Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Improving the nitrogen use efficiency (NUE) of Brassica napus is of significant importance for achieving the national goal of zero growth in chemical fertilizer application and ensuring the green development of the rapeseed industry. This study aims to explore the effects of the nitrate transporter gene BnaNRT1.5s on the nitrogen transport and NUE of B. napus, providing excellent genetic resources for the development of nitrogen-efficient B. napus varieties. The spatiotemporal expression of BnaA05.NRT1.5 as a key nitrogen responsive gene was profiled by qRT-PCR at different growth stages and for different tissue samples of B. napus 'Westar'. Subcellular localization was employed to examine its expression pattern in the cells. Additionally, CRISPR/Cas9 was used to create BnaNRT1.5s knockout lines, which were subjected to hydroponic experiments under high nitrogen (12.0 mmol/L) and low nitrogen (0.3 mmol/L) conditions. After the seedlings were cultivated for 21 days, root and shoot samples were collected for weighing, nitrogen content determination, xylem sap nitrate content assessment, and calculation of total nitrogen and NUE. The B. napus nitrate transporter BnaA05.NRT1.5 was localized to the cell membrane. During the seedling and early bolting stages, BnaA05.NRT1.5 was predominantly expressed in roots, while it was highly expressed in old leaves and mature silique skin during the reproductive stage. Compared with the wild type, the mutant BnaNRT1.5s showed significant increases in the dry weight and total nitrogen of seedlings under both high and low nitrogen conditions. Under low nitrogen conditions, NUE in the roots of BnaNRT1.5s significantly improved. Notably, under both high and low nitrogen conditions, the nitrate content in the shoots of BnaNRT1.5s decreased significantly, while that in the roots increased significantly, resulting in a significantly decreased shoot-to-root nitrate content ratio. BnaNRT1.5s is involved in regulating the transport of nitrate from the roots to the shoots, and its mutation enhances nitrogen absorption and utilization in B. napus seedlings, promoting seedling growth. This study not only provides references for understanding the physiological and molecular mechanisms by which BnaNRT1.5s regulates NUE but also offers valuable genetic resources for improving NUE in B. napus.
Brassica napus/genetics* ; Anion Transport Proteins/metabolism* ; Nitrogen/metabolism* ; Nitrate Transporters ; Plant Proteins/metabolism* ; Nitrates/metabolism* ; Gene Expression Regulation, Plant ; Biological Transport

AIM: To explore the effect of lncRNA SNHG6 on injury of human retinal microvascular endothelial cells(hRMECs)induced by high glucose and its possible mechanism.METHODS: The D-glucose-induced hRMECs were used to establish normal glucose(NG)and high glucose(HG)cell injured model. In the HG group, the hRMECs were cultured in DMEM medium at a concentration of 25 mmol/L D-glucose for 24 h, while in the NC group, they were cultured in DMEM medium at a concentration of 5.5 mmol/L D-glucose; according to experimental design, si-NC, si-SNHG6, si-SNHG6 and anti-miR-NC and si-SNHG6 and anti-miR-186-5p were transfected into hRMECs, and then incubated at a concentration of 25 mmol/L D-glucose for 24 h, with HG+si-NC group, HG+si-SNHG6 group, HG+si-SNHG6+anti-miR-NC group and HG+si-SNHG6+anti-miR-186-5p group marked, respectively. The quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression of lncRNA SNHG6 and miR-186-5p; dual-luciferase reporter assay was used to detect the targeting relationship; MTT assay and flow cytometry were used to detect the cell proliferation and apoptosis, respectively; enzyme linked immunosorbent assay(ELISA)was used to detect the levels of IL-1β, TNF-α, IL-8, IL-10; testing kits were used to detect activity of SOD and level of MDA; the Western blot was used to detect the protein expression of cleaved-caspase3, Bax and Bcl-2.RESULTS: The lncRNA SNHG6 expression increased in the HG group, while miR-186-5p expression decreased(both P<0.05). There was target binding of lncRNA SNHG6 with miR-186-5p. After the transfection of si-SNHG6, cell inhibition rate, apoptosis rate, cleaved-caspase3, Bax protein levels, IL-1β, TNF-α, IL-8 contents, and MDA activity were decreased(P<0.05), while Bcl-2 protein, IL-10 contents, and SOD activity were increased(P<0.05). Co-transfection of si-SNHG6 and anti-miR-186-5p increased cell proliferation inhibition rate, apoptosis rate, cleaved-caspase3, Bax, IL-1β, TNF-α, IL-8, and MDA(P<0.05), but decreased Bcl-2, IL-10 and SOD(P<0.05).CONCLUSION: Interfering with lncRNA SNHG6 could inhibit cell apoptosis, inflammation and oxidative stress of high-glucose- induced hRMECs by elevating the expression of miR-186-5p.

