Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Surgical technique of lung transplantation exerts significant impact on clinical prognosis of the recipients.Choosing an appropriate surgical incision determines the exposure of intraoperative visual field,which is the first step of surgical success and directly affects subsequent surgical procedures.Lung transplantation incision is usually considered as primary closure.Nevertheless,for patients with high-risk factors such as oversized lung allografts and primary graft failure after lung transplantation,primary closure cannot be achieved.Hence,delayed chest closure is an effective strategy.The selection of incisions and the adoption of delayed chest closure of lung transplantation exert profound impact upon perioperative prognosis,long-term quality of life and surgical complications of the recipients.Therefore,the development and research status of Clamshell incision,anterolateral incision,posterolateral incision and median sternal incision in lung transplantation were reviewed,highlighting the effect of incision patterns on clinical prognosis of lung transplantation and providing reference for the selection of incisions in clinical lung transplantation.

Objective To investigate the clinical value of peripheral eosinophil count(PEC)in predicting the outcome of diabetic nephropathy(DN).Methods A retrospective cohort trial was conducted on 220 DN patients identified by renal biopsy in Department of Nephrology of Second Affiliated Hospital from Army Medical University from March 2021 to March 2023.Clinical data,results of routine blood test and renal function were collected.X-tile bioinformatics software version 3.6.1 was used to determine the optimal cut-off value of PEC for predicting survival.Cox proportional hazards model and Kaplan-Meier survival analysis were applied to analyze the prognosis.Results The level of PEC in DN patients was positively correlated with the levels of serum creatinine(Scr)(r=0.245),blood urea nitrogen(BUN)(r=0.237)and blood uric acid(UA)(r=0.252),and negatively with estimated glomerular filtration rate(eGFR)(r=-0.236).According to the optimal PEC cut-off value,DN patients were divided into high-level group(＞0.29×109/L,n=41)and low-level group(≤0.29 × 109/L,n=179).The levels of Scr(P＜0.001),BUN(P=0.001)and UA(P=0.005)were significantly higher,while the eGFR(P＜0.001)was obviously lower in the high-level group than the low-level group.Multivariate Cox regression analysis showed that the high level of PEC was associated with poor prognosis of DN(HR=2.20,95％CI:1.05～4.60,P=0.036).Kaplan-Meier survival analysis demonstrated that the incidence of end-stage renal disease(ESRD)was notably higher in the high-level group than the low-level group(P=0.024).Conclusion PEC level of DN patients is closely associated with the progression and prognosis of DN,and the count is a potential biomarker for predicting the prognosis of DN.

To investigate the clinical significance of platelet-neutrophil ratio in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis(AAV),a total of 128 patients were recruited and retrospectively analyzed in our department from March 2015 to July 2023.Spearman correlation analysis indicated that there was negative correlation between the level of PNR and Birmingham vasculitis activity score(BVAS)in AAV patients(r=-0.268,P=0.002).According to the PNR optimal cutoff value(26.4)determinated by X-tile bioinformatics software version 3.6.1 for predicting the survival rate,AAV patients were divided into high level PNR(HPNR)group(≥26.4)(n=105)and low level PNR(LPNR)group(<26.4)(n=23).Kaplan-Meier survival analysis showed that the survival rate of HPNR group was significantly higher than that of LPNR group(P<0.001).The level of PNR was correlated with poor prognosis of kidney(OR=2.54,95%CI:1.1-5.88,P=0.029).In conclusion,the level of PNR is closely related to disease activity and prognosis of AAV,and it might be a potential biomarker for predicting the disease activity and predicting the prognosis.

