biological glue localization. In this paper, the development status, application scope, advantages and disadvantages of existing localization methods are briefly reviewed, which can provide references for clinical application and follow-up research.

BACKGROUNDLung cancer is one of the most malignant cancers which is hazarding the people's health and life in the world. At present, it is a highlight to exploit antitumor drug from plant at home and abroad. The aim of this study is to observe the effects of polysaccharid (PS-T) on expression of angiogenic-related gene mRNA in human high-metastatic large cell lung cancer cell line L9981, and to explore its possible molecular mechanism.

METHODSL9981 in vitro was cultured, and the growth data were obtained by trypan blue staining. The mRNA transcript expression of β-catenin, E-cadherin, TIMP-1, CD44V6, MMP-2, endostatin, VEGF was detected in L9981 by RT-PCR before and after treating with PS-T. The ability of invasion of L9981 was determined by Boyden chamber method.

RESULTS(1)PS-T had remarkably inhibitive effects on the growth of L9981 in vitro. The inhibitive rate of PS-T on L9981 was concentration-dependent. No significant difference of inhibitive rate was found among the PS-T (1g/L), cisplatin (3mg/L) and PS-T (0.05g/L) + cisplatin (1.5mg/L)(P > 0.05). (2)The mRNA expression level of β-catenin, E-cadherin, TIMP-1, endostatin and MMP-2 was upregulated, while that of VEGF and CD44V6 was downregulated. Out of them the mRNA expression level of TIMP-1 and endostatin was remarkably upregulated, the expression level of CD44V6 was significanyly downregulated. (3)The in vitro invasive abilities of L9981 was significantly decreased in the PS-T, DDP and PS-T+DDP groups compared with that in blank control group.

CONCLUSIONS(1)PT-S could inhibit the growth of human high-metastatic large cell lung cancer cell line L9981 in vitro, the effect is dose-dependent. (2)PS-T can down- or up-regulate the mRNA transcript expression of some angiogenic-related gene mRNA. (3)PS-T has remarkably coordinating effects with cisplatin in the L9981 lung cancer cell line.