The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Objective:To investigate the clinical effect of composite surgery in the treatment of chronic common carotid artery occlusion(CCAO).Methods:A retrospective descriptive study was conducted. The clinical data of 7 patients with CCAO admitted to Xuanwu Hospital, Capital Medical University from October 2020 to December 2023 were collected retrospectively. There were 6 males and 1 female. The age was (66.7±10.9) years, ranging from 52 to 83 years. Outpatient or telephone follow-up were conducted after surgery, carotid artery ultrasound or computed tomography angiography were performed at 3 months, 6 months, and 1 year postoperatively to determine vascular patency. The selection of surgical methods and clinical effect were analyzed. Normally distributed measurement data were expressed as mean±standard deviation ( ± s). The measurement data of skewed distribution were expressed by M ( Q1, Q3). Count data were expressed as frequency. Results:All 7 patients were diagnosed with chronic CCAO before operation, 6 on the left and 1 on the right. 3 cases affected the middle and distal segments of the common carotid artery, 1 case affected the proximal segment, and 1 case each affected the middle and distal segments, the remaining case involves the entire common carotid artery. All the procedures were successfully performed, among which 4 cases underwent carotid endarterectomy combined with stent placement, and 3 cases did not receive stent placement after carotid endarterectomy. 1 patient developed neck hematoma after surgery and the remaining patients recovered well after surgery without any complications or deaths. The follow-up time was 13.5(4.0, 20.5) months; 1 patient was lost to follow-up, and 6 patients received effective follow-up. the common carotid artery remained unobstructed in all 6 patients, and there were no transient ischemic attacks or strokes during the follow-up period.Conclusion:Composite surgery is a safe and feasible method that can be used to treat chronic CCAO lesions, and has satisfactory short-term results.

Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.

Objective:To investigate the clinical characteristics and surgical treatment experience of carotid body tumor (CBT).Methods:The clinical data of 12 patients with CBT admitted to the Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University from March 2013 to August 2020 were analyzed retrospectively. Among them, there were 6 males and 6 females, aged 31-83 years, with a median age of 57 years. Among the 12 patients, 2 patients were not treated surgically. The body mass index (BMI), tumor side, maximum diameter of tumor, and tumor classification, operation time, intraoperative bleeding volume, postoperative drainage volume and time, postoperative hospital stay and postoperative complications of patients undergoing surgery were recorded.Results:BMI of the 12 patients was 17.19-29.07 kg/m 2, with an average of (24.05±3.95) kg/m 2. Among the 12 patients, there were 4 tumors on the left side, 6 tumors on the right side and 2 patients had bilateral tumors. The maximum diameter of the tumor was 1.7-8.7 cm, with an average of (4.05 ± 1.89) cm. Among the 2 patients with bilateral tumors, 1 patient underwent staged resection within 9 months and 1 patient only removed the larger tumor. A total of 10 patients underwent surgical resection. All excised tumors were confirmed histopathologically to be paraganglioma. The average operation time and the amount of bleeding was(164.73 ± 74.39)min and 341.82 mL respectively. The drainage time was 1-3 d, with an average of (1.73 ± 0.65) d. The cumulative drainage volume was 22-237 mL, with an average of (77.18 ± 57.47) mL. Classification of 11 surgically resected tumors: 3 patients (3/11, 27.3%) were Shamblin Ⅰ, 7 patients (7/11, 63.6%) were Shamblin Ⅱ and 1 patient (1/11, 9.1%) were Shamblin Ⅲ. There were 1 patient of hematoma and 1 patient of acute cerebral infarction after operation. One patient with decrease in muscle strength of right limb, other surgical patients complained no complications such as stroke and cranial nerve injury when discharged. Patients undergoing surgery were hospitalized for 8-20 days, with an average of (13.36 ± 3.61) d. Conclusions:CBT is a rare paraganglioma in clinic. Surgical resection is an effective method to treat CBT. Careful operation should be carried out to avoid serious complications such as wound hematoma, cranial nerve injury and ischemic stroke.

Objective:To explore the method and effect of endovascular treatment to innominate artery stenosis or occlusion.Methods:The data of 11 patients with stenosis or occlusion of innominate artery from January 2014 to November 2019 at Xuanwu Hospital of Capital Medical University were collected. All patients received endovascular treatment. We summarized the changes of clinical symptoms, surgical methods, perioperative complications, stent patency, and analyzed the changes in systolic blood pressure and peak blood flow velocity on the involving side.Results:All 11 patients underwent endovascular treatment. The surgical technique success rate was 100%. All patients were followed up. The follow-up time was 4-69 months, with an average of (30.1±23.4)months. 2 patients used cerebral umbrella during the operation. 1 patient was performed ipsilateral carotid endarterectomy, 1 patient underwent contralateral carotid stent implantation, 1 patient was diagnosed as severe stenosis of the innominate artery and left common carotid artery, and an innominate artery stent implantation was performed at one stage, left common carotid artery stent implantation was performed after half a year. We done operation from the femoral artery puncture approach (6 patients), brachial artery puncture approach (2 patients), axillary artery and femoral artery puncture approach (1 patients), and right common carotid artery and the femoral artery puncture approach (2 patients). 3 patients had in-stent restenosis at 6, 7and 12 months after stenting, respectively. 1 patient underwent balloon dilatation, and 2 patients underwent re-stent implantation. We have not do further intervention to 1 case of in-stent occlusion occurred 14 months after the stenting, for the clinical symptoms did not improve significantly. The clinical re-intervention rate in this group was 3/11, and the primary patency rate was 7/11. The secondary patency rate was 10/11. The symptoms of 10 patients were relieved and the weakness of right upper extremity was not significantly changed in 1 patient. No puncture point complications occurred in all patients, and no cerebral infarction occurred during the perioperative period. There were statistically significant differences in systolic blood pressure, blood pressure difference and peak blood flow velocity before and after the operation ( P<0.05). Conclusions:Endovascular treatment of innominate arterial stenosis or occlusion was safe and effective, and the appropriate surgical approach and plan should be selected according to the lesion characteristics and the whole body conditions.

