Balanced medial-lateral wall vs selective 3-wall orbital decompression for sight-threatening Graves's orbitopathy: a clinical retrospective cohort study from 2016 to 2022.

PURPOSE: Although urgent orbital decompression surgery for sight-threatening Graves' orbitopathy unresponsive to available medical treatments continues to evolve, post-operative new-onset or worsened pre-operative strabismus or diplopia remains a significant complication. At present, the optimal surgical technique remains debatable. Here, we sought to compare long-term outcomes after balanced medial-lateral wall versus selective 3-wall decompression as an urgent treatment for unresponsive sight-threatening GO. METHODS: This retrospective study examined the post-operative outcome of 102 eyes (57 patients) that underwent urgent orbital decompression for sight-threatening GO. Treatment effectiveness was measured by visual acuity, proptosis, perimetry, and strabismus/diplopia, while fundus findings were detected by fundus color photography and optical coherence tomography and followed up for more than 12 months. RESULTS: Fifty-seven patients (102 orbits) with an average age of 52.7 ± 10.2 years were evaluated. Balanced medial-lateral wall (BMLW-OD) or selective 3-wall decompression(S3W-OD) were performed in 54 and 48 eyes, respectively. Twelve months after orbital decompression, all parameters significantly improved in both groups, including best-corrected visual acuity (BCVA), mean defect of visual field (VF-MD), pattern standard deviation of visual field (VF-PSD), and proptosis (all P < 0.01). However, new-onset esotropia occurred in 25.8% and 3.8% of patients who underwent BMLW-OD surgery or S3W-OD, respectively. Moreover, 6.5% and 38.5% of patients improved after decompression in the medial-lateral wall decompression group and the selective 3-wall decompression group, respectively. CONCLUSIONS: We demonstrated that S3W-OD provides a lower rate of new-onset strabismus/diplopia as compared with BMLW-OD surgery, while still allowing for satisfactory visual outcomes. TRIAL REGISTRATION NUMBER:  : NCT05627401. Date of registration: November 25, 2022.

Prognosis value of circulating tumor cell PD­L1 and baseline characteristics in patients with NSCLC treated with immune checkpoint inhibitors plus platinum­containing drugs.

Immune checkpoint inhibitors (ICIs) combined with platinum-containing chemotherapy are recommended as the standard first-line treatment for non-small cell lung cancer (NSCLC). However, specific prognostic markers for this combination therapy are yet to be identified. Evaluation of circulating tumor cells (CTCs) and cell surface programmed death-ligand 1 (PD-L1) exhibits potential in predicting the efficacy of the aforementioned combination therapy. Thus, the present study aimed to evaluate the prognostic value of CTC PD-L1 testing and other clinical characteristics in patients with NSCLC treated with combination therapy as first-line treatment. In total, 40 patients with advanced NSCLC were included in the present study, and all patients underwent CTC PD-L1 testing at initial diagnosis to determine the association between CTC PD-L1 and tissue PD-L1. The prognostic value of CTC PD-L1 and the baseline characteristics of 26 patients with NSCLC were analyzed, and the prognostic values of changes in CTC PD-L1 and baseline characteristics during 6 months of treatment were further explored. Results of the present study demonstrated that there was no association between CTC PD-L1 and tissue PD-L1 levels. After 6 months of combination therapy, tumor shrinkage, CYFA19 levels and treatment maintenance were associated with progression-free survival (PFS) of patients. Notably, CTC PD-L1 and tissue PD-L1 levels, TNM stage, nutritional score, inflammation score and other blood indicators were not associated with PFS. In conclusion, the evaluation of CTCs and CTC PD-L1 suggested that undetectable CTCs at 6 months of NSCLC treatment are associated with a good prognosis. In addition, negative CTC PD-L1 expression may change to positive CTC PD-L1 expression in line with disease progression, and this may be indicative of poor prognosis.

Escherichia coli and HPV16 coinfection may contribute to the development of cervical cancer.

