Objective:To explore the dosimetric differences of different dose accumulation method for brachytherapy combined with external beam radiation therapy (EBRT) of cervical cancer and establish clinical prediction models for radiation-induced late rectal injury (RLRI) after radiotherapy.Methods:A retrospective analysis was conducted for the clinical data of patients who received radical concurrent chemoradiotherapy (CCRT) for cervical cancer in the Department of Oncology of the Affiliated Hospital of North Sichuan Medical College from January 1, 2020 to November 30, 2021. EBRT combined with brachytherapy was employed for the patients, and dose assessment was performed in two means: the direct accumulation using equivalent dose in 2-Gy fractions (EQD2) and deformable image registration (DIR)-based dose accumulation of 3D planning images. The toxicity criteria of the Radiation Therapy Oncology Group were adopted as the RLRI grading criteria. The prediction models of RLRI using both dose assessment method were constructed. The areas under the receiver operating characteristic (ROC) curves were calculated to assess the predictive accuracy of the different dose assessment method.Results:In the case of brachytherapy, the D95% and D90% EQD2 doses to high-risk clinical target volumes (HR-CTVs) were 2.18 and 2.92 Gy higher respectively and the D2 cm 3, D1 cm 3, and D0.1 cm 3 EQD2 doses to the rectal were 1.74, 2.28, and 2.26 Gy higher, respectively compared to DIR-based dose accumulation ( t = 3.82, 5.21, 4.58, 5.17, 2.05, P < 0.05). For EBRT combined with brachytherapy, the D2 cm 3, D1 cm 3, and D0.1 cm 3 EQD2 doses to the rectal were 6.22, 7.61, 9.56 Gy higher than DIR-based doses, respectively, and the dosimetric differences were statistically significant ( t = 9.40, 10.59, 7.87, P < 0.001). The joint prediction model yielded an area under the ROC curve of 0.788. The sensitivity and specificity of the optimal cut-off value were 0.850 and 0.660, respectively. Furthermore, the Hosmer-Lemeshow goodness-of-fit tests indicated high goodness-of-fit ( P > 0.05). The prediction model for DIR-based dose accumulation of traditional predictors yielded areas under the ROC curves for D2 cm 3 and D1 cm 3 to the rectal of 0.784 and 0.763, respectively. The sensitivities of the optimal cut-off values were 0.850 and 0.750, respectively, and the specificities were 0.679 and 0.717, respectively. Conclusions:There are dosimetric differences between the direct dose accumulation using EQD2 and DIR-based dose accumulation of 3D planning images for brachytherapy combined with EBRT. Both the joint prediction model and the DIR-based dose accumulation of D2 cm 3 and D1 cm 3 to the rectal are effective in predicting RLRI. Given the complex calculation of the joint prediction model, it is recommended that RLRI should be predicted through DIR-based dose accumulation of D2 cm 3 and D1 cm 3 to the rectal clinically.

Objective To explore the causal relationship among 731 types of immune cells and breast cancer.Methods Genome-wide association data for immune cells and breast cancer were used.Mendelian randomization analysis was performed using the inverse variance weighting(IVW)and weighted median(WM)methods,and sensitivity analysis was conducted to assess heterogeneity and pleiotropy.Results A total of 19 immune cell phenotypes were identified to potentially have a causal association with breast cancer,using IVW as the main analysis method(P>0.05)and correcting P values using the false discovery rate method at a significance level of 0.05,excluding reverse causality.Of these,eight and 11 immune phenotypes may increase and decrease the risk of breast cancer,respectively.Conclusion This study explored the causal relationship between immune cells and breast cancer.Results show that certain immune cell phenotypes could serve as predictive markers for the early diagnosis of breast cancer and the development of new immun-otherapeutic strategies.

Strengthening practical teaching, together with improving innovation ability is one of the key tasks of Emerging Engineering Education. This paper is based on the revision of the training program of bioengineering in School of Chemical Engineering and Technology, Tianjin University, improved the practical teaching system and curriculum content, built a five-level teaching system for basic experiment, comprehensive experiment, course design, scientific research and practical training. In order to cultivate outstanding innovative talents with practical ability and innovative spirit, innovative teaching reform mode is proposed. Furthermore the new thought and new schemes for Emerging Engineering Education are put forward.
Bioengineering ; education ; Curriculum

