Objective: To investigate the effects of clinical routine X-ray irradiation dose (average irradiation dose: 29.7±0.54 Gy) on the function, apoptosis, activation state and mitochondrial function of platelets during in vitro storage, so as to provide experimental evidence for optimizing platelet irradiation strategies. Methods: A paired experimental design was adopted. Platelets were collected from 12 healthy donors, and each sample was equally divided into the irradiated group and the control group (non-irradiated). All samples were stored for 5 days under standard platelet preservation conditions (22±2℃, continuous oscillation). Flow cytometry was used to detect platelet count, apoptosis rate (Annexin V+ positive rate), activation markers (CD62P, PAC-1, CD42b) and reactive oxygen species (ROS) level. Meanwhile, mitochondrial-specific probes were used to evaluate changes in mitochondrial count, membrane potential and adenosine triphosphate (ATP) content. Additionally, transmission electron microscopy (TEM) was employed to observe the ultrastructure of platelets, with a focus on mitochondrial morphology, platelet membrane integrity and granule distribution. Results: Within 5 days of storage, the platelet count was (841±89.16)×10 /L in the irradiated group and (824.5±92.88)×10 /L in the control group, with no statistically significant difference between the two groups (P=0.54). The apoptosis rate was (4.94±1.39) % in the irradiated group and (5.50±0.83) % in the control group, showing no significant difference (P=0.31). For activation indicators, the CD62P expression rate was (24.32±7.57) % in the irradiated group versus (25.21±8.13) % in the control group (P=0.43). The PAC-1 positive rates were (12.15±4.43) % and (11.75±3.40) % in the irradiated group and control group, respectively (P=0.44). The CD42b expression rates were (12.14±4.43) % and (11.75±3.4) % in the two groups, respectively (P=0.47). The ROS levels were (31.98±8.1) % and (30.64±5.89) % in the two groups, respectively (P=0.45). No significant differences were found in the above indicators. For mitochondrial function indicators, the mitochondrial count was (55.88±11.49) % in the irradiated group and (53.5±7.24) % in the control group (P=0.57). The ATP contents were (42.45±5.29) % and (41.58±9.50) % in the irradiated group and control group, respectively (P=0.77). The relative membrane potential values were (59.53±10.89) % and (57.49±6.54) % in the two groups, respectively (P=0.47). No significant difference were observed on the mitochondrial function-related indicators. TEM further confirmed that the ultrastructure of platelets in the irradiation group was intact, the mitochondrial morphology was normal, and no pathological changes such as swelling or vacuolization were observed. Conclusion: This study evaluated the impact of conventional-dose X-ray irradiation on platelet storage quality, confirming that this dose does not significant impair platelet count, apoptosis rate, activation status, or mitochondrial function. This finding provides important experimental evidence for the clinical promotion of X-ray irradiation technology and suggests its potential as a safe alternative to γ irradiation. Future studies could further expand the sample size and extend the observation period to verify the effects of X-ray irradiation on long-term platelet storage and post-transfusion in vivo survival rate.

AIM:To investigate the effect of fibroblast growth factor 21(FGF21)on high glucose-induced oxidative stress in retinal pigment epithelial(RPE)cells and to clarify the underlying molecular mechanisms.METHODS:Single-cell sequencing data from the GEO database were analyzed to determine the expression profile of the FGF21 receptor FGFR1 in RPE cells. Human ARPE-19 cells were cultured and randomly assigned to control, high glucose(30 mmol/L), and high glucose+FGF21 analog treatment groups, with additional siFGFR1 and PI3K inhibitor groups. Cell viability in different treatment groups was assessed using CCK-8 assay, intracellular reactive oxygen species(ROS)levels were quantified using DCFH-DA fluorescent probing combined with immunofluorescence staining and flow cytometry. Transcriptome sequencing was performed on cells from the high glucose group and high glucose+FGF21 group to analyze the enrichment level of the PI3K/Akt signaling pathway. Western blotting was performed to detect phosphorylation levels of PI3K/Akt pathway components.RESULTS:Single-cell sequencing revealed specific expression of FGFR1 in RPE cells of retinal tissues from diabetic model mice. Under In vitro experiments, high glucose(30 mmol/L)exposure reduced ARPE-19 cell viability by 49.7% and increased ROS levels by approximately 2-fold. Whereas treatment with the FGF21 analog(60 ng/mL)restored cell viability and attenuated high glucose-induced ROS accumulation. Mechanistic studies demonstrated that FGFR1 knockdown inhibited the antioxidative stress of FGF21. Further validation of the molecular mechanism revealed that high glucose significantly suppressed the PI3K/Akt pathway activation(the levels of p-Akt and p-PI3K were decreased by 33.9% and 36.6%, respectively), while FGF21 effectively reversed this inhibitory effect and restored the expression of p-Akt and p-PI3K. Treatment with the PI3K inhibitor LY294002 inhibited the cytoprotective effect of FGF21 and significantly increased the ROS-positive cells, these findings confirm that PI3K/Akt signaling is indispensable downstream mechanism for FGF21 to exert its effects.CONCLUSION:FGF21 alleviates high glucose-induced oxidative stress and cellular injury in RPE cells by activating the PI3K/Akt signaling pathway through its receptor FGFR1.

Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

Objective To establish an individualized nomogram model and evaluate its efficacy to provide a possible evaluation basis for the prognosis of lower third and abdominal part of oesophageal adenocarcinoma (EAC). Methods Lower third and abdominal part of EAC patients from 2010 to 2015 were chosen from the SEER Research Plus Database (17 Regs, 2022nov sub). The patients were randomly allocated to the training cohort and the internal validation cohort with a ratio of 7∶3 using bootstrap resampling. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) in EAC patients, which would be elected to construct the nomogram prediction model. C-index, calibration curve and receiver operating characteristic (ROC) curve were performed to evaluate its efficacy. Finally, the efficacy to evaluate the OS of EAC patients was compared between the nomogram prediction model and TNM staging system. Results In total, 3945 patients with lower third and abdominal part of EAC were enrolled, including 3475 males and 470 females with a median age of 65 (57-72) years. The 2761 patients were allocated to the training cohort and the remaining 1184 patients to the internal validation cohort. In the training and the internal validation cohorts, the C-index of the nomogram model was 0.705 and 0.713, respectively. Meanwhile, the calibration curve also suggested that the nomogram model had a strong capability of predicting 1-, 3-, and 5-year OS rates of EAC patients. The nomogram also had a higher efficacy than the TNM staging system in predicting 1-, 3-, and 5-year OS rates of EAC patients. Conclusion This nomogram prediction model has a high efficiency for predicting OS in the patients with lower third and abdominal part of EAC, which is higher than that of the current TNM staging system.

Objective To evaluate the value of postoperative radiotherapy (PORT) in patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy. Methods Patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy were chosen from the SEER Research Plus Database [17 Registries, November 2012 Submission (2000-2019)]. The patients were divided into a PORT group and a non-PORT group according to whether the PORT was used. To balance baseline characteristics between non-PORT and PORT groups, R software was used to conduct a propensity score matching (PSM) with a ratio of 1 : 1 and a matching tolerance of 0.01. Both the Cox regression analysis and Kaplan-Meier survival analysis were conducted to evaluate the value of PORT in terms of overall survival (OS) and disease-specific survival (DSS). Results In total, 2468 patients with stage ⅢA-N2 non-small cell lung cancer were enrolled, including 1078 males and 1390 females with a median age of 65 (58-71) years. There were 1336 patients in the PORT group, and 1132 patients in the non-PORT group. Cox regression analysis showed that PORT was not significantly associated with OS (multivariate analysis: HR=1.051, 95%CI 0.949-1.164, P=0.338) and DSS (multivariate analysis: HR=1.094, 95%CI 0.976-1.225, P=0.123). No statistical difference was found in the OS or DSS between non-PORT group and PORT group after PSM analysis (P＞0.05). Conclusion PORT does not have a survival benefit for patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy.

Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia. However, the regulatory mechanisms governing this circuit necessitate further elucidation. We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin (5-HT) facilitation system on spinal PKCγ neurons. Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_2C receptors, disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia. Inhibiting spinal 5-HT_2C receptors restored the feedforward inhibitory circuit, effectively preventing neuropathic allodynia. These insights offer promising therapeutic targets for neuropathic allodynia management, emphasizing the potential of spinal 5-HT_2C receptors as a novel avenue for intervention.
Animals ; Neuralgia/physiopathology* ; Protein Kinase C/metabolism* ; Receptor, Serotonin, 5-HT2C/metabolism* ; Hyperalgesia/physiopathology* ; Mice, Transgenic ; Mice ; Spinal Cord/metabolism* ; Serotonin/metabolism* ; Male ; Neurons/metabolism* ; Mice, Inbred C57BL

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

OBJECTIVE: To assess the relationship between blood pressure reactivity index (BPRI) and in-hospital mortality risk in patients with sepsis-associated acute kidney injury (SA-AKI). METHODS: A retrospective cohort study was conducted to collect data from patients admitted to the intensive care unit (ICU) and clinically diagnosed with SA-AKI between 2008 and 2019 in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database in the United States. The collected data included demographic characteristics, comorbidities, vital signs, laboratory parameters, sequential organ failure assessment (SOFA) and simplified acute physiology scoreII(SAPSII) within 48 hours of SA-AKI diagnosis, stages of AKI, treatment regimens, mean BPRI during the first and second 24 hours (BPRI_0_24, BPRI_24_48), and outcome measures including primary outcome (in-hospital mortality) and secondary outcomes (ICU length of stay and total hospital length of stay). Variables with statistical significance in univariate analysis were included in LASSO regression analysis for variable selection, and the selected variables were subsequently incorporated into multivariate Logistic regression analysis to identify independent predictors associated with in-hospital mortality in SA-AKI patients. Restricted cubic spline (RCS) analysis was employed to examine whether there was a linear relationship between BPRI within 48 hours and in-hospital mortality in SA-AKI patients. Basic prediction models were constructed based on the independent predictors identified through multivariate Logistic regression analysis, and receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of each basic prediction model before and after incorporating BPRI. RESULTS: A total of 3 517 SA-AKI patients admitted to the ICU were included, of whom 826 died during hospitalization and 2 691 survived. The BPRI values within 48 hours of SA-AKI diagnosis were significantly lower in the death group compared with the survival group [BPRI_0_24: 4.53 (1.81, 8.11) vs. 17.39 (5.16, 52.43); BPRI_24_48: 4.76 (2.42, 12.44) vs. 32.23 (8.85, 85.52), all P < 0.05]. LASSO regression analysis identified 20 variables with non-zero coefficients that were included in the multivariate Logistic regression analysis. The results showed that respiratory rate, temperature, pulse oxygen saturation (SpO₂), white blood cell count (WBC), hematocrit (HCT), activated partial thromboplastin time (APTT), lactate, oxygenation index, SOFA score, fluid balance (FB), BPRI_0_24, and BPRI_24_48 were all independent predictors for in-hospital mortality in SA-AKI patients (all P < 0.05). RCS analysis revealed that both BPRI showed "L"-shaped non-linear relationships with the risk of in-hospital mortality in SA-AKI patients. When BPRI_0_24 ≤ 14.47 or BPRI_24_48 ≤ 24.21, the risk of in-hospital mortality in SA-AKI increased as BPRI values decreased. Three basic prediction models were constructed based on the identified independent predictors: Model 1 (physiological indicator model) included respiratory rate, temperature, SpO₂, and oxygenation index; Model 2 (laboratory indicator model) included WBC, HCT, APTT, and lactate; Model 3 (scoring indicator model) included SOFA score and FB. ROC curve analysis showed that the predictive performance of the basic models ranked from high to low as follows: Model 3, Model 2, and Model 1, with area under the curve (AUC) values of 0.755, 0.661, and 0.655, respectively. The incorporation of BPRI indicators resulted in significant improvement in the discriminative ability of each model (all P < 0.05), with AUC values increasing to 0.832 for Model 3+BPRI, 0.805 for Model 2+BPRI, and 0.808 for Model 1+BPRI. CONCLUSIONS BPRI is an independent predictor factor for in-hospital mortality in SA-AKI patients. Incorporating BPRI into the prediction model for in-hospital mortality risk in SA-AKI can significantly improve its predictive capability.
Humans ; Acute Kidney Injury/mortality* ; Sepsis/complications* ; Retrospective Studies ; Hospital Mortality ; Prognosis ; Blood Pressure ; Intensive Care Units ; Male ; Female ; Length of Stay ; Middle Aged ; Aged ; Adult ; Logistic Models