Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO₂), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO₂ maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Objective:To investigate the impact of tumor origin (ventral pancreatic origin and dorsal pancreatic origin) on prognosis in patients with pancreatic head cancer.Methods:A retrospective analysis was performed on the clinical data of 150 patients with pancreatic head cancer who received surgical treatment at the First Affiliated Hospital of the Naval Medical University from October 2014 to December 2017. Among these patients, 92 were male and 58 were female, aged (61.2±8.8) years. The 150 patients were divided into two groups based on tumor origin: the ventral pancreatic cancer group ( n=72) and the dorsal pancreatic cancer group ( n=78). A comparative analysis of clinical, pathological, and imaging charac-teristics was conducted between the two groups. Univariate and multivariable Cox proportional hazards models were used to analyze the association between pancreatic head cancer origin and overall survival (OS). Results:Patients with pancreatic head carcinoma arising from the ventral and dorsal pancreas accounted for 48%(72/150) and 52%(78/150) of the study cohort, respectively. Pancreatic head carcinoma arising from the dorsal pancreas were more likely to show pathological features of pancreatic parenchymal atrophy [73.1%(57/78) vs. 47.2%(34/72), χ2=10.49, P=0.001] and pancreatitis [44.9%(35/78) vs. 29.2%(21/72), χ2=3.95, P=0.047]. In contrast, patients with pancreatic head carcinoma arising from the ventral pancreas was more frequently associated with contact with the superior mesenteric artery [25.0%(18/72) vs. 1.3%(1/78), χ2=19.04, P<0.001], perineural invasion [100%(72/72) vs. 88.5%(69/78), χ2=8.84, P=0.003], and positive surgical margins [15.3%(11/72) vs. 2.6%(2/78), χ2=7.65, P=0.006], with all differences statistically significant. The ventral pancreatic cancer group demonstrated cumulative survival rates of 33.2% and 0 at 1-year and 2-year postoperative intervals, respectively, while the dorsal pancreatic cancer group exhibited rates of 56.7% and 24.8% at the corresponding timepoints. Comparison of Kaplan-Meier survival curves between the two groups showed a statistically significant difference ( χ2=6.00, P=0.014). Multivariable Cox proportional hazards analysis identified dorsal pancreatic origin pancreatic head cancer as an independent predictor of increased mortality risk compared to ventral origin tumors ( HR=2.75, 95% CI: 1.52-4.98, P=0.001). Conclusion:The embryonic origin of pancreatic head cancer determines its clinical, pathological, and imaging heterogeneity, and pancreatic head cancer arising from the ventral pancreas demonstrates significantly worse prognostic outcomes compared to dorsal pancreatic origin.

Objective:A prognosis prediction model for pancreatic cancer was constructed based on multi-scale radiomics combined with deep learning, and the prediction effect of the model was evaluated.Methods:A retrospective analysis was conducted on the clinical data of 215 patients who underwent radical resection of pancreatic cancer at the First Affiliated Hospital of Naval Medical University from January 2017 to December 2017. Among them, 134 were male and 81 were female, with an age of (61.9±9.2) years. Patients were randomly divided into the training set ( n=151) and the test set ( n=64) in a ratio of 7: 3. Habitat features, peritumoral radiomics features, 3D radiomics features, and 2.5D deep learning features were extracted from preoperative CT images respectively. After feature screening, a survival prediction model was constructed using the CoxBoost machine learning algorithm that integrated the Boosting algorithm and the Cox proportional hazards model. The performance of the model was evaluated using the area under the time-dependent receiver operating characteristic curve and the consistency index. The clinical benefits of the model were evaluated using decision curve analysis. The survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used for the comparison of survivals between groups. Results:The LASSO, random forest and extreme gradient boosting models were each used to screen out the top 10 most important features and take the union, ultimately obtaining 20 radiomics features for modeling. In the training set and test set, the consistency index of the CoxBoost model in predicting overall survival was 0.717 (95% CI: 0.669-0.765) and 0.688 (95% CI: 0.610-0.766), respectively, and the area under the curve for predicting overall survival at 1, 2, and 3 years after surgery was 0.830 (95% CI: 0.752-0.898), 0.753 (95% CI: 0.665-0.833), 0.828 (95% CI: 0.735-0.908) and 0.690 (95% CI: 0.549-0.824), 0.780 (95% CI: 0.649-0.887 and 0.793 (95% CI: 0.660-0.897), respectively. The area under the curve for predicting long-term survival after surgery (≥40 months) was above 0.8. Based on the optimal cutoff value of -0.19 for the predicted value of the CoxBoost model calculated by the R package " survminer", the patients were divided into high-risk (predicted value >-0.19) and low-risk (predicted value <-0.19) groups. In both the training set and the test set, the survival of patients in the low-risk group was better than that in the high-risk group (training set: χ2=39.01, P<0.001; test set: χ2=12.34, P<0.001). The median survival period of patients in the high-risk group was lower than that in the low-risk group (training set: 15.80 vs 34.07 months; test set: 16.87 vs 43.07; months). Decision curve analysis shows that patients obtain survival benefit when the threshold probability of the training set is greater than 0.25 and that of the test set is greater than 0.45. Conclusion:The CoxBoost model has a good predictive ability for the overall survival of pancreatic cancer patients after surgery and can effectively screen out patient subgroups that may significantly benefit from surgical treatment.

