New dimensions in alveolar fracture treatment: Open reduction and internal fixation by minimally invasive approach combined with computer-assisted surgery.

Alveolar fractures are a common type of maxillofacial trauma, and the conventional treatment involves closed reduction and dental splinting fixation. However, closed treatment is not suitable for some complex segmental alveolar fractures. In this case report, we introduce an innovative method for segmental alveolar fracture by using open reduction and internal fixation by minimally invasive approach combined with computer-assisted surgery. In this case, the new dimensions in the treatment followed AO principles of fracture management, achieving anatomical reduction of the fracture, absolute stability of the fracture ends, proper preservation of vascular supply to soft tissues and bone, and promoting recovery through early postoperative functional training. This case provides new insights into the treatment of the complex segmental alveolar fractures with tenuous vascular supply and cannot be treated by conventional splinting fixation.

Peripheral blood lymphocyte subpopulations as predictive biomarkers for first-line programmed death 1 inhibitors efficacy in esophageal squamous cell carcinoma: A retrospective study.

Esophageal cancer (EC) poses a significant global health burden, necessitating effective treatment strategies. Immune checkpoint inhibitors have emerged as a promising therapeutic option for EC, but the identification of predictive biomarkers remains crucial for optimizing patient outcomes. We conducted a retrospective analysis of medical records from advanced esophageal squamous cell carcinoma patients treated with first-line programmed death 1 inhibitors. Peripheral blood lymphocyte subpopulations were evaluated using flow cytometry, while hematological tests provided data on neutrophil, lymphocyte, and monocyte counts. Cox regression and logistic regression analyses were employed to explore the association between lymphocyte subpopulations, baseline characteristics, and progression-free survival (PFS). Among the 100 initially included patients, 70 met eligibility criteria. Multivariate Cox regression analysis revealed a significant association between high CD16+CD56+ lymphocyte proportions and longer PFS, independent of other clinical variables. Similarly, a high CD4+/CD8+ ratio was correlated with prolonged PFS. Kaplan-Meier survival curves supported these findings. Logistic regression analysis indicated no significant differences in the CD4+/CD8+ ratio and CD16+CD56+ lymphocytes concerning baseline characteristics, suggesting their potential as independent prognostic markers. Our study highlights the predictive value of peripheral blood CD16+CD56+ lymphocytes and the CD4+/CD8+ ratio for the efficacy of programmed death 1 inhibitors in advanced esophageal squamous cell carcinoma patients. These findings underscore the importance of peripheral blood biomarkers in guiding personalized immunotherapy strategies and improving outcomes for EC patients.

Lymph nodes in oral squamous cell carcinoma: a comprehensive anatomical perspective.

Oral squamous cell carcinoma (OSCC) often exhibits a propensity for metastasis to lymph nodes (LNs), significantly influencing prognosis. Neck dissection (ND) is an important part in the treatment of OSCC. Variations in the preference for and pathways of lymph node metastasis (LNM) in different regions of the oral cavity have been observed. Currently, there is a lack of sufficient emphasis on the anatomical perspectives of LNM and ND. This review elucidates the lymphatic system of the maxillofacial regions from an anatomical standpoint, details the distribution of the sentinel LNs across different subsites, and summarizes the various classifications of the cervical LNs. Additionally, we elaborate on the methods used to study the lymphatic system, particularly imaging techniques. Furthermore, we investigate the pathways of cervical LNM and evaluate the efficacy of ND from an anatomical viewpoint. The overall objective of this review is to provide essential anatomical knowledge for managing LNs in OSCC, in the hope of providing patients with effective treatment modalities to enhance their quality of life.

Intranodal lymphangiography combined with foam sclerotherapy embolization of thoracic duct in the treatment of postoperative chylous leakage for thyroid carcinoma: a case report and review.

