A single molecule carrier for ocular posterior segment diseases.

Eye drops are envisaged as the most promising non-invasive formulation for the treatment of the ocular posterior segment diseases, while it is hindered by a series of complex ocular barriers, both static and dynamic in nature. In this context, we propose a single molecule nanomedicine based on host-guest chemistry to achieve highly efficient drug delivery targeted to ocular posterior segment. Sulfonated azocalix[4]arene (SAC4A) serves as the single molecule carrier, owing the multiple features of small size (24.0 Šin length, 21.2 Šin width, 14.8 Šin height with a Van der Waals volume of 930 Å3), negative charge, hydrophilicity, loading universality and hypoxia-triggered release. As a proof-of-concept, an eye drop formed by the complexation of SAC4A with sunitinib (SUN) is prepared to treat wet age-related macular degeneration (wAMD). SAC4A successfully transports SUN to the ocular posterior segment (the amount of SUN reaching the retinal-choroid tissue in the SUN@SAC4A group was 2.47 times larger than that in the SUN group at 30 min), significantly enhancing its anti-choroidal neoangiogenesis effect of SUN to wAMD, which played a key role in the treatment. We believe that the single molecule nanomedicine paradigm is highly amenable for treating various ocular posterior segment diseases in the future.

A systematic review of gastritis as an immune-related adverse event in clinical interventions.

Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment, and the associated immune-related adverse events (irAEs) have garnered significant attention, yet reports on associated immune related gastritis are limited. The diagnosis of immune related gastritis remains predominantly exclusionary, meanwhile its management diverges significantly from that of conventional gastritis. Current guidelines lack standardized grading criteria, and substantial data from large-scale, tertiary clinical studies are absent, therefore we conducted a systematic review of Medline, Web of Science, and Embase databases, identifying 31 articles from 2017 to December 31, 2023, involving 258 patients. Clinical manifestations included epigastric pain (53.1%), mucosal erythema (56.1%), and lymphocyte infiltration (48.6%). Corticosteroid therapy was common (94.7%), with 86.7% experiencing post-treatment improvement. 80% of patients can be diagnosed through endoscopy and pathology, while the remaining 20% may require PET-CT. Hormonal therapy is favored but diverges from standard management. Accurate diagnosis is crucial in managing immune related gastritis effectively.

Formononetin Induces Ferroptosis in Activated Hepatic Stellate Cells to Attenuate Liver Fibrosis by Targeting NADPH Oxidase 4.

Ferroptosis is a newly discovered type of cell death that exerts a crucial role in hepatic fibrosis. Formononetin (FMN), a natural isoflavone compound mainly isolated from Spatholobus suberectus Dunn, shows multiple biological activities, including antioxidant, anti-inflammatory, and hepatoprotection. This research aims to explore the regulatory mechanism of FMN in liver fibrosis and the relationship between NADPH oxidase 4 (NOX4) and ferroptosis. The effects of FMN on HSC ferroptosis were evaluated in rat model of CCl4-induced hepatic fibrosis. In vitro, N-acetyl-L-cysteine (NAC) and deferoxamine (DFO) were used to block ferroptosis and then explored the anti-fibrotic effect of FMN. The target protein of FMN was identified by bio-orthogonal click chemistry reaction as well as drug affinity responsive target stability (DARTS), cellular thermal shift (CETSA), surface plasmon resonance (SPR) assays, and isothermal titration calorimetry (ITC) analysis. Here, we found that FMN exerted anti-fibrotic effects via inducing ferroptosis in activated HSCs. NAC and DFO prevented FMN-induced ferroptotic cell death and collagen reduction. Furthermore, FMN bound directly to NOX4 through possible active amino acid residues sites, and increased NOX4-based NADPH oxidase activity to enhance levels of NADP+/NADPH, thus promoting ferroptosis of activated HSCs and relieving liver fibrosis. These results demonstrate that the direct target and mechanism by which FMN improves liver fibrosis, suggesting that FMN may be a natural candidate for further development of liver fibrosis therapy.

A natural language processing system for the efficient extraction of cell markers.