Vacuum compression molding (VCM) is a novel technology supporting the research and development of pharmaceutical solid dispersions. It is widely applied due to its precision and convenience in sample preparation. This technology integrates the principles of heating, melting, cooling, and vacuum compression to transform solid powders into shaped solids directly. By selecting different molds, temperatures, and pressures, researchers can prepare samples with diverse characteristics. This paper presents an overview of the equipment composition and working principles of VCM technology, demonstrating its distinct advantages in the formulation screening process of amorphous solid dispersions through comparative analysis with hot melt extrusion using case studies, and introduces its applications in the development of drug delivery systems and rheological characterization analysis, with a perspective on the future development of its functions.

Objective To explore the protective effects of genetically modified porcine erythrocyte suspension as a subnormothermic normoxic mechanical perfusate on hypoxic-ischemic brain injury in cynomolgus monkeys caused by traumatic hemorrhage.Methods Cynomolgus monkeys were randomly divided into positive and negative control groups(a total of 3 monkeys,with 3 left cerebral hemispheres as the positive control group and 3 right cerebral hemispheres as the negative control group)and the subnormothermic perfusion group(n=3).The positive control group was directly sampled 1 hour after circulatory arrest,while the negative control group was placed at subnormothermic conditions for 6 hours after circulatory arrest.The subnormothermic perfusion group underwent 6 hours of subnormothermic normoxic mechanical perfusion of the bilateral common carotid arteries of the cynomolgus monkey hypoxic-ischemic brain injury model using genetically modified porcine erythrocyte suspension 1 hour after circulatory arrest.Before perfusion,cross-matching experiments were conducted between the six genetically modified pig and the cynomolgus monkeys.After the start of perfusion,the levels of routine blood indicators in the perfusate were detected at 0,1,2,3,4,5 and 6 hours.Blood oxygen saturation was recorded,and the levels of Na+,K+,Ca2+,glucose and blood pH in the perfusate were measured,as well as the levels of IgG and IgM in the perfusate.After 6 hours of perfusion,the water content of the brain tissue was measured.Nissl staining was performed on the frontal cortex and hippocampal regions,and immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP),ionized calcium-binding adapter molecule 1(Iba1)and neuronal nuclear antigen(NEUN).Results The cross-matching results between the six genetically modified pig and the cynomolgus monkeys were negative.The number of red blood cells in the perfusate decreased significantly at 3 hours of perfusion,and the hemoglobin level showed a downward trend at 1,3,5 and 6 hours.The number of white blood cells and platelets decreased at all time points.The blood oxygen saturation in the subnormothermic perfusion group remained stable at 95%-98%,and the levels of blood oxygen saturation,Na+,Ca2+,glucose and pH were stable,while the K+level first increased and then decreased.There was no significant difference in the levels of IgG and IgM before and after perfusion.The water content of brain tissue at the end of perfusion in the subnormothermic perfusion group was significantly higher than that in the positive control group(P<0.001).Nissl staining results showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex of the subnormothermic perfusion group maintained better morphological integrity,with no significant increase in enlarged and deformed cells.In the hippocampal CA1 region,there was a slight increase in enlarged and deformed cells,and a few cells with undamaged structures showed reduced cell size.In the hippocampal dentate gyrus,fewer granule neurons had compromised structural integrity,with increased cell edema.NEUN immunofluorescence staining showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex and hippocampal CA1 region of the subnormothermic perfusion group had better morphological states,with clear axons.The granule cells in the hippocampal dentate gyrus were well preserved,but the nuclei were less well protected.GFAP immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had sparser protrusions that were more tightly associated with neurons.Iba1 immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had thicker and fewer protrusions.Conclusions Compared with the positive control group,subnormothermic normoxic mechanical perfusion with genetically modified porcine erythrocyte perfusate increases brain tissue edema in cynomolgus monkeys,but better preserves the morphological integrity of neurons and glial cells.The protective effects may be related to the continuous oxygen and energy supply,maintenance of ion homeostasis and perfusate pH,reduced rejection,and low metabolic state of the whole brain.

