Objective:To observe the clinical effect of retrograde distal tibial intramedullary nail fixation in the treatment of proximal ankle fracture of the distal tibia.Methods:A three-dimensional CT examination of 40 adult tibias was performed to measure anatomical indicators such as the posterior medial posterior torsion angle of the distal tibia, the height of torsion, and the height of the safety zone for nail placement. Based on the anatomy database of the human skeleton model, a retrograde distal tibial nail and its supporting instruments were developed in accordance with the anatomical characteristics of the distal tibia and the proximal ankle of Chinese people. From June 2019 to June 2023, a total of 25 patients with distal tibial proximal ankle fractures treated with retrograde intramedullary nail internal fixation in the 909th Hospital were retrospectively analyzed. There were 18 males and 7 females, aged 41.3±10.8 years (range, 22-65 years). The sample size was 1∶1 matched according to gender and age. Twenty-five patients with distal tibial proximal ankle fractures who underwent antegrade intramedullary nail fixation during the same period were matched, including 20 males and 5 females, aged 41.2±9.4 years (range 19-60 years). The reduction quality, postoperative Baird-Jackson score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score, ankle range of motion and complications were observed.Results:All patients were successfully operated and followed up for 14.4±3.5 months (range, 12-24 months). The intraoperative blood loss and hospitalization time in retrograde intramedullary nail group were 33.12±7.38 ml and 10.32±1.75 d, less than 49.04±10.22 ml and 13.16±2.69 d in antegrade intramedullary nail group, and the difference was statistically significant ( P<0.05). The reduction quality was excellent in 23 cases and good in 2 cases in the retrograde intramedullary nail group, and was excellent in 17 cases and good in 8 cases in the anterograde intramedullary nail group. The proportion of excellent reduction quality in the retrograde intramedullary nail group was higher than that in the anterograde intramedullary nail group, and the difference was statistically significant (χ 2=4.500, P=0.034). The Baird-Jackson score and AOFAS ankle and hindfoot score in the retrograde intramedullary nail group were 85.6±2.5 and 85.8±3.3 at 3 months after operation, lower than those at 1 year after operation 95.3±3.1 and 95.8±3.6, and the difference was statistically significant ( P<0.05). The Baird-Jackson score and AOFAS ankle and hindfoot score of the antegrade intramedullary nail group were 85.1±3.3 and 86.1±2.5 at 3 months after operation, lower than 95.2±2.7 and 94.9±3.5 at 1 year after operation, and the difference was statistically significant ( P<0.05). There was no significant difference in Baird-Jackson score and AOFAS ankle and hindfoot score between the two groups at 3 months and 1 year after operation ( P>0.05). At the last follow-up, there was no ankle stiffness, neurovascular injury, deep vein thrombosis, infection or breakage of internal fixation in the two groups. Conclusion:The treatment of distal tibial proximal ankle fractures with retrograde intramedullary nail fixation has satisfactory reduction quality, good postoperative function recovery, and is helpful for early postoperative rehabilitation.

[This corrects the article DOI: 10.1016/j.apsb.2023.04.002.].

