Prognostic value of metabolic parameters of 18F-FDG PET/CT in advanced non-small cell lung cancer treated with first-line immunotherapy combined with chemotherapy / 中华放射医学与防护杂志

Objective:To investigate the prognostic value of metabolic parameters of 18F-fluorodeoxyglucose ( 18F-FDG) positron emission computed tomography/computed tomography(PET/CT) in advanced non-small cell lung cancer(NSCLC) treated with first-line immune checkpoint inhibitor (ICI) combined with chemotherapy. Methods:A retrospective study was conducted to evaluate patients with advanced NSCLC who underwent baseline PET/CT before treatment at the Affiliated Cancer Hospital of Zhengzhou University from 2019 to 2021. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-offs for metabolic parameters of PET/CT, including total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), and maximum standard uptake value (SUV max). Kaplan-Meier method, Log-rank test, and Cox regression model were used to calculate the overall survival (OS) and the progression-free survival(PFS). Results:A total of 44 patients were enrolled. Univariate analysis showed that the factors influencing PFS were TMTV and the number of metastatic sites ( χ2=4.19, 11.28, P<0.05) and the factors influencing OS were TMTV and TLG ( χ2=14.96, 6.05, P<0.05). Multivariate analysis suggested that number of metastatic sites was an independent prognostic marker for PFS ( P=0.011) and TMTV was an independent prognostic marker for OS ( P=0.038). Conclusions:TMTV is a prognostic indicator of OS while the number of metastatic sites is a prognostic indicator of PFS in advanced NSCLC patients who received first-line ICI combined with chemotherapy, but further prospective studies are needed.

Analysis of clinical efficacy of first-line immunotherapy combined with radiotherapy in patients with brain metastasis of non-small cell lung cancer / 中华放射肿瘤学杂志

Objective:To evaluate clinical efficacy of first-line immune checkpoint inhibitors (ICI) combined with radiotherapy (RT) in patients with newly diagnosed non-small cell lung cancer (NSCLC) with brain metastasis (BM).Methods:Clinical data of patients with BM of NSCLC diagnosed in Henan Cancer Hospital from December 2017 to June 2021 were retrospectively analyzed. Patients were treated with programmed death-1 (PD-1) / programmed death-ligand 1 (PD-L1) inhibitor combined with or without brain RT. The survival rate was calculated by Kaplan-Meier analysis. Univariate analysis was performed by log-rank test and multivariate analysis was performed by Cox model.Results:The median follow-up time was 13 months (range 4-49 months). The median overall survival (OS) time was 24 months, and the 1-, 2- and 3-year OS rates were 75.8%, 44.7%, and 33.6%, respectively. The 1-year intracerebral progression-free survival (iPFS) was 68.8%. The intracerebral objective response rate (icORR) of the RT-ICI group and ICI group was 71.4% and 52.6%, respectively, and the intracerebral disease control rate (icDCR) was 96.4% and 89.4%, respectively ( P=0.122,0.291). Univariate analysis showed that the 1-, 2- and 3-year OS rates of patients with high graded prognostic assessment (GPA) scores were 100%, 85.7% and 35.7%, respectively. The 1-, 2- and 3-year OS rates of patients with low GPA scores were 68.3%, 33.6% and 33.6%, respectively ( P=0.115). The 1-, 2- and 3-year OS rates of patients in the RT-ICI group were 88.7%, 58.7% and 44.0%, respectively, and 63.6%, 20.9% and 20.9% for their counterparts in the ICI group, respectively ( P=0.022). The 1-, 2- and 3-year OS rates of symptomatic patients with BM were 60.9%, 33.8% and 33.8%, respectively, while 84.6%, 53.1% and 39.8% for asymptomatic counterparts, respectively ( P=0.021). Multivariate analysis showed that no symptoms of BM and brain RT were the independent influencing factors of OS rate ( P=0.038, 0.037). Conclusions:First-line ICI combined with brain RT can improve the survival rate of patients with BM of NSCLC. It is recommended that patients with BM should receive RT as soon as possible, especially those with brain symptoms.