Persistent human papillomavirus HPV infection is a necessary but insufficient condition for cervical cancer. Microorganisms are crucial environmental factors in cancers susceptibility and progression, recently attracting considerable attention. This study aimed to determine the infection status and relationship between high-risk HPV (HR-HPV) and lower genital tract infectious pathogens in cervical cancer and its precursors. From a retrospective and a prospective cohort analysis, Escherichia coli (E. coli) dominated the pathogens isolated from cervical discharges, and an isolation rate uptrend has been shown recently. HPV16 and E. coli's coinfection rate gradually increased with the severity of cervical intraepithelial neoplasia. The adhesion and invasion abilities of the isolated E. coli to HPV16-positive SiHa cells were evaluated in vitro. The TCGA database and cervical tissues samples analysis showed that IL-10 was upregulated in cervical cancer. IL-10 expression levels increased in tissue samples with the severity of cervical cancer and its precursors with HPV16 and E. coli coinfection. Although no significant changes in IL-10 production were observed in the co-culture supernatant, we hypothesized that Treg immune cells in the tumour microenvironment might be responsible for the local IL-10 upregulation, according to our data showing Foxp3 upregulation and an upward trend with the cervical intraepithelial neoplasia grading to cancer and tumours with E. coli and HPV16 coinfection. Our data provide insights into the possible role of E. coli in cervical cancer progression and suggest that the application of HPV and E. coli screening programs may be an effective strategy to relieve the burden of cervical cancer and its precursor lesions.

Multi-omics reveals the switch role of abnormal methylation in the regulation of decidual macrophages function in recurrent spontaneous abortion.

RSA, recurrent spontaneous abortion, often causes serious physical damage and psychological pressure in reproductive women with unclarified pathogenesis. Abnormal function of decidual cells and aberrant DNA methylation have been reported to cause RSA, but their association remains unclear. Here, we integrated transcriptome, DNA methylome, and scRNA-seq to clarify the regulatory relationship between DNA methylation and decidual cells in RSA. We found that DNA methylation mainly influenced the function of decidual macrophages (DMs), of which four hub genes, HLA-A, HLA-F, SQSTM1/P62, and Interferon regulatory factor 7 (IRF7), related to 22 hypomethylated CpG sites, regulated 16 hub pathways to participate in RSA pathogenesis. In particular, using transcription factor analysis, it is suggested that the upregulation of IRF7 transcription was associated with enhanced recruitment of the transcription factor STAT1 by the hypomethylated promoter region of IRF7. As the current research on DNA methylation of macrophages in the uterine microenvironment of RSA is still blank, our systematic picture of abnormal DNA methylation in regulating DM function provides new insights into the role of DNA methylation in RSA occurrence, which may aid in further prevention and treatment of RSA.

Severe liver injury and clinical characteristics of occupational exposure to 2-amino-5-chloro-N,3-dimethylbenzamide: A case series.

BACKGROUND: The 2-amino-5-chloro-N,3-dimethylbenzamide is a key intermediate in the synthesis of pesticides and pharmaceuticals. However, no literature currently exists on 2-amino-5-chloro-N,3-dimethylbenzamide poisoning in humans. This study aimed to reveal the health hazard of this chemical for humans and summarize the clinical characteristics of patients with occupational 2-amino-5-chloro-N,3-dimethylbenzamide poisoning. METHODS: This observational study included four patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning from June 2022 to July 2022. The entire course of the incidents was described in detail. Blood 2-amino-5-chloro-N,3-dimethylbenzamide concentrations were detected by a mass spectrometer. Hematoxylin and eosin staining was performed to assess liver injury, and immunofluorescence was used to evaluate hepatic mitophagy. RESULTS: The 2-amino-5-chloro-N,3-dimethylbenzamide powder (99% purity) entered the human body mainly via the skin and respiratory tract due to poor personal protective measures. The typical course of 2-amino-5-chloro-N,3-dimethylbenzamide poisoning was divided into latency, rash, fever, organic damage, and recovery phases in accordance with the clinical evolution. Rash and fever may be the important premonitory symptoms for further organ injuries. The chemical was detected in the blood of all patients and caused multiple organ injuries, predominantly liver injury, including kidney, myocardium, and microcirculation. Three patients recovered smoothly after comprehensive treatments, including artificial liver therapy, continuous renal replacement therapy, glucocorticoids, and other symptomatic and supportive treatments. One patient survived by liver transplantation. The postoperative pathological findings of the removed liver showed acute liver failure, and immunofluorescence staining confirmed the abundance of mitophagy in residual hepatocytes. CONCLUSIONS: This study is the first to elaborate the clinical characteristics of patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning. The chemical enters the body through the respiratory tract and skin during industrial production. The 2-amino-5-chloro-N,3-dimethylbenzamide poisoning causes multiple-organ dysfunction with a predominance of liver injury. Liver transplantation may be an effective option for patients with severe liver failure. The mechanisms of liver injury induced by 2-amino-5-chloro-N,3-dimethylbenzamide might involve abnormal mitochondrial function and mitophagy.

