Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.

With the development of thyroid pathology in the past decade, thyroid pathological diagnosis has entered the era of molecular pathology. As the most influential academic journal in the field of pathology in China, Chinese Journal of Pathology has published nearly one hundred articles related to thyroid diseases in the past decade. These results have made a great difference to the scientific research and clinicopathological diagnosis of thyroid diseases in China, and have also provided Chinese data for the pathological communication of thyroid diseases internationally. Pathologists should make full use of thyroid cytology and histopathology, combined with molecular testing and digital intelligence technology, to play a core guiding role in the multidisciplinary precise diagnosis and treatment of thyroid diseases.

Chinese head and neck pathology has been comprehensively improved in the past ten year. This paper focuses on the observation and research of sinonasal epithelial tumors, non-epithelial tumors, inflammatory diseases, NK/T cell lymphoma, nasopharyngeal carcinoma, oropharyngeal HPV-associated squamous cell carcinoma, laryngeal squamous cell carcinoma, ear neuroendocrine tumor, adenoid cystic carcinoma, endolymphatic sac tumor, and hyperplastic disease of Waldeyer′s ring lymphoid tissue, etc. The difficult cases were reviewed. Hope to represent the whole picture of the progress of the subject. In the future, we will further strengthen the construction of discipline echelons, deepen the comprehensive and in-depth discussion and research of diseases, and make breakthroughs in the original understanding of diseases.

Chinese head and neck pathology has been comprehensively improved in the past ten year. This paper focuses on the observation and research of sinonasal epithelial tumors, non-epithelial tumors, inflammatory diseases, NK/T cell lymphoma, nasopharyngeal carcinoma, oropharyngeal HPV-associated squamous cell carcinoma, laryngeal squamous cell carcinoma, ear neuroendocrine tumor, adenoid cystic carcinoma, endolymphatic sac tumor, and hyperplastic disease of Waldeyer′s ring lymphoid tissue, etc. The difficult cases were reviewed. Hope to represent the whole picture of the progress of the subject. In the future, we will further strengthen the construction of discipline echelons, deepen the comprehensive and in-depth discussion and research of diseases, and make breakthroughs in the original understanding of diseases.

With the development of thyroid pathology in the past decade, thyroid pathological diagnosis has entered the era of molecular pathology. As the most influential academic journal in the field of pathology in China, Chinese Journal of Pathology has published nearly one hundred articles related to thyroid diseases in the past decade. These results have made a great difference to the scientific research and clinicopathological diagnosis of thyroid diseases in China, and have also provided Chinese data for the pathological communication of thyroid diseases internationally. Pathologists should make full use of thyroid cytology and histopathology, combined with molecular testing and digital intelligence technology, to play a core guiding role in the multidisciplinary precise diagnosis and treatment of thyroid diseases.

Objective To study the medication law of postoperative treatment of colorectal cancer by national TCM doctor Professor Piao Bingkui.Methods Professor Piao Bingkui's electronic medical records and paper medical records of colorectal cancer postoperative patients at Guang'anmen Hospital,China Academy of Chinese Medical Sciences and Beijing Yiqingtang Chinese Medicine Clinic were collected and organized from their outpatients from January 1st,2002 to February 28th,2022.R4.2.1 was used to study the prescriptions,including high-frequency drugs,drug types,properties of Chinese materia medica,yin yang and five elements and dosage of drugs,as well as the law of multi-drug association in postoperative patients with colorectal cancer.Results Totally 642 colorectal postoperative cancer patients were included,involving 2 226 prescriptions,180 kinds of Chinese materia medica,and a total frequency of 39 988 times.The high-frequency drugs were Astragali Radix,fried Aurantii Fructus with wheat bran,Dioscoreae Rhizoma,etc.The main drugs in terms of efficacy were tonics for tonifying deficiency,disinfectants,etc.;the main properties were warm and neutral,the main tastes were sweet,pungent and bitter,and the main meridians were spleen meridians and stomach meridians.Ascending medicines were often used,and the drug were basically non-toxic.The frequency of using yang tonifying medicine was high,and the five elements were commonly used as local medicines;the dosage was mostly 10,15 and 20 g.The complex network analysis and clustering analysis of the association between multiple drugs found that Professor Piao Bingkui's basic prescription for treating colorectal cancer included Astragali Radix,fried Aurantii Fructus with wheat bran,Dioscoreae Rhizoma,salt Alpiniae Oxyphyllae Fructus,Citri Reticulatae Pericarpium,Smilacis Glabrae Rhizoma,Pseudostellariae Radix,and fried Atractylodis Macrocephalae Rhizoma with wheat bran.Conclusion In the treatment of colorectal cancer,Professor Piao Bingkui focuses on reinforcing the healthy qi,nourishing spleen and stomach function,combined with detoxication method and clearing heat,expelling phlegm and dampness,guiding stagnation and dispelling stasis methods,making syndrome differentiation as well as tonifying and benefiting qi,regulating qi movement,so as to realize the"treating middle-energizer as balance"and achieve mild level when treating colorectal cancer.

