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 explore the curative effect of abdominal flap carried with combined perforating vessels in reconstruction of extra large and complicated defect in extremities.Methods:A retrospective analysis was conducted on 16 patients who were admitted to the Department of Hand Surgery, the Affiliated Traditional Chinese Medicine Hospital for treatment of extra large and complex wounds in extremities, from January 2020 to December 2023. There were 6 defects in upper limbs and 10 in lower limbs. Fourteen patients had a combination of fracture and 6 of tendon defects. The defects were large and sized from 30.0 cm×9.0 cm to 35.0 cm×15.0 cm. The defects were reconstructed by large sized abdominal flaps at 32.0 cm×10.0 cm to 36.0 cm×16.0 cm. According to the size of the defect, perforators of different arteries carried by the abdominal flap were combined by anastomosis in a manner of internal and external supercharging in order to boost the blood supply of the flap. The supercharging vessel anastomosis was as follows: one superficial circumflex iliac artery (or superficial inferior epigastric artery) was anastomosed with the contralateral branch of the deep inferior epigastric artery, with the veins were anastomosed with the corresponding veins, and the main trunk of the deep inferior epigastric artery was anastomosed end-to-end or end-to-side with the main branch of the recipient artery. Alternatively, both of the left and right superficial iliac circumflex (or inferior epigastric) arteries were directly anastomosed end-to-side or end-to-end with the main trunk or its branches in the recipient site, and the veins were anastomosed end-to-side or end-to-end with the adjacent veins. The donor site was pulled and relaxed by a pull-rod wound expander and sutured layer by layer. After surgery, routine anti-infection, anti-vasospasm, anticoagulation, enhancement of blood circulation and other symptomatic treatment were given. Postoperative follow-ups were conducted at outpatient clinic and via telephone and WeChat interviews. The colour and the sign of capillary reflux of the flap were closely observed.Results:All patients were included in the postoperative follow-up for 6-26 months, with an average of 13 months. Fifteen flaps survived after surgery. One flap had partial necrosis and the necrosis was found being caused by a thrombosis at the vessel anastomotic site. The necrotic tissue was removed and the defect was reconstructed by a flap transfer. The abdominal donor sites healed by first intention, and the navel was normal in terms of location and shape. There was no muscle hernia, except a minor scar hyperplasia. The flaps healed well, with satisfactory appearance and soft texture, without obvious bloating. The donor site healed well with partial scar formation.Conclusion:When an abdominal flap is used to reconstruct an extremely large and complex defect in extremities, the perforating vessels of different source arteries carried by the flaps can be anastomosed in a manner of combination, hence the flap can be flexibly freed, with satisfactory treatment effects.

Objective To explore the feasibility and safety of ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer.Methods Totally 84 patients who underwent ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer were enrolled,and the technical success rate,complete ablation rate,complication rate,pain relief rate and survival time,etc.were observed.Results The median age of 84 cases was 61.5 years.Totally 86 tumors,including 44.19％(38/86)at the head/neck and 55.81％(48/86)at the body/tail of pancreas were detected,and a total of 85 ablation sessions were performed with the median ablation energy applied per tumor of 9.90(1.08,21.60)kJ and the complete ablation rate of 42.86％(36/84).The technical success rate was 100％(85/85).Thirty-nine complication events occurred in 25 cases,no ablation-related death.Among 34 patients underwent ablation mainly for pain symptoms,the pain score decreased from(6.22±1.12)points before treatment to(1.94±1.64)points after treatment(P＜0.001).During 6.8(3.3,12.9)months' follow-up,the mean survival time was(8.5±6.7)months,and all 47 patients died due to tumor progression.Conclusion Ultrasound-guided percutaneous microwave ablation was safe and feasible for unresectable pancreatic cancer.

Objective:To explore the clinical value of multi-parameter combined monitoring in guiding low-molecular-weight heparin (LMWH) therapy for intensive care unit (ICU) patients.Methods:A retrospective case-control study was conducted. A total of 381 patients who received LMWH therapy with anti-Ⅹa activity monitoring in the ICU of West China Hospital, Sichuan University between January 31st, 2022, and November 30th, 2023, were enrolled in this study. The cohort comprised 264 males and 117 females, with the age of 58 (48, 71) years old. Clinical data and relevant laboratory parameters were collected, including anti-Ⅹa activity, antithrombin activity (AT), thrombin-antithrombin complex (TAT), plasmin-antiplasmin complex (PIC), conventional coagulation parameters such as activated partial thromboplastin time (APTT), and indicators of hepatic/renal impairment such as alanine aminotransferase (ALT) and creatinine( CREA). Patients were stratified into three groups based on thrombotic event: thrombosis-controlled, progressive thrombosis, and bleeding group. Single-factor and adjusted multifactorial Logistic regression analysis were used to identify independent predictors of anti-xa activity levels.Results:Among 381 patients, thrombosis was controlled in 213 (55.9%) patients, progressed in 81 (21.3%) patients , and bleeding events occurred in 87 (22.8%) patients. The patients whose anti-Ⅹa activity levels lay entirely within the target range(0.2-0.4 IU/ml): Only 35 (16.4%) cases in the thrombosis-controlled group, 16 (19.7%) cases in the progressive thrombosis group, and 16 (18.4%) in the bleeding group. No significant differences in anti-Ⅹ a levels activity among the three groups ( H=1.678, P=0.432). Both single-factor and adjusted multifactorial Logistic regression identified low AT activity as an independent risk factor for failure to achieve target anti-Ⅹ a activity levels (AT nadir, OR=1.031,95% CI 1.016-1.046, P<0.05). Compared with the progressive thrombosis and bleedinggroup, the thrombosis-controlled group exhibited significantly higher proportion of TAT values below the cut-off value ( H=8.519, P=0.014), and a higher proportion of TAT/PIC ratios below the cut-off ( H=15.56, P<0.001). Patients with bleeding demonstrated significantly lower AT activity ( H=14.968, P=0.001), prolonged APTT ( H=6.815, P=0.033), higher ALT ( H=13.774, P=0.001), and higher CREA ( H=14.068, P=0.001) compared with the thrombosis-controlled or progressive thrombosis group. Conclusion:Laboratory monitoring is required for low-molecular-weight heparin (LMWH) therapy in ICU patients. While anti-Ⅹa activity reflects the anticoagulant effect of LMWH, the utility of anti-Ⅹ a activity for predicting thrombotic or hemorrhagic risks in LMWH treated ICU patients is limited. Reductions in TAT levels and TAT/PIC ratios are associated with a lower risk of thrombotic progression. Furthermore, abnormalities in conventional coagulation tests and standard hepatic/renal function parameters occur more frequently in patients experiencing hemorrhagic events.