Objective To explore the protective effects of genetically modified porcine erythrocyte suspension as a subnormothermic normoxic mechanical perfusate on hypoxic-ischemic brain injury in cynomolgus monkeys caused by traumatic hemorrhage.Methods Cynomolgus monkeys were randomly divided into positive and negative control groups(a total of 3 monkeys,with 3 left cerebral hemispheres as the positive control group and 3 right cerebral hemispheres as the negative control group)and the subnormothermic perfusion group(n=3).The positive control group was directly sampled 1 hour after circulatory arrest,while the negative control group was placed at subnormothermic conditions for 6 hours after circulatory arrest.The subnormothermic perfusion group underwent 6 hours of subnormothermic normoxic mechanical perfusion of the bilateral common carotid arteries of the cynomolgus monkey hypoxic-ischemic brain injury model using genetically modified porcine erythrocyte suspension 1 hour after circulatory arrest.Before perfusion,cross-matching experiments were conducted between the six genetically modified pig and the cynomolgus monkeys.After the start of perfusion,the levels of routine blood indicators in the perfusate were detected at 0,1,2,3,4,5 and 6 hours.Blood oxygen saturation was recorded,and the levels of Na+,K+,Ca2+,glucose and blood pH in the perfusate were measured,as well as the levels of IgG and IgM in the perfusate.After 6 hours of perfusion,the water content of the brain tissue was measured.Nissl staining was performed on the frontal cortex and hippocampal regions,and immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP),ionized calcium-binding adapter molecule 1(Iba1)and neuronal nuclear antigen(NEUN).Results The cross-matching results between the six genetically modified pig and the cynomolgus monkeys were negative.The number of red blood cells in the perfusate decreased significantly at 3 hours of perfusion,and the hemoglobin level showed a downward trend at 1,3,5 and 6 hours.The number of white blood cells and platelets decreased at all time points.The blood oxygen saturation in the subnormothermic perfusion group remained stable at 95%-98%,and the levels of blood oxygen saturation,Na+,Ca2+,glucose and pH were stable,while the K+level first increased and then decreased.There was no significant difference in the levels of IgG and IgM before and after perfusion.The water content of brain tissue at the end of perfusion in the subnormothermic perfusion group was significantly higher than that in the positive control group(P<0.001).Nissl staining results showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex of the subnormothermic perfusion group maintained better morphological integrity,with no significant increase in enlarged and deformed cells.In the hippocampal CA1 region,there was a slight increase in enlarged and deformed cells,and a few cells with undamaged structures showed reduced cell size.In the hippocampal dentate gyrus,fewer granule neurons had compromised structural integrity,with increased cell edema.NEUN immunofluorescence staining showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex and hippocampal CA1 region of the subnormothermic perfusion group had better morphological states,with clear axons.The granule cells in the hippocampal dentate gyrus were well preserved,but the nuclei were less well protected.GFAP immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had sparser protrusions that were more tightly associated with neurons.Iba1 immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had thicker and fewer protrusions.Conclusions Compared with the positive control group,subnormothermic normoxic mechanical perfusion with genetically modified porcine erythrocyte perfusate increases brain tissue edema in cynomolgus monkeys,but better preserves the morphological integrity of neurons and glial cells.The protective effects may be related to the continuous oxygen and energy supply,maintenance of ion homeostasis and perfusate pH,reduced rejection,and low metabolic state of the whole brain.

