Subtype classification of age-related macular degeneration (AMD) based on optical coherence tomography (OCT) images serves as an effective auxiliary tool for clinicians in diagnosing disease progression and formulating treatment plans. To improve the classification accuracy of AMD subtypes, this study proposes a keypoint-based, attention-enhanced residual network (KPA-ResNet). The proposed architecture adopts a 50-layer residual network (ResNet-50) as the backbone, preceded by a keypoint localization module based on heatmap regression to outline critical lesion regions. A two-dimensional relative self-attention mechanism is incorporated into convolutional layers to enhance the representation of key lesion areas. Furthermore, the network depth is appropriately increased and an improved residual module, ConvNeXt, is introduced to enable comprehensive extraction of high-dimensional features and enrich the detail of lesion boundary contours, ultimately achieving higher classification accuracy of AMD subtypes. Experimental results demonstrate that KPA-ResNet achieves significant improvements in overall classification accuracy compared with conventional convolutional neural networks. Specifically, for the wet AMD subtypes, the classification accuracies for inactive choroidal neovascularization (CNV) and active CNV reach 92.8% and 95.2%, respectively, representing substantial improvement over ResNet-50. These findings validate the superior performance of KPA-ResNet in AMD subtype classification tasks. This work provides a high-accuracy, generalizable network architecture for OCT-based AMD subtype classification and offers new insights into integrating attention mechanisms with convolutional neural networks in ophthalmic image analysis.
Tomography, Optical Coherence/methods* ; Humans ; Macular Degeneration/diagnostic imaging* ; Neural Networks, Computer

Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.

Objective:To investigate the similarities and differences in clinical manifestations, lesion features, treatment options and prognosis in patients with kaposiform hemangioendothelioma (KHE) and tufted angioma (TA).Methods:The clinical data of KHE patients and TA patients diagnosed and treated in West China Hospital of Sichuan University from August 2016 to June 2020 were retrospectively analyzed. The similarities and differences in gender, the age of onset, clinical features, complications, histopathology, imaging manifestations, treatment and prognosis of the two diseases were compared. The χ2 test or Fisher’s exact test were used to analyze the qualitative data. The Mann-Whitney U test was used to analyze the quantitative data of the two groups that did not conform to the normal distribution. P<0.05 was considered to be statistically significant. Results:A total of 217 patients were included, including 183 patients with KHE and 34 patients with TA. There was no significant difference between KHE and TA in male to female ratio ( χ2=0.44, P=0.510), the age of onset ( U=2 757.00, Z=-1.09, P=0.278) and the sites of lesion ( χ2=3.64, P=0.162). The mixed type of KHE was the most common, reaching 63.39% (116/183), while the superficial type of TA was the most common, reaching 88.24% (30/34). The lesion diameter of KHE patients was 6.30(4.40, 9.70) cm, which was larger than that of TA patients 2.95(2.05, 4.03) cm, and the difference was statistically significant ( U=967.50, Z=-6.38, P<0.001). KHE is more likely to involve skeletal muscle, and cause thrombocytopenia and severe fibrinogenopenia. KHE mainly involved the dermis, subcutaneous tissue and even deep muscles, and manifested as an infiltrative mass. Magnetic resonance imaging (MRI) showed mass diffuse with high signal on T 2 phase. TA was often a superficial lesion that only involved the subcutaneous fat layer and was lumpy. MRI showed that the high signal was confined to the subcutaneous fat layer. The total effective rate of KHE [KHE(85.79%) vs. TA(91.18%)] and the total effective rate of drug therapy [KHE(85.32%) vs. TA(95.65%)] were lower than those of TA. Conclusions:Compared with TA, KHE has a larger tumor diameter, higher invasiveness, higher risk of complications. In addition, treatment plan was more complicated and treatment response rate was lower in patients with KHE compared with those in patients with TA.

Objective:To investigate the similarities and differences in clinical manifestations, lesion features, treatment options and prognosis in patients with kaposiform hemangioendothelioma (KHE) and tufted angioma (TA).Methods:The clinical data of KHE patients and TA patients diagnosed and treated in West China Hospital of Sichuan University from August 2016 to June 2020 were retrospectively analyzed. The similarities and differences in gender, the age of onset, clinical features, complications, histopathology, imaging manifestations, treatment and prognosis of the two diseases were compared. The χ2 test or Fisher’s exact test were used to analyze the qualitative data. The Mann-Whitney U test was used to analyze the quantitative data of the two groups that did not conform to the normal distribution. P<0.05 was considered to be statistically significant. Results:A total of 217 patients were included, including 183 patients with KHE and 34 patients with TA. There was no significant difference between KHE and TA in male to female ratio ( χ2=0.44, P=0.510), the age of onset ( U=2 757.00, Z=-1.09, P=0.278) and the sites of lesion ( χ2=3.64, P=0.162). The mixed type of KHE was the most common, reaching 63.39% (116/183), while the superficial type of TA was the most common, reaching 88.24% (30/34). The lesion diameter of KHE patients was 6.30(4.40, 9.70) cm, which was larger than that of TA patients 2.95(2.05, 4.03) cm, and the difference was statistically significant ( U=967.50, Z=-6.38, P<0.001). KHE is more likely to involve skeletal muscle, and cause thrombocytopenia and severe fibrinogenopenia. KHE mainly involved the dermis, subcutaneous tissue and even deep muscles, and manifested as an infiltrative mass. Magnetic resonance imaging (MRI) showed mass diffuse with high signal on T 2 phase. TA was often a superficial lesion that only involved the subcutaneous fat layer and was lumpy. MRI showed that the high signal was confined to the subcutaneous fat layer. The total effective rate of KHE [KHE(85.79%) vs. TA(91.18%)] and the total effective rate of drug therapy [KHE(85.32%) vs. TA(95.65%)] were lower than those of TA. Conclusions:Compared with TA, KHE has a larger tumor diameter, higher invasiveness, higher risk of complications. In addition, treatment plan was more complicated and treatment response rate was lower in patients with KHE compared with those in patients with TA.

