Prognostic value of body composition in patients with digestive tract cancers: A prospective cohort study of 8,267 adults from China.

BACKGROUND & AIMS: The characterization and prognostic value of body composition parameter/phenotype based on computed tomography (CT) in patients with digestive tract cancers remain incomplete. This study aimed to investigate the relationship between parameter/phenotype and clinical outcomes in patients with digestive tract cancers. METHODS: In this prospective cohort study, 8267 patients with digestive tract cancers were assessed using CT scans to determine body composition. Body composition data, including areas of skeletal muscle (SM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT), were collected at the third lumbar level on CT images obtained within 30 days before surgery. Body composition phenotypes (sarcopenia, cancer cachexia, sarcopenic obesity) were determined based on SM, SAT, and VAT areas. The primary endpoint was overall survival, obtained from electronic medical records and telephone follow-up surveys. Kaplan-Meier and log-rank analyses were employed to compare unadjusted survival, while multivariate survival analyses were conducted using a proportional hazards model adjusted for age, gender, and cancer-node-metastasis (TNM) stages. RESULTS: Adjusted hazard ratios (HRs) for all-cause mortality were calculated for the second (Q2), third (Q3), and fourth (Q4) quantiles relative to the first quantile (Q1) for SM areas, revealing adjusted summary HRs of 0.575 (95% CI, 0.361-0.916), 0.419 (95% CI, 0.241-0.729), and 0.384 (95% CI, 0.203-0.726), respectively. Sarcopenia-adjusted summary HRs were 1.795 (95% CI: 1.012-3.181) for male patients and 1.925 (95% CI: 1.065-3.478) for female patients. Cancer cachexia-adjusted summary HRs were 1.542 (95% CI: 1.023-2.324) for male patients and 1.569 (95% CI: 0.820-3.001) for female patients. Sarcopenic obesity-adjusted summary HRs were 1.122 (95% CI: 0.759-1.657) for male patients and 1.303 (95% CI: 0.623-2.725) for female patients. Subgroup analyses indicated varying prognostic values of body composition parameter/phenotype among different cancer types. CONCLUSIONS: Our findings suggest a large SM area is a favorable prognostic indicator, while cancer cachexia and sarcopenia signify poor prognosis in patients with digestive tract cancers. These findings have important implications for the personalized preoperative assessment of body composition in patients with digestive tract cancers.

Mini Endoscopic Septoplasty for High Localized Nasal Septum Deviation: Surgical Technique, Outcomes, and Comparison With Regular Septoplasty.

OBJECTIVES: This prospective cohort study aimed to describe the technique of mini endoscopic septoplasty for patients with a high localized nasal septum deviation in front of the middle turbinate and chronic sinusitis or nasal sinus fungus ball. Our primary objective was to investigate the indications and outcomes of this procedure, and the secondary objective was to compare it with regular endoscopic septoplasty. METHODS: Patients with chronic sinusitis or nasal sinus fungus ball and high localized nasal septum deviation underwent mini endoscopic septoplasty, while those with a broad deviation of the nasal septum underwent regular endoscopic septoplasty. The study evaluated the procedure duration, blood loss, and complications associated with both methods. All patients were followed up for 3 months. RESULTS: Thirty patients underwent mini endoscopic septoplasty; another 30 underwent regular endoscopic septoplasty. Mini endoscopic septoplasty demonstrated a significantly shorter procedure duration and lower blood loss than regular endoscopic septoplasty. Neither group experienced operative complications, such as nasal septum perforation or hematoma. CONCLUSION: Mini endoscopic septoplasty is a safe, time-efficient, and effective technique indicated for highly localized nasal septum deviations in patients with chronic sinusitis or nasal sinus fungus ball. This procedure offers advantages in terms of the surgical approach and postoperative debridement. Future research could explore the broader clinical implications of these findings.

Development and validation of nomograms to predict survival and recurrence after hepatectomy for intermediate/advanced (BCLC stage B/C) hepatocellular carcinoma.