Background: Chylous leakage (CL) is a rare but significant complication following cervical lymph node dissection, particularly in patients with papillary thyroid carcinoma (PTC). This condition is characterized by the leakage of lymphatic fluid, which can result in severe consequences such as malnutrition, immunosuppression, and prolonged hospital stays. Conventional treatments for CL include conservative measures and surgical interventions, but these approaches often face limitations and challenges. This case report discusses a successful treatment of CL using thoracic duct lymphangiography combined with local injection of sclerotherapy, demonstrating a novel and effective approach for managing this complication. Case presentation: A 72-year-old female patient with PTC underwent total thyroidectomy and bilateral Level VI and left Levels II, III, IV, and V cervical lymph node dissection. Postoperatively, the patient developed milky drainage indicative of CL. Despite initial conservative treatments including pressure bandaging, negative pressure drainage, and nutritional adjustments, the patient's condition did not improve. The patient declined surgical options, leading to the decision to perform thoracic duct lymphangiography combined with local injection of sclerotherapy. Under real-time ultrasound guidance, the inguinal lymph nodes were accessed, and lipiodol was injected to visualize the thoracic duct. Subsequently, foam sclerosant was injected at the leakage site under fluoroscopic guidance. The procedure resulted in a significant reduction of chyle leakage, and the patient was discharged with no recurrence during a 1-year follow-up. Conclusions: This case illustrates that thoracic duct angiography combined with local injection of sclerotherapy can be an effective treatment for high-output CL when conservative measures fail and surgical intervention is not preferred. The approach offers a minimally invasive alternative that can reduce complications and improve patient outcomes. The successful management of CL in this case underscores the potential of advanced interventional techniques in treating lymphatic system complications and highlights the need for further research to establish standardized treatment protocols.

From single-cell to spatial transcriptomics: decoding the glioma stem cell niche and its clinical implications.

Background: Gliomas are aggressive brain tumors associated with a poor prognosis. Cancer stem cells (CSCs) play a significant role in tumor recurrence and resistance to therapy. This study aimed to identify and characterize glioma stem cells (GSCs), analyze their interactions with various cell types, and develop a prognostic signature. Methods: Single-cell RNA sequencing data from 44 primary glioma samples were analyzed to identify GSC populations. Spatial transcriptomics and gene regulatory network analyses were performed to investigate GSC localization and transcription factor activity. CellChat analysis was conducted to infer cell-cell communication patterns. A GSC signature (GSCS) was developed using machine learning algorithms applied to bulk RNA sequencing data from multiple cohorts. In vitro and in vivo experiments were conducted to validate the role of TUBA1C, a key gene within the signature. Results: A distinct GSC population was identified, characterized by high proliferative potential and an enrichment of E2F1, E2F2, E2F7, and BRCA1 regulons. GSCs exhibited spatial proximity to myeloid-derived suppressor cells (MDSCs). CellChat analysis revealed an active MIF signaling pathway between GSCs and MDSCs. A 26-gene GSCS demonstrated superior performance compared to existing prognostic models. Knockdown of TUBA1C significantly inhibited glioma cell migration, and invasion in vitro, and reduced tumor growth in vivo. Conclusion: This study offers a comprehensive characterization of GSCs and their interactions with MDSCs, while presenting a robust GSCS. The findings offer new insights into glioma biology and identify potential therapeutic targets, particularly TUBA1C, aimed at improving patient outcomes.

Lymph node metastasis diagnosis of postoperative OSCC patients by analyzing extracellular vesicles in drainage fluid based on microfluidic isolation.

Lymph node metastasis (LNM) is a typical marker in oral squamous cell carcinoma (OSCC) indicating poor prognosis. Pathological examination by artificial image acquisition and analysis, as the main diagnostic method for LNM, often takes a week or longer which may cause great anxiety of the patient and also retard timely treatment. However, there are few efficient fast LNM diagnosis methods in clinical applications currently. Our previous study profiled the proteomics of extracellular vesicles (EVs) derived from postoperative drainage fluid (PDF) and showed the potential of detecting specific EVs that expressed aspartate ß-hydroxylase (ASPH) for LNM diagnosis in OSCC patients. Considering that the analysis of ASPH+ PDF-EVs is challenging due to their low abundance (counting less than 10% of total EVs in PDF) and the complex EV isolation process of ultra-centrifugation, we developed a facile platform containing two microfluidic chips filled with antibody-modified microbeads to isolate ASPH+ PDF-EVs, with both the capture and retrieval rate reaching around 90%. Clinical sample analysis based on our method revealed that a mean of 6 × 106 /mL ASPH+ PDF-EVs could be isolated from LNM+ OSCC patients compared to 2.5 × 106 /mL in LNM- OSCC ones. When combined with enzyme-linked immunosorbent assay (ELISA) technique that was commonly used in clinical laboratories in hospitals, this microfluidic platform could precisely distinguish postoperative OSCC patients with LNM or not in several hours, which were validated by a double-blind test containing 6 OSCC patients. We believe this strategy has promise for early diagnosis of LNM in postoperative OSCC patients and finally helps guiding timely and reasonable treatment in clinic.

