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Intelligent drug delivery is a promising strategy for cancer therapies. In recent years, with the rapid development of synthetic biology, some properties of bacteria, such as gene operability, excellent tumor colonization ability, and host-independent structure, make them ideal intelligent drug carriers and have attracted extensive attention. By implanting condition-responsive elements or gene circuits into bacteria, they can synthesize or release drugs by sensing stimuli. Therefore, compared with traditional drug delivery, the usage of bacteria for drug loading has better targeting ability and controllability, and can cope with the complex delivery environment of the body to achieve the intelligent delivery of drugs. This review mainly introduces the development of bacterial-based drug delivery carriers, including mechanisms of bacterial targeting to tumor colonization, gene deletions or mutations, environment-responsive elements, and gene circuits. Meanwhile, we summarize the challenges and prospects faced by bacteria in clinical research, and hope to provide ideas for clinical translation.
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Objective:To evaluate the role of salvage radiotherapy in the re-treatment of patients with regional lymph node oligo-recurrence after radical surgery for esophageal squamous cell carcinoma.Methods:Clinical data of patients diagnosed with thoracic esophageal squamous cell carcinoma treated with radical surgery and developed regional lymph node oligo-recurrence ( n=1-3) from January 2013 to January 2016 were retrospectively analyzed. A total of 74 cases with intact clinical data were extracted for analysis. The survival analysis was performed by Kaplan-Meier method. Group comparison was conducted by Log-rank method. Results:The median overall survival (OS) after recurrence was 9(2.5-43) months, and the median progression-free survival time (PFS) was 4(1-33) months. There were 47 cases in the salvage radiotherapy group and 27 cases in the non-radiotherapy group, and the objective response rates were 77%(36/47) and 30%(8/27), respectively. Patients in the salvage radiotherapy group had better OS ( P=0.042) and PFS ( P=0.01) compared with their counterparts in the non-radiotherapy group. Among the patients who received salvage radiotherapy, involved field irradiation and elective nodal irradiation yielded similar OS ( P=0.963) and PFS ( P=0.599), and patients treated an irradiation dose ≥ 60Gy had better OS ( P=0.001) and PFS ( P=0.001) compared with those with dose< 60Gy. Conclusions:Local salvage radiotherapy is an effective treatment of esophageal squamous cell carcinoma with regional lymph node oligo-recurrence after radical surgery. Salvage radiotherapy has better OS and PFS compared with non-radiotherapy. Prospective clinical studies should be carried out to standardize the target and dose of radiotherapy, and to further clarify the effect of radiotherapy.
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Objective To evaluate the recurrence pattern and identify the risk factors of esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery.Methods Clinical data of 275 patients with thoracic esophageal squamous cell carcinoma treated with neoadjuvant therapy combined with surgery from December 2011 to December 2015 were retrospectively analyzed.The follow-up data of the enrolled patients were complete and analyzable.The recurrence pattern,recurrence time,recurrence location and influencing factors after neoadjuvant therapy in combination with surgery were analyzed.The recurrence rate was calculated by Kaplan-Meier method.The multivariate analysis was performed by Cox regression model.Results The median follow-up time was 32 (3-84) months,and the median time of the first recurrence was 10.6(2.0-69.1) months.The 1-,2-and 3-year recurrence rates were 32.0％,45.1％ and 52.3％,respectively.A total of 152 cases (55.3％) had recurrence.Among them,77 cases (50.6％) had local-regional recurrence (LRR),34 cases (23.4％) had distant metastasis (DM),33 cases (21.7％) had LRR+DM and 8 cases (6.0％) had recurrence in unknown site.Among the patients with LRR,lymph node recurrence was the most common (n =98,89.1％).For DM patients,lung metastasis (n =33,49.3％),liver metastasis (n=16,23.9％),bone metastasis (n=14,20.9％) and non-regional lymph node metastasis (n=14,20.9％) were commonly observed.The multivariate analysis showed that postoperative T stage (P=0.008),N stage (P＜0.001) and the number of lymph node dissection (P＜0.001) were the independent risk factors for recurrence after treatment.Conclusions The recurrence rate after neoadjuvant therapy remains relatively high for esophageal squamous cell carcinoma,and the regional lymph node is the most common site of recurrence.Postoperative pathological T staging,N staging and the number of lymph node dissection are the independent risk factors for recurrence after treatment.