BACKGROUND: Despite the Barcelona Clinic Liver Cancer system discouraging hepatectomy for intermediate/advanced hepatocellular carcinoma, the procedure is still performed worldwide, particularly in Asia. This study aimed to develop and validate nomograms for predicting survival and recurrence for these patients. METHODS: We analyzed patients who underwent curative-intent hepatectomy for intermediate/advanced hepatocellular carcinoma between 2010 and 2020 across 3 Chinese hospitals. The Eastern Hepatobiliary Surgery Hospital cohort was used as the training cohort for the nomogram construction, and the Jilin First Hospital and Fujian Mengchao Hepatobiliary Hospital cohorts served as the external validation cohorts. Independent preoperative predictors for survival and recurrence were identified through univariable and multivariable Cox regression analyses. Predictive accuracy was measured using the concordance index and calibration curves. The predictive performance between nomograms and conventional hepatocellular carcinoma staging systems was compared. RESULTS: A total of 1,328 patients met the inclusion criteria. The nomograms for predicting survival and recurrence were developed using 10 and 6 independent variables, respectively. Nomograms' concordance indices in the training cohort were 0.777 (95% confidence interval 0.759-0.800) and 0.719 (95% confidence interval 0.697-0.742) for survival and recurrence, outperforming 4 conventional staging systems (P < .001). Nomograms accurately stratified risk into low, intermediate, and high subgroups. These results were validated well by 2 external validation cohorts. CONCLUSION: We developed and validated nomograms predicting survival and recurrence for patients with intermediate/advanced hepatocellular carcinoma, contradicting Barcelona Clinic Liver Cancer surgical guidelines. These nomograms may facilitate clinicians to formulate personalized surgical decisions, estimate long-term prognosis, and strategize neoadjuvant/adjuvant anti-recurrence therapy.

P62 promotes FSH-induced antral follicle formation by directing degradation of ubiquitinated WT1.

In females, the pathophysiological mechanism of poor ovarian response (POR) is not fully understood. Considering the expression level of p62 was significantly reduced in the granulosa cells (GCs) of POR patients, this study focused on identifying the role of the selective autophagy receptor p62 in conducting the effect of follicle-stimulating hormone (FSH) on antral follicles (AFs) formation in female mice. The results showed that p62 in GCs was FSH responsive and that its level increased to a peak and then decreased time-dependently either in ovaries or in GCs after gonadotropin induction in vivo. GC-specific deletion of p62 resulted in subfertility, a significantly reduced number of AFs and irregular estrous cycles, which were same as pathophysiological symptom of POR. By conducting mass spectrum analysis, we found the ubiquitination of proteins was decreased, and autophagic flux was blocked in GCs. Specifically, the level of nonubiquitinated Wilms tumor 1 homolog (WT1), a transcription factor and negative controller of GC differentiation, increased steadily. Co-IP results showed that p62 deletion increased the level of ubiquitin-specific peptidase 5 (USP5), which blocked the ubiquitination of WT1. Furthermore, a joint analysis of RNA-seq and the spatial transcriptome sequencing data showed the expression of steroid metabolic genes and FSH receptors pivotal for GCs differentiation decreased unanimously. Accordingly, the accumulation of WT1 in GCs deficient of p62 decreased steroid hormone levels and reduced FSH responsiveness, while the availability of p62 in GCs simultaneously ensured the degradation of WT1 through the ubiquitin‒proteasome system and autophagolysosomal system. Therefore, p62 in GCs participates in GC differentiation and AF formation in FSH induction by dynamically controlling the degradation of WT1. The findings of the study contributes to further study the pathology of POR.

Radiomics in Diagnosis, Grading, and Treatment Response Assessment of Soft Tissue Sarcomas: A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: To evaluate radiomics in soft tissue sarcomas (STSs) for diagnostic accuracy, grading, and treatment response assessment, with a focus on clinical relevance. METHODS: In this diagnostic accuracy study, radiomics was applied using multiple MRI sequences and AI classifiers, with histopathological diagnosis as the reference standard. Statistical analysis involved meta-analysis, random-effects model, and Deeks' funnel plot asymmetry test. RESULTS: Among 579 unique titles and abstracts, 24 articles were included in the systematic review, with 21 used for meta-analysis. Radiomics demonstrated a pooled sensitivity of 84% (95% CI: 80-87) and specificity of 63% (95% CI: 56-70), AUC of 0.93 for diagnosis, sensitivity of 84% (95% CI: 82-87) and specificity of 73% (95% CI: 68-77), AUC of 0.91 for grading, and sensitivity of 83% (95% CI: 67-94) and specificity of 67% (95% CI: 59-74), AUC of 0.87 for treatment response assessment. CONCLUSION: Radiomics exhibits potential for accurate diagnosis, grading, and treatment response assessment in STSs, emphasizing the need for standardization and prospective trials. CLINICAL RELEVANCE STATEMENT: Radiomics offers precise tools for STS diagnosis, grading, and treatment response assessment, with implications for optimizing patient care and treatment strategies in this complex malignancy.

[The Optimal Storage Condition and Storage Time of Umbilical Cord Blood from Collection to Preparation].