The MYC2 and MYB43 transcription factors cooperate to repress HMA2 and HMA4 expression, altering cadmium tolerance in Arabidopsis thaliana.

Cadmium (Cd) represents a hazardous heavy metal, prevalent in agricultural soil due to industrial and agricultural expansion. Its propensity for being absorbed by edible plants, even at minimal concentrations, and subsequently transferred along the food chain poses significant risks to human health. Accordingly, it is imperative to investigate novel genes and mechanisms that govern Cd tolerance and detoxification in plants. Here, we discovered that the transcription factor MYC2 directly binds to the promoters of HMA2 and HMA4 to repress their expression, thereby altering the distribution of Cd in plant tissues and negatively regulating Cd stress tolerance. Additionally, molecular, biochemical, and genetic analyses revealed that MYC2 interacts and cooperates with MYB43 to negatively regulate the expression of HMA2 and HMA4 and Cd stress tolerance. Notably, under Cd stress conditions, MYC2 undergoes degradation, thereby alleviating its inhibitory effect on HMA2 and HMA4 expression and plant tolerance to Cd stress. Thus, our study highlights the dynamic regulatory role of MYC2, in concert with MYB43, in regulating the expression of HMA2 and HMA4 under both normal and Cd stress conditions. These findings present MYC2 as a promising target for directed breeding efforts aimed at mitigating Cd accumulation in edible plant roots.

The role of cystathionine ß-synthase in cancer.

Cystathionine ß-synthase (CBS) occupies a key position as the initiating and rate-limiting enzyme in the sulfur transfer pathway and plays a vital role in health and disease. CBS is responsible for regulating the metabolism of cysteine, the precursor of glutathione (GSH), an important antioxidant in the body. Additionally, CBS is one of the three enzymes that produce hydrogen sulfide (H2S) in mammals through a variety of mechanisms. The dysregulation of CBS expression in cancer cells affects H2S production through direct or indirect pathways, thereby influencing cancer growth and metastasis by inducing angiogenesis, facilitating proliferation, migration, and invasion, modulating cellular energy metabolism, promoting cell cycle progression, and inhibiting apoptosis. It is noteworthy that CBS expression exhibits complex changes in different cancer models. In this paper, we focus on the CBS synthesis and metabolism, tissue distribution, potential mechanisms influencing tumor growth, and relevant signaling pathways. We also discuss the impact of pharmacological CBS inhibitors and silencing CBS in preclinical cancer models, supporting their potential as targeted cancer therapies.

Bacterioruberin extract from Haloarchaea Haloferax marinum: Component identification, antioxidant activity and anti-atrophy effect in LPS-treated C2C12 myotubes.