Objective:To investigate the impact of tumor origin (ventral pancreatic origin and dorsal pancreatic origin) on prognosis in patients with pancreatic head cancer.Methods:A retrospective analysis was performed on the clinical data of 150 patients with pancreatic head cancer who received surgical treatment at the First Affiliated Hospital of the Naval Medical University from October 2014 to December 2017. Among these patients, 92 were male and 58 were female, aged (61.2±8.8) years. The 150 patients were divided into two groups based on tumor origin: the ventral pancreatic cancer group ( n=72) and the dorsal pancreatic cancer group ( n=78). A comparative analysis of clinical, pathological, and imaging charac-teristics was conducted between the two groups. Univariate and multivariable Cox proportional hazards models were used to analyze the association between pancreatic head cancer origin and overall survival (OS). Results:Patients with pancreatic head carcinoma arising from the ventral and dorsal pancreas accounted for 48%(72/150) and 52%(78/150) of the study cohort, respectively. Pancreatic head carcinoma arising from the dorsal pancreas were more likely to show pathological features of pancreatic parenchymal atrophy [73.1%(57/78) vs. 47.2%(34/72), χ2=10.49, P=0.001] and pancreatitis [44.9%(35/78) vs. 29.2%(21/72), χ2=3.95, P=0.047]. In contrast, patients with pancreatic head carcinoma arising from the ventral pancreas was more frequently associated with contact with the superior mesenteric artery [25.0%(18/72) vs. 1.3%(1/78), χ2=19.04, P<0.001], perineural invasion [100%(72/72) vs. 88.5%(69/78), χ2=8.84, P=0.003], and positive surgical margins [15.3%(11/72) vs. 2.6%(2/78), χ2=7.65, P=0.006], with all differences statistically significant. The ventral pancreatic cancer group demonstrated cumulative survival rates of 33.2% and 0 at 1-year and 2-year postoperative intervals, respectively, while the dorsal pancreatic cancer group exhibited rates of 56.7% and 24.8% at the corresponding timepoints. Comparison of Kaplan-Meier survival curves between the two groups showed a statistically significant difference ( χ2=6.00, P=0.014). Multivariable Cox proportional hazards analysis identified dorsal pancreatic origin pancreatic head cancer as an independent predictor of increased mortality risk compared to ventral origin tumors ( HR=2.75, 95% CI: 1.52-4.98, P=0.001). Conclusion:The embryonic origin of pancreatic head cancer determines its clinical, pathological, and imaging heterogeneity, and pancreatic head cancer arising from the ventral pancreas demonstrates significantly worse prognostic outcomes compared to dorsal pancreatic origin.