OBJECTIVE: To explore the optimal storage condition and time of umbilical cord blood from collection to preparation. METHODS: Collect cord blood samples from 30 healthy newborns, with each new born's umbilical cord blood was divided into two parts on average. One part was stored in cold storage (4 ℃) and the other was stored at room temperature (20-24 ℃). Samples were taken at 24, 36, 48, 60 and 72 h, respectively, total nucleated cells (TNC) count and TNC viability was analyzed. Flow cytometry was used to detect the ratio of viable CD34+ cells to viable CD45+ cells and viability of CD34+ cells, and colony-forming unit-granulocyte-macrophage (CFU-GM) count was performed by hematopoietic progenitor cell colony culture. The change trend of each index over time was observed, and the differences in each index was compared between cold storage and room temperature storage under the same storage time. RESULTS: The TNC count (r 4 ℃=-0.9588， r 20-24 ℃=-0.9790), TNC viability (r 4 ℃=-0.9941， r 20-24 ℃=-0.9970), CD34+ cells viability (r 4 ℃=-0.9932， r 20-24 ℃=-0.9828) of cord blood stored in cold storage (4 ℃) and room temperature storage (20-24 ℃) showed a consistent downward trend with the prolongation of storage time. The percentage of viable CD34+ cells (r 4 ℃=0.9169， r 20-24 ℃=0.7470) and CFU-GM count (r 4 ℃=-0.2537， r 20-24 ℃=-0.8098) did not show consistent trends. When the storage time was the same, the TNC count, TNC viability, CD34+ cells viability and CFU-GM count of cord blood stored in cold storage were higher than those stored at room temperature. Under the same storage time (24, 36, 48, 60 or 72 h), TNC viability in room temperature storage was significantly lower than that in cold storage (P <0.001), but TNC count, percentage of viable CD34+ cells and CFU-GM count were not significantly different between room temperature storage and cold storage. When stored at room temperature for 24 h and 36 h, the viability of CD34+ cells was significantly lower than that in cold storage (P <0.001, P <0.01), when the storage time for 48, 60 and 72 h, there was no significant difference in the CD34+ cells viability between room temperature storage and cold storage. CONCLUSION: It is recommended that cord blood be stored in cold storage (4 ℃) from collection to preparation, and processed as soon as possible.

Comparative study of imaging and pathology of primary mucinous adenocarcinoma with different imaging manifestations.

BACKGROUND: Pulmonary mucinous adenocarcinoma is a special type of lung cancer. Its imaging manifestations are diverse, which brings challenges to clinical diagnosis. However, its formation mechanism is unclear. OBJECTIVE: The objective of this study is to analyse the relevant mechanisms of the formation of pulmonary mucinous adenocarcinoma by observing its different imaging and pathological manifestations. DATA AND METHODS: Retrospective analysis was conducted on imaging manifestations and pathological data of 103 patients with pulmonary mucinous adenocarcinoma confirmed intraoperatively or pathologically. RESULTS: Forty-three patients had pulmonary mucinous adenocarcinoma with a solitary nodule/mass, 41 patients with localized pneumonia and 19 patients with diffuse pneumonia. Their CT manifestations included 'falling snowflake sign', ground-glass opacity close to the heart, vacuous signs/honeycombing and withered tree branches. Under the microscope, all the three types of pulmonary mucinous adenocarcinoma had visibly formed mucus lakes but were made of tumour cells with totally different shapes, which included the goblet-like shape (tall column-like shape) and quasi-circular shape. Tall column-shaped tumour cells were negative or weakly positive for thyroid transcription factor-1 (TTF-1) and strongly positive for ALK mutation, whereas quasi-circular tumour cells were positive for TTF-1 and less positive for ALK mutation. CONCLUSION: The different imaging manifestations of mucinous adenocarcinoma are possibly due to the different amounts or viscosity of mucus produced, and the mechanisms of its formation may include (1) tumour cells in different shapes have different abilities to produce mucus; (2) tumours in different stages produce different amounts or viscosity of mucus; and (3) the TTF-1 and ALK genes affect the production of mucus.

In vivo EPID-based daily treatment error identification for volumetric-modulated arc therapy in head and neck cancers with a hierarchical convolutional neural network: a feasibility study.

We proposed a deep learning approach to classify various error types in daily VMAT treatment of head and neck cancer patients based on EPID dosimetry, which could provide additional information to support clinical decisions for adaptive planning. 146 arcs from 42 head and neck patients were analyzed. Anatomical changes and setup errors were simulated in 17,820 EPID images of 99 arcs obtained from 30 patients using in-house software for model training, validation, and testing. Subsequently, 141 clinical EPID images from 47 arcs belonging to the remaining 12 patients were utilized for clinical testing. The hierarchical convolutional neural network (HCNN) model was trained to classify error types and magnitudes using EPID dose difference maps. Gamma analysis with 3%/2 mm (dose difference/distance to agreement) criteria was also performed. The F1 score, a combination of precision and recall, was utilized to evaluate the performance of the HCNN model and gamma analysis. The adaptive fractioned doses were calculated to verify the HCNN classification results. For error type identification, the overall F1 score of the HCNN model was 0.99 and 0.91 for primary type and subtype identification, respectively. For error magnitude identification, the overall F1 score in the simulation dataset was 0.96 and 0.70 for the HCNN model and gamma analysis, respectively; while the overall F1 score in the clinical dataset was 0.79 and 0.20 for the HCNN model and gamma analysis, respectively. The HCNN model-based EPID dosimetry can identify changes in patient transmission doses and distinguish the treatment error category, which could potentially provide information for head and neck cancer treatment adaption.