Carotenoids are natural pigments utilized as colourants and antioxidants across food, pharmaceutical and cosmetic industries. They exist in carbon chain lengths of C30, C40, C45 and C50, with C40 variants being the most common. Bacterioruberin (BR) and its derivatives are part of the less common C50 carotenoid group, synthesized primarily by halophilic archaea. This study analysed the compositional characteristics of BR extract (BRE) isolated from 'Haloferax marinum' MBLA0078, a halophilic archaeon isolated from seawater near Yeoungheungdo Island in the Republic of Korea, and investigated its antioxidant activity and protective effect on lipopolysaccharide (LPS)-induced C2C12 myotube atrophy. The main components of BRE included all-trans-BR, monoanhydrobacterioruberin, 2-isopentenyl-3,4-dehydrorhodopin and all-trans-bisanhydrobacterioruberin. BRE exhibited higher antioxidant activity and DNA nicking protection activity than other well-known C40 carotenoids, such as ß-carotene, lycopene and astaxanthin. In C2C12 myotubes, LPS treatment led to a reduction in myotube diameter and number, as well as the hypertranscription of the muscle-specific ubiquitin ligase MAFbx and MuRF1. BRE mitigated these changes by activating the Akt/mTOR pathway. Furthermore, BRE abolished the elevated cellular reactive oxygen species levels and the inflammation response induced by LPS. This study demonstrated that 'Hfx. marinum' is an excellent source of natural microbial C50 carotenoids with strong antioxidant capacity and may offer potential protective effects against muscle atrophy.

Risk factors and clinical significance of posterior slip of the proximal vertebral body after lower lumbar fusion.

BACKGROUND: Adjacent segment disease (ASD) after fusion surgery is frequently manifests as a cranial segment instability, disc herniation, spinal canal stenosis, spondylolisthesis or retrolisthesis. The risk factors and mechanisms of ASD have been widely discussed but never clearly defined. AIM: To investigate the risk factors and clinical significance of retrograde movement of the proximal vertebral body after lower lumbar fusion. METHODS: This was a retrospective analysis of the clinical data of patients who underwent transforaminal lumbar interbody fusion surgery between September 2015 and July 2021 and who were followed up for more than 2 years. Ninety-one patients with degenerative lumbar diseases were included (22 males and 69 females), with an average age of 52.3 years (40-73 years). According to whether there was retrograde movement of the adjacent vertebral body on postoperative X-rays, the patients were divided into retrograde and nonretrograde groups. The sagittal parameters of the spine and pelvis were evaluated before surgery, after surgery, and at the final follow-up. At the same time, the Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) were used to evaluate the patients' quality of life. RESULTS: Nineteen patients (20.9%) who experienced retrograde movement of proximal adjacent segments were included in this study. The pelvic incidence (PI) of the patients in the retrograde group were significantly higher than those of the patients in the nonretrograde group before surgery, after surgery and at the final follow-up (P < 0.05). There was no significant difference in lumbar lordosis (LL) between the two groups before the operation, but LL in the retrograde group was significantly greater than that in the nonretrograde group postoperatively and at the final follow-up. No significant differences were detected in terms of the |PI-LL|, and there was no significant difference in the preoperative lordosis distribution index (LDI) between the two groups. The LDIs of the retrograde group were 68.1% ± 11.5% and 67.2% ± 11.9%, respectively, which were significantly lower than those of the nonretrograde group (75.7% ± 10.4% and 74.3% ± 9.4%, respectively) (P < 0.05). Moreover, the patients in the retrograde group had a greater incidence of a LDI < 50% than those in the nonretrograde group (P < 0.05). There were no significant differences in the ODI or VAS scores between the two groups before the operation, but the ODI and VAS scores in the retrograde group were significantly worse than those in the nonretrograde group after the operation and at the last follow-up, (P < 0.05). CONCLUSION: The incidence of posterior slippage after lower lumbar fusion was approximately 20.9%. The risk factors are related to a higher PI and distribution of lumbar lordosis. When a patient has a high PI and insufficient reconstruction of the lower lumbar spine, adjacent segment compensation via posterior vertebral body slippage is one of the factors that significantly affects surgical outcomes.

Suicide among patients with oral cancer: A population-based study.