Analysis of recurrence patterns of early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy / 中华放射肿瘤学杂志

Objective:To analyze the failure patterns and influencing factors of stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (ES-NSCLC).Methods:113 cases of ES-NSCLC treated with SABR from 2012 to 2020 in our hospital were retrospectively analyzed. The failure patterns, recurrence time, recurrence site and influencing factors were analyzed. Kaplan-Meier method was used to calculate the local recurrence rate, regional lymph node recurrence rate and distant metastasis rate. Univariate analysis was performed by Log-rank test, and multivariate analysis was performed by Cox model.Results:The median follow-up time was 58 months (range: 6-108 months), and a total of 45 patients (39.8%) recurred. The median recurrence time was 36 months. Distant metastasis (DM) occurred in 31 patients (27.4%) and DM alone in 24 patients (21.2%). Local recurrence (LR) was developed in 12 patients (10.6%) and LR alone in 7(6.2%). Regional lymph node recurrence (RR) occurred in 11 patients (9.7%) and RR alone in 6 patients (5.3%). LR combined with RR was observed in 1 case (0.9%), LR combined with DM in 3(2.7%), LR combined with RR and DM in 1(0.9%), and RR combined with DM in 3(2.7%). The 1-, 2-, 3-, 4-and 5-year recurrence rates were 5.4%, 16.6%, 27.5%, 44% and 51.2%, respectively. Univariate and multivariate analyses suggested that EGFR mutation was an influencing factor of high recurrence rate.Conclusion:ES-NSCLC patients treated with SABR alone have a high recurrence rate, and DM is the most common mode of failure. Follow-up consolidation therapy is recommended, especially for EGFR mutation-positive NSCLC patients.

Relationship between lung immune prognostic and the prognosis of locally advanced non-small cell lung cancer treated with radiochemotherapy / 中华放射医学与防护杂志

Objective:To investigate the relationship between lung immune prognostic index (LIPI) and the prognosis of locally advanced non-small cell lung cancer (LA-NSCLC) treated with radiochemotherapy.Methods:A retrospective analysis was conducted for the clinical data of LA-NSCLC patients who received radiochemotherapy in the Affiliated Cancer Hospital of Zhengzhou University from 2013 to 2019. According to the hematologic test result of the derived neutrophil-to-lymphocyte ratio (dNLR) and the lactate dehydrogenase (LDH), the patients were divided into three groups according to their LIPI scores, namely the good-LIPI group with dNLR ≤ 3 and LDH ≤ upper limit of normal (ULN), moderate-LIPI group with dNLR >3 or LDH > ULN, and poor-LIPI group with dNLR >3 and LDH > ULN. Moreover, the overall survival (OS) and the progression-free survival (PFS) were calculated using the Kaplan-Meier method, the Log-rank test, and the Cox regression model.Results:A total of 238 patients were enrolled, and their median follow-up time was 37.1 months, median PFS 16.1 months, and median OS 30.6 months. The OS and PFS of the poor-LIPI group were significantly worse than those of the good- and moderate-LIPI groups ( χ2= 9.04, 2.88, P<0.05). The univariate analysis showed that the factors influencing OS included gender, pathological type, epidermal growth factor receptor (EGFR) mutations, and LIPI ( χ2=6.10, 13.66, 10.58, 9.04, P<0.05), and the PFS was only affected by the LIPI ( χ2=2.88, P = 0.03). Multivariate analysis suggested that EGFR mutations and LIPI were independent prognostic markers for OS ( HR = 1.31, 1.36; 95% CI: 1.03-1.67, 1.05-1.76; P<0.05). Conclusions:The LIPI is a potential prognostic indicator of radiochemotherapy in LA-NSCLC, and this result should be further confirmed by prospective studies.

Analysis of efficacy of different treatment modalities and prognostic factors in patients with locally advanced Masaoka-Koga stage Ⅲ thymoma / 中华放射肿瘤学杂志