CT-based intratumoral and peritumoral deep transfer learning features prediction of lymph node metastasis in non-small cell lung cancer.

BACKGROUND: The main metastatic route for lung cancer is lymph node metastasis, and studies have shown that non-small cell lung cancer (NSCLC) has a high risk of lymph node infiltration. OBJECTIVE: This study aimed to compare the performance of handcrafted radiomics (HR) features and deep transfer learning (DTL) features in Computed Tomography (CT) of intratumoral and peritumoral regions in predicting the metastatic status of NSCLC lymph nodes in different machine learning classifier models. METHODS: We retrospectively collected data of 199 patients with pathologically confirmed NSCLC. All patients were divided into training (n = 159) and validation (n = 40) cohorts, respectively. The best HR and DTL features in the intratumoral and peritumoral regions were extracted and selected, respectively. Support Vector Machine (SVM), k-Nearest Neighbors (KNN), Light Gradient Boosting Machine (Light GBM), Multilayer Perceptron (MLP), and Logistic Regression (LR) models were constructed, and the performance of the models was evaluated. RESULTS: Among the five models in the training and validation cohorts, the LR classifier model performed best in terms of HR and DTL features. The AUCs of the training cohort were 0.841 (95% CI: 0.776-0.907) and 0.955 (95% CI: 0.926-0.983), and the AUCs of the validation cohort were 0.812 (95% CI: 0.677-0.948) and 0.893 (95% CI: 0.795-0.991), respectively. The DTL signature was superior to the handcrafted radiomics signature. CONCLUSIONS: Compared with the radiomics signature, the DTL signature constructed based on intratumoral and peritumoral areas in CT can better predict NSCLC lymph node metastasis.

Inhibition the ubiquitination of ENaC and Na,K-ATPase with erythropoietin promotes alveolar fluid clearance in sepsis-induced acute respiratory distress syndrome.

Sepsis-induced acute respiratory distress syndrome (ARDS) causes significant fatalities worldwide and lacks pharmacological intervention. Alveolar fluid clearance (AFC) plays a pivotal role in the remission of ARDS and is markedly impaired in the pathogenesis of ARDS. Here, we demonstrated that erythropoietin could effectively ameliorate lung injury manifestations and lethality, restore lung function and promote AFC in a rat model of lipopolysaccharide (LPS)-induced ARDS. Moreover, it was proven that EPO-induced restoration of AFC occurs through triggering the total protein expression of ENaC and Na,K-ATPase channels, enhancing their protein abundance in the membrane, and suppressing their ubiquitination for degeneration. Mechanistically, the data indicated the possible involvement of EPOR/JAK2/STAT3/SGK1/Nedd4-2 signaling in this process, and the pharmacological inhibition of the pathway markedly eliminated the stimulating effects of EPO on ENaC and Na,K-ATPase, and subsequently reversed the augmentation of AFC by EPO. Consistently, in vitro studies of alveolar epithelial cells paralleled with that EPO upregulated the expression of ENaC and Na,K-ATPase, and patch-clamp studies further demonstrated that EPO substantially strengthened sodium ion currents. Collectively, EPO could effectively promote AFC by improving ENaC and Na,K-ATPase protein expression and abundance in the membrane, dependent on inhibition of ENaC and Na,K-ATPase ubiquitination, and resulting in diminishing LPS-associated lung injuries.

Integrative analysis of RNA-sequencing and microarray for the identification of adverse effects of UVB exposure on human skin.

Background: Ultraviolet B (UVB) from sunlight represents a major environmental factor that causes toxic effects resulting in structural and functional cutaneous abnormalities in most living organisms. Although numerous studies have indicated the biological mechanisms linking UVB exposure and cutaneous manifestations, they have typically originated from a single study performed under limited conditions. Methods: We accessed all publicly accessible expression data of various skin cell types exposed to UVB, including skin biopsies, keratinocytes, and fibroblasts. We performed biological network analysis to identify the molecular mechanisms and identify genetic biomarkers. Results: We interpreted the inflammatory response and carcinogenesis as major UVB-induced signaling alternations and identified three candidate biomarkers (IL1B, CCL2, and LIF). Moreover, we confirmed that these three biomarkers contribute to the survival probability of patients with cutaneous melanoma, the most aggressive and lethal form of skin cancer. Conclusion: Our findings will aid the understanding of UVB-induced cutaneous toxicity and the accompanying molecular mechanisms. In addition, the three candidate biomarkers that change molecular signals due to UVB exposure of skin might be related to the survival rate of patients with cutaneous melanoma.

