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Objective:To investigate the clinical effect of programmed death receptor-1 (PD-1)/programmed death receptor ligand-1 (PD-L1) immunotherapy combined with concurrent radiotherapy and chemotherapy in the treatment of locally advanced cervical cancer (LACC).Methods:From November 2018 to October 2019, 51 LACC patients in Qinhuangdao First Hospital who received anti-PD-1/PD-L1 immunotherapy (pembrolizumab) combined with concurrent radiotherapy and chemotherapy [intensity modulated radiotherapy (IMRT)+ TP (taxol+ carboplatin) chemotherapy] were selected as the observation group. 51 LACC patients who received concurrent chemotherapy and radiotherapy were selected as the control group. The objective remission rate, disease control rate, tumor markers [squamous cell carcinoma antigen (SCCAg), soluble cytokeratin 19 fragment (CYFRA21-1), and carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125)], proliferation and apoptosis indicators [survivin (Survivin), B-cell lymphoma-2 (Bcl-2), Caspase-3 (Caspase-3), apoptosis-promoting substance (Bax)], PD-1/PD-L1 [soluble PD-L1 (sPD-L1), CD4 + T cell surface PD-1 expression (PD-1 CD4 + T cells), CD8 + T cell surface PD-1 expression (PD-1 CD8 + T cell) and CD14 + monocyte surface PD-L1 expression (PD-L1 CD14 + monocyte)], safety and survival rate within 1 year were compared between the two groups. Results:(1) Disease control and safety: the objective response rate and disease control rate of the observation group were 80.39%(41/51) and 92.16%(47/51), respectively, which were higher than those of the control group by 39.22%(20/51) and 70.59%(36/51) (all P<0.05), but there was no significant difference in the incidence of side effects between the groups (all P>0.05). (2) Tumor markers and proliferation and apoptosis indexes: compared with those before treatment, the levels of serum SCCAg, CYFRA21-1, CEA, CA125, survivin and Bcl-2 in the two groups after treatment were significantly lower, and the levels of Caspase-3 and Bax were significantly higher; the above indexes in the observation group were better than those in the control group after treatment (all P<0.05). (3) PD-1/PD-L1: after treatment, sPD-L1, PD-1 CD4 + T cells, PD-1 CD8 + T cells and PD-L1 CD14 + monocytes in the observation group were significantly lower than those before treatment (all P<0.05). After treatment, the sPD-L1, PD-1 CD4 + T cells, PD-1 CD8 + T cells, PD-L1 CD14 + monocytes in the observation group were lower than those in the control group (all P<0.05). (4) Survival: the survival rate of the observation group was higher than that of the control group within 1 year ( P<0.05). Conclusions:The clinical effect of anti-PD-1/PD-L1 immunotherapy combined with concurrent radiotherapy and chemotherapy in the treatment of LACC is significant. It can effectively inhibit the progression of the disease by regulating tumor markers, proliferation and apoptosis indicators and PD-1/PD-L1 expression without increasing the risk of treatment, and has a positive effect on improving the survival rate of patients.
