A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8⁺ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Objective To investigate the risk factors of relapse in patients with ischemic stroke using aspirin for single drug antiplatelet therapy.Methods A retrospective analysis was conducted on 200 patients with mild and medium ischemic stroke after 12 months of single drug treatment with aspirin,and the patients were divided into non-recurrence group and recurrence group according to the recurrence of stroke.Univariate analysis and multivariate logistic regression model were used to explore whether the related indicators were risk factors for recurrence.The ROC curve was used to predict the critical value of risk factors.Results Univariate analysis showed that platelet count,Hcy level and the A allele at rs12041331 site of PEAR1 gene were statistically significant risk factors(P<0.05).Multifactor analysis showed that the independent risk factor for recurrence was homocysteine level[OR = 1.16(1.089-1.240),P<0.001)].The critical value of ROC prediction was 8.35 μmol/L(sensitivity 0.847,specificity 0.532).Conclusions The Hcy level,platelet count and A allele at rs12041331 site of PEAR1 gene are risk factors for recurrence in patients with ischemic stroke treated with aspirin for Single drug antiplatelet therapy.Hcy level is independent risk factor and can be used to predict the risk of recurrence.

Objective:To explore the recurrence pattern and prognosis of cervical cancer after radical chemoradiotherapy.Methods:Clinical and follow-up data of 1 359 patients with stage Ⅰ-ⅣA (International Federation of Gynecology and Obstetrics 2009 staging) who received radical radiotherapy in Zhejiang Cancer Hospital from August 2011 to December 2017 were retrospectively analyzed. The survival and prognostic factors of 249 patients with recurrence / metastasis with detailed data were analyzed. The primary endpoint was post-recurrence / metastasis survival time. Kaplan-Meier method was used to calculate the survival rate, log-rank test was used for single factor analysis, and Cox model was used for multi-factor analysis.Results:The distant metastasis rate of 249 patients was 77.5%, and the local recurrence rate was 36.9%. According to the location of metastasis and recurrence, 56 cases with recurrence in the field of radiotherapy alone were assigned into group A, 157 cases with recurrence outside the radiation field alone were allocated into group B (56 cases with lymph node recurrence in group B1, 78 cases with blood metastasis in group B2, and 23 cases with lymph node and blood metastasis simultaneously in group B3), and 36 cases with combined recurrence and metastasis in and out of the field of radiotherapy were assigned into group C. The median survival time of patients in groups A, B1, B2, B3 and C was 13, 24, 13, 11 and 9 months, respectively (all P<0.001). According to the interval from initial diagnosis to recurrence / metastasis, 110 cases were classified in ≤1 year group, 74 cases in >1-2 years group, and 65 cases in >2 years group. The median survival time of patients in the three groups was 11, 14, and 22 months, respectively (all P<0.001). According to the management of recurrence / metastasis, 138 cases received palliative treatment, 15 cases received local treatment, 45 cases received systemic treatment, and 51 cases received combined treatment. The median survival time of patients among four groups was 9, 37, 20 and 32 months, respectively (all P<0.001). The results of multi-factor analysis showed that age, recurrence / metastatic site, retreatment methods, time interval between initial treatment and recurrence /metastasis were the independent prognostic factors affecting the survival (all P<0.05). Conclusions:Distant metastasis is the main failure pattern after radical radiotherapy. Patients with metastasis out of irradiated regions, especially those with only lymph node metastasis, have good prognosis. Active retreatment and time interval between initial diagnosis and recurrence / metastasis are important prognostic factors.