Immunotherapy drugs are a class of medications that treat diseases by modulating the function of immune system.As frontline therapies in clinical practice,they play a particularly crucial role in alleviating disease symptoms and improving adverse prognoses caused by severe inflammation.In recent years,with the rapid development of internet technology and the continuous innova-tion in the technology industry,various national directives have been issued,urging schools to strengthen online teaching and promote the development of"Internet+education".Online teaching,unaffected by time or geographical constraints,has facilitated resource sharing and stimulated student interest.However,in practice,both singular online or offline teaching models have their drawbacks.This article takes the severe inflammation immunotherapy drugs as an example,integrating the concept of intersubjectivity in teaching to explore a"two-line"teaching mode in immunotherapy drugs.This study views students as the main body of learning,emphasizes the importance of individual learning,and solves the drawbacks of"one-line"teaching mode.Exploration and application of intersubjective"two-line"teaching mode has guiding significance for educational reform in the internet era.

Objective: To investigate whether the artermisinin has beneficial efficacy to improve the learning and memory in aged mice, as well as the possible mechanisms regarding the inflammatory cytokines and monoamlne neurotransmitters. Methods: 30 aged mice(22 month old) were randomly divided into the aged mouse model control group(n=10), the artemisinin low dose group(artemisinin 0.1% in feed, n=10)and the artemisinin high dose group(artemisinin 0.3% in feed, n=10). Another 10 mice(2 month old) served as young mouse model control group. The artemisinin low dose group and the artemisinin high dose group fed artemisinin feed for 10 weeks. The aged mouse model control group and the young mouse model control group were fed standard feed.Morris water maze test was performed to assess learning and memory capacities for evaluation of the cognitive degree. Serum TNF-α and IL-6 were also detected by ELISA and dopamine, norepinephrine, serotonin in the brain were analyzed by HPLC. Results: (1) Morris water maze test showed, the retention time of the aged mouse model control group was significantly longer than that of the young mouse model control group (P<0.05). The retention time of the artemisinin low dose group and the artemisinin high dose group was significantly shorter than that of the aged mouse model control group (P<0.05). In the ninth days of the reverse recessive platform experiment, the retention time of the artemisinin low dose group ((50.1±19.9) s) and the artemisinin high dose group ((43.2±17.6) s) was significantly shorter than that of the aged mouse model control group ((66.1±29.1)s, P<0.05). (2) Serum inflammatory factors test showed, the level of IL-6 and TNF-αin the artemisinin low dose group (IL-6 : (28.4±4.3) pg/ml, TNF-α: (51.8±8.2) pg/ml) and the artemisinin high dose group(IL-6 : (17.6±2.3) pg/ml, TNF-α: (38.6±12.5) pg/ml) were significantly lower than those in aged mouse model control group(IL-6 : (36.12±7.98)pg/ml), TNF-α : (67.32±10.27) pg/ml, P<0.05). (3) Neurotransmitter content test in the brain showed, the content of DA((19.96±3.89) mmol/ml) and 5-HT((5.73±0.93)mmol/ml) in low dose artemisinin group was higher than that in aged mouth model control group. The content of DA((26.13±5.66) mmol/ml), NE((16.31±2.69) mmol/ml) and 5-HT((8.03±1.93) mmol/ml) in high dose artemisinin group was higher than that in aged mouth model group(DA(13.96±3.89) mmol/ml, NE(8.73±2.16) mmol/ml, 5-HT (3.82±1.09)mmol/ml, all P<0.05). Conclusion Artemisinin can improve the ability of learning and memory in aged mice. The mechanism may be related to inhibiting the inflammation and promoting the level of neurotransmitters in the brain of aged mice.

