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.

Objective:To investigate the effect of bed board of carbon fiber for treatment combined with fixed bottom board on verification results of Portal Dosimetry(PD)dose of intensity-modulated radiation therapy(IMRT)plan of fixed field for cervical cancer.Methods:A total of 15 patients with cervical cancer who admitted to Nanjing First Hospital from January 2019 to January 2020 were retrospectively selected,and the IMRT plans of fixed field for all patients were designed.The radiation field with 180° gantry angle was selected for each case to make the corresponding PD dose verification plan,and each verification plan included two subfields:AA180_0 and AA180_1.Three types of materials were placed between the accelerator head and the electronic portal imaging device(EPID),which included material without carbon fiber,bed board with carbon fiber for treatment,and the combination of the bed board with carbon fiber for treatment and the fixed bottom board with carbon fiber,when the Clinac iX accelerator was used to conduct verification plan for each case.The γ passing rates of the subfields(AA180_0 and AA180_1)and the total field(AA180)among three kinds of conditions,which included material without carbon fiber,bed board with carbon fiber for treatment,and the combination of the bed board with carbon fiber for treatment and the fixed bottom board with carbon fiber,were compared and analyzed.Results:For the subfield AA180_0,the γ passing rates under three different material conditions were respectively(96.09±1.38)%,(90.48±2.24)%and(81.85±2.46)%.For the subfield AA180_1,the γ passing rates under the above conditions were respectively(96.05±1.06)%,(91.86±2.22)%and(86.26±2.74)%.For the total field AA180,the γ passing rates were respectively(90.78±1.40)%,(84.82±2.56)%and(78.49±3.18)%.The γ passing rates of the subfield AA180_0,subfield AA180_1,and the total field AA180 showed statistically significant differences among the three different material conditions(F=177.80,80.00,91.42,P<0.01).Compared with materials without carbon fiber,the γ passing rate of the total field AA180 of the combination of the bed board with carbon fiber for treatment and the fixed bottom board with carbon fiber significantly decreased by 12.29%.Conclusion:In the PD dose verification of IMRT for cervical cancer,the bed board with carbon fiber for treatment combined with the fixed bottom board will produce adverse effect for the verification results.The effect of the single use of bed board for treatment is relatively small.The combined use of the bed board with carbon fiber for treatment and the fixed bottom board will lead to a significant deterioration in the verification result of PD dose.

Objective:To investigate the effect of bed board of carbon fiber for treatment combined with fixed bottom board on verification results of Portal Dosimetry(PD)dose of intensity-modulated radiation therapy(IMRT)plan of fixed field for cervical cancer.Methods:A total of 15 patients with cervical cancer who admitted to Nanjing First Hospital from January 2019 to January 2020 were retrospectively selected,and the IMRT plans of fixed field for all patients were designed.The radiation field with 180° gantry angle was selected for each case to make the corresponding PD dose verification plan,and each verification plan included two subfields:AA180_0 and AA180_1.Three types of materials were placed between the accelerator head and the electronic portal imaging device(EPID),which included material without carbon fiber,bed board with carbon fiber for treatment,and the combination of the bed board with carbon fiber for treatment and the fixed bottom board with carbon fiber,when the Clinac iX accelerator was used to conduct verification plan for each case.The γ passing rates of the subfields(AA180_0 and AA180_1)and the total field(AA180)among three kinds of conditions,which included material without carbon fiber,bed board with carbon fiber for treatment,and the combination of the bed board with carbon fiber for treatment and the fixed bottom board with carbon fiber,were compared and analyzed.Results:For the subfield AA180_0,the γ passing rates under three different material conditions were respectively(96.09±1.38)%,(90.48±2.24)%and(81.85±2.46)%.For the subfield AA180_1,the γ passing rates under the above conditions were respectively(96.05±1.06)%,(91.86±2.22)%and(86.26±2.74)%.For the total field AA180,the γ passing rates were respectively(90.78±1.40)%,(84.82±2.56)%and(78.49±3.18)%.The γ passing rates of the subfield AA180_0,subfield AA180_1,and the total field AA180 showed statistically significant differences among the three different material conditions(F=177.80,80.00,91.42,P<0.01).Compared with materials without carbon fiber,the γ passing rate of the total field AA180 of the combination of the bed board with carbon fiber for treatment and the fixed bottom board with carbon fiber significantly decreased by 12.29%.Conclusion:In the PD dose verification of IMRT for cervical cancer,the bed board with carbon fiber for treatment combined with the fixed bottom board will produce adverse effect for the verification results.The effect of the single use of bed board for treatment is relatively small.The combined use of the bed board with carbon fiber for treatment and the fixed bottom board will lead to a significant deterioration in the verification result of PD dose.