Objective:To compare the difference of prognosis in ⅢCr stage cervical cancer patients with different T stage and lymph node status who received radical radiotherapy.Methods:Clinical data of 279 patients with ⅢCr stage cervical cancer treated with radical radiotherapy at Zhejiang Cancer Hospital from September 2013 to December 2016 were retrospectively analyzed. According to the latest American Joint Committee on Cancer (AJCC) TNM stage, all patients were divided into T 2a, T 2b, T 3a and T 3b stage groups, and N 1 and N 2 stage groups based on lymph node status. They were also divided into <1.85 cm and ≥1.85 cm groups according to the maximum short diameter of lymph node. In addition, they were assigned into ≤3 and>3 groups according to the number of lymph node metastasis. The differences of progression-free survival (PFS) and overall survival (OS) between patients with different T stage and lymph node status were compared by Kaplan-Meier test and log-rank test. Multivariate survival analysis was performed by Cox regression analysis. Results:Among 279 patients with ⅢCr stage cervical cancer receiving radical radiotherapy, 6 (2.2%) patients were diagnosed with stage T 2a stage, 109 (39.1%) patients with T 2b stage, 13 (4.7%) patients with T 3a stage, and 151 (54.1%) patients with T 3b stage. And 246 (88.2%) patients were diagnosed with N 1 stage and 33 (11.8%) patients with N 2 stage. According to the maximum short diameter of lymph nodes, there were 229 (82.1%) patients in the<1.85 cm group and 50 (17.9%) in the ≥1.85 cm group. According to the number of lymph node metastasis, there were 269 (96.4%) patients in the ≤3 group and 10 (3.6%) in the>3 group. There was no significant difference in the 5-year PFS ( P=0.136) and OS rates ( P=0.050) among patients with different T stages, and patients with T 3a stage had the worst prognosis (5-year OS rate was 38.5%). The 5-year PFS (48.0% vs. 64.2%, P=0.016) and OS rates (52.0% vs. 73.8%, P=0.001) in the ≥1.85 cm group were significantly lower than those in the<1.85 cm group. There was no significant difference in the 5-year PFS (61.0% vs. 63.6%, P=0.796) and OS rates (67.5% vs. 69.7%, P=0.770) between patients with N 1 and N 2 stages. There was no significant difference in the 5-year PFS (61.0% vs. 70.0%, P=0.653) and OS rates (67.3% vs. 80.0%, P=0.447) between patients in the number of metastatic lymph nodes ≤3 and>3 groups. The prognosis of patients with T 2b stage and the maximum short diameter ≥1.85 cm was the worst (5-year OS rate was 31.3%), while patients with T 2b stage and the maximum short diameter <1.85 cm obtained the best prognosis (5-year OS rate was 76.3%). Multivariate analysis showed that the maximum short diameter and radiation dose of lymph nodes were the independent relevant factors for the OS of ⅢCr stage cervical cancer patients (both P<0.05). Conclusions:Among ⅢCr stage cervical cancer patients receiving radical radiotherapy, clinical efficacy and prognosis significantly differ according to different T stage and lymph node status. Current staging system should be optimized to provide effective diagnostic and therapeutic regimens.

Objective To explore the pain catastrophizing (PC) level of pain in patients with multiple fractures and its influencing factors. Methods A convenience sampling method was used to investigate 156 patients with multiple fractures in the orthopedic trauma department of the First Affiliated Hospital of Nanjing Medical University. The questionnaire included a general information survey, a Digital Pain Rating Scale, PC scale, Positive and Negative Emotion Scale, and Social Rating Scale. Results The average PC score of patients with multiple fractures was (23.22±12.05), with 27 patients (17.20%) reaching the PC level. The average score of the Digital Pain Rating Scale was (6.30±1.49), the score of the Positive Emotion Scale was (27.92±6.06), the score of the Negative Emotion Scale was (23.18±7.00), and the total score of the Social Rating Scale was (27.90±4.61). The results of multiple linear regression analysis showed that pain score, negative emotion level, and social support level had predictive effects in PC among patients with multiple fractures. Conclusion The incidence of PC among patients with multiple fractures is at a moderate to high level. Patients with high pain scores, high negative emotion scores, and low social support are more likely to develop PC.