Objective:Managing 33-C3 femur fractures with medial wall bone defects poses a significant challenge for orthopedic surgeons.The gold standard treatment for arbeitsgemeinschaftfür osteosynthesefragen(AO)/orthopedic trauma association(OTA)33-C3 distal femur fractures with medial wall bone defects remains elusive.This study employs finite element analysis to compare the stability and mechanical behavior of 3 internal fixation patterns(single lateral distal locking plate,retrograde intramedullary nail,and dual plates)for 33-C3 femur fractures with medial wall bone defects.The aim is to provide a theoretical basis for the selection of internal fixation modalities in clinical practice. Methods:Enrollment included a 43-year-old male volunteer weighing 60 kg,without a history of femur fracture.Bilateral femur normality was verified through X-ray and CT scan assessments.A finite element simulation model of AO/OTA 33-C3 distal femur fracture with medial wall bone defect was established.Three fixation methods,named single lateral locking plate(single-plate group),retrograde intramedullary nail(retrograde intramedullary nail group),and dual plates(dual-plate group),were evaluated using finite element analysis under an axial load of 300 N.The assessment included an examination of von Mises stress distribution,shear stress,and displacement patterns at the internal fixation and femur fracture sites. Results:The finite element analysis revealed that dual-plate fixation effectively reduced the concentration of von Mises stress at the plate on the fracture site.Under full weight-bearing conditions,the maximum von Mises stress in the implants occurred at the distal femur defect level,with values of 149.30,59.281,and 58.03 MPa for single-plate fixation,retrograde intramedullary nail,and dual-plate fixation methods,respectively.Similarly,the maximum shear stress in the implants was 77.867,30.136,and 33.505 MPa for single-plate fixation,retrograde intramedullary nail,and dual-plate fixation methods,respectively,all presenting at the distal femur defect level.The maximum relative displacements of implants during compressive loading were 1.34,1.25,and 0.83 mm for the single-plate,retrograde intramedullary nail,and dual-plate groups,respectively.Consistently,the maximum loading-point displacements of fracture sites were 1.529,1.264,and 0.880 mm for the single-plate fixation group,retrograde intramedullary nail group,and dual-plate fixation group,respectively.Furthermore,at the distal femur defect level,the maximum von Mises stress was 72.682,112.430,and 40.716 MPa for the single-plate,retrograde intramedullary nail,and dual-plate fixation groups,respectively. Conclusion:Dual-plate fixation demonstrates superior biomechanical outcomes and exhibites the lowest maximum von Mises stress and shear stress,along with minimal relative movements between fracture fragments.This configuration offers optimal mechanical stability for managing AO/OTA 33-C3 distal femur fractures with medial wall bone defects.Consequently,dual-plate fixation emerges as a better treatment strategy for patients presenting with comminuted intra-articular distal femur fractures accompanied by medial wall bone defects.

Tumors in which the microenvironment is characterized by lack of immune cell infiltration are referred as "cold tumors" and typically exhibit low responsiveness to immune therapy. Targeting the factors contributing to "cold tumors" formation and converting them into "hot tumors" is a novel strategy for improving the efficacy of immunotherapy. Adenosine, a hydrolysis product of ATP, accumulates with a significantly higher concentration in the tumor microenvironments compared with normal tissue and exerts inhibitory effects on tumor-specific adaptive immunity. Tumor cells, dendritic cells, macrophages, and T cells express abundant adenosine receptors on their surfaces. The binding of adenosine to these receptors initiates downstream signaling pathways that suppress tumor antigen presentation and immune cell activation, consequently dampening adaptive immune responses against tumors. Adenosine down-regulates the expression of major histocompatibility complex Ⅱ and co-stimulatory factors on dendritic cells and macrophages, thereby inhibiting antigen presentation to T cells. Adenosine also inhibits ligand-receptor binding and transmembrane signaling on T cells, concomitantly suppressing the secretion of anti-tumor cytokines and impairing T cell activation. Furthermore, adenosine hinders effector T cell trafficking to tumor sites and infiltration by inhibiting chemokine secretion and KCa3.1 channels. Additionally, adenosine promotes the secretion of immunosuppressive cytokines, increases immune checkpoint protein expression, and enhances the activity of immunosuppressive cells, collectively curbing cytotoxic T cell-mediated tumor cell killing. Given the immunosuppressive role of adenosine in adaptive antitumor immunity, several inhibitors targeting adenosine generation or adenosine receptor blockade are currently in preclinical or clinical development with the aim of enhancing the effectiveness of immunotherapies. This review provides an overview of the inhibitory effects of adenosine on adaptive antitumor immunity, elucidate the molecular mechanisms involved, and summarizes the latest advances in application of adenosine inhibition strategies for antitumor immunotherapy.
Humans ; Adenosine/pharmacology* ; T-Lymphocytes ; Adaptive Immunity ; Cytokines ; Neoplasms/therapy* ; Tumor Microenvironment