Single-cell RNA sequencing (scRNA-seq) has emerged as a pivotal tool for exploring cellular landscapes across diverse species and tissues. Precise annotation of cell types is essential for understanding these landscapes, relying heavily on empirical knowledge and curated cell marker databases. In this study, we introduce MarkerGeneBERT, a natural language processing (NLP) system designed to extract critical information from the literature regarding species, tissues, cell types, and cell marker genes in the context of single-cell sequencing studies. Leveraging MarkerGeneBERT, we systematically parsed full-text articles from 3702 single-cell sequencing-related studies, yielding a comprehensive collection of 7901 cell markers representing 1606 cell types across 425 human tissues/subtissues, and 8223 cell markers representing 1674 cell types across 482 mouse tissues/subtissues. Comparative analysis against manually curated databases demonstrated that our approach achieved 76% completeness and 75% accuracy, while also unveiling 89 cell types and 183 marker genes absent from existing databases. Furthermore, we successfully applied the compiled brain tissue marker gene list from MarkerGeneBERT to annotate scRNA-seq data, yielding results consistent with original studies. Conclusions: Our findings underscore the efficacy of NLP-based methods in expediting and augmenting the annotation and interpretation of scRNA-seq data, providing a systematic demonstration of the transformative potential of this approach. The 27323 manual reviewed sentences for training MarkerGeneBERT and the source code are hosted at https://github.com/chengpeng1116/MarkerGeneBERT .

Self-Produced O2 CNs-Based Nanocarriers of DNA Hydrophobization Strategy Triggers Photodynamic and Mitochondrial-Derived Ferroptosis for Hepatocellular Carcinoma Combined Treatment.

Hypoxia can aggravate tumor occurrence, development, invasion, and metastasis, and greatly inhibit the photodynamic therapy (PDT) effect. Herein, carbon nitride (CNs)-based DNA and photosensitizer co-delivery systems (BPSCNs) with oxygen-producing functions are developed to address this problem. Selenide glucose (Seglu) is used as the dopant to prepare red/NIR-active CNs (SegluCNs). The tumor-targeting unit Bio-PEG2000 is utilized to construct BPSCNs nanoparticles through esterification reactions. Furthermore, DNA hydrophobization is realized via mixing P53 gene with a positively charged mitochondrial-targeted near-infrared (NIR) emitting photosensitizer (MTTPY), which is encapsulated in non-cationic BPSCNs for synergistic delivery. Ester bonds in BPSCNs@MTTPY-P53 complexes can be disrupted by lipase in the liver to facilitate P53 release, upregulated P53 expression, and promoted HIF-1α degradation in mitochondria. In addition, the oxygen produced by the complexes improved the hypoxic microenvironment of hepatocellular carcinoma (HCC), synergistically downregulated HIF-1α expression in mitochondria, promoted mitochondrial-derived ferroptosis and enhanced the PDT effect of the MTTPY unit. Both in vivo and in vitro experiments indicated that the transfected P53-DNA, produced O2 and ROS by these complexes synergistically led to mitochondrial-derived ferroptosis in hepatoma cells through the HIF-1α/SLC7A11 pathway, and completely avoiding PDT resistance caused by hypoxia, exerting a significant therapeutic role in HCC treatment.

Oncological characteristics, treatments and prognostic outcomes in MMR-deficient colorectal cancer.

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally. It's recognized that the molecular subtype of CRC, characterized by mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H), plays a critical role in determining appropriate treatment strategies. This review examines the current molecular classifications, focusing on dMMR/MSI-H CRC and its subtypes: Lynch syndrome (LS), Lynch-like syndrome (LLS), and sporadic cases. Despite advances in understanding of these genetic backgrounds, clinical trials have not conclusively differentiated the efficacy of immune checkpoint inhibitors among these subgroups. Therefore, while this review details the molecular characteristics and their general implications for treatment and prognosis, it also highlights the limitations and the need for more refined clinical studies to ascertain tailored therapeutic strategies for each subtype. Furthermore, this review summarizes completed and ongoing clinical studies, emphasizing the importance of developing treatments aligned more closely with molecular profiles. By discussing these aspects, the review seeks to provide a comprehensive analysis of oncological characteristics, presenting a detailed understanding of their implications for treatment and prognosis in dMMR/MSI-H CRC.

Multiparametric mri-based radiomics nomogram for predicting lymph-vascular space invasion in cervical cancer.