Machine Learning Developed a Programmed Cell Death Signature for Predicting Prognosis, Ecosystem, and Drug Sensitivity in Ovarian Cancer.

Background: Ovarian cancer (OC) is the leading cause of gynecological cancer death and the fifth most common cause of cancer-related death in women in America. Programmed cell death played a vital role in tumor progression and immunotherapy response in cancer. Methods: The prognostic cell death signature (CDS) was constructed with an integrative machine learning procedure, including 10 methods, using TCGA, GSE14764, GSE26193, GSE26712, GSE63885, and GSE140082 datasets. Several methods and single-cell analysis were used to explore the correlation between CDS and the ecosystem and therapy response of OC patients. Results: The prognostic CDS constructed by the combination of StepCox (n = both) + Enet (alpha = 0.2) acted as an independent risk factor for the overall survival (OS) of OC patients and showed stable and powerful performance in predicting the OS rate of OC patients. Compared with tumor grade, clinical stage, and many developed signatures, the CDS had a higher C-index. OC patients with low CDS score had a higher level of CD8+ cytotoxic T, B cell, and M1-like macrophage, representing a related immunoactivated ecosystem. A low CDS score indicated a higher PD1 and CTLA4 immunophenoscore, higher tumor mutation burden score, lower tumor immune dysfunction and exclusion score, and lower tumor escape score in OC, demonstrating a better immunotherapy response. OC patients with high CDS score had a higher gene set score of cancer-related hallmarks, including angiogenesis, epithelial-mesenchymal transition, hypoxia, glycolysis, and notch signaling. Conclusion: The current study constructed a novel CDS for OC, which could serve as an indicator for predicting the prognosis, ecosystem, and immunotherapy benefits of OC patients.

[Occurrence and Fate of Steroid Hormones in Sewage Treatment Plants].

Sewage treatment plants (STPs) are one of the crucial barriers for the environmental emission of steroid hormones. Insights into the occurrence and fate of different categories of steroid hormones in STPs could provide theoretical support for improving steroid removal by STPs. The present study investigated 22 steroid hormones in each treatment process of two STPs located in Wuxi via eight monthly sampling campaigns and compared the efficacy of Anaerobic-Anoxic-Aerobic (A2/O) and reversed A2/O treatments. The results showed that the total steroid concentrations in the influent and effluent were 27.7-256.8 ng·L-1 and 5.7-211.0 ng·L-1, respectively, and 36.3-123.6 ng·g-1 in the excess sludge. Androsterone, androstenedione, estrone, estriol, and progesterone were the main species detected in the STPs. The concentrations of most steroids increased with the rise of rainfall and temperature, whereas the removal rates were not significantly different between winter and summer. Secondary and tertiary treatment processes showed better performance in steroid removal compared with that in the primary treatment; however, reversed A2/O did not show advantages over traditional A2/O. The organic-normalized partition coefficients (lg Koc) of steroids ranged between 2 and 4.5. The values of lg Koc in STP A were slightly greater than those in STP B, indicating that the partition behavior of steroids may influence their treatment efficacies.

A biocompatible pure organic porous nanocage for enhanced photodynamic therapy.

Porphyrin-based photosensitizers have been widely utilized in photodynamic therapy (PDT), but they suffer from deteriorating fluorescence and reactive oxygen species (ROS) due to their close π-π stacking. Herein, a biocompatible pure organic porphyrin nanocage (Py-Cage) with enhanced both type I and type II ROS generation is reported for PDT. The porphyrin skeleton within the Py-Cage is spatially separated by four biphenyls to avoid the close π-π stacking within the nanocage. The Py-Cage showed a large cavity and high porosity with a Brunauer-Emmett-Teller surface area of over 300 m2 g-1, facilitating a close contact between the Py-Cage and oxygen, as well as the fast release of ROS to the surrounding microenvironment. The Py-Cage shows superb ROS generation performance over its precursors and commercial ones such as Chlorin E6 and Rose Bengal. Intriguingly, the cationic π-conjugated Py-Cage also shows promising type I ROS (superoxide and hydroxyl radicals) generation that is more promising for hypoxic tumor treatment. Both in vitro cell and in vivo animal experiments further confirm the excellent antitumor activity of the Py-Cage. As compared to conventional metal coordination approaches to improve PDT efficacy of porphyrin derivatives, the pure organic porous Py-Cage demonstrates excellent biocompatibility, which is further verified in both mice and rats. This work of an organic porous nanocage shall provide a new paradigm for the design of novel, biocompatible and effective photosensitizers for PDT.