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Objective:To investigate the relationship between CD8 +FoxP3 +CD25 + T cell subsets and the therapeutic effect of programmed death receptor 1 (PD-1) inhibitor pembrolizumab in treatment of uterine cervical cancer. Methods:The data of 105 patients with uterine cervical cancer who received pemblizumab therapy based on chemotherapy in the First Hospital of Qinhuangdao from January 2018 to January 2020 were retrospectively analyzed. Flow cytometry was used to detect the ratio of CD8 +FoxP3 +CD25 + T cell in peripheral blood of patients. The efficacy and safety were analyzed. According to the efficacy, all patients were divided into remission group (complete remission + partial remission) and non-remission group (stable disease + progressive disease). The clinical characteristics and CD8 +FoxP3 +CD25 + T cell ratio of the two groups were compared. Multivariate logistic regression model was used to analyze the influencing factors for the efficacy. The efficacy of CD8 +FoxP3 +CD25 + T cell ratio predicting the therapeutic effect of patients was analyzed by using receiver operating characteristic (ROC) curve. Results:The objective remission rate of all patients was 17.14% (18/105), and the incidence of adverse reaction was 39.05% (41/105). The proportion of patients with a family history of cervical cancer in the remission group was lower than that than in the non-remission group [5.56% (1/18) vs. 34.48% (30/87)], and the difference was statistically significant ( χ2=6.00, P=0.014). The proportion of CD8 +FoxP3 +CD25 + T cell of 105 patients before and after treatment was (0.83±0.21)% and (0.77±0.10)%, respectively; the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the remission group was (0.55±0.26)%, (0.31±0.12)%, respectively; the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group was (0.89±0.30)%, (0.87±0.28)%, respectively. The proportion of CD8 +FoxP3 +CD25 + T cell after treatment in the remission group was lower than that before treatment ( P < 0.05); there was no statistically significant difference in the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group ( P>0.05). The proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group was higher than that in the remission group (all P<0.001). The proportion of CD8 +FoxP3 +CD25 + T cell higher than the mean value of both groups before treatment and the proportion of CD8 +FoxP3 +CD25 + T cell higher than the mean value of both groups after treatment were independent risk factor of disease remission ( OR=2.542, 95% CI 1.649-3.918, P<0.001; OR=2.936, 95% CI 2.154-4.002, P<0.001). ROC curve analysis showed that the area under the curve of CD8 +FoxP3 +CD25 + T cell ratio predicting the disease remission before treatment was 0.720, and its best cut-off value was 0.77%, the senfitivity was 77.78%, the specificity was 70.11%. Conclusions:Early detection of CD8 +FoxP3 +CD25 + T cell ratio helps to predict the effect of PD-1 inhibitor pembrolizumab therapy for uterine cervical cancer.
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Objective This paper investigated the clinical application of CRT+ARC technique in locally advanced lung cancer. Methods A total of 100 patients with locally advanced lung cancer who underwent radiotherapy in our hospital from March 1,2016 to March 1,2017 were randomly assigned to the experimental and control groups. Each group consisted of 50 patients. The CRT+ARC plans were made for the experimental group,and the CRT + intensity-modulated radiotherapy(IMRT)(CRT+IMRT) plans for the control group. According to the World Health Organization( WHO) criteria,the short-term efficacy of patients was as-sessed. According to the imaging examination and the Radiation Therapy Organization Group(RTOG)standard,the occurrence of major side effects of radiation pneumonia was identified. Results The effective rate of treatment was 82% in the experimental group and 76% in the control group. There was no difference in the effective rate between the two groups(χ2 =0. 542,P=0. 461). The incidence of pneumonia in the experimental group was 22% ,and 18% in the control group. There was also no difference in the incidence of pneumonia between the two groups(χ2 =0. 250,P=0. 617). Conclusion In the clinical application of locally advanced lung cancer, CRT+ARC technique has no difference in the short-term efficacy and the main side effects of radiation pneumonitis compared with CRT+IMRT.
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Objective To discuss the correlation between SIRT3 protein and clinicopathological parameters of gastric carcinoma.Methods Immunohistochemistry and Western blot were used to detect the expression of SIRT3 in the gastric carcinoma and normal gastric tissue.The correlation between the expression of SIRT3 and clinicopathological parameters was analyzed.Results The immunohistochemistry showed that the positive expression rate of SIRT3 protein in gastric carcinoma tissue (53.8 ％,43/80) was obviously lower than that in normal gastric tissue (86.0 ％,43/50),and the expression of SIRT3 protein showed close relationship with invasion depth,lymph node metastasis and TNM stage (P ＜ 0.05),rather than the age,gender,tumor size,or differentiation status (P ＞ 0.05).The Western blot showed that the expression rate of SIRT3 protein (SIRT3/β-actin) in gastric carcinoma tissue (0.655±0.317) was lower than that in normal gastric tissue (0.803±0.329) (P ＜ 0.05).Conclusion The expression of SIRT3 protein is lower in gastric cancer than that in normal gastric tissue,and relates to invasion depth,lymph node metastasis and TNM stage.SIRT3 may inhibit the occurrence and development of gastric cancer.