PURPOSE: To develop and validate a multiparametric magnetic resonance imaging (mpMRI)-based radiomics model for predicting lymph-vascular space invasion (LVSI) of cervical cancer (CC). METHODS: The data of 177 CC patients were retrospectively collected and randomly divided into the training cohort (n=123) and testing cohort (n = 54). All patients received preoperative MRI. Feature selection and radiomics model construction were performed using max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) on the training cohort. The models were established based on the extracted features. The optimal model was selected and combined with clinical independent risk factors to establish the radiomics fusion model and the nomogram. The diagnostic performance of the model was assessed by the area under the curve. RESULTS: Feature selection extracted the thirteen most important features for model construction. These radiomics features and one clinical characteristic were selected showed favorable discrimination between LVSI and non-LVSI groups. The AUCs of the radiomics nomogram and the mpMRI radiomics model were 0.838 and 0.835 in the training cohort, and 0.837 and 0.817 in the testing cohort. CONCLUSION: The nomogram model based on mpMRI radiomics has high diagnostic performance for preoperative prediction of LVSI in patients with CC.

Glial growth factor 2 treatment alleviates ischemia and reperfusion-damaged integrity of the blood-brain barrier through decreasing Mfsd2a/caveolin-1-mediated transcellular and Pdlim5/YAP/TAZ-mediated paracellular permeability.

The impairment of blood-brain barrier (BBB) integrity is the pathological basis of hemorrhage transformation and vasogenic edema following thrombolysis and endovascular therapy. There is no approved drug in the clinic to reduce BBB damage after acute ischemic stroke (AIS). Glial growth factor 2 (GGF2), a recombinant version of neuregulin-1ß that can stimulates glial cell proliferation and differentiation, has been shown to alleviate free radical release from activated microglial cells. We previously found that activated microglia and proinflammatory factors could disrupt BBB after AIS. In this study we investigated the effects of GGF2 on AIS-induced BBB damage as well as the underlying mechanisms. Mouse middle cerebral artery occlusion model was established: mice received a 90-min ischemia and 22.5 h reperfusion (I/R), and were treated with GGF2 (2.5, 12.5, 50 ng/kg, i.v.) before the reperfusion. We showed that GGF2 treatment dose-dependently decreased I/R-induced BBB damage detected by Evans blue (EB) and immunoglobulin G (IgG) leakage, and tight junction protein occludin degradation. In addition, we found that GGF2 dose-dependently reversed AIS-induced upregulation of vesicular transcytosis increase, caveolin-1 (Cav-1) as well as downregulation of major facilitator superfamily domain containing 2a (Mfsd2a). Moreover, GGF2 decreased I/R-induced upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that played an important role in BBB damage after AIS. In addition, GGF2 significantly alleviated I/R-induced reduction of YAP and TAZ, microglial cell activation and upregulation of inflammatory factors. Together, these results demonstrate that GGF2 treatment alleviates the I/R-compromised integrity of BBB by inhibiting Mfsd2a/Cav-1-mediated transcellular permeability and Pdlim5/YAP/TAZ-mediated paracellular permeability.

Multi-omics Analysis Reveals Key Gut Microbiota and Metabolites Closely Associated with Huntington's Disease.

Dysbiosis of the gut microbiota is closely associated with neurodegenerative diseases, including Huntington's disease (HD). Gut microbiome-derived metabolites are key factors in host-microbiome interactions. This study aimed to investigate the crucial gut microbiome and metabolites in HD and their correlations. Fecal and serum samples from 11 to 26 patients with HD, respectively, and 16 and 23 healthy controls, respectively, were collected. The fecal samples were used for shotgun metagenomics while the serum samples for metabolomics analysis. Integrated analysis of the metagenomics and metabolomics data was also conducted. Firmicutes, Bacteroidota, Proteobacteria, Uroviricota, Actinobacteria, and Verrucomicrobia were the dominant phyla. At the genus level, the presence of Bacteroides, Faecalibacterium, Parabacteroides, Alistipes, Dialister, and Christensenella was higher in HD patients, while the abundance of Lachnospira, Roseburia, Clostridium, Ruminococcus, Blautia, Butyricicoccus, Agathobaculum, Phocaeicola, Coprococcus, and Fusicatenibacter decreased. A total of 244 differential metabolites were identified and found to be enriched in the glycerophospholipid, nucleotide, biotin, galactose, and alpha-linolenic acid metabolic pathways. The AUC value from the integrated analysis (1) was higher than that from the analysis of the gut microbiota (0.8632). No significant differences were found in the ACE, Simpson, Shannon, Sobs, and Chao indexes between HD patients and controls. Our study determined crucial functional gut microbiota and potential biomarkers associated with HD pathogenesis, providing new insights into the role of the gut microbiota-brain axis in HD occurrence and development.

