Objective To establish a chronic rejection (CR) model of mouse heart transplantation and analyze its characteristics. Methods Allogeneic BALB/c and C57BL/6 mice were used as donor and recipient for heart transplantation, and intraperitoneal injection of cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig) was given 1 and 2 days after surgery. Graft survival time, donor specific antibody (DSA) level, graft pathology and inflammatory cell infiltration were observed. Results In allogeneic transplantation model, graft survival time was prolonged after CTLA4-Ig treatment [(28.2±4.1) d vs. (7.0±0.7) d, P < 0.01]. The level of serum DSA-IgG increased at 2, 3 and 4 weeks after surgery, while the level of DSA-IgM remained unchanged. Myocardial cell injury, inflammatory cell infiltration, interstitial fibrosis and C4d deposition in capillaries were aggravated 3 weeks after operation and worsened 4 weeks after operation. The infiltrated immune cells were mainly macrophages, T cells and plasma cells. Conclusions Mouse allogeneic heart transplantation combined with CTLA4-Ig successfully establishes a CR model, which provides a basis for subsequent studies on the pathogenesis and intervention of CR.

Objective To establish a rat model of acute antibody-mediated rejection (AMR) in kidney transplantation and investigate the preventive effect of dihydroartemisinin (DHA) on acute AMR. Methods BN rats were used as donors and Lewis rats as recipients. Kidney transplantation was performed 2 weeks after skin transplantation for sensitization. After establishing the acute AMR model in rat kidney transplantation, the recipients of experimental groups included the syngeneic kidney transplantation group (6 rats), the allogeneic kidney transplantation group (6 rats), the syngeneic skin transplantation followed by kidney transplantation group (12 rats), and the allogeneic skin transplantation followed by kidney transplantation group (24 rats). The groups for investigating the preventive effect of DHA on acute AMR included the control group (allogeneic skin transplantation followed by kidney transplantation) and the DHA group (allogeneic skin transplantation followed by kidney transplantation + DHA), with 12 rats in each group. The survival time of recipient rats, serum donor-specific antibody (DSA) levels and graft pathological changes were used to identify the acute AMR model. On this basis, DSA levels, pathological changes in the transplant kidneys and peripheral blood B-cell levels were detected to assess the preventive effect of DHA on acute AMR. Results Compared with the allogeneic kidney transplantation group, skin transplantation sensitization significantly shortened the survival time of recipient rats (P<0.01). Compared with the syngeneic skin transplantation followed by kidney transplantation group, the allogeneic skin transplantation followed by kidney transplantation group showed significantly elevated serum DSA-IgG levels from 7 days after skin transplantation to 5 days after kidney transplantation (P<0.01), and significantly elevated DSA-IgM levels at 7 and 14 days after skin transplantation(all P<0.01). The transplant kidneys in the allogeneic skin transplantation followed by kidney transplantation group showed a small number of inflammatory cell infiltrations, tubular necrosis, capillaritis, and C4d deposition starting from 1 day after kidney transplantation, with these pathological changes worsening as the post-transplantation days increased. The kidney damage became significant starting from 3 days after transplantation. The above pathology manifestations were consistent with the characteristics of acute AMR. On the basis of establishing the acute AMR model, DHA treatment significantly prolonged the survival time of recipient rats (P<0.01) , and reduced serum DSA-IgG and DSA-IgM levels. DHA treatment significantly alleviated the pathological manifestations of acute AMR, including kidney damage, inflammatory cell infiltration, capillaritis and tubular necrosis, and also reduced C4d deposition in the transplant kidneys, inflammatory cell infiltration and peripheral blood CD19⁺ B-cell levels. Conclusions An acute AMR model is established by performing kidney transplantation 2 weeks after allogeneic skin transplantation in rats. It is discovered that DHA has immunosuppressive effects and may effectively prevent acute AMR, which provides a new strategy for the management of clinical AMR.

