BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Objective To explore the application value of a special fence in percutaneous transhepatic cholangial drainage(PTCD)under the guidance of C-arm CT.Methods A total of 43 patients who underwent PTCD were randomly divided into observation group and control group.The intervention operation in the observation group was guided by C-arm CT and located by special fence;in the control group,the intervention operation was only performed under digital subtraction angiography(DSA)fluoroscopy.Respectively,the differences in operation time,number of puncture needles and number of complications between the two groups were compared.Results The operation time,puncture times and complications in the observation group were(39.33±12.96)min,(1.67±0.80)times and 3 cases respectively;in the control group were(86.77±22.70)min,(3.41±1.26)times and 13 cases respectively;There were significant differences between the two groups(P<0.05).Conclusion The application of special fence in PTCD under the guidance of C-arm CT can short the operation time,reduce the number of punctures and reduce complications,which has important clinical application value.

BACKGROUND:Halo gravity traction is a pre-operative traction method recognized by many scholars,but most of them rely on clinical observation and lack finite element analysis. OBJECTIVE:To explore the best traction force of Halo gravity traction on Lenke 3 scoliosis by finite element method and to provide a theoretical basis for clinics from a biomechanical point of view. METHODS:The CT images scanned by patients with scoliosis were processed by reverse modeling,and a finite element model was established.The validity of the model was verified by taking normal segments(T1-T4 vertebral bodies).Five groups of different stress conditions were set on the lumbar-thoracic scoliosis model to simulate the correction of patients under different traction forces.In all five groups,the lower surface of L5 was completely restrained,and different traction forces were applied to the upper surface of T1 along the positive direction of the Z axis(the opposite direction of gravity),which were 50,100,150,200,and 250 N,respectively.The displacement of the scoliosis spine,Cobb angle change of the main bending,elongation of the spine,and Von Mises stress were compared under different traction forces. RESULTS AND CONCLUSION:(1)When the Halo gravity traction force was 150 N to 200 N,the reduction of the Cobb angle of the main bending was 69.4%to 88.9%of the maximum reduction;the elongation of the Z axis was 69.4%to 85.9%,and the stress was 63.6%to 82.9%of the maximum stress.(2)When the traction force was greater than 200 N,the reduction of the Cobb angle and the elongation of the Z axis did not change obviously,but the stress value increased sharply.At this time,the distance from the centroids of T6,T7,and T8 to the vertical line of L5 was the most obvious.(3)When the Halo gravity traction force was 150 N to 200 N,the correction effect on this type of patient was the best—the reduction of Cobb angle and the elongation of the Z axis were better without the sharp increase in stress.(4)It has certain theoretical support for clinical correction and can ensure the safety of patients when scoliosis is corrected to a large extent.

Sesquiterpenoids are natural compounds composed of 15 carbon atoms， which can be divided into sesquiterpene alcohols， ketones， lactones， aldehydes， and carboxylic acids according to oxygen groups. These compounds are widely distributed in nature， and their physiological activities are diverse. For example， many sesquiterpenes with potential anticancer effects have been found for anti-tumor effects， including cytotoxicity， antioxidant， immune regulation， cell proliferation， and so on. In addition， some sesquiterpenoids have good application prospects in antibacterial， anti-inflammatory， and anti-cardiovascular diseases. Malignant tumors， inflammation， bacterial diseases， and cardiovascular diseases are the main diseases that cause human death， and natural products have unique advantages in the treatment of these diseases. Therefore， the development of new drugs that are easy to promote has become a new research hotspot. In this paper， the sesquiterpenes extracted from the natural components of Chinese herbs and plants with anti-tumor， anti-inflammatory， antibacterial， and anti-cardiovascular activities， such as Xanthium， Atractylodes， Convolvulus， Acanthium， Ligularia， Artemisia， Ligularia， Ligularia， Labiaceae Mint， Acanthophyllum， Turmeria， Ginger， and other Chinese herbs and plants， were discussed. The biological activities and related mechanisms of this compound were reviewed， which provided a reference for further research and clinical application of sesquiterpenes.