[Characterization of Metal Elements in Atmospheric Fine Particulate Matter and Their Sources in Winter in the Southern Sichuan Urban Agglomeration].

To investigate the concentration characteristics and sources of metal elements in PM2.5 during winter heavy pollution in the southern Sichuan urban agglomeration (Zigong, Luzhou, Neijiang, and Yibin), the metal elements in PM2.5 were measured using membrane sampling methods from December 30, 2018 to January 14, 2019, and the enrichment factor method (EF) and positive matrix factorization(PMF) were applied to investigate the sources of metal elements. The metal element observation data of Zigong in the same period of 2015 were also used to investigate the changes in metal element pollution and enrichment in Zigong in the middle and end of the implementation of China's Air Pollution Prevention and Control Action Plan. The main findings were as follows:① The concentrations and percentages of metal elements in particulate matter in different cities did not differ significantly. The elements with higher concentrations in the four cities showed similarities, with Al, Sb, and Fe at the top. From the comparison of different observation periods in Zigong, the concentrations of all elements except Tl changed. ② The results of the enrichment factor calculation showed that the enrichment of the elements Cr (Zigong and Yibin), Ni, Cu, As, Se, Ag, Cd, Sb, Tl, and Pb in the urban agglomeration was high. The comparison of the enrichment levels of elements in Zigong for different observation periods showed that the enrichment levels of all elements, except Cu, tended to decrease in the winter observation period of 2018. ③ The results of PMF source analysis showed that the metal elements in each city mainly originated from dust sources, coal-fired sources, industrial sources, and traffic sources, whereas there was a mixed contribution among the sources. The contribution of the main sources differed among cities, in which Zigong was dominated by traffic dust sources and mixed sources, Luzhou was dominated by industrial sources, Neijiang had a similar contribution from different sources, and Yibin was dominated by traffic sources.

Aggregation-Induced Emission CN-Based Nanoparticles to Alleviate Hypoxic Liver Fibrosis via Triggering HSC Ferroptosis and Enhancing Photodynamic Therapy.

Hypoxia can lead to liver fibrosis and severely limits the efficacy of photodynamic therapy (PDT). Herein, carbon nitride (CN)-based hybrid nanoparticles (NPs) VPSGCNs@TSI for light-driven water splitting were utilized to solve this problem. CNs were doped with selenide glucose (Se-glu) to enhance their red/NIR region absorption. Then, vitamin A-poly(ethylene glycol) (VA-PEG) fragments and aggregation-induced emission (AIE) photosensitizers TSI were introduced into Se-glu-doped CN NPs (VPSGCNs) to construct VPSGCNs@TSI NPs. The introduction of VA-PEG fragments enhanced the targeting of the NPs to activated hepatic stellate cells (HSCs) and reduced their toxicity to ordinary liver cells. VPSGCN units could trigger water splitting to generate O2 under 660 nm laser irradiation, improve the hypoxic environment of the fibrosis site, downregulate HIF-1α expression, and activate HSC ferroptosis via the HIF-1α/SLC7A11 pathway. In addition, generated O2 could also increase the reactive oxygen species (ROS) production of TSI units in a hypoxic environment, thereby completely reversing hypoxia-triggered PDT resistance to enhance the PDT effect. The combination of water-splitting materials and photodynamic materials showed a 1 + 1 > 2 effect in increasing oxygen levels in liver fibrosis, promoting ferroptosis of activated HSCs and reversing PDT resistance caused by hypoxia.

Therapeutic Effectiveness of Leukocyte- and Platelet-rich Fibrin for Diabetic Foot Ulcers: A Retrospective Study.