BACKGROUND: Patients with oral cancer usually experience disfigurement and dysfunction which are shared risk factors of suicide. The aim of the study was to comprehensively assess the characteristics of suicide and risk factors for suicide in patients with oral cancer. METHODS: Surveillance, Epidemiology, and End Results database was used to acquire information of patients with common malignant tumors including oral cancer from 1975 to 2020. The aim was to explore the incidence of suicide, and timing of suicide among patients with oral cancer. A Fine-Gray competing risks regression model was employed to analyze risk factors associated with suicide among patients with various demographic and tumor characteristics. RESULTS: Totally, 7685 patients with different malignant tumors committed suicide. Among them, 203 patients with oral cancer died due to suicide, presenting a suicide rate of 54.5/100,000 person-years, which was almost 3.5 times that of the US general population and 1.5 times that of the overall US patients with cancer in our study. Approximately 18 %, 40 %, and 55 % of suicides occurred in first year, first 3 years, and first 5 years after diagnosis. Being male, White race, and having a single primary tumor might be regarded as the risk factors for suicide. CONCLUSION: As oral cavity is closely associated with appearance, pronunciation and ingestion, patients with oral cancer have a significant high risk of suicide. Tremendous attention needs to be paid to patients with oral cancer particularly those exhibiting characteristics associated with a high risk of suicide.

Improved therapeutic index of the liposomal docetaxel-glutathione prepared by active click loading.

The clinical usage of docetaxel (DTX) is severely hindered by the dose-limiting neutropenia and peripheral neurotoxicity of polysorbate 80-solubilized DTX injection, and there are no alternative formulations until now. In this study, we developed a new liposomal formulation of DTX to reduce its toxicities, accompanying with the greatly improved antitumor activity. The DTX was encapsulated into liposomes in the form of hydrophilic glutathione (GSH)-conjugated prodrugs using a click drug loading method, which achieved a high encapsulation efficiency (∼95 %) and loading capacity (∼30 % wt). The resulting liposomal DTX-GSH provided a sustained and efficient DTX release (∼50 % within 48 h) in plasma, resulting in a greatly improved antitumor activities as compared with that of polysorbate 80-solubilized DTX injection in the subcutaneous and orthotopic 4T1 breast tumor bearing mice. Even large tumors > 500 mm3 could be effectively inhibited and shrunk after the administration of liposomal DTX-GSH. More importantly, the liposomal DTX-GSH significantly decreased the neutropenia and peripheral neurotoxicity as compared with that of polysorbate 80-solubilized DTX injection at the equivalent dose. These data suggested that the liposomal DTX-GSH might become a superior alternative formulation to the commercial DTX injection.

Tumor microenvironment-responsive macrophage-mediated immunotherapeutic drug delivery.

Immunotherapy, as a promising treatment strategy for cancer, has been widely employed in clinics, while its efficiency is limited by the immunosuppression of tumor microenvironment (TME). Tumor-associate macrophages (TAMs) are the most abundant immune cells infiltrating the TME and play a crucial role in immune regulation. Herein, a M0-type macrophage-mediated drug delivery system (PR-M) was designed for carrying Toll-like receptors (TLRs) agonist-loaded nanoparticles. When TLR agonist R848 was released by responding to the TME, the PR-Ms were polarized from M0-type to M1-type and TAMs were also stimulated from M2-type to M1-type, which eventually reversed the immunosuppressive states of TME. By synergizing with the released R848 agonists, the PR-M significantly activated CD4+ and CD8+ T cells in the TME and turned the 'cold' tumor into 'hot' tumor by regulating the secretion of cytokines including IFN-γ, TNF-α, IL-10, and IL-12, thus ultimately promoting the activation of antitumor immunity. In a colorectal cancer mouse model, the PR-M treatment effectively accumulated at the tumor site, with a 5.47-fold increase in M1-type and a 65.08 % decrease in M2-type, resulting in an 85.25 % inhibition of tumor growth and a 87.55 % reduction of tumor volume compared with the non-treatment group. Our work suggests that immune cell-mediated drug delivery systems can effectively increase drug accumulation at the tumor site and reduce toxic side effects, resulting in a strong immune system for tumor immunotherapy. STATEMENT OF SIGNIFICANCE: The formation of TME and the activation of TAMs create an immunosuppressive network that allows tumor to escape the immune system and promotes its growth and spread. In this study, we designed an M0-type macrophage-mediated drug delivery system (PR-M). It leverages the synergistic effect of macrophages and agonists to improve the tumor immunosuppressive micro-environment by increasing M1-type macrophages and decreasing M2-type macrophages. As part of the treatment, the drug-loaded macrophages endowed the system with excellent tumor targeting. Furthermore, loading R848 into TME-responsive nanoparticles could protect macrophages and reduce the potential toxicity of agonists. Further investigations demonstrated that the designed PR-M could be a feasible strategy with high efficacy in tumor targeting, drug loading, autoimmunity activation, and lower side effects.

