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.

Yang being solid is an important summary of the normal functional state of yang qi in The Yellow Emperor's Inner Classic.Based on the theory of yang being solid and able to hold on,it is proposed that yang being solid is essential to maintain the state of tightness,thoroughness and quietness for maintaining the health of the human body.Yang losing its solidity is the core patho-genesis of the onset and progression of malignant tumors,which manifests as yang deficiency,yang depression and yang restlessness.If yang is not solid due to its deficiency,yang will lose its warmth and defense and the evil qi will be retained;if yang is not solid due to its depression,yang will lose its warmth and circulation and phlegm and stasis will gather;if yang is not solid due to its restlessness,yang will lose its tranquility,burn yin and consume essence.Aiming at the core pathogenesis of yang losing its solidity,the treatment methods of warming yang and replenishing qi to treat the disease before it occurs,unblocking yang and removing turbidity to disperse the staleness,and clearing and resolving restless yang to fight cancer and detoxify are used in clinical practice.Restoring the solidity of yang is taken as the goal of treating malignant tumors,which provides ideas for the clinical practice of treating malignant tumors with traditional Chinese medicine.

Yang being solid is an important summary of the normal functional state of yang qi in The Yellow Emperor's Inner Classic.Based on the theory of yang being solid and able to hold on,it is proposed that yang being solid is essential to maintain the state of tightness,thoroughness and quietness for maintaining the health of the human body.Yang losing its solidity is the core patho-genesis of the onset and progression of malignant tumors,which manifests as yang deficiency,yang depression and yang restlessness.If yang is not solid due to its deficiency,yang will lose its warmth and defense and the evil qi will be retained;if yang is not solid due to its depression,yang will lose its warmth and circulation and phlegm and stasis will gather;if yang is not solid due to its restlessness,yang will lose its tranquility,burn yin and consume essence.Aiming at the core pathogenesis of yang losing its solidity,the treatment methods of warming yang and replenishing qi to treat the disease before it occurs,unblocking yang and removing turbidity to disperse the staleness,and clearing and resolving restless yang to fight cancer and detoxify are used in clinical practice.Restoring the solidity of yang is taken as the goal of treating malignant tumors,which provides ideas for the clinical practice of treating malignant tumors with traditional Chinese medicine.

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 explore the long-term efficacy and safety of gene therapy with pUDK-hepatocyte growth factor (pUDK-HGF) for rest pain and ulcers caused by critical limb ischemia.Methods:Long-term follow-up were conducted through outpatient and telephone on patients who completed the pUDK-HGF Phase Ⅱ randomized double-blind placebo-controlled trial. The occurrence of tumors was observed, and tumor markers detection, fundus examination, visual analogue scale (VAS), and lower limb CT angiography (CTA) were performed according to voluntary principle. The results were analyzed descri-ptively and statistically.Results:A total of 53 patients were included in the analysis, of which 15 (28.3%) were in the placebo group and 38 (71.7%) were in the pUDK-HGF treatment group in the Phase Ⅱ clinical trial. The median follow-up time was 2.8 years, ranging from 1.7 to 3.5 years. During the follow-up period, no tumor was found in the 53 patients. Among the 38 patients in the pUDK-HGF treatment group, 18 underwent comprehensive examination and evaluation, including tumor markers, fundus and CTA examination, and patients with resting pain underwent VAS evaluation. Among them, 1 patient had transient mild elevation of carcinoembryonic antigen, and no abnormal tumor markers were found in the other 17 patients; no proliferative retinal vasculopathy was found in the fundus examination. At the end of the phase Ⅱ clinical trial (out-group), 3 were effective and 2 were ineffective of the 5 patients with rest pain; at the end of this follow-up period, 4 were evaluated as effectiveness and 1 as ineffectiveness according to CTA, and 5 were all evaluated as effectiveness according to VAS. Of the 13 patients with ulcer, 9 were evaluated as effectiveness and 4 were as ineffectiveness according to CTA at out-group; 10 were evaluated as effectiveness and 3 were as ineffectiveness at the end of this follow-up.Conclusions:pUDK-HGF had relatively good safety in the treatment of rest pain and ulcers caused by critical limb ischemia. No risk of carcinogenesis and proliferative retinal vasculopathy has been found, and the long-term efficacy of pUDK-HGF is good.

Objective:To explore the long-term efficacy and safety of gene therapy with pUDK-hepatocyte growth factor (pUDK-HGF) for rest pain and ulcers caused by critical limb ischemia.Methods:Long-term follow-up were conducted through outpatient and telephone on patients who completed the pUDK-HGF Phase Ⅱ randomized double-blind placebo-controlled trial. The occurrence of tumors was observed, and tumor markers detection, fundus examination, visual analogue scale (VAS), and lower limb CT angiography (CTA) were performed according to voluntary principle. The results were analyzed descri-ptively and statistically.Results:A total of 53 patients were included in the analysis, of which 15 (28.3%) were in the placebo group and 38 (71.7%) were in the pUDK-HGF treatment group in the Phase Ⅱ clinical trial. The median follow-up time was 2.8 years, ranging from 1.7 to 3.5 years. During the follow-up period, no tumor was found in the 53 patients. Among the 38 patients in the pUDK-HGF treatment group, 18 underwent comprehensive examination and evaluation, including tumor markers, fundus and CTA examination, and patients with resting pain underwent VAS evaluation. Among them, 1 patient had transient mild elevation of carcinoembryonic antigen, and no abnormal tumor markers were found in the other 17 patients; no proliferative retinal vasculopathy was found in the fundus examination. At the end of the phase Ⅱ clinical trial (out-group), 3 were effective and 2 were ineffective of the 5 patients with rest pain; at the end of this follow-up period, 4 were evaluated as effectiveness and 1 as ineffectiveness according to CTA, and 5 were all evaluated as effectiveness according to VAS. Of the 13 patients with ulcer, 9 were evaluated as effectiveness and 4 were as ineffectiveness according to CTA at out-group; 10 were evaluated as effectiveness and 3 were as ineffectiveness at the end of this follow-up.Conclusions:pUDK-HGF had relatively good safety in the treatment of rest pain and ulcers caused by critical limb ischemia. No risk of carcinogenesis and proliferative retinal vasculopathy has been found, and the long-term efficacy of pUDK-HGF is good.

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.