OBJECTIVE: Diabetic foot ulcer (DFU) is one of the most serious complications of diabetes. Leukocyte- and platelet-rich fibrin (L-PRF) is a second-generation autologous platelet-rich plasma. This study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical practice. METHODS: Patients with DFU who received L-PRF treatment and standard of care (SOC) from 2018 to 2019 in Tongji Hospital were enrolled. The clinical information including patient characteristics, wound evaluation (area, severity, infection, blood supply), SOC of DFU, and images of ulcers was retrospectively extracted and analyzed. L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction (PVR) greater than 80%. Therapeutic effectiveness, including overall PVR and the overall and weekly healing rates, was evaluated. RESULTS: Totally, 26 patients with DFU were enrolled, and they had an ulcer duration of 47.0 (35.0, 72.3) days. The severity and infection of ulcers varied, as indicated by the Site, Ischemia, Neuropathy, Bacterial Infection, and Depth (SINBAD) scores of 2-6, Wagner grades of 1-4, and the Perfusion, Extent, Depth, Infection and Sensation (PEDIS) scores of 2-4. The initial ulcer volume before L-PRF treatment was 4.94 (1.50, 13.83) cm3, and the final ulcer volume was 0.35 (0.03, 1.76) cm3. The median number of L-PRF doses was 3 (2, 5). A total of 11 patients achieved complete epithelialization after the fifth week of treatment, and 19 patients achieved at least an 80% volume reduction after the seventh week. The overall wound-healing rate was 1.47 (0.63, 3.29) cm3/week, and the healing rate was faster in the first 2 weeks than in the remaining weeks. Concurrent treatment did not change the percentage of complete epithelialization or healing rate. CONCLUSION: Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index, SINBAD score, or Wagner grade, indicating that this method is appropriate for DFU treatment under different clinical conditions.

Gradient inflammation in the pancreatic stump after pancreaticoduodenectomy: Two case reports and review of literature.

BACKGROUND: Postoperative pancreatic fistula (POPF) contributes significantly to morbidity and mortality after pancreaticoduodenectomy (PD). However, the underlying mechanisms remain unclear. This study explored this pathology in the pancreatic stumps and elucidated the mechanisms of POPF following PD. CASE SUMMARY: Pathological analysis and 16S rRNA gene sequencing were performed on specimens obtained from two patients who underwent complete pancreatectomy for grade C POPF after PD. Gradient inflammation is present in the pancreatic stump. The apoptosis was lower than that in the normal pancreas. Moreover, neutrophil-dominated inflammatory cells are concentrated in the ductal system. Notably, neutrophils migrated through the ductal wall in acinar duct metaplasia-formed ducts. Additionally, evidence indicates that gut microbes migrate from the digestive tract. Gradient inflammation occurs in pancreatic stumps after PD. CONCLUSION: The mechanisms underlying POPF include high biochemical activity in the pancreas, mechanical injury, and digestive reflux. To prevent POPF and address pancreatic inflammation and reflux, breaking the link with anastomotic dehiscence is practical.

[Effect of Shikonin on Autophagy and Apoptosis of Human Promyelocytic Leukemia Cells].

OBJECTIVE: To explore the effect of shikonin on autophagy and apoptosis of human promyelocytic leukemia cells and its possible mechanism. METHODS: Human promyelocytic leukemia cells NB4 in the logarithmic growth phase were divided into control group (untreated NB4 cells), shikonin group (0.3 µmol/L shikonin treatment), 740Y-P group (15 µmol/L PI3K/Akt/mTOR pathway activator 740Y-P treatment), shikonin+740Y-P group (0.3 µmol/L shikonin and 15 µmol/L 740Y-P co-treatment), after 24 hours of treatment, the cells were used for subsequent experiments. CCK-8 method was used to detect cell viability, monodansylcadaverine (MDC) staining to detect the aggregation of autophagic vesicles, flow cytometry to detect cell apoptosis, and Western blot to detect the expression of Beclin1, LC3, p62, Bax, cleaved caspase-3, Bcl-2 and PI3K/Akt/mTOR pathway related proteins. RESULTS: Compared with the control group, the purple punctate fluorescence intensity, apoptosis rate, Beclin1, LC3-Ⅱ/LC3-Ⅰ, cleaved caspase-3, and Bax protein expression in NB4 cells were increased in the shikonin group, while OD450 value (24, 48 h) and the expressions of Bcl-2 and p62 proteins were decreased (all P < 0.05). Compared with the control group, the purple punctate fluorescence intensity, apoptosis rate, Beclin1, LC3-Ⅱ/LC3-Ⅰ, cleaved caspase-3, and Bax protein expression in NB4 cells were decreased, while OD450 value (24, 48 h) and the expressions of Bcl-2 and p62 proteins were increased in the 740Y-P group (all P < 0.05). Compared with the shikonin group, the purple punctate fluorescence intensity, apoptosis rate, Beclin1, LC3-Ⅱ/LC3-Ⅰ, cleaved caspase-3, and Bax protein expression in NB4 cells were decreased, while OD450 value (24, 48 h) and the expressions of Bcl-2 and p62 proteins were increased in the shikonin+740Y-P group (all P < 0.05). Compared with the control group, the expression of PI3K/Akt/mTOR pathway related proteins p-PI3K, p-Akt, and p-mTOR in NB4 cells were significantly decreased in the shikonin group, while those in the 740Y-P group were increased (all P < 0.05). Compared with the shikonin group, the expressions of p-PI3K, p-Akt, and p-mTOR proteins in NB4 cells were significantly increased in the shikonin+740Y-P group (all P < 0.05). CONCLUSION: Shikonin may promote autophagy and apoptosis of NB4 cells by inhibiting PI3K/Akt/mTOR pathway.

