Objective To explore the method for establishing a pig left lung orthotopic transplantation model. Methods A total of 4 male Yorkshire pigs weighing (40.0±2.5) kg underwent surgical procedures, including anesthesia, tracheal intubation, donor lung procurement, and recipient lung transplantation. Histological morphology and blood gas analysis of the transplanted lungs were assessed 2 hours after reperfusion to evaluate the histological changes and function of the transplanted lungs. Results The pigs underwent left lung in situ transplantation, effectively simulating conditions relevant to human lung transplantation. Two hours after the transplantation, arterial blood gas analysis showed that arterial partial pressure of oxygen was 155.4-178.6 mm Hg, arterial partial pressure of carbon dioxide was 53.1-62.4 mm Hg, and the oxygenation index was 310.8-357.2 mm Hg. Hematoxylin and eosin staining indicated a low degree of pulmonary edema and minimal cellular infiltration. Conclusion The pig left lung orthotopic transplantation model possesses strong operability and stability. Researchers can replicate this model according to the described methods and further conduct basic research and explore clinical translational applications.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Spinal cord injury is a highly disabling central nervous system disorder whose pathological progression is closely associated with blood-spinal cord barrier (BSCB) disruption. Physical trauma to the spine or spinal cord may compromise BSCB integrity, triggering secondary damage including spinal edema, hemorrhage, oxidative stress, and excessive inflammatory responses. For the pivotal role of protecting the spinal cord microenvironment, the repair of BSCB is crucial in the treatment of spinal cord injury. Although present studies have explored BSCB repair strategies such as biological factor regulation, biomaterial applications, and traditional Chinese medicine interventions, most studies focus on improving the overall barrier function and fail to systematically elucidate how these strategies target the core functional units of BSCB, namely the endothelial cells and their junction structures, to achieve functional and structural restoration of the barrier. Therefore, the authors reviewed the composition and key repair targets of BSCB, along with research advances in BSCB repair strategies based on endothelial cells and junction structures, aiming to provide insights for basic research and clinical treatment of spinal cord injury.

Objective:This study aimed to validated the diagnostic accuracy of Global Leadership Initiative on Malnutrition(GLIM)criteria for malnutrition in pancreatic cancer patients undergoing pancreaticoduodenectomy and to evaluated its prognostic value for postoperative outcome.Methods:A retrospective analysis was conducted on 230 consecutive pancreatic cancer patients who underwent pancreaticoduodenectomy at the Department of Pancreatobiliary Surgery,Sun Yat-sen University Cancer Center,between January 2018 to January 2024.Patients were stratified into malnutrition group and non-malnutrition group using Nutritional Risk Screening 2002(NRS 2002)and GLIM criteria.Multivariable logistic regression identified independent risk factors for postoperative morbidity.Results:GLIM criteria identified malnutrition in 96 patients(41.7％).Compared with the non-malnourished group,the number of preoperative nutritional support(t=20.038,P<0.001),the number of preoperative enteral nutrition support(t=8.377,P=0.004),the number of preoperative parenteral nutrition support(t=22.302,P<0.001),the number of anemia(t=8.037,P=0.005)and preoperative parenteral nutrition use days(t=-2.898,P=0.009),the difference was statistically significant.There were statistically significant differences in C-reactive protein(t=10.944,P=0.008),NLR(t=-2.523,P=0.012)and PNI(t=-2.397,P=0.017)between the two groups before surgery.Preoperative BMI(t=-4.410,P<0.001)was significantly lower in the malnourished group.The number of postoperative parenteral nutrition days(Z=-2.283,P=0.022)and amino acid supplementation during postoperative hospitalization were significantly higher in the malnourished group(Z=-2.309,P=0.021).The incidence of malnutrition was higher in patients with Clavien-Dindo grade≥Ⅲ(P=0.030)and intra-abdominal infections(P=0.049).Multivariable analysis identified preoperative weight loss(OR=2.154,95％CI:1.158～4.005;P=0.015)and BMI reduction(OR=0.175,95％CI:0.040～0.775;P=0.022)as independent predictors of postoperative complications.Conclusions:The GLIM standard effectively characterize malnutrition status in pancreatic cancer patients after pancreaticoduodenectomy patients and demonstrate superior predictive performance for postoperative morbidity.It has good predictive performance and clinical application value.