Capecitabine mitigates cardiac allograft rejection via inhibition of TYMS-Mediated Th1 differentiation in mice.

OBJECTIVES: Previous studies elucidated that capecitabine (CAP) works as an anti-tumor agent with putative immunosuppressive effects. However, the intricate mechanisms underpinning these effects remain to be elucidated. In this study, we aimed to unravel the molecular pathways by which CAP exerts its immunosuppressive effects to reduce allograft rejection. METHODS: Hearts were transplanted from male BALB/c donors to male C57BL/6 recipients and treated with CAP for seven days. The rejection of these heart transplants was assessed using a range of techniques, including H&E staining, immunohistochemistry, RNA sequencing, LS-MS/MS, and flow cytometry. In vitro, naïve CD4+ T cells were isolated and cultured under Th1 condition medium with varying treatments, flow cytometry, LS-MS/MS were employed to delineate the role of thymidine synthase (TYMS) during Th1 differentiation. RESULTS: CAP treatment significantly mitigated acute allograft rejection and enhanced graft survival by reducing graft damage, T cell infiltration, and levels of circulating pro-inflammatory cytokines. Additionally, it curtailed CD4+ T cell proliferation and the presence of Th1 cells in the spleen. RNA-seq showed that TYMS, the target of CAP, was robustly increased post-transplantation in splenocytes. In vitro, TYMS and its metabolic product dTMP were differentially expressed in Th0 and Th1, and were required after activation of CD4+ T cell and Th1 differentiation. TYMS-specific inhibitor, raltitrexed, and the metabolite of capecitabine, 5-fluorouracil, could inhibit the proliferation and differentiation of Th1. Finally, the combined use of CAP and the commonly used immunosuppressant rapamycin can induce long-term survival of allograft. CONCLUSION: CAP undergoes metabolism conversion to interfere pyrimidine metabolism, which targets TYMS-mediated differentiation of Th1, thereby playing a significant role in mitigating acute cardiac allograft rejection in murine models.

Prediction of early remission after infliximab in Crohn's disease using baseline microbiome and metabolomics.

To characterize the microbiome and metabolic profile in Crohn's disease (CD) patients with different outcome after infliximab (IFX) treatment. The clinical data of a cohort of 35 patients with moderate-to-severe CD admitted at Jinling hospital between Oct 2022 and Dec 2023 were collected. Stool samples at baseline were collected to perform 16SrRNA and ITS2 sequencing and LC-MS untargeted metabolomics. Of these, seven discontinued IFX and underwent surgery during the induction period, and 28 received IFX at weeks 0, 2, and 6, each administered intravenously. Clinical remission was assessed based on the clinical symptoms and HBI at baseline and week 14. Baseline microbial richness and evenness was not significantly different between remission and non-remission group. The taxonomic community analysis identified decrease of Ruminococcus, Lachnoclostridium, Akkermansia in bacterial community and decrease of Asterotremella and Wallemia in fungal community in the non-remission group. LC-MS analysis showed that histamine, creatinine and L-proline significantly increased in remission group, while androsterone, berberine and episterol significantly decreased. The combined prediction model of histamine, androsterone, and episterol demonstrated a high predictive value of remission in patients after IFX treatment (AUC=0.898, p<0.001). Together, these data might facilitate a priori determination of optimal therapeutics for CD patients.

Long non-coding RNA TPT1-AS1 inhibits ferroptosis in ovarian cancer by regulating GPX4 via CREB1 regulation.