Cross-linking mass spectrometry (XL-MS) technology has become a key tool for identifying protein-protein interactions (PPIs) and revealing the protein structures in living cells, tissues, or organelles. The XL-MS technology has demonstrated remarkable superiority compared with conventional methods for studying PPIs and protein structures. In the past few years, new cross-linker structures have been arising continuously. They have not only broadened the range of cross-linking reactions but also provided additional methods for the enrichment of cross-linking peptides. Moreover, owing to the advancement of computer software and artificial intelligence, cross - linking data search engines and visualization software have also been enhancing the speed and accuracy of cross-linking peptide identification. The evolution of cross-linkers and cross-linking peptide search engines has promoted the application of the XL-MS technology in the research on protein-protein interactions (PPIs) within organelles and even living cells and in the analysis of protein structures.

Objective To investigate the association between the variability of remnant cholesterol inflammatory index(RCII),a novel composite biomarker,and the risk of stroke,in order to provide a theoretical basis for stroke prevention.Methods A prospective cohort study was conducted on 38 659 Kailuan individuals who took annual physical examinations in 2006,2008,and 2010.These subjects were grouped based on the quartiles of RCII variability,which was represented by standard deviation(SD)and average real variability(ARV),and were followed up every 2 years,with the occurrence of stroke(including ischemic and hemorrhagic strokes),death,or the end of follow-up on December 31,2022 as the endpoints.Kaplan-Meier method was used to calculate the cumulative incidence rate of endpoint events across different groups,and log-rank test was used to compare the difference of cumulative incidence of endpoint events in each group.Multivariate Cox proportional hazards regression model was adopted to analyze the association between RCII variability and risk of stroke.Results Among the 38 659 participants,a total of 2 539 strokes occurred during a mean follow-up period of 11.22±2.26 years.After adjusting confounding factors,when the participants were grouped by the quartiles of RCII-SD,the hazard ratio(HR)for stroke was 1.034(95%CI:0.917～1.167,P=0.584),1.146(95%CI:1.018～1.290,P=0.025),and 1.209(95%CI:1.066～1.370,P=0.003),respectively in the Q2,Q3,and Q4 groups,when compared with the Q1 group(Ptrend<0.05).When they were grouped by the quartiles of RCII-ARV,the HR for stroke was 1.008(95%CI:0.894～1.136,P=0.901),1.109(95%CI:0.986～1.248,P=0.085),and 1.152(95%CI:1.018～1.303,P=0.025),respectively,in the Q2,Q3,and Q4 groups,when compared with the Q1 group.Furthermore,both sensitivity and stratified analyses yielded similar results.Conclusion RCII variability is significantly associated with stroke,and the risk of stroke is gradually increasing with increment of the variability.Countermeasures Relevant authorities can focus on reducing RCII variability as a central objective by establishing regular monitoring mechanism,strengthening lifestyle interventions,and standardizing dietary,exercise,and weight management in order to suppress the index fluctuations.The principle of stable lipid-lowering in medication and optimization of therapeutic regimens with stable efficacy should be emphasized to prevent the risk of additional vascular damage.