Objective To explore the regulatory effect of TAK 1 inhibitors on MAPK and NF-κB signaling pathway in diabetic rats and its renal protection mechanism .Methods A total of 48 rats accorded to the random number table method were divided into DN group , TAK1 group and control group ,each group with 16 rats,control group with normal fed , DN group and TAK1 group by the intraperitoneal injection of 1%50 mg/kg STZ DN model rat.8 rats were killed in each group at 4 weeks and 8 weeks respectively ,the pathological changes of renal tissue were observed ,serum TNF-α,MCP-1,IL-1βlevels were detected by enzyme linked immunosorbent assay ,p38MAPK,NF-κBp63 protein expression were detected by Western blotting ,p38MAPK、NF-κBp63 mRNA levels in renal tissue were detected by real time fluorescence quantitative PCR.Results At 4 weeks and 8 weeks, the body weight, blood glucose and UAER of DN group and TAKl group were significantly higher than those in control group (P <0.05).The body weight and UAER of DN group were significantly higher than those of TAK1 group (P <0.05).The serum TNF-α,MCP-1,IL-1βlevels in DN group and TAK1 group were significantly higher than those in control group (P <0.05),and DN group serum TNF-α,MCP-1,IL-1βlevels were significantly higher than those in TAK1 group (P <0.05).The expression levels of p38MAPK,NF-κBp63 protein and mRNA in DN group, TAK1 group were significantly higher than those in control group (P <0.05), and p38MAPK,NF-κBp63 protein and mRNA in DN group was significantly higher than that in TAK 1 group ( P <0.05 ) .Conclusions TAK1 induces inflammation by activating MAPK and NF-κB signaling pathways,and participates in diabetic renal injury . TAK1 inhibitors with anti-inflammatory effect by down regulate the expression of inflammatory factors .

OBJECTIVE:To compare therapeutic efficacies of Shengxuening tablet and Iron sucrose injection for anemia in maintenance hemodialysis(MHD)patients,and their effects on oxidative stress and micro-inflammation state. METHODS:80 pa-tients who had received MHD over half year were assigned into shengxuening group and iron sucrose group with 40 cases in each group. Both groups received MHD 3 times a week,4 h/time,blood flow of 200~300 ml/min;erythropoietin(EPO)was used at a dose of 10 000 IU/time hypodermically in each group. Shengxuening group was additionally given Shengxuening tablet orally,0.5 g/time,tid. Iron sucrose group was given Iron sucrose injection 100 mg 2 h intravenously via dialyser after the beginning of hemo-dialysis,twice a week,received iron treatment every one week until complete the total dose of 1 000 mg,to maintain ferritin be-tween 100~300 μg/L. The levels of Hb,Hct,SF,TSAT,hs-CRP,IL-6,TNF-α,MDA,SOD and GSH-Px were tested in 2 groups before and 12 weeks after the treatment. RESULTS:After 12 weeks of treatment,the levels of Hb,Hct,SF and TSAT in 2 groups were significantly increased,with statistical significance (P<0.01);but there was no statistical significance between 2 groups (P>0.05). Compared with before treatment,the levels of hs-CRP,IL-6,TNF-α and MDA increased significantly in iron sucrose group,while SOD and GSH-Px levels declined significantly,with statistical significance (P<0.01). Above indicators of shengxuening group had no significant change,compared with before treatment;there was statistical significance between 2 groups after treatment(P<0.01). No obvious ADR was found in 2 groups. CONCLUSIONS:Therapeutic efficacy of shengxuening is simi-lar to that of iron sucrose in improving the anemia and iron deficiency status of MHD patients,but doesn't aggravate oxidative stress and micro-inflammation state. It is an safe and effective oral iron supplement drugs.

OBJECTIVETo observe the effect of SIRT1 on intestinal barrier function of epithelial Caco-2 cells under hypoxia and investigate its mechanism.

METHODSCaco-2 cells were randomly divided into three groups: normoxia group (Nx), hypoxia group (Hx,1%O2 for 6 h) and hypoxia plus 40 μmol/L Resveratrol (agonist of SIRT1) group (Hx+Res). Transepithelial electrical resistance (TER) was determined. mRNA and protein expressions of SIRT1 and tight junctions (ZO-1, Occludin, Claudin-1) were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.

