The αPD-L1 antibody-based immune checkpoint blockade therapy is still limited by the poor clinical response rate as it is mainly utilized to block surface PD-L1 on tumor cells while ignoring abundant PD-L1 exosomes secreted in the environment, causing tumor immune evasion. Here, we proposed an exosome biogenesis inhibition strategy to suppress tumor exosomes secretion from the source, reducing the inhibitory effect on T cells and enhancing chemo-immunotherapy efficacy. We developed sulfafurazole homodimers (SAS) with disulfide linkages, effectively releasing the drug in response to glutathione (GSH) and inhibiting 4T1 tumor-derived exosomes secretion. Subsequently, gemcitabine (Gem) was encapsulated to induce immunogenic cell death (ICD). Consequently, Gem@SAS inhibited the secretion of tumor exosomes by more than 70%, increased proliferation and granzyme B secretion ability of T cells by more than 2 times, and showed superior efficacy in breast cancer treatment as well as lung metastasis of breast cancer.

Objective To establish an optimal limiting dose for dose limiting rings placed in the anterior and posterior regions of the neck for reducing head and neck lymphedema under intensity-modulated radiation therapy(IMRT)for early nasopharyngeal carcinoma(NPC)from a dosimetric perspective.Method Fifteen newly diagnosed early-stage nasopharyngeal carcinoma patients who underwent CT localization for radiotherapy at the Cancer Hospital of Guangzhou Medical University from January to September 2022 were included in the study.Each case was designed with five sets of radiotherapy plans.Plan A consisted of conventional unlimited-field plans,while Plans B-E consisted of limited-field plans with dose constraints set at 20,18,16,and 14 Gy,respectively,with the remaining parameters consistent with Plan A.The impact on target coverage and organ-at-risk constraints was evaluated through variance analysis and pairwise multiple comparisons using a randomized block design to determine the optimal dose limits.Results The gradient of 16Gy was determined as the optimal dose limiting cutoff point for achieving the balance between target coverage and organ limiting dose.Compared with the conventional plan,The plans with the placement of a cervical anterior and posterior dose limiting ring(16Gy)did not change the target dose coverage(P>0.05),but only yielded a slight change in the homogeneity index(P<0.05).It did not cause any changes of the dosage in the inner ear,mandible,and brainstem(all P>0.05),but lead to statisti-cally significant reductions in the oral cavity,throat,and thyroid(all P<0.05).It caused a slight increase of the dose in the parotid gland and spinal cord(both P<0.05),but the increased dose was anyhow within the tolerance range.Conclusion The dosimetric investigation determines an optimal dose limit cutoff point for the cervical ante-rior and posterior dose limiting rings.It is expected to provide a design method for IMRT plans to reduce head and neck lymphedema after radiotherapy for early NPC.

Objective:To establish the ultra-high performance liquid chromatography (UPLC) fingerprint and high performance liquid chromatography (HPLC) content determination method of Curcumae Radix standard decoction; To predict the quality markers of Curcumae Radix standard decoction combined with network pharmacology.Methods:UPLC method was used to establish the fingerprint of Curcumae Radix standard decoction, and the common peaks were determined. Combined with chemical pattern recognition techniques such as similarity analysis and clustering analysis, Curcumae Radix standard decoction from different producing areas was studied, and curcumol was used as an index to determine the content of 24 batches of Curcumae Radix standard decoction. At the same time, network pharmacology was used to predict potential of curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one.Results:A total of 24 batches of Curcumae Radix standard decoction from different habitats were compared and analyzed, and 10 common peaks were calibrated. The similarity of 24 batches of samples ranged from 0.982 to 0.999. Clustering analysis and principal component analysis divided them into three categories. Heat map analysis showed that peak 8 (curcumol) and peak 9 ((1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one) were the main components. The content of curcumol in 24 batches of Curcumae Radix standard decoction was 0.69-1.87 mg/g; curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β- (3-oxobutyl) bicyclo [4.1.0] heptan-3-one may regulate the neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation by regulating neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation. It was preliminarily predicted that curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one were potential quality markers of Curcumae Radix.Conclusion:Curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one are potential quality markers of Curcumae Radix standard decoction, and the established fingerprint can be used for the quality control of Curcumae Radix standard decoction.