Enhanced Postsurgical Cancer Treatment Using Methacrylated Glycol Chitosan Hydrogel for Sustained DNA/Doxorubicin Delivery and Immunotherapy.

Background: Cancer recurrence and metastasis are major contributors to treatment failure following tumor resection surgery. We developed a novel implantable drug delivery system utilizing glycol chitosan to address these issues. Glycol chitosan is a natural adjuvant, inducing dendritic cell activation to promote T helper 1 cell immune responses, macrophage activation, and cytokine production. Effective antigen production by dendritic cells initiates T-cell-mediated immune responses, aiding tumor growth control. Methods: In this study, we fabricated multifunctional methacrylated glycol chitosan (MGC) hydrogels with extended release of DNA/doxorubicin (DOX) complex for cancer immunotherapy. We constructed the resection model of breast cancer to verify the anticancer effects of MGC hydrogel with DNA/DOX complex. Results: This study demonstrated the potential of MGC hydrogel with extended release of DNA/DOX complex for local and efficient cancer therapy. The MGC hydrogel was implanted directly into the surgical site after tumor resection, activating tumor-related immune cells both locally and over a prolonged period of time through immune-reactive molecules. Conclusions: The MGC hydrogel effectively suppressed tumor recurrence and metastasis while enhancing immunotherapeutic efficacy and minimizing side effects. This biomaterial-based drug delivery system, combined with cancer immunotherapy, can substantial improve treatment outcomes and patient prognosis.

[Clinical outcomes and bone resection analysis of unilateral double-channel endoscopic technique in treating lumbar disc herniation].

OBJECTIVE: To explore clinical outcomes and bone resection of interlaminar fenestration decompression and unilateral biportal endoscopic (UBE) technique in treating lumbar disc herniation(LDH). METHODS: A retrospective study was performed on 105 patients with single-level LDH treated from December 2019 to December 2021. Fifty-four patients in UBE group,including 32 males and 22 females,aged from 18 to 50 years old with an average of(38.7±9.3) years old,were treated with UBE,29 patients with L4,5 and 25 patients with L5S1. There were 51 patients in small fenestration group,including 27 males and 24 females,aged from 18 to 50 years old with an average of (39.9±10.0) years old,were treated with small fenestration,25 patients with L4,5 and 26 patients with L5S1. Perioperative indexes,such as operation time,postoperative time of getting out of bed and hospital stay were observed and compared between two groups. Visual analogue scale (VAS) and Oswestry disability index (ODI) were compared between two groups before operation and 1,3,6 and 12 months after operation,respectively;and modified MacNab evaluation criteria was used to evaluate clinical efficacy. Amount of bone resection and retention rate of inferior articular process laminoid complex were compared between two groups. RESULTS: All 105 patients were successfully completed operation. Both of two groups were followed up from 6 to 12 months with an average of (10.69±2.49) months. Operation time,postoperative time of getting out of bed and hospital stay were (58.20±5.54) min,(2.40±0.57) d and (3.80±0.61) d in UBE group,and (62.90±7.14) min,(4.40±0.64) d and (4.40±0.64) d in small fenestrum group,respectively;and had statistically difference between two groups(P<0.05). Postoperative VAS of low back and leg pain and ODI in both groups were significantly lower than those before surgery (P<0.05). VAS of lumbar pain in UBE group (1.37±0.49) score was lower than that of small fenestration group (2.45±0.64) score,and had statistically difference (t=9.745,P<0.05). Postoperative ODI in UBE group at 1 and 3 months were (28.54±3.31) % and (22.87±3.23) %,respectively,which were lower than those in small fenestra group (36.31±9.08) % and (29.90±8.36) %,and the difference was statistically significant (P<0.05). There were no significant difference in VAS and ODI between two groups at other time points (P>0.05). According to the modified MacNab evaluation criteria at the latest follow-up,49 patients got excellent result,3 good,and 2 fair in UBE group. In small fenestration group,35 patients got excellent,12 good,and 4 fair. In UBE group,amount of bone resection on L4,5 segment was (0.45±0.08) cm3 and (0.31±0.08) cm3 on the segment of L5S1. In small fenestration group,amount of bone resection on L4,5 segment was (0.57±0.07) cm3 and (0.49±0.04) cm3 on the segment of L5S1,and amount of bone resection of lower articular process laminar complex on the same segment in UBE group was less than that in small fenestration group (P<0.05). In UBE group,retention rate of laminoid complex on L4,5 segment was (0.73±0.04) and L5S1 segment was (0.83±0.03),while L4,5 segment was(0.68±0.06) and L5S1 segment was (0.74±0.04) in small fenestration group,the lower articular process laminar complex retention rate in UBE group was higher than that in small fenestration group(P<0.05). CONCLUSION: Both unilateral double-channel endoscopy and small fenestration of laminae could achieve good clinical results in treating LDH,but UBE has advantages of less trauma,higher efficiency,faster postoperative recovery and less damage to bone structure.