RESULTSBoth mRNA and protein expressions of SIRT1 were significantly reduced in Hx group as compared with Nx group (0.40±0.02 vs. 0.70±0.07, P=0.001; 0.37±0.03 vs. 0.76±0.03, P=0.001). The mRNA and protein expressions of SIRT1 were significantly increased in Hx+Res group as compared with Hx group(0.50±0.02 vs. 0.40±0.02, P=0.026; 0.54±0.02 vs. 0.37±0.03, P=0.011). The expression levels of ZO-1, Occludin and Claudin-1 in Hx group were lower than those in Nx group (P<0.05), however, pretreatment with Resveratrol could attenuate the decreased expression of above 3 molecules under hypoxia(P<0.05). TERs of Nx group, Hx group and Hx+Res group were (142±7) Ohm/cm(2), (94±3) Ohm/cm(2) and (119±7) Ohm/cm(2) respectively. Compare with the Nx group, the TER of Hx group was significantly decreased(P<0.05). TER of Hx+Res group was significantly increased compare with Hx group, but it was still significantly lower than that in Nx group(P<0.05).

CONCLUSIONSExpression of SIRT1 is significantly reduced under hypoxia. Activation of SIRT1 can maintain the epithelial barrier function through regulating the expression of tight junctions under hypoxia.

Caco-2 Cells ; Cell Hypoxia ; Claudin-1 ; metabolism ; Epithelial Cells ; metabolism ; Humans ; Intestinal Mucosa ; cytology ; Occludin ; metabolism ; Sirtuin 1 ; metabolism ; Zonula Occludens-1 Protein ; metabolism

OBJECTIVETo evaluate the efficacy and safety of trastuzumab combined with chemotherapy in the treatment for HER-2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma.

METHODSTwenty consecutive cases of chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma treated in Peking University Cancer Hospital between 2009 June and 2013 August were included in this study. The patients with adenocarcinoma were previously confirmed and were eligible if their tumor showed overexpression of HER-2+++ by immunohistochemistry or HER-2 gene amplification-positive by FISH, and if they failed to at least one previous chemotherapy. Response and toxicities were evaluated with RECIST 1.0 and CTC AE 3.0 criteria.

RESULTSThe twenty patients received trastuzumab plus second- or later-line chemotherapy, consisting of nine platinum with fluoropyrimidines, five paclitaxel with fluoropyrimidines, three fluoropyrimidines monotherapy, two irinotecan monotherapy, and one docetaxel monotherapy. In these 20 cases, 3 PR (15.0%) and 10 SD (50.0%) were achieved, with a disease control rate of 65.0%. The median PFS was 6.1 months (95%CI 3.0-9.2) and median OS was 11.1 months (95%CI 8.4-13.7). The median cycle number of Trastuzumab administration was 6.5. The patients treated with Trastuzumab ≥ 6 times had a median OS of 13.8 months, significantly longer than that of 9.5 months in the patients treated <6 times (P < 0.001). The patients treated with Trastuzumab ≥ 6 times had a median PFS of 7.8 months, significantly longer than that of 3.7 months in patients treated <6 times (P = 0.029). Among the 20 cases, loss of appetite (13 cases of grade 1-2), neutropenia (12 cases of grade 1-2 and 3 cases of grade 3-4) and fatigue (9 cases of grade 1-2 and 3 cases of grade 3-4) were the most frequent adverse events. No cardiac events including asymptomatic decreases in LVEF ≥ 10% and no treatment-related death were recorded.

CONCLUSIONSCombination of trastuzumab with chemotherapy is effective and safe in patients with HER2-positive advanced chemo-refractory gastric or gastro-esophageal junction adenocarninoma. However, prospective studies are warranted to further confirm its efficacy and safety.

Adenocarcinoma ; drug therapy ; metabolism ; secondary ; surgery ; Adult ; Aged ; Anorexia ; chemically induced ; Antibodies, Monoclonal, Humanized ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Cisplatin ; administration & dosage ; adverse effects ; Disease Progression ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Esophagogastric Junction ; Fatigue ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Neutropenia ; chemically induced ; Paclitaxel ; administration & dosage ; adverse effects ; Pyrimidines ; administration & dosage ; adverse effects ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; metabolism ; secondary ; surgery ; Survival Rate ; Trastuzumab