Proteomic profiling analysis of human endometrium in women with unexplained recurrent spontaneous abortion.

Unexplained recurrent spontaneous abortion (URSA) seriously affects female reproductive health, causing a great burden to patients both physically and mentally. Endometrial decidualization plays an important role in pregnancy, and impaired decidualization is an essential cause of URSA, but the cause of the damage is still poorly understood. This study aimed to reveal the pathogenesis of URSA by analyzing the differential protein expression profiles in the decidual tissue of patients with recurrent abortion compared to those with normal pregnancy. Morphological analysis revealed abnormal decidualization of endometrial tissue in patients with URSA. Quantitative proteomics analysis showed that a total of 146 differentially expressed proteins were identified between the two groups, among which 95 proteins were downregulated and 51 proteins were upregulated. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that the protein expression profile and signaling pathways of endometrium in patients with URSA changed significantly, and cytoskeleton remodeling and morphological transformation disorders were associated with abortion induced by incomplete decidualization. Meanwhile, transcription factors analysis showed that the 3 most affected families were zf-C2H2, MYB and HMG. Therefore, our study may provide a basis for searching for potential markers of decidualization injury. SIGNIFICANCE: At present, there are still about 50% of RSA patients with unknown causes, which brings great difficulties and blindness to clinical diagnosis and treatment.The limited proteomic studies on URSA further contribute to the lack of understanding in this field. However, in this study, the focus was on proteomic profiling analysis of the human endometrium in URSA patients compared to normal women. The findings revealed that cytoskeletal remodeling disorder is a significant contributor to the failure of decidualization in URSA patients. This insight highlights the potential role of cytoskeleton-related proteins in the pathogenesis of URSA, providing valuable information for further research and potential therapeutic interventions.

LILRB2/PirB mediates macrophage recruitment in fibrogenesis of nonalcoholic steatohepatitis.

Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB-/- bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH.

Correlation of the gut microbiome and immune-related adverse events in gastrointestinal cancer patients treated with immune checkpoint inhibitors.

Introduction: The wide application of immune checkpoint inhibitors has significantly improved the survival expectation of cancer patients. While immunotherapy brings benefits to patients, it also results in a series of immune-related adverse events (irAEs). Increasing evidence suggests that the gut microbiome is critical for immunotherapy response and the development of irAEs. Methods: In this prospective study, we recruited 95 patients with advanced/unresectable gastrointestinal cancers treated with immunotherapy and report a comprehensive analysis of the association of the gut microbiome with irAEs. Metagenome sequencing was used to analyze the differences in bacterial composition and metabolic pathways of baseline fecal samples. Results: In summary, we identified bacterial species and metabolic pathways that might be associated with the occurrence of irAEs in gastric, esophageal, and colon cancers. Ruminococcus callidus and Bacteroides xylanisolvens were enriched in patients without severe irAEs. Several microbial metabolic pathways involved in the urea cycle, including citrulline and arginine biosynthesis, were associated with irAEs. We also found that irAEs in different cancer types and toxicity in specific organs and the endocrine system were associated with different gut microbiota profiles. These findings provide the basis for future mechanistic exploration.

Enrichment of Circulating Tumor Cells of Lung Cancer and Correlation With Serum Leukomonocyte and Tumor Biomarkers: A Retrospective Study.

STUDY DESIGN: Circulating tumor cells is important in the clinical diagnosis of cancer and there are a number of circulating tumor cell detection systems associated with different isolation strategies being validated. There is a novel platform, the CytoBot 2000, which utilizes a combination of physical and immunological technologies to isolate and capture circulating tumor cells. METHODS: In this retrospective study, 39 lung cancer patients and 11 normal healthy individuals were enrolled and performed circulating tumor cell tests and immunofluorescence staining with CytoBot 2000. The performance of this device was assessed by receiver operating characteristic curve. The clinical relevance of circulating tumor cells was assessed by Chi-square. The correlations between circulating tumor cell number and blood lymphocytes and tumor biomarkers were analyzed by Pearson correlation coefficient. RESULTS: The number of circulating tumor cell is significantly increased in lung cancer patients (3.74 > 0.45, P < .0001). The CytoBot 2000 presented a 100% (39/39) circulating tumor cell detection rate in lung cancer patients and 36% (4/11) in healthy individual blood samples, the sensitivity and specificity were 89.7% and 90.9%, respectively, and with the area under curve of 0.966. Further, there was a positive correlation between circulating tumor cell count and carcinoembryonic antigen 211 (R2 = 0.125, P = .027), but not blood lymphocytes (P = .089). CONCLUSIONS: This automatic platform showed excellent performance of circulating tumor cell detection by clinical sample. The tumor biomarkers increased with the number of circulating tumor cell in the lung cancer patients.