Objective:To compare the clinical efficacy and toxicity of intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in radical radiotherapy for cervical cancer.Methods:Clinical data of 1002 patients with cervical cancer treated with radical radiotherapy at Zhejiang Cancer Hospital from September 2013 to December 2016 were retrospectively analyzed. All patients were divided into the IMRT group and 3D-CRT group according to the technology of external beam radiation therapy (EBRT). After 1∶1 propensity score matching (PSM), clinical prognosis of patients receiving IMRT or 3D-CRT was compared. Continuous data were expressed as Mean ± SD or median . Categorical data were described by case number (percentage). Quantitative data were compared by t-test. Qualitative data were compared by chi-square test or Fisher's exact test. Survival rates in two groups were calculated by Kaplan-Meier method and log-rank test. Results:The percentage of patients who received pelvic and para-aortic radiotherapy in the IMRT group was significantly higher than that in the 3D-CRT group (14.9% vs. 1.2%, P<0.001). The percentage of patients whose positive lymph nodes dose reached 55 Gy or more in the IMRT group was significantly higher than that in the 3D-CRT group (26.6% vs. 15.5%, P=0.002). In the IMRT group, the 5-year disease-free survival (DFS) rate (74.6% vs. 68.9%, P=0.084) and overall survival (OS) rate (79.4% vs. 74.9%, P=0.270) were slightly higher than those in the 3D-CRT group, but there were no significant differences between two groups. In the IMRT group, the local recurrence (3.0% vs. 6.9%, P=0.020) and distant lymph node metastasis rates (4.2% vs. 9.0%, P=0.013) were significantly lower compared with those in the 3D-CRT group. In terms of acute radiotherapy toxicities, grade 3-4 leukopenia (46.3% vs. 37.9%, P=0.028) and anemia (18.8% vs. 14.0%, P<0.001) occurred significantly more frequently in the IMRT group than in the 3D-CRT group. Conclusions:Both IMRT and 3D-CRT could achieve good therapeutic outcomes in radical radiotherapy of cervical cancer. IMRT can boost the radiation dose of metastatic lymph nodes and has significant advantages in reducing local recurrence and distant lymph node metastasis.

Integrins are transmembrane receptors that have been implicated in the biology of various human physiological and pathological processes. These molecules facilitate cell-extracellular matrix and cell-cell interactions, and they have been implicated in fibrosis, inflammation, thrombosis, and tumor metastasis. The role of integrins in tumor progression makes them promising targets for cancer treatment, and certain integrin antagonists, such as antibodies and synthetic peptides, have been effectively utilized in the clinic for cancer therapy. Here, we discuss the evidence and knowledge on the contribution of integrins to cancer biology. Furthermore, we summarize the clinical attempts targeting this family in anti-cancer therapy development.

Aim To study the anti-inflammatory activity of the Channa argus bile.Methods The bile was isolated and purified by extraction and silica gel column chromatography.Then the compounds were identified by hydrogen and carbon spectra.The spleen lymphocytes proliferation assay and Lipopolysaccharide(LPS) induced mouse macrophage RAW264.7 releasing Nitrogen Monoxide(NO) experiment were used to evaluate the anti-inflammatory activity.Results Compound(C1) of sodium taurocholate and compound(C2) of sodium taurochenodeoxycholate were isolated by activity tracing.The cell relative viabilities of the two compounds on Concanavalin A(Con A) induced spleen lymphocytes proliferation assay were 65.9%±11.7% and 60.5%±9.4%, which were significantly different from the result of model group (P<0.01), respectively.The NO production of LPS-induced RAW264.7 release of NO was (16.4±1.9) μmol·L-1 and (15.5±1.7) μmol·L-1, which were significantly different from the result of model group(P<0.01).Conclusion Sodium taurocholate and sodium taurochenodeoxycholate from Channa argus perform the anti-inflammatory activities but have no cytotoxic effect on spleen lymphocytes and macrophage.