Objective To assess transcriptomic differences between carbon tetrachloride(CCl4)-induced and diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate(DDC)diet-induced mouse models of liver fibrosis to provide a framework for future research using mouse liver fibrosis models.Methods Mouse models of liver fibrosis were induced by a 10％ CCl4(2 mL/kg)injection or a 0.1％DDC diet.After 4 weeks of induction,serum levels of ALT,AST,and TBil were measured.HE and Sirius red staining were used to observe hepatic inflammation and collagen deposition.Jamall's method was used to evaluate hydroxyproline(Hyp)content in liver tissues.Hepatic tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β were measured by ELISA.Total RNA was extracted from murine liver tissues for RNA-sequencing(RNA-seq).Differentially expressed genes of the two models were analyzed by R software and then GO and KEGG enrichment was performed.Then,genes with significant differences were verified.Results Compared with normal mice,serum levels of ALT,AST,and TBil and hepatic expression of TNF-α,IL-6,and IL-1β were significantly increased in mice that received CCl4 and DDC,while the Alb serum level was decreased.Pathological staining showed that the structures of liver tissues were destroyed and a large number of hepatocytes around the central vein were hyalinized and necrotic in CCl4-treated mice.In DDC diet-treated mice,a large amount of porphyrins had been deposited in the liver and a large number of inflammatory cells had infiltrated into the portal area and bile duct.Different degrees of collagen deposition were observed in the liver tissues of the two model mice.Different genes(DEGs)of CCl4-and DDC diet-treated mice were screened using a filter(|logFC|＞2-fold and P＜0.05).As a result,1820 and 2373 DEGs in CCl4-and DDC diet-treated mice were analyzed,including 1302 and 1978 upregulated genes,and 518 and 395 downregulated genes,respectively.GO annotation showed that the two models had important functions in molecular function,biological process,and cell component.KEGG analysis showed that 22 and 29 signaling pathways were activated in CCl4-and DDC diet-induced models,respectively.Among them,16 signaling pathways,such as extracellular matrix receptor interaction,cell cycle,protein digestion and absorption,focal adhesion,and PI3K-Akt,were significantly enriched in the two models(P＜0.05).Cluster analysis showed that Mup11,Mup15,Mup17,and Mup1 were significantly down-regulated in both models,which were identified by RT-qPCR(P＜0.05).Conclusions This study conducted a comparative analysis of the RNA-Seq transcriptomic features of liver fibrosis models induced by exposure to CCl4 and a DDC diet.It examined the gene expression patterns and the pathways influenced by gene expression.The findings serve as a valuable resource for selecting appropriate animal models for future research on the pathogenesis and treatment of liver fibrosis.

Objective:To prospectively observe the changes of tumor-related symptoms in patients with nasopharyngeal carcinoma following the administration of nimotuzumab one week before radiotherapy.Methods:Non-metastatic nasopharyngeal carcinoma patients with positive epidermal growth factor receptor (EGFR) expression and symptoms caused by the primary lesion or metastatic cervical lymph nodes admitted to Cancer Hospital of Chinese Academy of Medical Sciences were prospectively recruited. Investigators recorded tumor-related symptoms in recruited patients one day before the first administration of nimotuzumab (D0) and conducted follow-up visits from day 2 to day 7 after the first administration (D2-D7) to document symptom changes. All recruited patients were asked to assess tumor-related symptoms on D0 and D7 by visual analogue scale (VAS) scores. VAS scores were analyzed by paired t-test. Results:From June 2020 to April 2023, a total of 21 patients met the inclusion criteria. The median age was 49 years (range: 27-69 years), with a male-to-female ratio of 1.3:1. Among the patients, 17 patients (81%) received concurrent nimotuzumab for 8 cycles, 7 cycles for 3 cases (14%), and 6 cycles for 1 case (5%), respectively. All patients completed symptom assessments as required. The overall response rate of symptoms after the first administration of nimotuzumab was 62%, with response rates of 4/6、5/8、4/10、4/10、4/11、3/11 for tinnitus, headache, aural fullness, secondary pain caused by neck mass, nasal bleeding, and nasal obstruction, respectively. The VAS scores for overall symptoms were significantly decreased after the administration of nimotuzumab one week before radiotherapy ( P<0.001), with the most significant decrease in VAS scores for tinnitus, aural fullness, and headache. Conclusion:The administration of nimotuzumab one week before radiotherapy significantly alleviates tumor-related symptoms in patients with nasopharyngeal carcinoma, particularly in alleviating tinnitus, aural fullness, and headache.