Assessment of radiation exposure and public health before and after the operation of Sanmen nuclear power plant.

Introduction: Sanmen nuclear power plant (SNPP) operates the first advanced passive (AP1000) nuclear power unit in China. Methods: To assess the radiological impacts of SNPP operation on the surrounding environment and the public health, annual effective dose (AED) and excess risk (ER) were estimated based on continuous radioactivity monitoring in drinking water and ambient dose before and after its operation during 2014-2021. In addition, the residents' cancer incidence was further analyzed through authorized health data collection. Results: The results showed that the gross α and gross ß radioactivity in all types of drinking water were ranged from 0.008 to 0.017 Bq/L and 0.032 to 0.112 Bq/L, respectively. The cumulative ambient dose in Sanmen county ranged from 0.254 to 0.460 mSv/y, with an average of 0.354 ± 0.075 mSv/y. There is no statistical difference in drinking water radioactivity and ambient dose before and after the operation of SNPP according to Mann-Whitney U test. The Mann-Kendall test also indicates there is neither increasing nor decreasing trend during the period from 2014 to 2021. The age-dependent annual effective doses due to the ingestion of drinking water or exposure to the outdoor ambient environment are lower than the recommended threshold of 0.1 mSv/y. The incidence of cancer (include leukemia and thyroid cancer) in the population around SNPP is slightly higher than that in other areas, while it is still in a stable state characterized by annual percentage changes. Discussion: The current comprehensive results show that the operation of SNPP has so far no evident radiological impact on the surrounding environment and public health, but continued monitoring is still needed in the future.

Geiparvarin Inhibits the Progression of Osteosarcoma by Down-regulating COX2 Expression.

BACKGROUND: Geiparvarin (GN) is a natural compound isolated from the leaves of Geijera parviflora and exhibits anticancer activity. Nevertheless, little is known about its anticancer mechanism and anti-osteosarcoma (OS) effects. AIM: This study explored whether GN effectively inhibits the growth and metastasis of osteosarcoma (OS) through a series of in vitro and in vivo experiments. METHODS: Cell proliferation was measured by colony formation and MTT assays, and cell invasion was detected by Transwell assay. Flow cytometry and caspase-3 activity assays were carried out to examine cell apoptosis, and western blot analysis was performed to assess protein expression. In the animal experiments, the changes in relevant indexes were determined by immunohistochemistry and tumor vessel imaging. RESULTS: Animal experiments showed that GN treatment significantly inhibited the growth and lung metastasis of OS, accompanied by increased apoptosis. In addition, GN treatment notably diminished COX2 expression and angiogenesis in OS. Moreover, COX2 overexpression nullified GN-induced decline in angiogenesis, growth, and lung metastasis and increased apoptosis in OS. Of note, the body weight of mice was enhanced after GN treatment, and the pathological examination manifested that GN treatment did not cause any damage to major organs. CONCLUSION: Our data indicated that GN might depress the growth, metastasis, and angiogenesis of OS by decreasing COX2 expression, suggesting GN is a favorable candidate drug for OS treatment without side effects. Hence, it can be concluded that geiparvarin inhibits OS progression by reducing COX2 expression.

Discovery of mobocertinib, a potent, oral inhibitor of EGFR exon 20 insertion mutations in non-small cell lung cancer.