Objective:To evaluate the efficacy and side effects of PD-1 monoclonal antibody in the treatment of advanced metastatic renal cell carcinoma in China.Methods:The clinical data of 117 patients with advanced metastatic renal cell carcinoma (mRCC) treated with PD-1 monoclonal antibody from October 2016 to February 2022 were retrospectively analyzed. There were 87 males (74.4%) and 30 females (25.6%), with an average age of (57.9±10.9) years old, BMI of (23.6±3.4) kg/m 2and smoking history of 79 (67.5%). There were 44 cases (37.6%) with hypertension, 19 (16.2%) cases of diabetes. The ECOG score of 59.8% (70/117) patients was 0, 33.3% (39/117) was 1, 4.3% (5/117) was 2, and 2.5% (3/117) was 3. The pathological type of 104 cases were renal clear cell carcinoma (ccRCC), 8 cases of papillary renal cell carcinoma, 2 cases of chromophobe cell carcinoma, 2 cases of collecting duct carcinoma and 1 case of eosinophilic cell carcinoma. The general condition of the overall population and the overall survival (OS) of relevant subgroups were analyzed. Secondary goals included progression free survival (PFS), objective response rate (ORR), adverse reactions, overall survival (OS), and progression free survival (PFS). Results:65.8% (77 / 117) of the patients chose targeted combined with PD-1 monoclonal antibody in the first-line treatment. The main targeted drugs were acitinib (81.8%, 63 / 77), tirelizumab (37.6%, 29 / 77) and cindilimab (25.9%, 20 / 77). After first-line treatment, 19.6.1% (23 / 117) patients needed to be converted to second-line treatment, and 15 patients changed the type of PD-1 antibody during treatment. In addition, the targeted drug of combined therapy was replaced by acitinib in 8 patients. The main causes of drug withdrawal were disease progression (70.7%, 29 / 41) and death (29.2%, 12 / 41). The median OS of the overall population was 35.6 (19-60) months and PFS was 12.1 (1-60) months. The ORR of the overall population was 47.8% (56 / 117). 4.2% (5/117) patients had complete remission, another 17.0% (20/117) patients were in stable condition, and 43.5% (51 / 117) patients were in partial remission. In the first-line treatment, the median PFS time of targeted combined with PD-1 monoclonal antibody was 12.6 (1-30) months, the median PFS time of PD-1 single drug immunotherapy was 10.5 (1-60) months. In the second-line treatment, the PFS of patients treated with PD-1 monoclonal antibody was 10.1 (4-19) months, and that of patients treated with PD-1 monoclonal antibody combined with targeted therapy was 11.7 (1-25) months. The most common adverse reactions were elevated blood pressure (18.5%, 23 / 124), followed by hypothyroidism (15.3%%, 19/124), rash (14.5%, 18 / 124), elevated transaminase (10.5%, 13 / 124) and bone marrow suppression (9.7%, 12/124). 9.4% (11 / 117) patients needed to reduce the related adverse reactions by interrupting the treatment control of PD-1 monoclonal antibody.Conclusions:The safety and efficacy of PD-1 monoclonal antibody in domestic patients are better, and the side effects are less. The efficacy and safety of PD-1 monoclonal antibody combined with targeted therapy in the real world population are consistent with many key clinical trials abroad. PD-1 monoclonal antibody combined with targeted drugs can be popularized in the domestic MRCC population.

Recent advancement in natural language processing (NLP) and medical imaging empowers the wide applicability of deep learning models. These developments have increased not only data understanding, but also knowledge of state-of-the-art architectures and their real-world potentials. Medical imaging researchers have recognized the limitations of only targeting images, as well as the importance of integrating multimodal inputs into medical image analysis. The lack of comprehensive surveys of the current literature, however, impedes the progress of this domain. Existing research perspectives, as well as the architectures, tasks, datasets, and performance measures examined in the present literature, are reviewed in this work, and we also provide a brief description of possible future directions in the field, aiming to provide researchers and healthcare professionals with a detailed summary of existing academic research and to provide rational insights to facilitate future research.
Humans ; Natural Language Processing ; Surveys and Questionnaires

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.