Wound microenvironment-responsive peptide hydrogel with multifunctionalities for accelerating wound healing.

The fabrication of wound microenvironment-responsive peptide hydrogels with hemostatic ability, antibacterial activity, and wound healing potential remains a challenge. Herein, we constructed a multifunctional dressing by inducing the self-assembly of a peptide (Pep-1) and water-soluble new methylene blue (NMB) through electrostatic interaction. The self-assembly mechanism was demonstrated using a combination of transmission electron microscopy, circular dichroism spectrum, fluorescence spectrum, Zeta potential, and rheological analysis. The Pep-1/NMB hydrogel also exhibited a faster drug release rate in wound acidic environment. Furthermore, when Pep-1/NMB was exposed to a 635 nm laser, its antibacterial ratios increased sharply to 95.3%, indicating remarkably improved antibacterial effects. The findings from the blood coagulation and hemostasis assay indicated that Pep-1/NMB effectively enhanced the speed of blood clotting in vitro and efficiently controlled hemorrhage in a mouse liver hemorrhage model. Meanwhile, hemolytic and cytotoxicity evaluation revealed that the hydrogel had excellent hemocompatibility and cytocompatibility. Finally, the findings from the wound healing studies and H&E staining indicated that the Pep-1/NMB hydrogel had a significant impact on cell migration and wound repair. The results indicated that wound microenvironment-responsive Pep-1/NMB hydrogel had significant potential as a highly effective wound dressing platform, offering rapid hemostasis, antibacterial, and wound healing acceleration properties.

Phosphatidylethanolamine (18:2e/18:2) may inhibit adipose tissue wasting in patients with cancer cachexia by increasing lysophosphatidic acid receptor 6.

BACKGROUND: Cancer associated cachexia is characterized by the significant loss of adipose tissue, leading to devastating weight loss and muscle wasting in the majority of cancer patients. The effects and underlying mechanisms of degradation metabolites on adipocytes in cachectic patients remain poorly understood. To address this knowledge gap, we conducted a comprehensive study combining lipidomic analysis of subcutaneous and visceral adipose tissue with transcriptomics data from the database to investigate the mechanisms of lipid regulation in adipocytes. METHODS: We collected subcutaneous and visceral adipose tissue samples from cachectic and noncachectic cancer patients. Lipidomic analysis was performed to identify differentially expressed lipids in both types of adipose tissue. Additionally, transcriptomics data from the GEO database were analyzed to explore gene expression patterns in adipocytes. Bioinformatics analysis was employed to determine the enrichment of differentially expressed genes in specific pathways. Furthermore, molecular docking studies were conducted to predict potential protein targets of specific lipids, with a focus on the PI3K-Akt signaling pathway. Western blot analysis was used to validate protein levels of the identified target gene, lysophosphatidic acid receptor 6 (LPAR6), in subcutaneous and visceral adipose tissue from cachectic and noncachectic patients. RESULTS: Significant lipid differences in subcutaneous and visceral adipose tissue between cachectic and noncachectic patients were identified by multivariate statistical analysis. Cachectic patients exhibited elevated Ceramides levels and reduced CerG2GNAc1 levels (P < 0.05). A total of 10 shared lipids correlated with weight loss and IL-6 levels, enriched in Sphingolipid metabolism, GPI-anchor biosynthesis, and Glyceropholipid metabolism pathways. LPAR6 expression was significantly elevated in both adipose tissues of cachectic patients (P < 0.05). Molecular docking analysis indicated strong binding of Phosphatidylethanolamine (PE) (18:2e/18:2) to LPAR6. CONCLUSIONS: Our findings suggest that specific lipids, including PE(18:2e/18:2), may mitigate adipose tissue wasting in cachexia by modulating the expression of LPAR6 through the PI3K-Akt signaling pathway. The identification of these potential targets and mechanisms provides a foundation for future investigations and therapeutic strategies to combat cachexia. By understanding the underlying lipid regulation in adipocytes, we aim to develop targeted interventions to ameliorate the devastating impact of cachexia on patient outcomes and quality of life. Nevertheless, further studies and validation are warranted to fully elucidate the intricate mechanisms involved and translate these findings into effective clinical interventions.

Single-cell profiling of African swine fever virus disease in the pig spleen reveals viral and host dynamics.