In the treatment of non-small cell lung cancer (NSCLC), patients harboring exon 20 insertion mutations in the epidermal growth factor receptor (EGFR) gene (EGFR) have few effective therapies because this subset of mutants is generally resistant to most currently approved EGFR inhibitors. This report describes the structure-guided design of a novel series of potent, irreversible inhibitors of EGFR exon 20 insertion mutations, including the V769_D770insASV and D770_N771insSVD mutants. Extensive structure-activity relationship (SAR) studies led to the discovery of mobocertinib (compound 21c), which inhibited growth of Ba/F3 cells expressing the ASV insertion with a half-maximal inhibitory concentration of 11 nM and with selectivity over wild-type EGFR. Daily oral administration of mobocertinib induced tumor regression in a Ba/F3 ASV xenograft mouse model at well-tolerated doses. Mobocertinib was approved in September 2021 for the treatment of adult patients with advanced NSCLC with EGFR exon 20 insertion mutations with progression on or after platinum-based chemotherapy.

Integrative analyses of a mitophagy-related gene signature for predicting prognosis in patients with uveal melanoma.

We aimed to create a mitophagy-related risk model via data mining of gene expression profiles to predict prognosis in uveal melanoma (UM) and develop a novel method for improving the prediction of clinical outcomes. Together with clinical information, RNA-seq and microarray data were gathered from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ConsensusClusterPlus was used to detect mitophagy-related subgroups. The genes involved with mitophagy, and the UM prognosis were discovered using univariate Cox regression analysis. In an outside population, a mitophagy risk sign was constructed and verified using least absolute shrinkage and selection operator (LASSO) regression. Data from both survival studies and receiver operating characteristic (ROC) curve analyses were used to evaluate model performance, a bootstrap method was used test the model. Functional enrichment and immune infiltration were examined. A risk model was developed using six mitophagy-related genes (ATG12, CSNK2B, MTERF3, TOMM5, TOMM40, and TOMM70), and patients with UM were divided into low- and high-risk subgroups. Patients in the high-risk group had a lower chance of living longer than those in the low-risk group (p < 0.001). The ROC test indicated the accuracy of the signature. Moreover, prognostic nomograms and calibration plots, which included mitophagy signals, were produced with high predictive performance, and the risk model was strongly associated with the control of immune infiltration. Furthermore, functional enrichment analysis demonstrated that several mitophagy subtypes may be implicated in cancer, mitochondrial metabolism, and immunological control signaling pathways. The mitophagy-related risk model we developed may be used to anticipate the clinical outcomes of UM and highlight the involvement of mitophagy-related genes as prospective therapeutic options in UM. Furthermore, our study emphasizes the essential role of mitophagy in UM.

A comparative study on efficacies of posterior microscopic mini-open and open technique for thoracolumbar burst fractures with severe traumatic spinal stenosis.

PURPOSE: This study compares the efficacies of minimally invasive decompression by posterior microscopic mini-open technique combined with percutaneous pedicle fixation (hereafter MOT) to traditional open surgery in patients with severe traumatic spinal canal stenosis resulting from Arbeitsgemeinschaft für Osteosynthesefragen (AO) type A3 or A4 thoracolumbar burst fractures and provides references for clinical treatment. METHODS: In total, 133 patients with severe traumatic spinal canal stenosis caused by AO type A3 or A4 thoracolumbar burst fractures who underwent MOT (group A) or traditional open surgery (group B) were retrospectively enrolled. The demographic and radiological data of the two groups were analyzed and compared. RESULTS: A total of 64 patients were finally recruited in this study. There were no significant differences in gender, age, follow-up time, injury mechanism, injury level, AO classification, American Spinal Injury Association (ASIA) score, visual analogue scale (VAS) score, and duration of hospital stay between the two groups (P > 0.05). After the procedures, the prevertebral height ratio (PHR), the Cobb angle, and the mid-sagittal canal diameter compression ratio (MSDCR) were significantly improved (P < 0.05) in both groups. However, group A demonstrated less intraoperative bleeding and a greater VAS score improvement postoperatively and at the last follow-up but involved a longer operation time (P < 0.05). The PHR and the Cobb angle in the two groups showed no significant difference postoperatively and at the last follow-up (P > 0.05). In contrast, a significant improvement in MSDCR was observed at the last follow-up when compared with the postoperative value (P < 0.05). However, the Cobb angle in group A was better maintained than in group B at the last follow-up (P < 0.05), while the MSDCR in group B demonstrated a greater improvement at the last follow-up than in group A (P < 0.05). CONCLUSIONS: Both the MOT and traditional open surgery are effective treatment options for AO type A3 and A4 thoracolumbar burst fractures with severe traumatic spinal stenosis. The advantages of MOT include the minimally invasive procedure, extremely fine spinal canal decompression, less intraoperative bleeding, and significant pain relief. We suggest that MOT should be preferentially performed for AO type A3 or A4 thoracolumbar burst fractures with severe traumatic spinal stenosis.