Objective To observe the effect of SIRT1 on intestinal barrier function of epithelial Caco-2 cells under hypoxia and investigate its mechanism. Methods Caco-2 cells were randomly divided into three groups: normoxia group (Nx), hypoxia group (Hx,1%O2 for 6 h) and hypoxia plus 40 μmol/L Resveratrol (agonist of SIRT1) group (Hx+Res). Transepithelial electrical resistance (TER) was determined. mRNA and protein expressions of SIRT1 and tight junctions (ZO-1, Occludin, Claudin-1) were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Results Both mRNA and protein expressions of SIRT1 were significantly reduced in Hx group as compared with Nx group (0.40±0.02 vs. 0.70±0.07, P=0.001; 0.37±0.03 vs. 0.76±0.03, P=0.001). The mRNA and protein expressions of SIRT1 were significantly increased in Hx+Res group as compared with Hx group(0.50±0.02 vs. 0.40±0.02, P=0.026; 0.54±0.02 vs. 0.37±0.03, P=0.011). The expression levels of ZO-1 , Occludin and Claudin-1 in Hx group were lower than those in Nx group (P<0.05), however, pretreatment with Resveratrol could attenuate the decreased expression of above 3 molecules under hypoxia (P<0.05). TERs of Nx group, Hx group and Hx+Res group were (142±7) Ohm/cm2, (94±3) Ohm/cm2 and (119±7) Ohm/cm2 respectively. Compare with the Nx group, the TER of Hx group was significantly decreased (P<0.05). TER of Hx+Res group was significantly increased compare with Hx group, but it was still significantly lower than that in Nx group (P<0.05). Conclusions Expression of SIRT1 is significantly reduced under hypoxia. Activation of SIRT1 can maintain the epithelial barrier function through regulating the expression of tight juncions under hypoxia.

Objective To observe the effect of SIRT1 on intestinal barrier function of epithelial Caco-2 cells under hypoxia and investigate its mechanism. Methods Caco-2 cells were randomly divided into three groups: normoxia group (Nx), hypoxia group (Hx,1%O2 for 6 h) and hypoxia plus 40 μmol/L Resveratrol (agonist of SIRT1) group (Hx+Res). Transepithelial electrical resistance (TER) was determined. mRNA and protein expressions of SIRT1 and tight junctions (ZO-1, Occludin, Claudin-1) were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Results Both mRNA and protein expressions of SIRT1 were significantly reduced in Hx group as compared with Nx group (0.40±0.02 vs. 0.70±0.07, P=0.001; 0.37±0.03 vs. 0.76±0.03, P=0.001). The mRNA and protein expressions of SIRT1 were significantly increased in Hx+Res group as compared with Hx group(0.50±0.02 vs. 0.40±0.02, P=0.026; 0.54±0.02 vs. 0.37±0.03, P=0.011). The expression levels of ZO-1 , Occludin and Claudin-1 in Hx group were lower than those in Nx group (P<0.05), however, pretreatment with Resveratrol could attenuate the decreased expression of above 3 molecules under hypoxia (P<0.05). TERs of Nx group, Hx group and Hx+Res group were (142±7) Ohm/cm2, (94±3) Ohm/cm2 and (119±7) Ohm/cm2 respectively. Compare with the Nx group, the TER of Hx group was significantly decreased (P<0.05). TER of Hx+Res group was significantly increased compare with Hx group, but it was still significantly lower than that in Nx group (P<0.05). Conclusions Expression of SIRT1 is significantly reduced under hypoxia. Activation of SIRT1 can maintain the epithelial barrier function through regulating the expression of tight juncions under hypoxia.

Objective To investigate the relationship between thyroid nodules with calcification and thyroid carcinoma and its significance in the screening of thyroid carcinoma in high risk group.Methods The clinical data of 1771 patient undergoing surgery for thyroid nodules from March, 2006 to March, 2009 in Huashan Hospital, Fudan University were retrospectively analyzed. Results Among 1771 patients, 500 were finally identified as having malignant tumors. Incidence of calcification in thyroid carcinoma was 68. 4%, and that in benign thyroid nodules was 27.0% ( χ2 = 259. 5, P ＜ 0. 05 ). The specificity of microcalcification for the diagnosis of carcinoma was 89. 4%, and its positive predictive value was 66. 3% ( χ2 = 368.6, P ＜ 0. 01 ). The incidence of thyroid carcinoma in patients ＜ 45 years was 39.2%, while that in patients ≥ 45 years was 22.9% ( χ2 = 51.12, P ＜ 0. 05 ). The incidence of carcinoma in patients of single thyroid nodule was 31.7% and that in those with multiple nodules was 26. 4% (χ2 =4. 766,P ＜ 0. 05). Metastasis was pathologically diagnosed in 26. 8% of lymph nodes found by preoperative ultrasonography. Conclusions The specificity of thyroid nodule calcification, especially microcalcification is high for the diagnosis of thyroid carcinoma. High-risk index for carcinoma includes thyroid nodules with microcalcification, ＜ 45 years old and single thyroid nodule.