Objective:To examine the treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations.Methods:This is a retrospective case series study. Clinic data from 24 children with tracheal stenosis who underwent surgical treatment in the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to March 2023 were retrospectively collected. There were 16 males and 8 females, aged ( M(IQR)) 6.5 (19.6) months (range: 2.2 to 66.3 months) and weighted 5.95 (4.76) kg (range: 3.2 to 20.0 kg). All patients had obvious respiratory symptoms. Eighteen patients underwent cardiac malformation correction and tracheoplasty at the same time (simultaneous group). Six patients in the staged operation group were treated with cardiac malformation correction in the first stage operation and tracheoplasty in the second stage operation due to missed diagnosis or delayed diagnosis of tracheal stenosis or no condition for tracheoplasty. Slide tracheoplasty was used to correct tracheal stenosis in both groups. The recovery of the children was followed. Wilcoxon sign rank test was used for comparison between the two groups. Results:There was no death during the perioperative period and hospitalization. In the simultaneous group, 1 case with delayed chest closure underwent bedside chest closure after 52 hours, 2 cases were intubated again after operation, and 1 case was implanted with an endotracheal stent. The duration of mechanical ventilation was 40.5 (39.6) hours (range: 19.0 to 438.8 hours). In the staged group, there was 1 case of re-intubation after operation, combined with left vocal cord paralysis and respiratory multidrug-resistant bacterial infection ( Acinetobacter baumanii). One patient underwent 3 times of bronchoscopic balloon dilatation of the right middle bronchus, and heart rate returned to normal range. The duration of mechanical ventilation was 19.0 (21.4) hours (range: 17.1 to 96.7 hours). During follow-up, a patient in the simultaneous group was prone to respiratory infection and had good exercise tolerance, 1 case in the staged group still had sputum stridor in the throat 3 months after the operation, and symptoms improved significantly 6 months after the operation. The other children didn′t have obvious respiratory symptoms. Conclusions:The diagnosis of tracheal stenosis may be delayed or missed when tracheal stenosis is complicated by non-vascular ring cardiac malformations. One-stage correction of tracheal stenosis and cardiac malformation can achieve a good outcome.

Objective:To examine the treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations.Methods:This is a retrospective case series study. Clinic data from 24 children with tracheal stenosis who underwent surgical treatment in the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to March 2023 were retrospectively collected. There were 16 males and 8 females, aged ( M(IQR)) 6.5 (19.6) months (range: 2.2 to 66.3 months) and weighted 5.95 (4.76) kg (range: 3.2 to 20.0 kg). All patients had obvious respiratory symptoms. Eighteen patients underwent cardiac malformation correction and tracheoplasty at the same time (simultaneous group). Six patients in the staged operation group were treated with cardiac malformation correction in the first stage operation and tracheoplasty in the second stage operation due to missed diagnosis or delayed diagnosis of tracheal stenosis or no condition for tracheoplasty. Slide tracheoplasty was used to correct tracheal stenosis in both groups. The recovery of the children was followed. Wilcoxon sign rank test was used for comparison between the two groups. Results:There was no death during the perioperative period and hospitalization. In the simultaneous group, 1 case with delayed chest closure underwent bedside chest closure after 52 hours, 2 cases were intubated again after operation, and 1 case was implanted with an endotracheal stent. The duration of mechanical ventilation was 40.5 (39.6) hours (range: 19.0 to 438.8 hours). In the staged group, there was 1 case of re-intubation after operation, combined with left vocal cord paralysis and respiratory multidrug-resistant bacterial infection ( Acinetobacter baumanii). One patient underwent 3 times of bronchoscopic balloon dilatation of the right middle bronchus, and heart rate returned to normal range. The duration of mechanical ventilation was 19.0 (21.4) hours (range: 17.1 to 96.7 hours). During follow-up, a patient in the simultaneous group was prone to respiratory infection and had good exercise tolerance, 1 case in the staged group still had sputum stridor in the throat 3 months after the operation, and symptoms improved significantly 6 months after the operation. The other children didn′t have obvious respiratory symptoms. Conclusions:The diagnosis of tracheal stenosis may be delayed or missed when tracheal stenosis is complicated by non-vascular ring cardiac malformations. One-stage correction of tracheal stenosis and cardiac malformation can achieve a good outcome.