BACKGROUND: Long non-coding RNAs (lncRNAs) play crucial roles in cellular processes, with dysregulation implicated in various diseases, including cancers. The lncRNA TPT1-AS1 (TPT1 Antisense RNA 1) promotes tumor progression in several cancers, including ovarian cancer (OC), but its influence on ferroptosis and interaction with other proteins remains underexplored. METHODS: In this study, we employed a multi-faceted approach to investigate the functional significance of TPT1-AS1 in OC. We assessed TPT1-AS1 expression in OC specimens and cell lines using RT-qPCR, in situ hybridization (ISH), and fluorescence in situ hybridization (FISH) assays. Functional assays included evaluating the impact of TPT1-AS1 knockdown on OC cell proliferation, migration, invasiveness, and cell cycle progression. Further, we explored and validated the interaction of TPT1-AS1 with other proteins using bioinformatics. Finally, we investigated TPT1-AS1 involvement in erastin-induced ferroptosis using Iron Assay, Malondialdehyde (MDA) assay, and reactive oxygen species (ROS) detection. RESULTS: Our findings revealed that TPT1-AS1 overexpression in OC correlated with an unfavorable prognosis. TPT1-AS1 knockdown suppressed cell proliferation, migration, and invasiveness. Additionally, TPT1-AS1 inhibited erastin-induced ferroptosis, and in vivo experiments confirmed its oncogenic impact on tumor development. Mechanistically, TPT1-AS1 was found to regulate Glutathione Peroxidase 4 (GPX4) transcription via CREB1 (cAMP response element-binding protein 1) and interact with RNA-binding protein (RBP) KHDRBS3 (KH RNA Binding Domain Containing, Signal Transduction Associated 3) to regulate CREB1. CONCLUSION: TPT1-AS1 promotes OC progression by inhibiting ferroptosis and upregulating CREB1, forming a regulatory axis with KHDRBS3. These findings highlight the regulatory network involving lncRNAs, RBPs, and transcription factors in cancer progression.

Retrospective Analysis of Risk Factors for Urinary Tract Infection after Ureteral Calculi Surgery.

BACKGROUND: Ureteral calculi are a common diagnosis in the field of urology worldwide, and they represent a prevalent subtype of urolithiasis. Ureteroscopic stone surgery is the cornerstone treatment, but postoperative urinary tract infection (UTI) remains a clinical concern. Our study aims to analyse specific risk factors associated with postoperative UTIs following ureteroscopic stone surgery. METHODS: We conducted a case-control study and collected clinical data from 145 patients who underwent ureteroscopic lithotripsy at our hospital from January 2021 to January 2023. Binary logistic regression analysis was used to investigate risk factors for postoperative UTI. Receiver operating characteristic curves were plotted, and area under the curve (AUC) was calculated to evaluate the predictive value of each factor. RESULTS: Forty patients developed UTI after ureteroscopic stone surgery. Compared with the control group, the case group showed significant differences in stone size, history of diabetes mellitus and preoperative urine culture results (p < 0.05). Multivariable binary logistic regression analysis revealed that stone size (Odds Ratio (OR) = 1.952, p = 0.010), history of diabetes mellitus (OR = 2.438, p = 0.038) and preoperative urine culture (OR = 2.914, p = 0.009) were independent risk factors for postoperative UTI. The AUC values of stone size, history of diabetes mellitus and preoperative urine culture were 0.680, 0.627 and 0.630, respectively. The AUC of the combined prediction was 0.756. CONCLUSIONS: This study identified risk factors for postoperative UTI following ureteroscopic stone surgery and emphasised the importance of stone size, history of diabetes mellitus and preoperative urine culture in the diagnosis.

Multi-omics integration reveals the oncogenic role of eccDNAs in diffuse large B-cell lymphoma through STING signalling.