Objective:To establish ultra-performance liquid chromatography (UPLC) fingerprint chromatograms for Erigeron breviscapu from different origins and storage conditions; To identify the Erigeron breviscapus from different habitats by chemometric analysis.Methods:Acquity UPLC HSS T3 (2.1 mm×100 mm,1.8 μm) chromatography column was used; mobile phase was 0.1% formic acid aqueous solution-acetonitrile; detection wavelength was 268 nm; flow rate was 0.25 ml/min; column temperature was 35 ℃; injection volume was 2 μl gradient elution. The UPLC fingerprint of Erigeron breviscapu from different origins was established. Similarity evaluation combined with chemometric analysis methods such as clustering analysis (CA), principal component analysis (PCA), orthogonal partial least squares method - discriminant analysis (OPLS-DA) were used to identify the origin of Breviscapine from different places. Fingerprint technology was used to evaluate the similarity of storage conditions for Erigeron breviscapu.Results:The UPLC fingerprint method met the methodological requirements. 30 batches of Erigeron breviscapus had 24 common peaks, and the similarity between Xingyi in Guizhou and Huize in Qujing was 0.702-0.783, while the similarity between Honghe Luli, Kunming Fuming and Dali was 0.861-0.970. All samples were divided into two categories according to their origin by CA: category Ⅰ: Xingyi in Guizhou and Huize in Qujing, and category Ⅱ: Dali, Kunming Fuming and Honghe Luli. The results of PCA were consistent with CA. OPLS-DA screened out 10 differential markers of Erigeron breviscapus from different habitats. Moreover, a total of 40 common peaks were identified in six batches of Erigeron breviscapus samples stored under different conditions. Based on the similarity analysis, Erigeron breviscapus samples stored at 30% humidity and 70% humidity were classified into two separate categories.Conclusions:The fingerprint method constructed in this study is stable and reliable, and the predictive ability and reliability of the OPLS-DA model are excellent. By combining the two methods, a clear division can be made between Erigeron breviscapus from Yunnan and Guizhou. Humidity conditions are an important factor in storing Erigeron breviscapus.

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

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 explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective To investigate the impact of county-level"Unified ECG Network"construction on the treatment efficiency and clinical outcomes of patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A retrospective analysis was conducted on the clinical data of STEMI patients from Beichuan County and Yanting County in Mianyang City,and Jiange County in Guangyuan City,Sichuan Province,during the 18 months before(128 cases)and 18 months after(187 cases)the establishment of the"Unified ECG Network."Differences in demographic characteristics,treatment efficiency,therapeutic methods,and clinical outcomes between the two groups were compared.Results There was no statistically significant difference in general demographic characteristics between the two groups(all P＞0.05).Compared with the pre-construction group,the post-construction group showed significantly shorter times in initial ECG completion[5(3,7)min vs.6(4,8)min],initial ECG diagnosis[3(2,4)min vs.5(2,6)min],first medical contact to preliminary diagnosis[10(9,12)min vs.13(11,15)min],network hospital door-in-door-out time[21(19,23)min vs.26(23,30)min],and first medical contact to wire-crossing time[(94.82±11.87)min vs.(107.97±18.39)min](allP＜0.001).The proportion of patients bypassing the emergency department and coronary care unit significantly increased(64.17％vs.32.81％,P＜0.001).The proportion of patients undergoing emergency percutaneous coronary intervention significantly increased(72.73％vs.51.56％,P＜0.001),while the proportions of thrombolytic therapy and non-reperfusion therapy significantly decreased(both P＜0.05).Additionally,in-hospital mortality rate,Killip class≥Ⅱ proportion,incidence of major adverse cardiovascular events,and average length of hospital stay were all significantly reduced(all P＜0.05).There were no statistically significant differences among the three county-level chest pain centers in terms of major treatment efficiency,therapeutic strategies,or clinical outcomes(all P＞0.05).Conclusions The construction of the county-level"Unified ECG Network"can significantly improve the treatment efficiency of STEMI patients,optimize reperfusion therapy strategies,improve clinical outcomes,and demonstrate substantial clinical promotion value.

Objective By establishing a model to screen out patients with potentially large positional deviations based on their abdominal circumference,personalized solutions can be taken to address setup errors in these patients and ensure treatment efficacy.Methods A total of 81 patients treated at Tianjin People's Hospital from May 2021 to June 2023 were selected as the study subjects.The correlations between setup errors in the lateral,longitudinal,and vertical directions and abdominal circumference were analyzed.Subsequently,linear regression was performed for the direction with a significant correlation to abdominal circumference to establish a linear regression model.Finally,the 81 patients were divided into a normal setup group and an abnormal setup group with 0.7 cm as the critical value.A receiver operating characteristic(ROC)curve was plotted,and the maximum Youden index was calculated to determine the optimal cutoff value for identifying patients prone to abnormal setup.Results The correlation analysis of abdominal circumference and setup errors in various directions showed that the correlation coefficient between abdominal circumference and longitudinal direction positioning error was 0.406 2,and the correlation was statistically significant and positively correlated.The correlation coefficients for abdominal circumference and the lateral as well as longitudinal directions were-0.117 5 and-0.067 47,respectively,with P values greater than 0.05,indicating no statistical significance.A linear regression model was established for abdominal circumference and longitudinal direction,and the results showed an R2of 0.165,with a regression coefficient B of 0.008(t=3.951,P<0.01),indicating that the model was well constructed.ROC curve analysis showed an area under the curve of 0.715,with a 95%confidence interval of 0.57-0.86 and a maximum Youden index of 0.478.The corresponding optimal cutoff value was determined to be at 87 cm,with sensitivity at 0.875 and specificity at 0.603.Conclusion The abdominal circumference is significant to diagnose whether the longitudinal setup error is abnormal.Patients with an abdominal circumference greater than 87 cm are more likely to experience abnormal positioning during radiotherapy,which is reflected in the longitudinal setup errors being the largest.It is recommended to provide individualized target area margins for patients with an abdominal circumference greater than 87 cm,or perform daily cone-beam computed tomography to correct setup errors,thereby ensuring target coverage and treatment efficacy.