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Objective To evaluate the clinical efficacy and prognostic factors of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery.Methods From December 2011 to December 2015,152 cases of recurrent thoracic esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery were retrospectively analyzed.The overall survival (OS) after treatment failure,clinical efficacy and prognostic factors of different salvage treatments were analyzed.OS was calculated by Kaplan-Meier method.Prognostic analysis was performed by using multivariate Cox regression model.Results The median interval of the first recurrence was 10.6(2.0 to 69.1) months.The median OS after recurrence was 8.0(0.8 to 43.3) months.The 1-,2-and 3-year OS rates after recurrence were 36.0％,15.1％ and 5.2％,respectively.The median OS of patients with locoregional recurrence alone,distant metastasis alone and locoregional recurrence combined with distant metastasis was 11.3(1.8 to 43.3) months,6.7(1.2 to 28.6) months and 5.1 (0.8 to 22.9) months,respectively.Multivariate analysis demonstrated that neoadjuvant chemotherapy (P=0.009),ypTNM stage (P=0.012),comprehensive treatment after recurrence (P=0.000) and locoregional recurrence (P=0.026) were independently correlated with the OS of patients with recurrent esophageal squamous cell carcinoma.Conclusions Neoadjuvant therapy,ypTNM stage,recurrence pattern and postrecurrence treatment are the independent risk factors for clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery.Clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy is not satisfactory.After recurrence,combined treatment mode should be adopted according to the site of recurrence and neoadjuvant treatment mode to maximize the benefits of salvage treatment.
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Objective@#To evaluate the clinical efficacy and prognostic factors of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery.@*Methods@#From December 2011 to December 2015, 152 cases of recurrent thoracic esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery were retrospectively analyzed. The overall survival (OS) after treatment failure, clinical efficacy and prognostic factors of different salvage treatments were analyzed. OS was calculated by Kaplan-Meier method. Prognostic analysis was performed by using multivariate Cox regression model.@*Results@#The median interval of the first recurrence was 10.6(2.0 to 69.1) months. The median OS after recurrence was 8.0(0.8 to 43.3) months. The 1-, 2-and 3-year OS rates after recurrence were 36.0%, 15.1% and 5.2%, respectively. The median OS of patients with locoregional recurrence alone, distant metastasis alone and locoregional recurrence combined with distant metastasis was 11.3(1.8 to 43.3) months, 6.7(1.2 to 28.6) months and 5.1(0.8 to 22.9) months, respectively. Multivariate analysis demonstrated that neoadjuvant chemotherapy (P=0.009), ypTNM stage (P=0.012), comprehensive treatment after recurrence (P=0.000) and locoregional recurrence (P=0.026) were independently correlated with the OS of patients with recurrent esophageal squamous cell carcinoma.@*Conclusions@#Neoadjuvant therapy, ypTNM stage, recurrence pattern and post-recurrence treatment are the independent risk factors for clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery. Clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy is not satisfactory. After recurrence, combined treatment mode should be adopted according to the site of recurrence and neoadjuvant treatment mode to maximize the benefits of salvage treatment.
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Objective@#To compare the effect of neoadjuvant chemoradiotherapy (NCRT) and neoadjuvant chemotherapy (NCT) on the survival of patients with esophageal cancer.@*Methods@#Clinical data of 275 cases of thoracic esophageal squamous cell carcinoma treated with neoadjuvant therapy combined with surgery from December 2011 to December 2015 were analyzed retrospectively. The data of treatment and follow-up were complete and analyzable. There were 70 cases in the NCRT group and 205 cases in the NCT group. The survival rate was calculated by Kaplan-Meier method and statistically compared by log-rank test, and multivariate analysis was performed by Cox regression model.@*Results@#The median follow-up time was 32(3-84) months. The median survival time and recurrence-free survival time was 42(3-84) months and 30(3-84) months, respectively. The overall 3-and 5-year survival rates were 56.8% and 45.9%, respectively, and the 3-and 5-year recurrence-free survival rates were 45.1% and 38.9%, respectively. The median survival time in the NCRT and NCT groups was 46(7-84) and 40(4-74) months, and the median recurrence-free survival time was 31(3-84) and 28(3-69) months, respectively. The 3-and 5-year overall survival of the two groups were 59.1%, 47.1% and 56.3%, 47.5%(P=0.515), and the 3-and 5-year recurrence-free survival were 44.5%, 40.1% and 47%, 39%, respectively. There was no significant difference in the survival between two neoadjuvant therapy modes (P=0.554). Multivariate analysis showed that postoperative pathological TNM staging was an independent factor affecting the prognosis of patients with esophageal cancer (P=0.001).@*Conclusions@#The survival results of NCRT are similar to those of NCT. Postoperative pathological staging is an independent survival factor.