African swine fever, one of the major viral diseases of swine, poses an imminent threat to the global pig industry. The high-efficient replication of the causative agent African swine fever virus (ASFV) in various organs in pigs greatly contributes to the disease. However, how ASFV manipulates the cell population to drive high-efficient replication of the virus in vivo remains unclear. Here, we found that the spleen reveals the most severe pathological manifestation with the highest viral loads among various organs in pigs during ASFV infection. By using single-cell-RNA-sequencing technology and multiple methods, we determined that macrophages and monocytes are the major cell types infected by ASFV in the spleen, showing high viral-load heterogeneity. A rare subpopulation of immature monocytes represents the major population infected at late infection stage. ASFV causes massive death of macrophages, but shifts its infection into these monocytes which significantly arise after the infection. The apoptosis, interferon response, and antigen-presentation capacity are inhibited in these monocytes which benefits prolonged infection of ASFV in vivo. Until now, the role of immature monocytes as an important target by ASFV has been overlooked due to that they do not express classical monocyte marker CD14. The present study indicates that the shift of viral infection from macrophages to the immature monocytes is critical for maintaining prolonged ASFV infection in vivo. This study sheds light on ASFV tropism, replication, and infection dynamics, and elicited immune response, which may instruct future research on antiviral strategies.

Elevated 18F-FDG uptake in subcutaneous adipose tissue correlates negatively with nutritional status and prognostic survival in cachexia patients with gastric cancer.

BACKGROUND: Browning of white adipose tissue is a crucial factor contributing to adipose loss in cachexia patients, detectable via 18F-Fluorodeoxyglucose (18F-FDG) uptake. The present study elucidates the clinical relevance of 18F-FDG uptake in the subcutaneous adipose tissue of gastric cancer patients, specifically focusing on adipose browning and its implications on patient clinical parameters and prognosis. METHODS: This investigation encompassed 770 gastric cancer patients, with PET-CT imaging and clinical data meticulously combined. The 18F-FDG uptake in subcutaneous adipose tissue at the third lumbar layer was quantified, and its correlation with clinical parameters, particularly those related to nutritional status and fat metabolism, was examined. Kaplan-Meier curves were subsequently employed to probe the relationship between 18F-FDG uptake and overall survival. RESULTS: Of the 770 gastric cancer patients, 252 exhibited cancer-associated cachexia, while 518 did not. Cachectic patients demonstrated elevated 18F-FDG uptake in subcutaneous adipose tissue relative to non-cachectic patients (P < 0.001). Increased 18F-FDG uptake was also correlated with reduced plasma concentrations of albumin, prealbumin, hemoglobin, platelets, cholesterol, apolipoprotein A, low-density lipoprotein, and elevated IL-6 concentrations (all P < 0.05). A significant inverse correlation was observed between 18F-FDG uptake and BMI, albumin, low-density lipoprotein, cholesterol, and apolipoprotein A (all P < 0.05). Patients with higher 18F-FDG uptake exhibited diminished overall survival rates compared to those with lower 18F-FDG uptake (P = 0.0065). Furthermore, 18F-FDG uptake in subcutaneous adipose tissue was an independent prognostic indicator in gastric cancer patients (P = 0.028). CONCLUSIONS: Browning of subcutaneous adipose tissue was markedly elevated in cachectic gastric cancer patients compared to non-cachectic counterparts. Increased 18F-FDG uptake in subcutaneous adipose tissue in cachectic gastric cancer patients was inversely correlated with nutritional status and survival prognosis.

Susceptibility to radiation adverse effects in veterans with Gulf War illness and healthy civilians.

We evaluated whether veterans with Gulf War illness (VGWI) report greater ionizing radiation adverse effects (RadAEs) than controls; whether radiation-sensitivity is tied to reported chemical-sensitivity; and whether environmental exposures are apparent risk factors for reported RadAEs (rRadAEs). 81 participants (41 VGWI, 40 controls) rated exposure to, and rRadAEs from, four radiation types. The relations of RadAE-propensity (defined as the ratio of rRadAEs to summed radiation exposures) to Gulf War illness (GWI) presence and severity, and to reported chemical-sensitivity were assessed. Ordinal logistic regression evaluated exposure prediction of RadAE-propensity in the full sample, in VGWI, and stratified by age and chemical-sensitivity. RadAE-propensity was increased in VGWI (vs. controls) and related to GWI severity (p < 0.01) and chemical-sensitivity (p < 0.01). Past carbon monoxide (CO) exposure emerged as a strong, robust predictor of RadAE-propensity on univariable and multivariable analyses (p < 0.001 on multivariable assessment, without and with adjustment for VGWI case status), retaining significance in age-stratified and chemical-sensitivity-stratified replication analyses. Thus, RadAE-propensity, a newly-described GWI-feature, relates to chemical-sensitivity, and is predicted by CO exposure-both features reported for nonionizing radiation sensitivity, consistent with shared mitochondrial/oxidative toxicity across radiation frequencies. Greater RadAE vulnerability fits an emerging picture of heightened drug/chemical susceptibility in VGWI.