The lateral hypothalamic area (LHA) plays a pivotal role in regulating consciousness transition, in which orexinergic neurons, GABAergic neurons, and melanin-concentrating hormone neurons are involved. Glutamatergic neurons have a large population in the LHA, but their anesthesia-related effect has not been explored. Here, we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice. In contrast, chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery. Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram (EEG) and shifted EEG features to an arousal pattern. Photostimulation of LHA glutamatergic projections to the lateral habenula (LHb) also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level. Collectively, LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.

Transcriptional regulators (TRs) participate in essential processes in cancer pathogenesis and are critical therapeutic targets. Identification of drug response-related TRs from cell line-based compound screening data is often challenging due to low mRNA abundance of TRs, protein modifications, and other confounders (CFs). In this study, we developed a regression-based pharmacogenomic and ChIP-seq data integration method (RePhine) to infer the impact of TRs on drug response through integrative analyses of pharmacogenomic and ChIP-seq data. RePhine was evaluated in simulation and pharmacogenomic data and was applied to pan-cancer datasets with the goal of biological discovery. In simulation data with added noises or CFs and in pharmacogenomic data, RePhine demonstrated an improved performance in comparison with three commonly used methods (including Pearson correlation analysis, logistic regression model, and gene set enrichment analysis). Utilizing RePhine and Cancer Cell Line Encyclopedia data, we observed that RePhine-derived TR signatures could effectively cluster drugs with different mechanisms of action. RePhine predicted that loss-of-function of EZH2/PRC2 reduces cancer cell sensitivity toward the BRAF inhibitor PLX4720. Experimental validation confirmed that pharmacological EZH2 inhibition increases the resistance of cancer cells to PLX4720 treatment. Our results support that RePhine is a useful tool for inferring drug response-related TRs and for potential therapeutic applications. The source code for RePhine is freely available at https://github.com/coexps/RePhine.

Objective:To investigate differentially expressed long noncoding RNAs (lncRNAs) and mRNAs between proliferating and involuting infantile hemangioma (IH) .Methods:Eight IH specimens were surgically resected from 4 children with proliferating IH and 4 with involuting IH in Department of Pediatric Surgery, West China Hospital, Sichuan University from January to March in 2019. Differentially expressed lncRNAs and mRNAs between proliferating and involuting IH (a P value < 0.05 and a fold change ≥ 2.0) were screened by microarray analysis, and verified by real-time fluorescence-based quantitative PCR (qRT-PCR) . Bioinformatics analysis was further performed, including GO and KEGG pathway analyses of differentially expressed mRNAs, construction of a lncRNA-mRNA co-expression network, and prediction of cis-acting target genes of differentially expressed lncRNAs. Results:A total of 405 differentially expressed lncRNAs and 772 differentially expressed mRNAs were identified between the proliferating and involuting IH specimens by using microarray technology. Of them, 108 lncRNAs and 107 mRNAs were downregulated, 297 lncRNAs and 665 mRNAs were upregulated in the proliferating IH specimens. Four lncRNAs (n335248, ENST00000450864, n333319, and n335185) and 4 mRNAs (EDNRA, IFI6, HK2, and ITGA1) were verified by qRT-PCR, and the results were consistent with those of microarray analysis. GO and KEGG enrichment analyses showed that differentially expressed mRNAs were mainly involved in the biological processes blood coagulation, axon guidance, angiogenesis and cell adhesion. Besides, differentially expressed mRNAs were mostly enriched in the metabolic pathways focal cell adhesion, regulation of actin cytoskeleton, leukocyte transendothelial migration and phosphatidylinositol 3-kinase/serine-threonine protein kinase and other signaling pathways. In addition, a lncRNA-mRNA co-expression network was constructed with 23 mRNAs and 58 lncRNAs with the degree ≥ 15.Conclusion:Lots of differentially expressed lncRNAs and mRNAs were identified between proliferating and involuting IH tissues, and these lncRNAs may play important roles in the development of IH by regulating corresponding target mRNAs.