Objective: To study the significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma (BSCC) of the larynx. Methods: Twenty-nine cases of laryngeal BSCC from Beijing Tongren Hospital from January 2005 to December 2011 were reviewed. HPV typing by polymerase chain reaction-reverse dot blot (PCR-RDB) and p53, Ki-67, p16, p21 and cyclin D1 expression by immunohistochemistry were performed. The relationship between these indicators, various pathologic parameters (TNM, tumor size, tumor site and lymph node metastasis) and HPV status was analyzed. Results: There were 27 male and 2 female patients. The median age was 62 years. Lymph node metastasis and supraglottic tumor location were slightly higher than that of "usual" SCC, but not statistically significant (P>0.05). HPV DNA was detected in 27.6% (8/29) of the laryngeal BSCC, and all were HPV16. The expression of HPV was not related to age, alcohol consumption, tumor stage and tumor size. p53 was expressed in 31.0%(9/29) of laryngeal BSCC, and these cases were more likely supraglottic and had lymph node metastases (P<0.05). p16 staining was seen in 24.1% (7/29) of laryngeal BSCC, and these cases showed slightly higher rate of lymph node metastasis compared to p16 negative cases. The expression rates of p21 and cyclinD1 were 27.6% (8/29) and 69.0%(20/29), respectively, which were not related to age, tumor size, stage, lymph node metastasis, smoking and drinking. There were only 3 p16+ /HPV+ cases, which showed higher p21 and Ki-67 index compared to the HPV negative group (P<0.05). Conclusion Some laryngeal BSCC expresses HPV DNA, possibly indicating an association with HPV; but p16 expression is not a reliable indicator for HPV infection.

Objective To explore the CT and MRI imaging and clinicopathological features of extranodal NK/T cell lymphoma (NK/TCL). Methods Sixty-six patients with NK/TCL diagnosed from 2002 June to 2016 April in Beijing Tongren Hospital with intact CT and/or MRI imaging results were enrolled in this study. All the patients had tailed clinical information and follow-up. The imaging and clinicopathological features were analyzed retrospectively and their prognostic value on overall survival was analyzed. Results There were 49 males and 17 females with median age of 42 years. The median follow-up time was 18 months. The cases showed surrounding invasions including 10 cases (15.2 %) in soft palate, 5 cases (7.6 %) in hard palate, 2 cases(3.0 %) in tonsil, 8 cases(12.1 %) in upper lip, 13 cases(19.7 %) in maxillofacial soft tissue, 9 cases (13.6 %) in eyelid, 10 cases (15.2 %) in orbital, 3 cases (4.5 %) in maxilla, 6 cases (9.1 %) in pterygopalatine fossa,6 cases(9.1 %)in infratemporal fossa,3 cases(4.5 %)in skull base, 3 cases(4.5 %) in eyeball and 2 cases (3.0 %) in brain tissue. Kaplan-Meier survival analysis found that the 2-year overall survival rates of the patients with the involvement of hard palate, upper lip, maxillofacial soft tissue, eyelid, orbital, maxillary, eyeball and brain organizer were lower than those of the patients without the involvement of these sites(χ2values were 4.470,4.041,4.456,13.933,8.986,4.000,44.121,6.527,16.822,respectively, all P< 0.05). Further multivariate Cox regression analysis showed that maxilla and brain involvement were independent adverse factors (RR=34.717, 95 % CI 3.404-354.035, P=0.003; RR=37.545, 95 % CI 3.188-442.187, P= 0.004). Conclusions MRI and CT examinations are of great value in diagnosis and prognostic assessment of NK/TCL. Clinicians can make correct and timely diagnosis by comprehensive clinical, radiological and pathological features and can make a detailed clinical assessment to give patients appropriate treatment,thus improving the outcome of the NK/TCL patients.