Objective:A prognosis prediction model for pancreatic cancer was constructed based on multi-scale radiomics combined with deep learning, and the prediction effect of the model was evaluated.Methods:A retrospective analysis was conducted on the clinical data of 215 patients who underwent radical resection of pancreatic cancer at the First Affiliated Hospital of Naval Medical University from January 2017 to December 2017. Among them, 134 were male and 81 were female, with an age of (61.9±9.2) years. Patients were randomly divided into the training set ( n=151) and the test set ( n=64) in a ratio of 7: 3. Habitat features, peritumoral radiomics features, 3D radiomics features, and 2.5D deep learning features were extracted from preoperative CT images respectively. After feature screening, a survival prediction model was constructed using the CoxBoost machine learning algorithm that integrated the Boosting algorithm and the Cox proportional hazards model. The performance of the model was evaluated using the area under the time-dependent receiver operating characteristic curve and the consistency index. The clinical benefits of the model were evaluated using decision curve analysis. The survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used for the comparison of survivals between groups. Results:The LASSO, random forest and extreme gradient boosting models were each used to screen out the top 10 most important features and take the union, ultimately obtaining 20 radiomics features for modeling. In the training set and test set, the consistency index of the CoxBoost model in predicting overall survival was 0.717 (95% CI: 0.669-0.765) and 0.688 (95% CI: 0.610-0.766), respectively, and the area under the curve for predicting overall survival at 1, 2, and 3 years after surgery was 0.830 (95% CI: 0.752-0.898), 0.753 (95% CI: 0.665-0.833), 0.828 (95% CI: 0.735-0.908) and 0.690 (95% CI: 0.549-0.824), 0.780 (95% CI: 0.649-0.887 and 0.793 (95% CI: 0.660-0.897), respectively. The area under the curve for predicting long-term survival after surgery (≥40 months) was above 0.8. Based on the optimal cutoff value of -0.19 for the predicted value of the CoxBoost model calculated by the R package " survminer", the patients were divided into high-risk (predicted value >-0.19) and low-risk (predicted value <-0.19) groups. In both the training set and the test set, the survival of patients in the low-risk group was better than that in the high-risk group (training set: χ2=39.01, P<0.001; test set: χ2=12.34, P<0.001). The median survival period of patients in the high-risk group was lower than that in the low-risk group (training set: 15.80 vs 34.07 months; test set: 16.87 vs 43.07; months). Decision curve analysis shows that patients obtain survival benefit when the threshold probability of the training set is greater than 0.25 and that of the test set is greater than 0.45. Conclusion:The CoxBoost model has a good predictive ability for the overall survival of pancreatic cancer patients after surgery and can effectively screen out patient subgroups that may significantly benefit from surgical treatment.

BACKGROUND: Primary pulmonary lymphoepithelial carcinoma (PPLEC) is a rare form of lung malignancy, accounting for only 0.7% of all lung cancers. It is currently classified as a distinct subtype within squamous cell carcinomas. This study aims to explore the clinicopathological characteristics of PPLEC and its subtypes, with the objective of enhancing understanding and improving diagnostic accuracy for this disease. METHODS: A retrospective analysis was conducted on the clinical, pathological, imaging, and prognostic data of 14 patients diagnosed with PPLEC at the First Affiliated Hospital of Soochow University between February 2019 and June 2023. RESULTS: A total of 14 cases of PPLEC were identified, including 5 cases of the Regaud type, with ages ranging from 33 to 73 years, comprising 2 males and 3 females; and 9 cases of the Schmincke type, with ages ranging from 36 to 79 years, including 4 males and 5 females. Computed tomography (CT) scans consistently demonstrated soft tissue masses or nodular shadows. Reagud type mainly showed peripheral masses and Schmincke type mainly showed central masses. Pathological examination revealed tumor cells exhibiting syncytial-like growth, accompanied by lymphocytic infiltration and stromal fibrosis, with the Regaud type showing well-defined borders combined with granulomatous inflammation, while the Schmincke type exhibited indistinct tumor margins. Immunohistochemistry showed that CK, CK5/6, P40 and P63 were positive, and the Ki-67 index of Regaud type was lower than that of Schmincke type; notably, all 8 cases tested for programmed death-ligand 1 (PD-L1) were positive. Epstein-Barr virus-encoded RNA (EBER) in situ hybridization was positive in all instances. Among these cases, 6 underwent surgical treatment, and 8 received comprehensive therapy; by the end of the follow-up period, all 14 patients remained alive. CONCLUSIONS PPLEC is a rare form of malignant lung tumor associated with Epstein-Barr virus (EBV) infection. The Regaud and Schmincke subtypes display distinct imaging and pathological characteristics. In the early stages of the disease, surgical intervention is the primary treatment method; however, for advanced stages, a multimodal treatment approach is utilized, resulting in a relatively favorable prognosis. Immunotherapy represents a promising and effective treatment modality for patients with middle to advanced stage disease exhibiting high PD-L1 expression levels.
Humans ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Adult ; Retrospective Studies ; Prognosis ; Tomography, X-Ray Computed