Identification of potential ferroptosis-related biomarkers and a pharmacological compound in diabetic retinopathy based on machine learning and molecular docking.

Background: Diabetic retinopathy (DR), a neurovascular disease, is a leading cause of visual loss worldwide and severely affects quality of life. Several studies have shown that ferroptosis plays an important role in the pathogenesis of DR; however, its molecule mechanism remains incompletely elucidated. Hence, this study aimed to investigate the pathogenesis of ferroptosis and explore potential ferroptosis-related gene biomarkers and a pharmacological compound for treating DR. Methods: Ferroptosis-related differentially expressed genes (DEGs) were identified in the GSE102485 dataset. Functional enrichment analyses were then performed and a protein-protein interaction (PPI) network was constructed to screen candidates of ferroptosis-related hub genes (FRHGs). FRHGs were further screened based on least absolute shrinkage and selection operator (LASSO) regression and random forest algorithms, and were then validated with the GSE60436 dataset and previous studies. A receiver operating characteristic (ROC) curve monofactor analysis was conducted to evaluate the diagnostic performance of the FRHGs, and immune infiltration analysis was performed. Moreover, the pharmacological compound targeting the FRHGs were verified by molecular docking. Finally, the FRHGs were validated using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Results: The 40 ferroptosis-related DEGs were extracted, and functional enrichment analyses mainly implicated apoptotic signaling, response to oxidative stress, ferroptosis, and lipid and atherosclerosis pathways. By integrating the PPI, LASSO regression, and random forest analyses to screen the FRHGs, and through validation, we identified five FRHGs that performed well in the diagnosis (CAV1, CD44, NOX4, TLR4, and TP53). Immune infiltration analysis revealed that immune microenvironment changes in DR patients may be related to these five FRHGs. Molecular docking also showed that glutathione strongly bound the CAV1 and TLR4 proteins. Finally, the upregulated expression of FRHGs (CD44, NOX4, TLR4, and TP53) was validated by qRT-PCR analysis in human retinal capillary endothelial cells cultured under high-glucose environment. Conclusions: CAV1, CD44, NOX4, TLR4, and TP53 are potential biomarkers for DR and may be involved in its occurrence and progression by regulating ferroptosis and the immune microenvironment. Further, glutathione exhibits potential therapeutic efficacy on DR by targeting ferroptosis. Our study provides new insights into the ferroptosis-related pathogenesis of DR, as well as its diagnosis and treatment.

Transport and retention of nano emulsified vegetable oil in porous media: Effect of pore straining, roughness wedging, and interfacial effects.

Emulsified vegetable oil (EVO), as one of the novel green substrates, has been widely used in subsurface remediation. In these applications, the retention behavior of EVO presents a challenge to remediation efficiency as mechanism insights into the retention of EVO is limited. Herein, Brinell funnels experiments with X-ray microtomography (XMT) were conducted to examine the drainage and retention of nanoscale EVO in porous media, with a specific focus on investigating the impact of pore straining, grain surface roughness, and interfacial effects on Nano-EVO (NEVO) retention. This study demonstrated that the retention of NEVO in porous media is the synergistic result of pore straining, roughness wedging, and interface attachment. With the action of these effects, three residual states of NEVO, incorporating retention at porous ganglia, grain-grain contacts, and grain surface, were identified by XMT in porous media. After multiple periods of drainage and imbibition, the NEVO arrived at stable retention proportions of 46.3%, 72.2%, and 85.9% in three independent systems with coarse, medium, and fine sand as porous media, respectively. The interfacial effects, including the attachment of solid-phase and air-liquid interface, are confirmed as the dominant factors for the retention of NEVO in porous media, which contributed 35.63-47.33% of total retention for the conditions employed. Correspondingly, the contributions of pore straining and roughness wedging only ranged 3.78-24.06% and 3.87-9.94%, respectively. The consistency of the contributions between the actual measurement of XMT and computational evaluation further confirmed the rationality and reliability of the results. In such the dominant factor, interfacial tension, contact angle, and capillary radius play an essential role in NEVO retention, which could be reflected by capillary rise height. These findings advance our understanding on NEVO retention caused by substrate-media interaction and also offer a promising direction for subsurface remediation.