Objective: To investigate the effect of endovascular treatment of cerebral infarction with right aortic arch and Kommerell's diverticulum. Methods: Retrospective analysis was done to assess the treatment effect of a case from vascular surgery, Xuanwu Hospital of Capital Medical University. This case was diagnosed as cerebral infarction with right aortic arch and Kommerell's diverticulum. Results: One month after the treatment of cerebral infarction, we successfully used the thoracic aortic stent to isolate the Kommerell's diverticulum. There were no operative complications occurred. The stent had good shape and smooth blood flow was seen in the stent. Conclusions Endovascular treatment to cerebral infarction with right aortic arch and Kommerell's diverticulum is safe and feasible, and the clinical outcome requires further long-term follow-up.

Objective The incidence of chronic lower limb ischemia caused by arteriosclerotic obliteration of lower extremities is increasing recent years and there is a high risk of amputation and mortality.This study was to find out the changes in a single center for 16 years.Methods A retrospective analysis of the data of patients in single-center vascular surgery in the past 16 years was carried out.The patients with chronic lower limb ischemia caused by lower limb arteriosclerosis obliterans were screened out,and the data of operation information,amputation,length of stay and hospitalization expenses during hospitalization were collected.Results A total of 4 602 patients were included,of whom 57.39％ were diabetic.It was found that the number of patients admitted,the number of endovascular treatment,the average cost of hospitalization increased year by year,and the average length of hospitalization decreased year by year.The amputation rate decreased from 8.12％ (from 2002 to 2007) to 0.92％ (from 2008 to 2017) (P ＜ 0.01).The average days of hospitalization decreased from 28.20 days (from 2002 to 2007) to 11.65 days (from 2008 to 2017) (P ＜ 0.01).The average hospitalization cost rose from 54 466.94 yuan (from 2002 to 2007) to 73 685.22 yuan (from 2008-2017) (P ＜ 0.01).There was no significant difference in amputation rate,hospitalization days and hospitalization costs between diabetic group and non-diabetic group.In diabetic subgroup,amputation rate decreased from 8.83％ (between 2002 and 2007) to 1.05％ (between 2008 and 2017) (P ＜ 0.01).The average hospitalization days decreased from 30.12 days (between 2002 and 2007) to 12.60 days (between 2008 and 2017) (P ＜ 0.01).The average cost of hospitalization rose from 58 530.94 yuan (between 2002 and 2007) to 74 433.75 yuan (between 2008 and 2017) (P ＜ 0.01).Conclusions From 2002 to 2017,the number of patients with chronic lower limb ischemia increased gradually,and so as the number of endovascular treatment.While the amputation rate and average hospitalization time decreased,and the average hospitalization cost increased.The same trend was observed in the diabetic subgroup.The significant decrease in amputation rate may be related to the development of endovascular therapy and angiogenesis therapy.

Objective To evaluate the clinical outcomes and report the second-look arthroscopic findings of reconstructed anterior cruciate ligament (ACL) using deep-frozen allograft.Methods Sixty-six patients undergoing ACL reconstruction using deep-frozen allograft in our institute with at least twelve months follow-up from January 2012 to March 2016 were included and received second-look arthroscopy.The patients consisted of 51 males and 15 females with an average age of 30.6 years (range,18 to 55 years) at the time of ACL reconstruction.Knee functions were evaluated by Lysholm score and International Knee Documentation Committee (IKDC) score.Knee stability was evaluated by drawer test,Lachman test and KT-1000 arthrometer.Second-look arthroscopic evaluation was performed in all patients,focused on continuity of the reconstructed ACL,the synovial coverage and subjective tension of the graft,and the prevalence of cyclops-like lesion and other changes after reconstruction procedures.Resuits All patients were followed up for average 18.3 months (range,12 to 36 months).Thirty-one patients underwent second-look arthroscopy from 12 to 18 months,and the other 35 patients underwent second-look arthroscopy from 18 to 36 months after ACL reconstruction.No infection,rejection reaction and other serious complication were reported after operation.The knee range of motion was normal in all cases,except that 10° extension limitation in one case.The Lysholm score significantly improved from preoperative 54.95±9.01 to 12 months postoperatively 86.14±5.86,and the IKDC improved from 54.79±9.12 to 85.11±5.77.Lachman test was positive in 8 cases,but negative in 58 cases postoperatively.KT-1000 arthrometer measurement showed that the side-toside difference significantly improved from preoperative 6.70± 1.24 mm to postoperative 1.52± 1.02 mm.Complete discontinuity occurred in 2 cases of the reconstructed grafts,graft tear in 4 cases.Cyclops-like mass was identified in 2 cases.The overall synovial coverage was slightly better in the patients who were followed up more than 18 months than those less than 18 months.However,there was no significant difference among the groups in the field of graft tension.The patients with taut grafts showed statistically better KT-1000 values (1.14±0.35 mm) than those with lax grafts (2.95±1.38 mm).Conclusion Frozen allograft could be a reasonable choice for ACL reconstruction.However,the graft integration and remodeling could tend to be slow.

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.