MRI-Based Kinetic Heterogeneity Evaluation in the Accurate Access of Axillary Lymph Node Status in Breast Cancer Using a Hybrid CNN-RNN Model.

BACKGROUND: Accurate evaluation of the axillary lymph node (ALN) status is needed for determining the treatment protocol for breast cancer (BC). The value of magnetic resonance imaging (MRI)-based tumor heterogeneity in assessing ALN metastasis in BC is unclear. PURPOSE: To assess the value of deep learning (DL)-derived kinetic heterogeneity parameters based on BC dynamic contrast-enhanced (DCE)-MRI to infer the ALN status. STUDY TYPE: Retrospective. SUBJECTS: 1256/539/153/115 patients in the training cohort, internal validation cohort, and external validation cohorts I and II, respectively. FIELD STRENGTH/SEQUENCE: 1.5 T/3.0 T, non-contrast T1-weighted spin-echo sequence imaging (T1WI), DCE-T1WI, and diffusion-weighted imaging. ASSESSMENT: Clinical pathological and MRI semantic features were obtained by reviewing histopathology and MRI reports. The segmentation of the tumor lesion on the first phase of T1WI DCE-MRI images was applied to other phases after registration. A DL architecture termed convolutional recurrent neural network (ConvRNN) was developed to generate the KHimage (kinetic heterogeneity of DCE-MRI image) score that indicated the ALN status in patients with BC. The model was trained and optimized on training and internal validation cohorts, tested on two external validation cohorts. We compared ConvRNN model with other 10 models and the subgroup analyses of tumor size, magnetic field strength, and molecular subtype were also evaluated. STATISTICAL TESTS: Chi-squared, Fisher's exact, Student's t, Mann-Whitney U tests, and receiver operating characteristics (ROC) analysis were performed. P < 0.05 was considered significant. RESULTS: The ConvRNN model achieved area under the curve (AUC) of 0.802 in the internal validation cohort and 0.785-0.806 in the external validation cohorts. The ConvRNN model could well evaluate the ALN status of the four molecular subtypes (AUC = 0.685-0.868). The patients with larger tumor sizes (>5 cm) were more susceptible to ALN metastasis with KHimage scores of 0.527-0.827. DATA CONCLUSION: A ConvRNN model outperformed traditional models for determining the ALN status in patients with BC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Preparation and characterization of monoclonal antibodies against porcine gasdermin D protein.

Pyroptosis is a newly discovered type of pro-inflammatory programmed cell death that plays a vital role in various processes such as inflammations, immune responses, and pathogen infections. As one of the main executioners of pyroptosis, gasdermin D (GSDMD) is a membrane pore-forming protein that typically exists in a self-inhibitory state. Once activated, GSDMD will be cleaved into an N-terminal fragment with pore-forming activity, becoming the key indicator of pyroptosis activation, and a C-terminal fragment. Although commercial antibodies against human and murine GSDMD proteins are currently available, their reactivity with porcine GSDMD (pGSDMD) is poor, which limits research on the biological functions of pGSDMD and pyroptosis in pigs in vivo and in vitro. Here, five monoclonal antibodies (mAbs) were prepared by immunizing BALB/c mice with procaryotically expressed full-length pGSDMD, all of which did not cross react with human and murine GSDMD proteins. Epitope mapping demonstrated that 15H6 recognizes amino acids (aa) at positions 28-34 of pGSDMD (LQTSDRF), 19H3 recognizes 257-260aa (PPQF), 23H10 and 27A10 recognize 78-82aa (GPFYF), and 25E2 recognizes 429-435aa (PPTLLGS). The affinity constant and isotype of 15H6, 19H3, 23H10, 27A10, and 25E2 mAbs were determined to be 1.32 × 10-9, 3.66 × 10-9, 9.04 × 10-9, 1.83 × 10-9, and 8.00 × 10-8 mol/L and IgG1/κ, IgG2a/κ, IgG2a/κ, IgG1/κ, and IgG1/κ, respectively. Heavy- and light-chain variable regions sequencing showed that the heavy-chain complementarity-determining region (CDR) sequences of all five mAbs are completely different, while the light-chain CDR sequences of the four mAbs that recognize the N-terminus of pGSDMD are identical. Our prepared mAbs provide valuable materials for studying pGSDMD function and pyroptosis. KEY POINTS: • A total of five mouse anti-pGSDMD mAbs were prepared, of which four recognize the N-terminus of pGSDMD and one recognize its C-terminus. • The main performance parameters of the five mAbs, including epitope, antibody titer, affinity constant, isotype, and heavy- and light-chain CDR, were characterized. • All five mAbs specifically recognize pGSDMD protein and do not cross react with human and murine GSDMD proteins.