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Objective To explore the association of COX-2 Gly587Arg polymorphism with the risk of primary liver cancer.Methods Two hundred and seventy patients with primary liver cancer and 540 health people were selected as our subjects.DNA were extracted from peripheral blood lymphocytes,and genotypes were measured by polymerase chain reaction-restriction fragment length polymorphism method.Odds ratios(OR) and 95％ confidence intervals(CI) were estimated by logistic regression.Results Two kinds of genotype (587Gly/ Gly and Gly/Arg) were found in all participants.No one carried 587Arg/Arg genotype.Among primary liver cancer patients,91.5％ (247/270,) 8.5％ (23/270) of individuals carried 587Gly/Arg and Gly/Arg genotype,which was significantly higher than that of controls (96.5％ (521/540,) 3.5％ (19/540)).Multivariate Logistic regression analysis showed that individual carried 587Gly/Arg genotype had an increased risk of developing primary liver cancer (OR =2.56,95％ CI =1.37-4.79,P =0.003) compared with 587Gly/Gly carriers.Conclusion COX-2 Gly587Arg polymorphism is a risk factor for primary liver cancer in Han.
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Objective To investigate the significance of plasma D-dimers,high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol (LDL-C) and apolipoprotein a (LP (a)) of patients with gastrointestinal cancer.Methods One hundred and thirty-nine cases with gastrointestinal cancer and 155 healthy persons were selected as subjects.Latex enhanced immunoassays method was used to measure the D dimer concentration.Direct method was applied to detect the levels of serum HDL-C,LDL-C,LP (a)Chemiluminescence method was applied to detect serum carcinoembryonic antigen (CEA)concentration.Determine the sensitivity and specificity of each index in gastrointestinal cancer,and explore the relationship between the concentration and the lymph node metastasis and distant metastasis.Results The levels of D-dimer,LDL-C,LP (a),CEA in patients with gastrointestinal carcinoma were 0.80 (2.37) mg/L,3.46 (1.46) mmol/L,317 (262) mg/L,2.61 (3.62) μ,g/L respectively,significant higher than those of health control(0.21 (0.22) mg/L,2.86 (0.98) mtmol/L,139 (187) g/L,1.29 (1.42) μg/L respectively; Z =-8.388,-6.150,-8.589,-7.142,P ＜0.001).The level of HDL-C in gastrointestinal cancer patients was 0.86(0.38) mmoL/L,lower than that of health control(1.29(1.42) mmol/L; Z =-10.643,P ＜0.001)The area of ROC curve of D-dimmer,HDL-C,LDL-C,LP (a),CEA were 0.783,0.859,0.708,0.790,0.741 respectively.Compared with area of ROC curve of CEA,that of D-dimer,LDL-C,LP(a) were significant different (Z =1.110,0.809,1.257 ; P =0.27,0.42,0.21).Compared with CEA AUC,HDL-C AUC was significant different (Z =3.225,P =0.0013).Compared with patients with no lymph node metastasis,the levels of D-dimers,LDL-C,LP (a) in patients with lymph node metastasis were higher (P =0.003,0.002,0.005 respectively).And the concentration of HDL-C decreased significantly (P =0.001).Compared with patients without metastases,serum D-dimer,LDL-CLP (a) concentration in patients with distant metastasis were significant higher(P ＜ 0.001) and the concentration of HDL-C decreased (P ＜ 0.001).Conclusion The levels of D-dimer and lipoprotein might be proved the base for diagnosis or assessment of gastrointestinal malignant tumor.