Celastrol is extracted from the traditional Chinese medicine Tripterygium wilfordii Hook.f..It is a kind of traditional Chinese medicine monomer with extensive pharmacological activity and has anti-tumor,anti-inflammation,anti-oxidation and neuroprotective effects.Studies have found that celastrol is not only closely related to obesity,tumor and cardiovascular diseases,but also plays a neuroprotective role in the cerebrovascular system by regulating various signaling pathways.At present,effective drugs for stroke are still limited,but with the deepening of the research on celastrol,its therapeutic potential in stroke has received more and more attention,especially in ischemic and hemorrhagic stroke,which has shown good therapeutic effects.Therefore,this is the first time to systematically summarize the therapeutic effects of celastrol on stroke and the underlying mechanisms involved,in order to provide further directions and references for the neuroprotective effects of celastrol.

[Absract] Objective This paper was designed to reveal the new mechanism on ASI Ⅱ triggered CD4+T cells activation via regulating CD45 molecular and provide a basis for the theoretical foundation of antitumor immunotherapy of Astragalus.Methods The CD4+T cells were randomly divided into negative group,stimulated control group,ASI Ⅱ group,CD45 inhibitor group,and the combination of ASI Ⅱ and CD45 inhibitor group.Besides negative group,the cells from other groups were activated by anti-CD3/CD28 antibody.ASI Ⅱ group was treated with 10 nmol/L ASI Ⅱ,CD45 inhibitor group was treated with 0.8 μmol/L CD45 inhibitor,and the combination group were treated with 10 nmol/L ASI Ⅱ and 0.8 iμmol/L CD45 inhibitor.After 36h culture,the proliferation of CD4+T cells was detected by Ki-67 intracellular staining assay.Cytokine production of Th1 and Th2 were examined ELISA method.The proportion of surface marker (CD44 and CD25)and Th1 intracellular cytokines (IFN-γ) were detected by flow cytometry.Results Compared with stimulated group,Astragaloside Ⅱ group in CD4+Ki67+T positive proportion (5.37％ ± 0.92％ vs.1.19％ ± 0.23％),in CD4+CD25+ positive proportion (50.23％ ± 4.65 ％ vs.15.89％ ± 1.13％),in CD4+CD44+ positive proportion (33.16％ ± 6.08％ vs.15.36％ 4 1.45％),in CD4+IFN-γ+ positive proportion (1.42％ ± 0.44 ％ vs.0.38％ ± 0.06％) were significntly increased.And the secretion of IFN-γ,IL-4 and IL-2 in ASI Ⅱ group were higher than stimulated group.The anti-mouse CD45 Ab treatment markedly blocked the proliferation and Th1 cytokines production which induced by ASI Ⅱ.Furthermore,the anti-mouse CD45 Ab treatment significantly decreased the expression of surface marker (CD44 and CD25).Conclusions Activating CD45 protein tyrosine phosphatase may be involved in ASI Ⅱ triggered CD4+T cells activation.This study will provide a basis for antitumor immunotherapy of Astragalus.

Objective To understand nurses'perceived transformational leadership behaviors of head nurses, and to survey the status quo of transformational leadership behaviors of head nurses and nurses' performance for goal attainment, to explore the relationship between transformational leadership behaviors of head nurses and nurses'performance for goal attainment. Methods A total of 450 clinical nurses from six 3A hospitals were chosen as the research objects, the nurse general information questionnaire, the transformational leadership questionnaire and nurse's performance for goal attainment scale were used to analyze the status. SPSS17.0 was conducted to sort and analyze data. Results (1)The total score of nurses' perceived transformational leadership behaviors of head nurses was 114.74 ± 18.66,and moral modeling score was significantly higher in 4 dimensions. The total score of nurses'performance for goal attainment was 172.87 ± 25.96, autonomous decision-making score was significantly higher in 7 dimensions.(2)There was a positive correlation relationship between transformational leadership behaviors and each dimension of nurses'performance for goal attainment (r=0.393, P<0.01). Conclusions The results show that the nurses'performance for goal attainment can be positive predict by transformational leadership behaviors. Nursing managers should fully play the positive role of transformational leadership behavior so as to improve nurses'performance for goal attainment.

Objective To investigate the regularity and predictors of weight loss during concurrent chemo-radiotherapy for nasopharyngeal carcinoma patients. Methods A retrospective study was carried out on 82 patients with nasopharyngeal carcinoma ,with average age of 45 years ,who received concurrent chemoradiotherapy at the Affiliated Cancer Hospital of Guangzhou Medical University. Paired t-test was used to analyze the weight loss pattern during chemoradiotherapy. The Spearman′s rank correlation analysis was used to investigate the correlation between high weight loss(HWL)and the clinical factors. Results The paired t-test showed that the weight of the patients decreased continuously every week during chemoradiotherapy(P < 0.05),and the value dropped most significantly during the 4th week. Among these 82 patients,32 were determined as HWL(weight loss > 10%). Spearman′s rank correlation analysis showed that HWL was associated with older age,female,higher T and TNM stage,3D-CRT technology,the higher dose of radiotherapy in nasopharynx and in neck lymph node,and decreases of leukopenia and hemoglobin over degree Ⅱ(P<0.05). Conlousions Weight may decrease continuously every week during chemoradiotherapy for nasopharyngeal carcinoma patients. Age,gender,T stage,TNM stage,radio-therapy dose,and leukopenia and hemoglobin decreases may be predictors for weight loss degree during concurrent chemoradiotherapy for nasopharyngeal carcinoma patients.