BACKGROUND: Extrachromosomal circular DNAs (eccDNAs), a type of double-stranded DNAs (dsDNAs) that facilitate the activation of the DNA sensing machinery, have been implicated in the progression and prognosis of various diseases. While the roles of eccDNAs remain contentious, their significance in diffuse large B-cell lymphoma (DLBCL) has not been reported. METHODS: Circular DNA sequencing (circle-seq) was used to demonstrate the expression profile of eccDNAs in DLBCL, and atomic force microscopy to validate the presence of eccDNAs. CCK-8 and scRNA-seq techniques were employed to uncover the activation of eccDNA in the STING pathway, leading to enhanced cell proliferation. Chemotherapeutic drugs were used to test the hypothesis that DNA damage induces the production of eccDNA, thereby activating the STING pathway independent of cGAS. GEO databases were used for verification of the prognosis of the eccDNA-related genes, and animal models were used to investigate the synergistic effects of DNA damage therapy in combination with STING inhibitors on anti-tumour responses. RESULTS: EccDNAs were widely expressed in DLBCL and associated with the prognosis of patients. Elevated abundance of eccDNAs promoted the progression of DLBCL. Chemotherapeutic drugs-induced DNA damage triggered the generation of eccDNAs, resulting in the activation of the STING signalling in a cGAS-independent manner. Moreover, inhibition of STING exerted a synergistic anti-tumour effect with cisplatin. CONCLUSIONS: EccDNAs induced by DNA damage exert an oncogenic role in DLBCL via activating the STING signalling independently of cGAS. This finding offers a rational therapeutic strategy combining chemotherapy with targeting STING. HIGHLIGHTS: EccDNAs induced by DNA damage exert an oncogenic role in DLBCL via activating the STING signalling independently of cGAS. The combined treatment of chemotherapeutic drugs with STING inhibitor significantly delayed the tumor progression, providing new insights into the therapeutic strategy for patients with DLBCL, particularly the relapsed and/or refractory (R/R) ones.

Gene Mutations in Gastrointestinal Stromal Tumors: Advances in Treatment and Mechanism Research.

Although gastrointestinal stromal tumors (GISTs) has been reported in patients of all ages, its diagnosis is more common in elders. The two most common types of mutation, receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor a (PDGFRA) mutations, hold about 75 and 15% of GISTs cases, respectively. Tumors without KIT or PDGFRA mutations are known as wild type (WT)-GISTs, which takes up for 15% of all cases. WT-GISTs have other genetic alterations, including mutations of the succinate dehydrogenase and serine-threonine protein kinase BRAF and neurofibromatosis type 1. Other GISTs without any of the above genetic mutations are named "quadruple WT" GISTs. More types of rare mutations are being reported. These mutations or gene fusions were initially thought to be mutually exclusive in primary GISTs, but recently it has been reported that some of these rare mutations coexist with KIT or PDGFRA mutations. The treatment and management differ according to molecular subtypes of GISTs. Especially for patients with late-stage tumors, developing a personalized chemotherapy regimen based on mutation status is of great help to improve patient survival and quality of life. At present, imatinib mesylate is an effective first-line drug for the treatment of unresectable or metastatic recurrent GISTs, but how to overcome drug resistance is still an important clinical problem. The effectiveness of other drugs is being further evaluated. The progress in the study of relevant mechanisms also provides the possibility to develop new targets or new drugs.

H2O2 oxidation - CaO precipitation pretreatment combining forward osmosis for electroless nickel spent tank liquid (ENSTL) reduction.

The electroless nickel spent tank liquid (ENSTL), as a typical hazardous waste, contains a variety of refractory organic substances as well as heavy metals and inorganic salts. Generally, ENSTL is delegated for disposing by qualified hazardous waste disposal departments in China. However, the temporary storage, transportation, and higher entrusted disposal expenses increase the burden on enterprises producing the hazardous ENSTL. This paper explored an oxidation/precipitation pretreatment and forward osmosis (FO) combined process for ENSTL reduction. 400 mmol/L Hydrogen peroxide and 5.0 wt% calcium oxide were selected as the optimal pretreatment in order to minimize the osmotic pressure of ENSTL, by which the conductivity was significantly reduced from 50.8 mS/cm to 26.8 mS/cm. As a result, the concentrating factor (N) could be dramatically increased from 2.45 by the direct FO to 8.71 by the combined system. Accordingly, the average water flux during the 24 h concentrating cycle increased from 2.47 L/(m2·h) to 4.56 L/(m2·h). TOC rejection rate decreased from 90.23% to 84.39% due to the transformation of organic matter forms by the chemical oxidation during the pretreatment. Meanwhile, TP, Ni and NH4+ rejection rates decreased to a certain extent, which may related to the mitigation of membrane fouling by the pretreatment.