Objective:To preliminarily assess the clinical value of sirolimus combined with prednisone in the treatment of Kaposiform hemangioendothelioma (KHE) complicated by Kasabach-Merritt phenomenon (KMP) .Methods:A retrospective study was conducted. General clinical data and relevant data on efficacy and adverse reactions were collected from 36 patients with KHE complicated by KMP, who received oral sirolimus combined with prednisone in Department of Pediatric Surgery, West China Hospital, Sichuan University from January 2011 to January 2018.Results:Among the 36 patients with KHE complicated by KMP, the male-to-female ratio was 1∶0.8; their average age was 15.0 months (range, 4.0 - 60.0 months) , and the average age of onset was 6.3 months (range, 0.8 - 48.0 months) ; 32 (88.9%) patients were diagnosed with mixed KHE, and 4 (11.1%) with deep KHE; the tumor size ranged from 2.5 cm × 4.0 cm to 20.0 cm × 24.0 cm. During the combined treatment, the average duration of prednisone administration was 6.4 weeks (range, 5.0 - 9.0 weeks) , and that of sirolimus administration was 19.3 months (range, 13.0 - 27.0 months) . After 1-5 weeks of combined treatment, platelet counts and fibrinogen levels of the 36 patients gradually returned to normal. After short-term prednisone combined with long-term sirolimus treatment, the average disease severity score decreased from 4.0 before treatment to 2.4 at 6 months and 1.6 at 12 months. After 12 months of the combined treatment, tumors mostly regressed in 32 (88.9%) patients, partially regressed in 3 (8.3%) , showed no obvious change in 1 (2.8%) . During the treatment, common adverse reactions included gastrointestinal discomfort and oral ulcers, no patient discontinued the treatment due to severe adverse reactions, and no drug toxicity-related death occurred.Conclusion:Sirolimus combined with prednisone is effective and safe for the treatment of KHE complicated by KMP.

Objective: To investigate the clinical symptoms, treatment intervention and prognosis of Kaposiform lymphangiomatosis(KLA). Methods: Medical information and clinical characteristics data of 8 KLA patients who were admitted to Department of Pediatric Surgery of West China Hospital of Sichuan University from January 2016 to February 2019 were retrospectively reviewed and analyzed. There were 5 males and 3 females with age of 5.8 years old (from 8 months to 29 years old). Results: The lesions in all patients were diffusely distributed. In all 8 patients, the lung and mediastinum were involved with different degrees. Three cases had lesions involving pelvic and abdominal organs. Three cases had lesions involving bones. One case simultaneously involved pelvic and abdominal organs, and 1 case was involved laryngeal and neck. The clinical characteristics were mainly respiratory symptoms. In the laboratory tests, 6 patients had different degrees of thrombocytopenia (minimum 3 × 10⁹/L), and 4 patients had severe fibrinogen reduction (minimum 0.42 g/L). Three patients had prolonged activated partial thromboplastin time (up to 64.2 seconds) and 3 patients had prolonged prothrombin time (up to 18.6 seconds). After surgery (including thoracotomy, chest tube, pericardiocentesis, splenectomy) and empiric medicine therapy (vincristine, sirolimus and corticosteroid), the symptoms improved in 1 case, 2 cases died of complications, 2 cases were stable and 3 cases progressed up to February 2019. Conclusions KLA is a rare disease that should be differentiated from other types of vascular diseases. Currently, there is no consensus treatment guidelines exist. Accurate diagnosis in KLA can be a challenge. The situation in patients with KLA is prone to rapid deterioration and progress. Future research efforts should seek to develop target-specific drugs for KLA.

PURPOSE: We evaluated the usefulness of intracranial stent implantation for treating patients with atherosclerotic stenosis and with recurrent, ischemic, neurological symptoms despite having undergone medical therapy. MATERIALS AND METHODS: Between March 2004 and April 2010, we attempted intracranial, stent-assisted angioplasty in 77 patients with 85 lesions (anterior circulation 73 cases, posterior circulation 12 cases) and who had ischemic neurological symptoms with more than 50% major cerebral artery stenosis. We analyzed the results regarding the technical success rate, complication rate, and restenosis rate during the mean 29.4 month follow-up period. RESULTS: Intracranial stent implantation was successfully performed in 74 cases (87.1%). In nine cases among the 11, failed cases, stent implantation failure was due to the tortuosity of the target vessel. One patient experienced middle cerebral artery rupture during the procedure, and we embolized the vessel using a microcoil. Five patients developed cerebral infarction in three weeks after the procedure, three of whom improved using conservative management, although the other, two patients expired. The mean number of residual stenoses decreased from 72.3% to 14.7%. Three patients demonstrated significant in-stent restenosis, i.e. more than 50%, during the follow-up period. CONCLUSION: As stent-assisted angioplasty in intracranial, atherosclerotic stenosis is effective and relatively safe, it can be considered as an alternative treatment for patients with recurrent, ischemic, neurologic symptoms despite having undergone medical therapy.
Angioplasty ; Cerebral Arteries ; Cerebral Infarction ; Constriction, Pathologic ; Follow-Up Studies ; Glycosaminoglycans ; Humans ; Intracranial Arteriosclerosis ; Middle Cerebral Artery ; Neurologic Manifestations ; Rupture ; Stents