Objective To identify the role of miR-124 in regulating the radiosensitivity and the epithelial-mesenchymal transition (EMT) of nasopharyngeal carcinoma (NPC). Methods Transient transfection of cells with miR-124 mimic or inhibitor was performed and wound-healing assay was used to investigate the role of miR-124 in the EMT of NPC. The apoptosis affected by miR-124 was also measured after irradiation , followed by investigating the cell proliferation by EdU assay. Finally , proteins of Akt and ERK associated with EMT and radiosensitivity, were measured by western blot. Results The migration index from NPC cell line indicated that miR-124 repressed the EMT. The results from caspase-3 activity assay showed that caspase-3 activity after irradiation significantly increased in miR-124 mimic group compared with the control group (P < 0.01). It was also confirmed that irradiation led to a higher percentage of apoptosis in miR-124 group compared with the control group in NPC cells. Cell proliferation after irradiation was significantly decreased in MiR-124 group as compared with control group . MiR-124 inhibited the protein expression of p-Akt . Conclusion MiR-124 may repress the EMT and decrease radio-resistance of NPC via p-Akt signaling pathway , which may provide a new insight into radio-resistance in NPC.

Objective To investigate the present status of early diagnosis and misdiagnosis of nasopharyngeal carcinoma (NPC). Methods A total of 50 patients diagnosed as NPC were recruited at the department of nasopharyngeal carcinoma in our hospital. The time from that patients felt discomfort to be diagnosed of NPC was determined bydifferent symptoms and signs. Furthermore , the status of misdiagnosis were also investigated. The spearmans rank correlation was used to analyze the correlation between the cancer stage and the time of confirmeddiagnosis , and the relationship between the rate of misdiagnosed and the rank of the hospital they visited. The χ2 test was then used to analyze the cancer stage with the time when they were diagnosed. Results Results indicated that the time when patients were diagnosed significantly correlated with pTNM stage (P < 0.05). Patients diagnosed in one month were most at stage Ⅱ, diagnosed in six months were stage III, and diagnosed after twelve months were stage Ⅳ(P < 0.05). Furthermore, we found that the rate of misdiagnosis of NPC was 12%. Moreover,the misdiagnosed rate was associated with the rank of the hospital patients visited. Discussion In conclusion , the present status of the early diagnosis of NPC is not optimistic. Most of the patients with NPC were misdiagnosed in basic medical institutions , especially in town or village health center. Thus, it is important to popularize the health knowledge about the secondary prevention of NPC and train the doctor in basic medical institutions.

Objective The radiotherapy resistance is one of important causes for nasopharyngeal carcinoma(NPC) treatment failure.Junctional adhesion molecule A(JAMA)is closely correlated with the tumor poor prognosis.Thus this experiment is to in vestigate the relationship between JAMA expression and the radiosensitivity of NPC.Methods To overexpress or interfere the JAMA expression in CNE2 and HONE1 cell lines.Then different doses of X-ray were adopted to conduct irradiation.The cell clone formation capacity and cellular apoptosis change were detected after 24 h.The role of JAMA in the NPC radiotherapy was understand.The related signal pathway protein in cell lines with different JAMA expression was detected by Western blot.Results The cell lines with low JAMA expression were more sensitive to radiotherapy:After low JAMA expression,the D0 value in the CNE2 cell line was decreased from 3.26 ±0.78 to 1.92 ± 0.23;the Dq value was decreased from 46.51 ± 4.27 to 32.12 ± 3.19.The radio therapy induced apoptosis was significantly increased in the cell lines with low JAMA expression,after low JAMA expressing,thcellular apoptosis was elevated from 6.9 ％ ± 0.9 ％ to 13.7 ％ ± 1.3 ％;the HONE1 cellular apoptosis was elevated from 6.5 ％ + 1.1 ％ to 12.3 ％ ± 1.7％;JAMA overexpression cell lines were significantly decreased.The preliminary mechanism research results showed that JAMA played the effect via Akt signal pathway.Conclusion This research results verifiy that JAMA expression level is closely correlated with the radiosensitivity of NPC cell line:JAMA can increase the radiotherapy resistance of NPC cell lines,which provides a new feasible research direction for NPC enhancing radiosensitivity.