Objective:This study aimed to evaluate the clinical features and treatment outcomes of the value of response-adapted treatment following radiotherapy and induction chemotherapy follwing subsequent comprehensive therapy in patients with resectable locally advanced hypopharyngeal carcinoma. Methods:This cohort study was conducted from September 2010 to September 2020 in our hospital, 231 patients pathologically confirmed stage Ⅲ and ⅣB resectable locally advanced hypopharyngeal carcinoma included. For the IC-directed ART strategy, IC is used to select good candidates to receive radical RT or CCRT, and others undergo surgery. He response-adapted strategy was determined based on the primary tumor response, which was evaluated at a dose of 50 Gy. If the response reached complete response or partial response（more than 80% tumor regression）, patients received radical RT or CCRT; otherwise, they received surgery, if possible, at 4 to 6 weeks after RT. The end points of the study were OS（overall survival）, progression free survival（PFS）, locoregional recurrence-free survival（LRRFS） and LDFS. Results:In IC-directed group, 75.0%（57/76） patients reached PR after 2 cycles of induction chemotherapy. While in RT-directed group, 70.3%（109/155） patients reached large PR at dose of 50 Gy. The median interquartile range follow-up period of the whole cohort was 63.8 months. The 5-year OS, PFS, LRRFS and SFL of the whole cohort were 47.9%、39.6%、44.3% and 36.2%, respectively. In evaluations based on the different treatment strategies, the 5-year OS and SFL were 51.3% versus 37.0%（HR 0.67; 95%CI 0.43-1.05; P=0.07） and 27.8% versus 39.8%（HR 0.68; 95%CI 0.46-0.99; P=0.04） between IC-directed and RT-directed groups. In additional, surgery complications did not significantly differ between these two groups. Conclusion:In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, and higher laryngeal preservation compared with IC-directed strategies. This approach could provide a feasible laryngeal preservation strategy in patients with resectable locally advanced hypopharyngeal carcinoma.
Male ; Humans ; Cohort Studies ; Chemoradiotherapy ; Carcinoma ; Hypopharyngeal Neoplasms/therapy* ; Induction Chemotherapy

Objective:To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. Methods:A retrospective analysis was performed on 468 pathologically confirmed oropharyngeal cancer as the primary tumor patients with p16 status, excluded distant metastasis, and admitted to the Chinese Academy of Medical Sciences from January 2010 to December 2020. The clinical features and prognosis of the secondary primary tumor were analyzed. Results:Among 468 patients with oropharyngeal cancer treated at initial diagnosed, 222 cases were P16-negative. With a median follow-up time of 64.3 months, 66 cases developed second primary cancer, with an incidence of 29.3%, among which 63.6%（42/66） were synchronous and 36.4%（24/66） were heterochronous, esophagus was the most commonly involved site. The 5-year OS of p16-negative oropharyngeal carcinoma with synchronous second primary cancer, without second primary cancer and with heterogeneous second primary cancer were 26.3% and 57.3% and 73.2%（P=0.001）; The second primary cancer accounted for 11.2%（12/107） of the deaths in the whole group, among them, the heterochronous second primary accounted for 75.0%（9/12）. There were 246 patients with p16 positive, with a median follow-up time of 52.4 months, 20 patients developed second primary cancer（8.1%）. Among them, 65.0%（13/20） were synchronous and 35.0%（7/20） were heterochronous. Esophagus was the most commonly involved site. The 4-year OS of p16-positive with synchronous, heterochronous and non-second primary cancer group were 51.9%, 80.7% and 83.3%. Secondary primary cancer accounted for 3.8%（2/52） of all deaths in p16 positvie group. Conclusion:The incidence of second primary cancer of p16 positive and negative oropharyngeal carcinoma were different. The esophagus was the most commonly involved site regardless of p16 status. Regardless of p16 status, the survival of patients with synchronous second primary cancer was worse than those without second primary cancer. For p16-negative oropharyngeal carcinoma, the prognosis was better in patients with heterogeneous second primary cancer, the second primary cancer is one of the main causes of death.
Humans ; Carcinoma/diagnosis* ; Oropharyngeal Neoplasms/diagnosis* ; Retrospective Studies ; Neoplasms, Second Primary/diagnosis*