Objective:To investigate the application value of fluorescence imaging in single-port thoracoscopic anatomic segmentectomy.Methods:The clinical data of 280 patients (145 patients with fluorescence method and 135 patients with modified inflation-deflation method) who underwent thoracoscopic anatomic segmentectomy were retrospectively studied in the Anhui Chest Hospital from June 2020 to June 2021. There were 113 patients in the simple segmentectomy group and 167 patients in the complex segmentectomy group. The baseline data of the fluorescence method and the modified inflation-deflation method in the complex segmentectomy group were corrected by propensity score matching, and the perioperative results were compared between the groups.Results:There were no significant differences in segmental resection time, intraoperative blood loss, postoperative drainage, postoperative pain, postoperative extubation time, length of hospital stay, incidence of complications and cost of hand-holding between the fluorescence method and the modified method of the simple segmentectomy group.In the complex segmentectomy group, the time of segmental resection with the fluorescence method was significantly shorter than that with the modified inflation-deflation method( P<0.05), and other indexes had no significant difference. Conclusion:Fluorescence method single-port thoracoscopic anatomic segmentectomy has the same perioperative safety and short-term efficacy as modified inflation-deflation method, which can significantly shorten the operative time and improve the operative efficiency in complex anatomic segmentectomy.

Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8⁺ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.

Objective:By using balloon occlusive hepatic angiography in cirrhotic portal hypertension to evaluate contrast doses on the detection rate of intrahepatic venous-lateral branch shunt (HVVC), and the effect on hepatic venous pressure gradient (HVPG) and portal vein pressure gradient (PPG).Methods:From Jan 2018 to Jun 2021, 131 patients received transjugular intrahepatic portosystemic shunt (TIPS) at Beijing Shijitan Hospital.Results:A positive correlation between PVP and weged hepatic venous pressure (WHVP) ( r=0.241, P=0.001) was found when only by right hepatic vein approach. Ten ml of iodine contrast medium when compared to 5ml doses found more cases of intrahepatic venous-venous lateral branch shunt. The mean PPG of patients with HVVC was significantly higher than the mean of HVPG( P<0.05).The right hepatic vein was the only reliable vein by which WHVP was measured. Conclusions:Right hepatic vein manometry,adequate ballon occlusion and using 10ml of iodine contrast help get reliable WHVP and found HVVC; HVVC can affect the consistency of HVPG and PPG.

The clinical data of two children with refractory/relapsed acute B-lymphoblastic leukemia (ALL-B)treated with Blinatumomab in Department of Pediatrics, Peking University People′s Hospital from September 2019 to May 2021 were retrospectively analyzed.After 1 course of Blinatumomab infusion, both children achieved complete hematologic remission.During the infusion process, grade 2 cytokine release syndrome (CRS) was observed, and there were no fatal adverse reactions.One case underwent bridging hematopoietic stem cell transplantation after remission and achieves disease-free survival currently.The other case is still alive after subsequent consolidation chemotherapy.As a novel bispecific antibody, Blinatumomab has a good response rate to refractory/relapsed ALL-B and induces fewer adverse events, so it can be used as a candidate immunotherapy for patients with high tumor burden.

Objective:To identify the risk factors of heart failure in elderly patients with hip fracture by Meta-analysis.Methods:The clinical studies on perioperative heart failure in elderly patients with hip fracture were searched by computer in Pubmed, EMbase, Cochrane Library, Medline, Web of Science, CNKI, CBM, Wanfang and VIP database. The retrieval period was from the establishment of the databases to October 2021. The literature screening, data extraction and quality evaluation were completed by two researchers, and the selected literature were statistically analyzed by RevMan5.3 software.Results:A total of 17 articles were included in this study, involving 1 76 611 patients and 24 related risk factors. Cardiac history ( OR= 4.47, 95% CI 3.56-5.62), positive balance of perioperative inflow and outflow ( OR=5.99, 95% CI 3.30-10.87), anemia ( OR= 3.78, 95% CI 2.50-5.69), and the number of complications >4 ( OR=6.21, 95% CI 3.71-10.38), electrolyte disorder ( OR=7.40, 95% CI 3.77-14.54), preoperative cognitive impairment ( OR=3.60, 95% CI 1.39-9.31) and American Society of Anesthesiologists (ASA) grade ≥ 3 ( OR= 4.73, 95% CI 2.73-8.12) were statistically significant risk factors ( P<0.05). Conclusions:Cardiac history, positive balance of perioperative inflow and outflow, anemia, number of complications >4, electrolyte disorder, preoperative cognitive impairment and ASA grade ≥3 were the risk factors of perioperative heart failure in elderly patients with hip fracture.