Background and aims:Advanced hepatocellular carcinoma(HCC)with pulmonary metastasis(PM)has a poor prognosis,and optimal treatment strategies remain controversial.This study aimed to compare the long-term outcomes of patients with advanced HCC with PM who were treated with resection of pul-monary metastases versus those treated with targeted therapies combined with immunotherapy.Methods:A retrospective analysis was conducted on the medical records of HCC patients with PM who underwent either pulmonary metastasectomy or immunotherapy combined with targeted therapies at the Eastern Hepatobiliary Surgery Hospital,Changhai Hospital of Shanghai,Fujian Provincial Hospital,and West China Hospital of Sichuan University from September 2013 to October 2022.One-to-one propensity score matching(PSM)was employed to control the influence of potential confounders,and the survival outcomes were compared.Results:A total of 119 HCC patients with PM were included in this study.The overall survival(OS)of patients who underwent pulmonary metastasectomy was significantly longer than that of patients who received immunotherapy targeted combinations(OS:1-year,80.0％vs.59.3％;2-year,31.7％vs.20.3％;3-year,20.0％vs.0;P＜0.001).After PSM,the long-term prognosis of the pulmonary metastasectomy group remained significantly better than that of the immunotherapy combination group(OS:1-year,87.0％vs.69.6％;2-year,34.8％vs.30.4％;3-year,21.7％vs.0;P=0.005).Multivariate analysis revealed that treat-ment allocation(hazard ratio(HR)=2.177,95％confidence interval(CI)=1.068-4.439)and hepatic tumor T stage(HR=2.342,95％CI=1.209-4.538)were independent risk factors for OS.Conclusions:Pulmonary metastasectomy was associated with improved survival compared to immu-notherapy combined with targeted therapies and may represent an optimal treatment option for highly selected HCC patients with resectable PM.

How to improve the long-term prognosis of transplant kidney and solve the shortage of donor kidney are still two major problems that plague clinicians. Among them, ischemia-reperfusion injury (IRI), rejection, infection, and immunosuppressive therapy are important issues in the research field of renal transplantation. Therefore, strengthening the literature study in the field of renal transplantation and understanding the nature of transplant kidney related diseases and international frontier research hotspots, help to further improve the function and prolong the survival time of the transplant kidney in clinic. This article interpreted literatures on the research hotspots and new progress in the field of renal transplantation in the third quarter of 2020, combined with the meeting minutes of the 12th Lingnan Reading Club, and reviewed from the three aspects of IRI, rejection and infection.

Objective: To investigate the effect of three-dimensional (3D) printing guide plate on improving femoral rotational alignment and patellar tracking in total knee arthroplasty (TKA). Methods: Between January 2018 and October 2018, 60 patients (60 knees) with advanced knee osteoarthritis who received TKA and met the selection criteria were selected as the study subjects. Patients were randomly divided into two groups according to the random number table method, with 30 patients in each group. The TKA was done with the help of 3D printing guide plate in the guide group and following traditional procedure in the control group. There was no significant difference in gender, age, disease duration, side, and preoperative hip-knee-ankle angle (HKA), posterior condylar angle (PCA), patella transverse axis-femoral transepicondylar axis angle (PFA), Hospital for Special Surgery (HSS) score, and American Knee Society (AKS) score ( P>0.05). Results: All incisions healed by first intention and no complications related to the operation occurred. All patients were followed up 10-12 months, with an average of 11 months. HSS score and AKS score of the two groups at 6 months after operation were significantly higher than those before operation ( P<0.05), but there was no significant difference between the two groups ( P>0.05). Postoperative X-ray films showed that the prosthesis was in good position, and no prosthesis loosening or sinking occurred during follow-up. HKA, PCA, and PFA significantly improved in the two groups at 10 months after operation compared with those before operation ( P<0.05). There was no significant difference in HKA at 10 months between the two groups ( t=1.031, P=0.307). PCA and PFA in the guide group were smaller than those in the control group ( P<0.05). Conclusion: Application of 3D printing guide plate in TKA can not only correct the deformity of the knee joint and alleviate the pain symptoms, but also achieve the goal of the accurate femoral rotation alignment and good patellar tracking.

Objective To investigate the training process of clinical practice ability in medical undergraduates in the context of tutorial system,as well as new clinical training models and evaluation methods.Methods A total of 40 medical undergraduates who entered the stage of clinical practice were randomly divided into tutorial group and control group,with 20 undergraduates in each group.A diversified evaluation system was used to perform a comprehensive evaluation of clinical practice ability of medical undergraduates at different stages,with a combination of professional theory examination,Mini-Clinical Evaluation Exercise,Direct Observation of Procedural Skills,and clinical case report.All the data were analyzed by SPSS 23.0,t test was used for statistical analysis.Results Compared with the control group after the internship ended,the tutorial group had significantly higher scores of clinical professional theory (86.24 ± 2.93),clinical practice ability (7.53 ± 0.48),clinical operation skills (4.35 ± 0.47),and clinical thinking ability (6.31 ± 0.52) (all P＜0.05).Conclusion The application of the tutorial training mode during the internship of medical undergraduates can improve their comprehensive qualities such as professional quality,medical theory,and practical skills.The diversified evaluation system can evaluate the teaching effect and reflect the cultivation of comprehensive quality among students.