Background and aims Cancer cachexia is prevalent in various cancers and is associated with chemotherapy toxicity. However, limited data exist on the relationship between cachexia and immune-related adverse events (irAEs). The aim of this study is to explore the correlation between cancer cachexia and irAEs and its possible mechanism. Methods A murine model of orthotopic hepatocellular carcinoma (HCC) with cachexia was developed to evaluate the impact of T-cell infiltration into multiple tumor-free organs on the occurrence of irAEs. Single-cell RNA sequencing of thymic stromal cells was performed. Additionally, patients with advanced cancers receiving anti-programmed cell death protein 1/ligand 1 (PD-1/L1) antibody treatment were followed to investigate the relationship between cachexia and irAEs. Results Inflammatory cell infiltration was observed in multiple tumor-free organs of cachexic HCC mice but not in non-cachexic controls. Immunofluorescence confirmed that the infiltrating cells included CD4+ and CD8+ T cells. Morphological assessment and hematoxylin–eosin staining revealed thymic atrophy in cachexic HCC mice. Single-cell RNA sequencing of thymic stromal cells showed a reduction in medullary thymic epithelial cells (mTECs) II and III in cachexic mice. Autoimmune regulator (Aire) downregulation was accompanied by decreased expression of tissue-restricted antigens in mTECs. T cells from cachexic HCC mice induced organ-specific inflammation and T-cell infiltration in multiple organs of tumor-free mice. Following anti-mouse PD-1 antibody treatment, the incidence of inflammation in multiple organs markedly increased in cachexic HCC mice and in tumor-free mice that had received T cells from the cachexic HCC mice. Flow cytometry and immunofluorescence analyses revealed enrichment of thymic monocytic myeloid-derived suppressor cells (M-MDSCs) in cachexic HCC mice. M-MDSCs infiltrated the thymus in cachexic mice with cancer, and they induced apoptosis of mTECs from tumor-free mice in vitro via nitric oxide production. Transfer of M-MDSCs led to inflammatory cell infiltration in multiple organs and thymic involution in tumor-free mice without affecting body weight. Sixty-four patients with advanced cancer receiving anti-PD-1/L1 therapy were enrolled. Patients who developed irAEs had higher levels of circulating M-MDSCs than those who did not. Moreover, patients with cachexia (body mass index (BMI) < 20 kg/m2 or ≥5% weight loss over the past 6 months) had elevated M-MDSC levels. Patients with both high M-MDSC levels and low BMI or weight loss ≥5% experienced more irAEs (hazard ratio: 2.333; 95% confidence interval: 1.231–4.423). Conclusions M-MDSCs in cachexic mice induced mTEC apoptosis through nitric oxide production, impairing T-cell negative selection and promoting autoimmune T-cell infiltration into tumor-free organs. Cancer cachexia-related M-MDSCs may serve as predictive biomarkers for irAEs in patients with advanced cancer. Graphical abstract

Redox-sensitive cysteine(RSC)thiol plays an important role in many biological processes such as photosynthesis,cellular metabolism,and transcription.Therefore,it is necessary to identify red-ox-sensitive cysteine accurately.However,traditional redox-sensitive cysteine identification is very ex-pensive and time-consuming.At present,there is an urgent need for a mathematical calculation method to identify sequence information and redox-sensitive cysteines quickly and accurately.Here,we devel-oped an effective predictor called iRSC-PseAAC,which used the dimension reduction algorithm LDA combined with the support vector machine to predict redox-sensitive cysteine sites.In the cross-validation results,the specificity(Sp),sensitivity(Sn),accuracy(Acc)and Matthews correlation coefficient(MCC)were 0.841,0.868,0.859 and 0.692 respectively.In the independent dataset results,the Sp,Sn,Acc and MCC were 0.906,0.882,0.890 and 0.767 respectively.compared with existing prediction methods,iRSC-PseAAC had obvious improvement effect.The method proposed for this study can also be used for many problems in computational proteomics.

Tooth extraction is a common and widely employed therapeutic procedure in oral and maxillofacial surgery.Minimally invasive tooth extraction can reduce both physical and psychological trauma to the patients,and is widely recommended as a first-line clinical treatment.But currently no guidelines or consensus has been available to provide a systematic introduction of minimally invasive tooth extraction to guide the clinical practices.To address this issue,this consensus,based on a comprehensive literature review and clinical experiences of experts,systematically summarizes the indications,target patients,and contraindications of minimally invasive tooth extraction,the overall workflow of this procedure(preoperative preparation,surgical steps,postoperative management,postoperative instructions,medications,and follow-up),and its common postoperative complications to provide a comprehensive guidance for clinical application of this technique.

Tooth extraction is a common and widely employed therapeutic procedure in oral and maxillofacial surgery.Minimally invasive tooth extraction can reduce both physical and psychological trauma to the patients,and is widely recommended as a first-line clinical treatment.But currently no guidelines or consensus has been available to provide a systematic introduction of minimally invasive tooth extraction to guide the clinical practices.To address this issue,this consensus,based on a comprehensive literature review and clinical experiences of experts,systematically summarizes the indications,target patients,and contraindications of minimally invasive tooth extraction,the overall workflow of this procedure(preoperative preparation,surgical steps,postoperative management,postoperative instructions,medications,and follow-up),and its common postoperative complications to provide a comprehensive guidance for clinical application of this technique.

Complex brain diseases seriously endanger human health, and early diagnostic biomarkers and effective treatments are currently lacking. Due to ethical constraints on human research, establishing monkey models is crucial to address these issues. With the rapid development of technology, transgenic monkey models of a range of brain diseases, especially autism spectrum disorder (ASD), have been successfully established. However, to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies, there is still a lack of a standard tool, i.e., a system for collecting and analyzing the daily behaviors of brain disease model monkeys. Therefore, with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes, we established a standard daily behavior collection and analysis system, including behavioral data collection protocols and a monkey daily behavior ethogram (MDBE) for rhesus and cynomolgus monkeys, which are the most commonly used non-human primates in model construction. Then, we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms. We then established a sub-ethogram (ASD monkey core behavior ethogram (MCBE-ASD)) specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE. Subsequently, we demonstrated the high reproducibility of the system.
Animals ; Autism Spectrum Disorder ; Macaca mulatta ; Disease Models, Animal ; Behavior, Animal ; Macaca fascicularis ; Male ; Humans

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.