Objective:To evaluate the efficacy and safety of nimotuzumab in the treatment of advanced head and neck tumors by using meta-analysis.Methods:Randomized controlled trials (RCT) of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) treated with nimotuzumab were searched from databases (Cochrane Library, PubMed, Embase, Wanfang Data and CNKI) for meta-analysis. The efficacy evaluation indexes included overall survival, progression-free survival, disease-free survival, objective response rate, and complete response rate. Adverse reactions were analyzed for safety evaluation. The heterogeneity results were evaluated by Chi-square test, the degree of heterogeneity was evaluated by I2, and the literature was statistically analyzed by random effects model. Results:A total of 11 RCT were included, consisting of 1 202 patients (602 in the intervention group and 600 in the control group). Compared with the control group, the overall survival was significantly prolonged, death risk was decreased by 22% ( HR=0.78, 95% CI=0.63-0.95, P=0.014), the progression-free survival was prolonged and the risk of disease progression was declined by 35% ( HR=0.65, 95% CI=0.53-0.81, P<0.01), and the disease-free survival was prolonged and the risk of recurrence was decreased by 29% ( HR=0.71, 95% CI=0.55-0.91, P<0.01), the objective response rate ( RR=1.37, 95% CI=1.20-1.55, P<0.01) and complete response rate ( RR=1.30, 95% CI=1.15-1.46, P<0.01) were significantly improved in the intervention group. In addition, adding nimotuzumab did not increase the incidence of adverse reaction ( RR=0.98, 95% CI=0.93-1.03, P=0.41). Conclusion:Nimotuzumab can significantly prolong long-term survival and improve short-term efficacy with high safety in LA-HNSCC patients.

Objective:To evaluate the incidence, clinical characteristics and prognosis of second primary malignancies (SPMs) among patients with hypopharyngeal carcinoma (HPC) in real-world analysis.Methods:A total of 594 HPC patients admitted to Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 2010 to 2018 were retrospectively analyzed.The incidence and clinical characteristics of HPC patients complicated with SPMs were analyzed. Clinical efficacy was compared among different groups.Results:With a median follow-up time of 66.9 months, SPMs were present in 36.4% (216/594) of HPC patients: 22.2% (132/594) were synchronous and 14.1% (84/594) were metachronous. The upper aerodigestive tract was the most common involved region. Compared with patients without SPMs, patients with synchronous and metachronous carcinoma in situ had similar 5-year overall survival (OS) of 42.2% vs. 44.5% ( P=0.958) and 62.2% vs. 44.5% ( P=0.240), respectively. Patients with synchronous invasive SPMs had a worse 5-year OS of 27.2% vs. 44.5% in their counterparts without SPMs ( P=0.001). Patients with metachronous invasive SPMs had similar 5-year OS of 50.2% vs. 44.5% in their counterparts without SPMs ( P=0.587). SPMs accounted for 42.5% of total death in metachronous invasive SPMs group. Conclusions:Patients with HPC have a high probability of developing SPMs. Moreover, the incidence of complicated with esophageal/gastric carcinoma in situ or metachronous SPMs exerts no effect on prognosis, while the occurrence of synchronous SPMs significantly affectes the prognosis of patients. However, the incidence of SPMs is still one of the main death causes in metachronous invasive SPMs group.