Objective: To explore the gait trajectory characteristics of patients after total knee arthroplasty (TKA) assisted by three-dimensional (3D) printing navigation template. Methods: Twenty female patients (20 knees) with knee osteoarthritis who were treated with TKA assisted by 3D printing navigation template between February 2017 and February 2018 were selected as the 3D printing group. The patients were 50-69 years old, with an average age of 57.2 years. The disease duration was 4-7 years, with an average of 5.6 years. The osteoarthritis was classified as Kellgren-Lawrence Ⅲ level in 5 cases and Ⅳ level in 15 cases. The preoperative hip-knee-ankle angle (HKA) was (170.8±5.6)°. All patients were varus deformity. According to age and affected side, 20 healthy female volunteers were selected as the control group. The volunteers were 51-70 years old, with an average age of 56.7 years. Preoperative HKA was (178.8±0.6)°. There was significant difference in HKA between the two groups ( P>0.05). The HKA, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and visual analogue scale (VAS) scores of the 3D printing group before and after operation were compared. At 6 months after operation, the gait trajectory characteristics of 3D printing group and control group were analyzed by Vicon gait capture system. The kinematics parameters included velocity, cadence, stride length, maximum knee flexion angle (stance), minimum knee flexion angle (stance), maximum knee flexion angle (swing), mean hip rotation angle (stance), mean ankle rotation angle (stance). Results: The incisions of 3D printing group healed by first intention, with no complications. All patients were followed up 7-12 months (mean, 9.0 months). The WOMAC and VAS scores at 6 months after operation were significant lower than those before operation ( P<0.05). The HKA was (178.8±0.8)° at 4 weeks after operation and the difference was significant when compared with that before operation ( t=39.203, P=0.000). The position of the prosthesis was good. The femoral posterior condyle osteotomy line, surgical transepicondylar axis, and patella transverse line were parallel, varus deformity was corrected, and lower limb alignment was restored to neutral position. Gait analysis at 6 months after operation showed that the differences in all kinematics parameters between the two groups were significant ( P<0.05). Conclusion: Assisted by 3D printing navigation template, TKA can alleviate pain symptoms and correct deformity, with satisfactory early effectiveness. Compared with healthy people, the early postoperative gait of the patients were characterized by decreasing velocity, cadence, stride length, knee flexion range, and increasing compensatory hip and ankle rotation range.

Objective: To summarize the clinical application and research status of open wedge high tibial osteotomy (OWHTO). Methods: Relevant literature at home and abroad was reviewed, and the clinical application, effectiveness and complications, technical comparison, and surgical skills of OWHTO were summarized and analyzed. Results: OWHTO is an effective treatment for mild to moderate medial compartment osteoarthritis due to knee varus. This method can delay the injury process of medial compartment of the knee, delay the time of total knee arthroplasty, and even avoid joint replacement surgery by adjusting the axial alignment of the lower extremity to the non-pathological lateral compartment through osteotomy and orthopedic. OWHTO has the advantages of small incision, dynamic adjustment of the axial alignment of the lower extremity, accurate correction of malformation, and rapid postoperative recovery. Conclusion: With the development of surgical instruments and techniques, OWHTO once again enter the sight of orthopedic surgeons. This technique can solve the pain symptoms of arthritis, correct the tibial varus deformity and reconstruct the axial alignment of the lower extremity, and satisfactory clinical results has been obtained.