Objective:To develop a convolutional neural network model of whole slide imaging of cerebrospinal fluid cells for rapid and accurate identification and classification of tumor cells in cerebrospinal fluid.Methods:A total of 8 692 cerebrospinal fluid cytology smears from Huashan Hospital Affiliated to Fudan University from January 2nd, 2019, to December 27th, 2024. As randomly assigned, the training set included 4 941 benign and 1 745 malignant samples, while the validation set comprised of 1 368 benign and 638 malignant samples. Whole-slide digital images were acquired using a cytopathology scanner, cells (clusters) were annotated for classification, and a deep learning model was constructed via tiled image patches for cell detection and classification. Model performance was evaluated using accuracy, sensitivity, specificity, and other indicators. The classification efficiency of manual microscopy was compared.Results:The model achieved a mean precision of 96.75% for cerebrospinal fluid cell classification. For malignant tumor cells, the classification accuracy was 96.61% (mAP=98.36%, AUC=0.97). Subtype classification accuracies for epithelial/epithelioid tumors and small round cell tumors were 97.13% (AUC=0.98) and 95.58% (AUC=0.93), respectively. Compared with manual microscopy, which took (9.70±0.82) minutes for classifying 200 cells, (18.27±1.21) minutes for 500 cells, and often exceeded 60 minutes or infeasible for full slides, the AI model took (3.46±0.49) seconds for 200 cells, (6.76±0.82) seconds for 500 cells, and a median of 48.57 seconds for full slides ( P<0.001), representing an efficiency improvement of approximately 161-170 times, significantly enhancing diagnostic efficiency. Conclusion:This fully automated hierarchical deep learning model enables efficient and accurate tumor cell identification and classification in CSF, providing an effective auxiliary tool for the rapid diagnosis of meningeal carcinomatosis.

To address the limitations of traditional minimally invasive thermal ablation technology such as poor conformability, carbonization and electromagnetic radiation, this paper proposes a steam thermal ablation technology that uses saturated steam internal energy to replace the traditional electromagnetic radiation energy. Through the steam thermal ablation system and the steam thermal ablation needle designed based on simulation, the ex vivo pig liver experiments were carried out. The results have the characteristics of the maximum ablation axis ratio (short diameter / long diameter) and non-carbonization with the same type of thermal ablation technology. Based on the near-infrared light, in this paper the curative effect of the reduced scattering coefficient of the steam thermal ablation results was evaluated. The reduced scattering coefficients of the coagulation area all exceeded 16, reaching the completely damaged state, which verified that the steam thermal ablation can effectively inactivate the tumor cells.
Steam ; Animals ; Swine ; Liver Neoplasms/surgery* ; Ablation Techniques/methods* ; Liver/surgery* ; Equipment Design

The minimally invasive thermal ablation technology differs from traditional surgical operations, which requires auxiliary equipment to evaluate ablation results. However, the ultrasound and CT currently used in clinical practice have shortcomings such as artifacts and radiation. Therefore, this paper proposes a design for a minimally invasive thermal ablation evaluation system based on the principle of electrical impedance tomography technology to monitor the ablation range. At the same time, the innovative introduction of a programmable gain feedforward signal as the parameter signal of the multiplier demodulator in the electrical impedance tomography system design can effectively solve the problem of weak signals being submerged in noise and improve imaging accuracy. The system controls the amplitude of the excitation current signal and the acquisition / processing of boundary voltages via an STM32, uploads the collected data to an upper computer, and reconstructs the conductivity distribution using the Newton-Raphson algorithm to map the size of the ablation area. Experimental results show that the system can effectively reflect the size of the microwave ablation area. Under the same minimally invasive ablation parameters, the average imaging errors are 0.6 mm for the long diameter, 0.8 mm for the short diameter, and 1.75% for the axial ratio (long diameter / short diameter), demonstrating high consistency. This verifies the technical potential of electrical impedance tomography in minimally invasive thermal ablation.
Electric Impedance ; Tomography/instrumentation* ; Equipment Design

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.