Objective:To investigate the efficacy and safety of radium-223 in combination with new-generation hormonal agents in patients with bone metastases of prostate cancer.Methods:The clinical data of 17 patients (12 from the First Affiliated Hospital of Airforce Military Medical University and 5 from Xi'an International Medical Center Hospital) with metastatic castration-resistant prostate cancer(mCRPC) treated by radium-223 combined with new-generation hormonal agents from January 2021 to June 2022 were retrospectively analyzed. In all cases, the average age was (73.3±8.5) years old. Before treatment, the median prostate-specific antigen (PSA) was 15.7 (3.2, 36.5) ng/ml, the median alkaline phosphatase (ALP) was 131.5 (79.0, 430.7) U/L. All patients had ≥ 2 bone metastases but no visceral or lymph node metastases. The median number of bone scan lesions was 10(8, 15). Bone pain symptom was present in 16(94.1%) patients. There were 9 cases (52.9%) with Eastern Cooperative Oncology Group (ECOG) score of ≥2, 1 case (5.9%) with ECOG score of 1 and 6 cases (35.2%) with ECOG score of 0. All patients were treated with radium-223 (55 kBq/kg, injected every 4 weeks for a maximum of 6 cycles), of which 5 patients were combined with enzalutamide, 8 patients combined with apatamide and 4 patients combined with bicalutamide. PSA response (PSA decreased by ≥30% from baseline and maintained for at least 1 month), ALP response (ALP decreased by ≥30% from baseline and maintained for at least 1 month) and pain relief rates were analyzed. Imaging evaluation was performed before and after treatment to calculate the objective response rate of metastases. The incidence of treatment-related adverse effects and skeletal related event (SRE) were also recorded.Results:Eleven patients completed 6 courses, 3 patients completed 5 courses and 3 patients completed ≥4 courses. The median ALP after 1 month of last treatment was 83.2 (51.5, 126.5) U/L, which was significantly decreased than baseline. 12 patients (70.6%) showed an ALP response and the other 5 (29.4%) showed varying degrees of ALP elevation. PSA response was observed in 4 patients (23.5%), of which 2 (11.8%) had a continuous decrease and 2 (11.8%) had a late-stage increase in PSA. Pain relief was relieved in 15 cases (88.2%) during treatment, 1 case (5.9%) had worsening pain due to disease progression and 1 case (5.9%) had no change during treatment. The ECOG score decreased in 15 (88.2%) patients. The median number of bone metastases in patients decreased to 5 (4, 9). One patient (5.9%) had complete remission during treatment, 11 patients (64.7%) had a partial response, 4 patients (23.5%) were stable, and 1 (5.9%) showed imaging progression after 4 months of treatment. The overall objective remission response rate was 70.5% (12/17). Treatment-related hematologic adverse effects included anemia (1 case, 5.9%, grade 3), thrombocytopenia (1 case, 5.9%, grade 3) and leukopenia (1 case, 5.9%, grade 2). Non-hematologic adverse effects included fatigue (3 cases, 17.6%, 2 cases in grade 1, 1 case in grade 2), gastrointestinal bleeding (1 case, 5.9%, grade 3), diarrhea (1 case, 5.9%, grade 2) and fever (1 case, 5.9%, grade 1). Patients with grades 1 to 2 relieved with symptomatic management. Three cases (17.6%) were discontinued due to intolerance of grade 3 adverse reactions and 1 case (5.9%) terminated on its own. There was no SRE during treatment and follow-up.Conclusions:Radium-223 combined with New-generation hormonal agents has a high objective remission rate in patients with mCRPC, which could provide pain relief and improve quality of life. The incidence of adverse reactions was low and well tolerated.

Objective     To provide experience for clinical diagnosis and treatment through exploring the perioperative characteristics and short-term treatment outcomes of adult cardiac surgery in patients with prior coronavirus disease-2019 (COVID-19). Methods    A retrospective analysis was performed on patients undergoing coronary artery bypass grafting (CABG) or valve surgery in the Department of Cardiac Surgery of Beijing Anzhen Hospital from December 26, 2022 to December 31, 2022, and previously diagnosed with COVID-19 before surgery. Results    Finally 108 patients were collected, including 81 males and 27 females, with an average age of 60.73±8.66 years. Two (1.9%) patients received emergency surgery, and the others received elective surgery. The 86.1% of patients had been vaccinated, and the duration of COVID-19 was 5.0 (4.0, 7.0) days. The time from COVID-19 to operation was 15.0 (12.0, 17.8) days. Eighty-nine patients received CABG, of which off-pump CABG was dominant (92.1%). Nineteen patients received valve surgery. The rate of delayed extubation of ventilator was 17.6%. The ICU stay was 21.0 (17.3, 24.0) hours, and the postoperative hospital stay was 7.0 (6.0, 8.0) days. Three (2.8%) patients were treated with intra-aortic balloon  pump (IABP), one (0.9%) patient was treated with extracorporeal membrane oxygenation (ECMO), one (0.9%) patient was treated with continuous renal replacement therapy (CRRT) due to acute renal insufficiency, three (2.8%) patients were treated with temporary pacemaker, and one (0.9%) patient underwent rethoracotomy. In terms of postoperative complications, the incidence of cerebrovascular accident, acute renal insufficiency, gastrointestinal bleeding and septicemia was 0.9%, respectively, and the incidence of acute heart failure, lung infection, and liver insufficiency was 1.9%, respectively. All patients recovered and were discharged from hospital, and no in-hospital death occurred. Conclusion     The utilization rate of postoperative IABP, ECMO, CRRT, temporary pacemaker and the incidence of serious complications in patients with prior COVID-19 are not higher than those of normal patients, and the short-term treatment outcome is good.