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Objective To evaluate the prognostic value of a novel prediction model based on fibrinogen concentration in combination with neutrophil-to-lymphocyte ratio (F-NLR score) in patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant therapy and investigate their relationship with pathologic complete response (pCR).Methods Clinical data of 218 eligible ESCC patients treated with neoadjuvant therapy in the Affiliated Cancer Hospital of Zhengzhou University between 2012 and 2015 were retrospectively analyzed.The cut-off values for fibrinogen and neutrophil-to-lymphocyte ratio (NLR)were defined by the receiver operating characteristic (ROC) curve.The effects of different F-NLR scores on survival and pCR were evaluated.The survival rate was analyzed using the Kaplan-Meier method.The relationship among fibrinogen,NLR and pCR was analyzed by using Wilcoxon rank sum test.Results The 3-year overall survival (OS) rates with F-NLR scores of 0,1 and 2 were 72.1％,66.5％ and 50.2％(P=0.010),respectively.The corresponding 3-year disease-free survival (DFS) rates were 64.1％,60.2％ and 45.4％ (P=0.012),respectively.The clinical prognosis of patients with an F-NLR score of 2 was significantly worse compared with those of their counterparts with an F-NLR score of 0-1 (P=0.003).Multivariate analysis demonstrated that the F-NLR score (P=0.004) and TNM stage (P=0.000) were the independent prognostic factors.Conclusions The F-NLR score can be used as an independent prognostic factor for ESCC patients treated with neoadjuvant therapy,which is promising supplement to current TNM staging system,thereby facilitating more accurate risk stratification analysis and achieving individualized multidisciplinary treatment for ESCC patients.
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<p><b>OBJECTIVE</b>To observe the difference of clinical effects of acupoints selected based on meridian differen-tiation and conventional method for cervical spondylosis radiculopathy(CSR) treated with acupuncture and moxibustion.</p><p><b>METHODS</b>Sixty patients with CSR were randomly divided into an observation group and a control group,30 cases in each one.points of the injured meridians in the neck,namely six-points,were selected in the observation group,matched with-connecting points of the injured meridians on the same side and the interiorly-exteriorly correlated meridians on the opposite side. Conventional acupuncture was used on Fengchi(GB 20),Jiaji(EX-B 2) of the neck,Tianzhu(BL 10),Jianjing(GB 21),Houxi(SI 3),Hegu(LI 4) and Waiguan(TE 5) on the affected side in the control group. Treatment was given once every other day,three times a week and total 12 times in the two groups. Twenty subscales for CSR and visual analogue scale(VAS) were observed before and after treatment,and total effects were evaluated after treatment.</p><p><b>RESULTS</b>The effective rate of the observation group was 93.3%(28/30),which was better than 66.7%(20/30) of the control group(<0.05). The scores of 20 subscales and VAS after treatment were all improved compared with those before treatment in the two groups(all<0.01),with more apparent change in the observation group(both<0.05).</p><p><b>CONCLUSIONS</b>The effect of acupuncture and moxibustion based on meridian differentiation is obvious,and superior to that of conventional acupoints selection.</p>
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Objective: To observe hypoglycemic effects of Yunu Decoction, Zuogui Pill and Shenqi Pill, three compound traditional Chinese herbal medicines, in treatment of diabetes mellitus induced by alloxan in rats, and to compare the therapeutic effects among the three recipes for nourishing yin, clearing away heat, and nourishing yin and warming yang. Methods: Diabetes mellitus was induced in rats with alloxan at a dose of 60 mg/kg via tail vain injection. The diabetic rats were randomly divided into four groups: alloxan model group, Yunu Decoction-treated group, Zuogui Pill-treated group and Shenqi Pill-treated group. Rats in the three recipe groups were administered intragastrically with water extraction of Yunu Decoction, Zuogui Pill, and Shenqi Pill accordingly for 10 days. Then the level of blood glucose was measured by glucose oxidase method and the glucose tolerance was determined. Results: Compared with the normal rats, blood glucose level in the alloxan model group was obviously increased (P<0.05). Glucose levels in the three recipe groups were obviously decreased as compared with the alloxan model group (P<0.05), and glucose level in the Yunu Decoction-treated group after treatment was significant lower than before treatment (P<0.05). The glucose tolerance test indicated that rats in the alloxan model and three recipe groups revealed impaired glucose tolerance as compared with the normal rats, and there were no significant differences between the alloxan model group and the three recipe groups. Conclusion: Yunu Decoction, Zuogui Pill and Shenqi Pill can effectively decrease the glucose level of the rats with diabetes mellitus induced by alloxan, and Yunu Decoction showed the best therapeutic effects. The glucose tolerance test shows that the three recipes cannot correct the abnormal metabolism of glucose.