Study on the postoperative visual function recovery of children with concomitant exotropia based on an augmented reality plasticity model.

Objective: This study aimed to investigate the clinical application effect of an augmented reality (AR) plasticity model on the postoperative visual function recovery of children with concomitant exotropia. Methods: Between September 2019 and October 2021, 28 patients with concomitant exotropia who visited Shenzhen Children's Hospital (9 male and 19 female) were enrolled in this study. The average age of the patients was 6.4 ± 1.8 years. Postoperative rehabilitation training was conducted using a personalized AR binocular visual perception plasticity model developed based on the patient's examination results. After 1 month, 3 months, and 6 months of training, the patients returned to the hospital for examinations of perceptual eye position, static zero-order stereopsis, dynamic first-order fine stereopsis, and dynamic second-order coarse stereopsis to compare the changes in eye position control and stereovision function. Results: After 6 months of eye position training, the horizontal perception eye position of the 28 patients was significantly lower than that before training. The difference in eye position at the first and third months compared with that before training was not statistically significant (1st month: z = -2.255, p = 0.024 > 0.017; 3rd month: z = -2.277, p = 0.023 > 0.017; 6th month: z = -3.051, p = 0.002 < 0.017). The difference in vertical perceptual eye position after training compared with that before training was not statistically significant (1st month: z = -0.252, p = 0.801 > 0.017; 3rd month: z = -1.189, p = 0.234 > 0.017; 6th month: z = -2.225, p = 0.026 > 0.017). The difference in 0.8-m static zero-order stereopsis before and after training was not statistically significant (1st month: z = -2.111, p = 0.035 > 0.017; 3rd month: z = -1.097, p = 0.273 > 0.017; 6th month: z = -1.653, p = 0.098 > 0.017). The 1.5-m static zero-order stereopsis was improved after 1 month, 3 months, and 6 months of training compared with that before training (1st month: z = -3.134, p = 0.002 < 0.017; 3rd month: z = -2.835, p = 0.005 < 0.017; 6th month: z = -3.096, p = 0.002 < 0.017). Dynamic first-order fine stereopsis and dynamic second-order coarse stereopsis were measured in the 28 patients before and after training. Patients 1 and 18 had no dynamic first-order fine stereopsis before training, but both regained dynamic stereopsis after 1 month, 3 months, and 6 months of training. Patient 16 had no dynamic first-order fine stereopsis or dynamic second-order coarse stereopsis before training, but first-order and second-order stereopsis had been reconstructed after 1 month, 3 months, and 6 months of training. Conclusion: Concomitant exotropia surgery improved the basic problem of eye position at the ocular muscle level, but the patient's perceptual eye position and visual function defects at the brain visual level remained. This might partly explain the poor postoperative clinical effect. The AR plasticity model can improve patients' horizontal perceptual eye position and multi-dimensional stereoscopic function, and its clinical effect warrants further study.

Light controlled self-escape capability of non-cationic carbon nitride-based nanosheets in lysosomes for hepatocellular carcinoma targeting stimulus-responsive gene delivery.