Objective:To examine the effect of surgical treatment in children with pulmonary artery sling and the surgical treatment strategy.Methods:Relevant data of 110 children with pulmonary artery sling admitted to the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to July 2022 were retrospectively analyzed. There were 55 males and 55 females, aging ( M(IQR)) 9.0 (10.6) months (range: 1 to 96 months). The weight was 7.8 (3.5) kg (range: 2.5 to 25.0 kg). Of the 110 patients, 108 had different degrees of tracheal stenosis and 2 had normal trachea. Left pulmonary artery transplantation and tracheoplasty were performed in 78 patients. Left pulmonary artery transplantation was performed in 30 patients (11 in our hospital and 19 in other hospitals) due to the lack of an early tracheoplasty technique, in which 24 patients needed stage Ⅱ tracheoplasty due to obvious respiratory symptoms and limited activity endurance, and 6 cases did not intervene. Two children with normal trachea only underwent left pulmonary artery transplantation. Results:Among the 78 children who underwent surgery in the same period, 70 cases recovered smoothly after surgery, of whom respiratory symptoms were significantly reduced or disappeared during the 1 to 65 months follow-up, with similar activity endurance to normal children of the same age. Eight cases died, including 4 cases of postoperative multi-drug resistant bacteria infection, died from tracheal anastomotic opening or septic shock, 1 cases with severe congenital heart disease died from postoperative low cardiac output syndrome difficult to correct, 1 case died from blood pressure could not be maintained due to the compressed left pulmonary artery after transplantation, 2 cases of postoperative digestive system diseases (adhesive intestinal obstruction, gastrointestinal bleeding, etc.). The 24 patients in the staging group were followed for 1 to 84 months. All patients needed stage Ⅱ tracheoplasty due to respiratory symptoms and decreased endurance to activity. Eight cases of the non-intervention tracheal group were successfully separated from the ventilator, cured and discharged in a short period of time.Conclusions:Most children with pulmonary artery sling have tracheal stenosis. Children with low degree of tracheal stenosis and inconspicuous respiratory symptoms can only undergo left pulmonary artery transplantation by lateral thoracotomy. For patients combined with severe tracheal stenosis or obvious respiratory symptoms, a simultaneous left pulmonary artery transplantat and tracheoplasty is recommended.

Objective:To examine the effect of surgical treatment in children with pulmonary artery sling and the surgical treatment strategy.Methods:Relevant data of 110 children with pulmonary artery sling admitted to the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to July 2022 were retrospectively analyzed. There were 55 males and 55 females, aging ( M(IQR)) 9.0 (10.6) months (range: 1 to 96 months). The weight was 7.8 (3.5) kg (range: 2.5 to 25.0 kg). Of the 110 patients, 108 had different degrees of tracheal stenosis and 2 had normal trachea. Left pulmonary artery transplantation and tracheoplasty were performed in 78 patients. Left pulmonary artery transplantation was performed in 30 patients (11 in our hospital and 19 in other hospitals) due to the lack of an early tracheoplasty technique, in which 24 patients needed stage Ⅱ tracheoplasty due to obvious respiratory symptoms and limited activity endurance, and 6 cases did not intervene. Two children with normal trachea only underwent left pulmonary artery transplantation. Results:Among the 78 children who underwent surgery in the same period, 70 cases recovered smoothly after surgery, of whom respiratory symptoms were significantly reduced or disappeared during the 1 to 65 months follow-up, with similar activity endurance to normal children of the same age. Eight cases died, including 4 cases of postoperative multi-drug resistant bacteria infection, died from tracheal anastomotic opening or septic shock, 1 cases with severe congenital heart disease died from postoperative low cardiac output syndrome difficult to correct, 1 case died from blood pressure could not be maintained due to the compressed left pulmonary artery after transplantation, 2 cases of postoperative digestive system diseases (adhesive intestinal obstruction, gastrointestinal bleeding, etc.). The 24 patients in the staging group were followed for 1 to 84 months. All patients needed stage Ⅱ tracheoplasty due to respiratory symptoms and decreased endurance to activity. Eight cases of the non-intervention tracheal group were successfully separated from the ventilator, cured and discharged in a short period of time.Conclusions:Most children with pulmonary artery sling have tracheal stenosis. Children with low degree of tracheal stenosis and inconspicuous respiratory symptoms can only undergo left pulmonary artery transplantation by lateral thoracotomy. For patients combined with severe tracheal stenosis or obvious respiratory symptoms, a simultaneous left pulmonary artery transplantat and tracheoplasty is recommended.