Objective To investigate the efficacy of postoperative concurrent chemoradiotherapy for early-stage cervical adenosquamous carcinoma and adenocarcinoma.Methods A total of 62 patients with cervical adenosquamous carcinoma,149 patients with cervical adenocarcinoma,and 2687 patients with cervical squamous cell carcinoma,all of whom were in stage Ⅰ B-Ⅱ A and were treated from 2006 to 2012,were enrolled,and some of them received postoperative pelvic radiotherapy ± para-aortic extended field radiation ±afterloading radiotherapy.The chemotherapy regimen consisting of DDP,TP,and FP was given to these patients.The chi-square test was used for comparison of general clinical data,the Kaplan-Meier method was used for calculating survival rates,and the log-rank test was used for survival difference analysis.Results Cervical adenosquamous carcinoma and adenocarcinoma had no significant differences in clinicopathological features (P=0.107-0.639).The high-risk patients with adenocarcinoma had a higher recurrence rate than their low-risk counterparts even after adjuvant radiotherapy or chemoradiotherapy (P=0.000).In the patients treated with surgery and radiotherapy,those with adenosquamous carcinoma had the shortest median survival time,followed by those with adenocarcinoma and squamous cell carcinoma (P =0.134,0.787);in the patients treated with surgery and concurrent chemoradiotherapy,those with adenocarcinoma had the shortest median survival time,followed by those with adenosquamous carcinoma and squamous cell carcinoma (P=0.131,0.643),and the median survival time showed a significant difference between the patients with adenocarcinoma and those with squamous cell carcinoma (P =0.000).In the patients with adenosquamous carcinoma and adenocarcinoma,the patients treated with postoperative concurrent chemoradiotherapy had higher incidence rates of short-term adverse reactions than those treated with postoperative radiotherapy (P=0.037,0.003),but the incidence rates of long-term adverse reactions showed no difference between the two groups of patients (P=0.861,0.655).In the patients with adenosquamous carcinoma,the patients treated with postoperative concurrent chemoradiotherapy had a lower rate of distant metastasis (P =0.003) and prolonged median overall survival and disease-free survival (both increased by 17 months) (P=0.811,0.799),as compared with those treated with postoperative radiotherapy,while in the patients with adenocarcinoma,the median overall survival and disease-free survival were reduced by 11 and 9 months,respectively (P=0.330,0.115).Conclusions Compared with postoperative radiotherapy,postoperative concurrent chemoradiotherapy for early-stage high-risk cervical adenosquamous carcinoma can reduce the rate of distance metastasis.Compared with radiotherapy,postoperative concurrent chemoradiotherapy for adenosquamous carcinoma and adenocarcinoma cannot improve survival time.

Aims Toevaluatethepharmacodynamic efficacy of different types of antiangiogenic agents as HM-3 on a non-small cell lung cancer xenografts tumor model .To explore the interaction between the antian-giogenic agents and the tumor microenvironment,and to offer suggestions for clinical therapy.Methods Thenon-smallcelllungcarcinomaxenograftmodelwas established in Balb/c nude mice.The model mice were treated with Docetaxel(10 mg·kg-1 )as the positive control.The mice were parallelly treated with,HM-3 at the doses of 3 mg · kg-1 and 48 mg · kg-1 and, Avastin(5 mg·kg-1 ).The parameters include tumor volume,tumor weight and immunohistochemical analy-sis.Result Animalexperimentsshowedthatdocetaxel had good anti-tumor activity.Tumor growth inhibition by tumor weight of G2 docetaxel(10 mg·kg-1 )group was 60. 80%.Tumor growth inhibition by tumor weight of G3 HM-3(3 mg·kg-1 )group,G4 HM-3(48 mg· kg-1 )group ,G4 Avastin(5 mg·kg-1 )group,were 43. 60%,-34. 80%,44. 40%,respectively.Con-clusion Theantigiogeniceffectisaffectedbytumor growth stage,tumor microenvironment and their work-ing mechanisms.Angiogenesis inhibitors HM-3 has a certain effect of inhibiting tumor growth,but to little a-vail.HM-3 shows on inhibitory effect in a dose-de-pendent manner at the doses of 0~6 mg·kg-1 .HM-3 at a high dose of 48 mg · kg-1 has no inhibitory but promoting effects on human non-small cell lung carci-noma A549 xenografts in nude mice .Special dose-effect relationship indicates that dosage should be paid attention to in the clinical use of blood vessel inhibi-tors.