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Objective To evaluate the diagnostic value of the level of plasma D-dimer, lipoproteins and carcino-embry-onic antigen(CEA) in gastrointestinal cancer.Methods The plasma D-dimer ,lipoproteins,CEA and clinicopathological data of 139 gastrointestinal cancer patients and 155 normal controls were collected and analyzed .Lipoproteins included high-density lipoprotein(HDL),low-density lipoprotein(LDL) and lipoprotein a[LP(a)].SPSS 13.0 statistical software was used to analyze the sensitivity and specificity of each examination method and to find the appropriate combination .Results The plasma D-dimer,LDL,LP( a) and CEA levels were distinctly higher in patients than those in normal controls ( P<0.001).HDL levels were significantly lower in patients than those in normal controls (P<0.001).The cutoff of D-dimer was 0.495 μg/ml , the sensitivity of D-dimer was 62.6%,and the specificity was 86.5%.The cutoff of HDL was 1.025 mmol/L, the sensitivity was 72.7%,and the specificity was 85.2%.The cutoff of LDL was 3.375 mmol/L, the sensitivity was 54%,and the specificity was 82.6%.The cutoff of LP(a) was 27.3 mg/dl, the sensitivity was 58.3%,and the speci-ficity was 87.1%.The cutoff of CEA was 2.14 ng/ml, the sensitivity was 59.7%,and the specificity was 76.8%.The sensitivity and specificity of HDL +CEA were 77.7%and 88.4%, respectively.The sensitivity and specificity of HDL +D-dimer were 70.5% and 96.1%, respectively.The sensitivity of HDL +LP(a) was 76.3%,and the specificity was 93.5%.The sensitivity of D-dimer +HDL+LP(a) was 84.2%,and the specificity was 92.3%.The sensitivity of D-dimer +HDL+CEA was 87.1%, and the specificity was 85.8%.The sensitivity and specificity of HDL +LP(a) +CEA were 85.6%and 92.3%, respectively.The sensitivity of D-dimer +HDL+CEA +LP(a) was 89.9%while the specificity was 92.3%.Conclusions Plasma D-dimer and lipoproteins can serve as tumor markers in gastrointestinal cancer .Combined detection has higher sensitivity and specificity .
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Objective To discuss the clinical application of CT-guided percutaneous puncture biopsy in diagnosing thyroid nodes. Methods A total of 65 patients with thyroid nodes were enrolled in this study. CT-guided percutaneous puncture biopsy of thyroid nodes was carried out in all 65 patients. The puncture biopsy results were compared with the postoperative pathologic findings. Results Successful puncturing of thyroid node was accomplished in all 65 patients. One patient developed subcutaneous hematoma. The coincidence rate between puncture biopsy results and postoperative pathologic findings was 93.8%(61/65). Five of 6 cases with thyroid cancer agreed with the pathologic diagnosis. Conclusion For the diagnosis of thyroid diseases, CT-guided percutaneous puncture biopsy is simple, safe and reliable, with higher success rate.
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Objective To evaluate the efficacy and safety of radiation combined with targeted therapy of EGFR-TKI in the patients with stage IV non-small cell lung cancer ( NSCLC). Methods There were 17 female and 9 male patients with NSCLC enrolled into this study, which included 19 adenocarcinoma, 4 alveolar carcinoma and 3 uncertain carcinoma according to the iconography findings. Sixteen patients suffered from single or multiple bone metastasis,and 10 cases with brain metastasis. Gefitinib 250 mg or Erlotinib ISO mg per day were administrated during and after the process of radiation until the disease progressed. Results All patients had complete combined therapy, 12 of them suffered from diarrhea, 8 from emesia and 12 from erythra. The average score of ECOG improved from 3 to 2 after combined therapy. The bone metastasis control rate was 93.8% ,brain metastasis control rate was 70.0% , and the 6-month local lung lumps control rate was 84. 6%. Conclusion Palliative radiation combined with targeted therapy of EGFR-TKI is an effect and safe therapy for the patients with the stage IV of NSCLC, but the influence on survival shall be observed in further study.
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Objective To evaluate the association of COX2 genetic variants with the risk of esophageal cancer and the interaction of COX2 genetic variants with Hp infection. Methods A total of 119 patients with esophageal cancer and 238 frequency-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. Odds ratios (OR) and 95% confidence intervals ( CI) were estimated by logistic regression. Results Case-control analysis showed an increased risk of developing esophageal cancer for 1195 GA(OR =2.69,95% CI= 1. 46-5. 14) and 1195AA ( OR = 2. 30,95% CI = 1.23-4. 89) genotype carriers,respectively, compared with non 1195 GG carriers. When stratified by Hp status, the significantly increased risk of esophageal cancer was found among Hp carrier with OR (95%CI) =2.74 (1.35-5.96) ,but not among Hp non-carriers. Conclusion Genetic polymorphism in COX2 promoter region may play an important role in esophageal cancer by Hp infection.