High positive charge-induced toxicity, easy lysosomal degradation of nucleic acid drugs, and poor lesion sites targeting are major problems faced in the development of gene carriers. Herein, we proposed the concept of self-escape non-cationic gene carriers for targeted delivery and treatment of photocontrolled hepatocellular carcinoma (HCC) with sufficient lysosome escape and multiple response capacities. Functional DNA was bound to the surface of biotin-PEG2000-modified graphitic carbon nitride (Bio-PEG-CN) nanosheets to form non-cationic nanocomplexes Bio-PEG-CN/DNA. These nanocomposites could actively target HCC tissue. Once these nanocomplexes were taken up by tumor cells, the accumulated reactive oxygen species (ROS) generated by Bio-PEG-CN under LED irradiation would disrupt the lysosome structure, thereby facilitating nanocomposites escape. Due to the acidic microenvironment and lipase in the HCC tissue, the reversible release of DNA could be promoted to complete the transfection process. Meanwhile, the fluorescence signal of Bio-PEG-CN could be monitored in real time by fluorescence imaging technology to investigate the transfection process and mechanism. In vitro and in vivo results further demonstrated that these nanocomplexes could remarkably upregulate the expression of tumor suppressor protein P53, increased tumor sensitivity to ROS generated by nanocarriers, and realized effective gene therapy for HCC via loading P53 gene.

Insomnia Burden among Informal Caregivers of Hospitalized Lung Cancer Patients and Its Influencing Factors.

Objective: This study aimed to reveal the insomnia burden and relevant influencing factors among informal caregivers (ICs) of hospitalized patients with lung cancer. Methods: A cross-sectional study on ICs of hospitalized patients with lung cancer was conducted from December 31, 2020 to December 31, 2021. ICs' burden was assessed using the Caregiver Reaction Assessment (CRA), Hospital Anxiety and Depression Scale (HADS), and Insomnia Severity Index (ISI). Linear and logistic regression models were used to identify the influencing factors. Results: Among 289 ICs of hospitalized patients with lung cancer, 83 (28.72%), 53 (18.34%), and 14 (4.84%) ICs experienced mild, moderate, and severe insomnia, respectively. The scores concerning self-esteem, lack of family support, financial problems, disturbed schedule, and health problems were 4.32 ± 0.53, 2.24 ± 0.79, 2.84 ± 1.14, 3.63 ± 0.77, and 2.44 ± 0.95, respectively. ICs with higher Activities of Daily Living Scale (ADLS) scores were associated with a lower risk of insomnia, with an odd ratio ( OR) and 95% confidence interval ( CI) of 0.940 (0.898-0.983). Among the ICs, female gender ( OR = 2.597), alcohol consumption ( OR = 3.745), underlying medical conditions ( OR = 11.765), long-term caregiving experience ( OR = 37.037), and higher monthly expenses ( OR = 5.714) were associated with a high risk of insomnia. Conclusion: Of the hospitalized patients with lung cancer, 51.9% experienced insomnia. Patients' ADL, ICs gender, alcohol consumption, underlying medical conditions, caregiving duration, and monthly expenses were influencing factors. Therefore, prompt screening and early intervention for ICs of patients with lung cancer is necessary.

Carbon Nitride-Based siRNA Vectors with Self-Produced O2 Effects for Targeting Combination Therapy of Liver Fibrosis via HIF-1α-Mediated TGF-ß1/Smad Pathway.

Hypoxia is an important feature, which can upregulate the hypoxia-inducible factor-1α (HIF-1α) expression and promote the activation of hepatic stellate cells (HSCs), leading to liver fibrosis. Currently, effective treatment for liver fibrosis is extremely lacking. Herein, a safe and effective method is established to downregulate the expression of HIF-1α in HSCs via targeted delivery of VA-PEG-modified CNs-based nanosheets-encapsulated (VA-PEG-CN@GQDs) HIF-1α small interfering RNA (HIF-1α-siRNA). Due to the presence of lipase in the liver, the reversible release of siRNA can be promoted to complete the transfection process. Simultaneously, VA-PEG-CN@GQD nanosheets enable trigger the water splitting process to produce O2 under near-infrared (NIR) irradiation, thereby improving the hypoxic environment of the liver fibrosis site and maximizing the downregulation of HIF-1α expression to improve the therapeutic effect, as demonstrated in liver fibrosis mice. Such combination therapy can inhibit the activation of HSCs via HIF-1α-mediated TGF-ß1/Smad pathway, achieving outstanding therapeutic effects in liver fibrosis mice. In conclusion, this study proposes a novel strategy for the treatment of liver fibrosis by regulating the hypoxic environment and the expression of HIF-1α at lesion site.