Objective:To investigate the relationship between Helicobacter pylori(Hp)infection and carotid atherosclerosis(CAS)in the elderly, in order to provide an empirical basis for the prevention and treatment of cardiovascular and cerebrovascular diseases in the elderly.Methods:A total of 287 patients aged 60 years and over admitted to the First Affiliated Hospital of Guangxi Medical University, who underwent the 13C-urea breath test( 13C-UBT), carotid color and two-dimensional Doppler ultrasonography from October 2015 to January 2019, were retrospectively enrolled.Patients were divided into the Hp infection group(n=137)and the non-Hp infection group(n=150). Common high-risk pathogenic factors, blood biochemical indicators, carotid intima-media thickness(IMT)and detection rate of carotid plaque were compared between the two groups. Results:Common high-risk pathogenic factors including age, gender, hypertension, diabetes, obesity, smoking, alcohol consumption, dyslipidemia, and hyperuricemia showed no significant difference between the two groups( P>0.05). The level of high-density lipoprotein cholesterol(HDL-C)was lower in the Hp infection group than in the non-Hp infection group( P<0.05). There was no difference in levels of white blood cells, neutrophils, total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), homocysteine, fasting blood glucose, creatinine or uric acid between the two groups( P>0.05). The detection rates of increased carotid IMT and carotid plaques were higher in the Hp infection group than in the non-Hp infection group(65.0% or 89 cases vs.48.7% or 73 cases, 76.6% or 105 cases vs.64.7% or 97 cases, P<0.01 and 0.05). The detection rate of carotid plaques in the Hp-infected group was higher than that in the non-Hp-infected group( P<0.05). The combined detection rate of increased carotid IMT and plaques was higher in the Hp infection group than in the non-Hp infection group(56.2% or 77cases vs.32.7% or 49 cases, P<0.01). Conclusions:Hp infection may play a role in the occurrence and progression of carotid atherosclerosis through initiating abnormal lipid metabolism.Early intervention and treatment may reduce the incidence of carotid atherosclerosis in patients with Hp infection.

Objective To evaluate the prognostic significance of the candidate selection Hangzhou criteria for liver transplantation of HCC patients undergoing hepatectomy.Methods 199 HCC patients undergoing hepatectomy between 2009 and 2011 were enrolled retrospectively.Predictors of survival were identified using the Kaplan-Meier method.The disease state was staged by the Hangzhou criteria (HC) and Milan staging systems.Calculating the area under the receiver operating characteristic (ROC) curve (AUC) evaluates the discriminatory ability for the prediction of survival of both staging system.Results Portal vein thrombosis,poor differentiation,and tumor size (＞ 8 cm) were independent risk factors for survival after hepatectomy.Milan criteria and Hangzhou criteria functioned well in predicting tumor-recurrence.For 1-year AUROC,the AUROC for Milan criteria and Hangzhou criteria are 0.602 and 0.741,respectively.For 3-year AUROC,the AUROC for Milan criteria and Hangzhou criteria are 0.643 and 0.733,respectively.Conclusions The HC were shown to be a promising survival predictor in a Chinese cohort of HCC patients after hepatectomy.

Objective:To explore the effects and mechanism of anti IL-9 antibody on malignant ascites ( MA) of hepatic carci-noma in mice.Methods:A mouse model of MA was established by mouse H 22 cell line.45 mice were divided randomly into experi-mental group,negative control group and blank control group at 24 hours after modeling,with 15 mice in each group.The experimental group was injected intraperitoneally with anti IL-9 antibody;the negative control group was injected with isotype IgG antibody;the blank control group was injected with normal saline .The weight and behavior of the mice were measured before each injection .Five mice of each group was sacrificed at 24 hours after the last injection to measure the volume of MA .The level of VEGF,MMP-2,IL-9 and IFN-γin MA were determined with ELISA assay;the survival time of rest mice were recorded and compared .Results:The mean volume of MA of experimental group,negative control group and blank control group were (6.70±1.52)ml,(10.28±1.75)ml,(10.36±2.30) ml,respectively,the MA volume of experimental group were lower as compared to negative control group and blank control group ( P<0.05).The mean survival time of experimental group was (17.2±2.1)d,which was significantly prolonged compared with the negative control group (14.5±1.2)d and the blank control group (14.8±1.4)d (P<0.05).The levels of VEGF of MA in experimental group was significantly lower compared to the negative control group and blank control group (P<0.05).The levels of IL-9 of MA in experi-mental group was significantly lower compared to the negative control group (P<0.05).The levels of MMP-2 and IFN-γin experimental group had no significant difference compared with the negative control group and blank control group ( P>0.05 ) .Conclusion:Intraper-itoneal injection anti IL-9 antibody on H22 ascites-bearing mice can effectively inhibit the generation of the MA .The mechanism may be related to the inhibition of the expression of the VEGF and IL-9.