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Objective To assess the prediction value of technetium-99m methoxyisobutylisonitrile(~(99)Tc~m-MIBI) for the effect of chemotherapy in small cell lung cancer (SCLC) patients. Methods Fifty-three patients with SCLC were divided into two groups according to the chest computed tomography (CT) examination, 39 patients in group A with complete or partial remission, and 14 patients in groups B with stable or progressive status. ~(99)Tc~m-MIBI was performed before chemotherapy. Following i. v. administration of 740 MBq ~(99)Tc~m-MIBI, SPECT imagings at 10 -30 minutes (early) and 2 -3 hours (delayed) were performed to obtain the uptake ratio of early phase tumor/normal lung tissue (ER) and the uptake ratio of delayed phase tumor/normal lung tissue (DR). The retention index (RI) was calculated as (DR-ER)/ ER × 100%. The differences of ER,DR and RI between the two groups were tested through t-test and rank sum test. Results ~(99)Tc~m-MIBI uptake was significantly higher in group A than group B: 2.33(SD:0.21) vs 2.02(SD:0.31) for the early ratio (ER) (t = -3.401, P<0.05) and 2.44(SD:0.19) vs 1.86 (SD :0.30) for the delayed ratio (DR) (t = - 6.724,P < 0.05). The median of RI in group A was signifi-cantly higher than that in group B (5.31% vs -9.26%,P <0.05). Conclusions ER,DR and RI of ~(99)Tc~m-MIBI SPECT may be helpful in predicting the response to chemotherapy in patients with SCLC.
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A total of 101 patients undergoing operations for malignant gastrointestinal tumors (stage Ⅱ to Ⅲ) were enrolled and randomly assigned to receive intraperitoneal hyperthermal chemotherapy plus intravenous chemical injection (treatment group, n=51) or routine intravenous chemical injection (control group, n=50). Our results indicated that the recurrence rate and the metastatic rate in the treatment group were significantly lower than those in the control group (25.5% vs. 50.0%, 13.7% vs. 30.0%, both P< 0. 05), although the 3-and 5 year-survival rates were significantly higher (both P < 0. 05). Our data suggest that intraperitaneal hyperthermal chemotherapy plus general chemotherapy after surgery for malignant gastrointestinal tumors could effectively reduce tumor recurrence and metastases and improve long-term survival.
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Sixty-one patients with moderate to severe malignant ascites were enrolled and randomly assigned to receive intraperitoneal hyperthermal chemotherapy+intravenous chemical injection (treatment group; n=31) or routine intravenous chemical injection (control group; n=30). Short-term response and reverse effects were observed. Our results indicated that the complete remission rate, part remission rate,and clinical benefit rate in the treatment group was significantly higher than those in the control group (38.71% vs 13.33% ,41.94% vs 16. 67%, and 90.32% vs 66.67%, respectively). No difference in reverse effects was found between the two groups. Our data suggest that intraperitoneal hyperthermal chemotherapy plus general chemotherapy may effectively control the malignant ascites, and the reverse effects might be well tolerated.
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<p><b>BACKGROUND</b>To detect DNA adduct in lung cancer tissues and analyze the factors influencing formation of DNA adduct.</p><p><b>METHODS</b>DNA was extracted from the tumor tissues derived from 34 patients with lung cancer. DNA adducts were analyzed using 32P-postlabeling method with P 1 nuclear modification.</p><p><b>RESULTS</b>DNA adduct level was significantly higher in smoking patients than that in non smoking patients(P < 0.05). DNA adduct level was related to the histological classification, degree of cell differentiation and lymph node metastasis, but not to age and sex.</p><p><b>CONCLUSIONS</b>DNA adduct level might be used as a potential marker to estimate malignant degree for lung cancer.</p>