Objective:To analyze the clinical efficacy of different treatment modalities and prognostic factors of patients with Masaoka-Koga stage Ⅲ thymoma.Methods:Clinical data of patients diagnosed with Masaoka-Koga stage Ⅲ thymoma admitted to Affiliated Cancer Hospital of Zhengzhou University from January 2000 to December 2018 were analyzed retrospectively. A total of 133 patients had complete treatment and follow-up data. Kaplan-Meier method was used to calculate the cumulative survival rate, log-rank method was used to compare the survival between two groups, and Cox regression model was used for multivariate analysis.Results:The median follow-up time was 50 months (3-221 months). The median overall survival (OS) was 51 (3-221) months, and the median disease-free survival (DFS) was 45 (2-221) months. The survival rate in the radical surgery group was better than that in the palliative surgery group. The 5- and 10-year OS rates in radical surgery group were 88.2% and 74.4% respectively, while in palliative surgery group were 51.8% and 32.4% respectively ( P<0.001). The 5- and 10-year DFS rates in radical surgery group were 72.2% and 45.5%, respectively, while in palliative surgery group were 32.3% and 16.1% respectively ( P=0.001). The OS in the surgery combined with radiotherapy group was better than that in the surgery alone group. The 5- and 10-year OS rates in the radical surgery group were 82.8% and 64.2% respectively, while in the palliative surgery group were 55.8% and 50.2% ( P=0.033). There was no significant difference in DFS between two groups ( P=0.176). Multivariate analysis showed that age < 50 years old ( HR=0.264, P=0.001), radical resection ( HR=0.134, P<0.001), surgery combined with radiotherapy ( HR=2.778, P=0.009) were independently associated with better OS. Age < 50 years old ( HR=0.550, P=0.046), radical resection ( HR=0.555, P=0.042), and invasion of single organ ( HR=0.111, P=0.003) were independently associated with better DFS. Conclusions:OS and DFS in patients undergoing radical surgery are significantly better than those in their counterparts treated with palliative surgery, which is the most important factor affecting prognosis. Surgery combined with radiotherapy yields better OS. It is necessary to design a rigorous and reasonable multicenter prospective study to evaluate the efficacy of various treatment modalities and prognostic factors.

Analysis of invasion characteristics and prognostic factors of patients with Masaoka-Koga stage Ⅲ thymoma / 中华放射肿瘤学杂志

Objective:To analyze the invasion characteristics and prognostic factors of patients with Masaoka-Koga stage Ⅲ thymoma.Methods:The tumor invasion characteristics of 179 patients who were diagnosed with Masaoka-Koga stage Ⅲ thymoma and treated in Affiliated Cancer Hospital of Zhengzhou University from January 2000 to June 2018 were analyzed retrospectively. According to the treatment methods, all patients were divided into the radical operation group ( n=94), palliative operation group ( n=39) and simple biopsy group ( n=46). The χ2 test was used to compare the classified variables, Kaplan- Meier method was utilized to calculate the cumulative survival rate, log-rank method was used for group comparison and univariate analysis, and Cox’s regression model was used for multivariate analysis. Results:Mediastinal pleural invasion (86.0%) was the most common site, followed by pericardium (50.8%), great vessel (40.8%) and lung (36.3%). The proportion of macrovascular invasion in the radical operation group was 14.9%, significantly lower than 79.5% and 60.9% in the palliative surgery group and biopsy group (both P<0.001). Multivariate analysis showed that the nature of operation ( P<0.001), age ( P=0.011), radiotherapy ( P=0.020) were the independent factors affecting overall survival (OS), while nature of operation ( P<0.001), age ( P=0.004), radiotherapy ( P=0.020), number of invasive organs ( P=0.023) and pathological type ( P=0.016) were the independent factors affecting progress-free survival (PFS). Conclusions:For patients with Masaoka-Koga stage Ⅲ thymoma, mediastinal pleura is the most common site of invasion, pericardium, lung and great vessels are also commonly invaded. The invasion of mediastinal pleura, pericardium and lung exerts slight effect on surgical resectability, whereas great vessel involvement can significantly affect surgical resectability. OS and PFS in patients undergoing radical resection are significantly better than those in patients treated with palliative resection and biopsy. Radical resection is the most important factor affecting prognosis.

Long-term therapeutic effect of stereotactic ablative radiotherapy for pulmonary oligometastasis / 中华放射肿瘤学杂志

Objective:To evaluate the efficacy and safety of stereotactic ablative radiotherapy (SABR) in patients with pulmonary oligometastases.Methods:Clinical data of patients with pulmonary metastases treated with SABR from 2011 to 2018 were retrospectively analyzed. The local control rate (LCR) and overall survival (OS) were calculated by Kaplan- Meier method. log-rank test was used for univariate analysis and Cox’s regression model for multivariate analysis. Results:A total of 214 lung metastases were detected in 159 patients, and the median follow-up time was 43 months. The 1-, 3-and 5-year LCR were 90.1%, 73.9% and 65.8%, respectively. The 1-, 3-and 5-year OS were 73.8%, 43.6% and 11.9%, respectively. Univariate analysis showed that biological effective dose (BED)≥100 Gy was significantly correlated with LCR ( P=0.033). Cox’s multivariate analysis showed that BED and primary tumor source were the independent prognostic factors of LCR ( P=0.023, P=0.043). No>grade 3 adverse events were observed in all patients during treatment. Conclusions:SABR is a safe and effective treatment of lung oligometastases. SABR should be actively aD ministered for pulmonary oligometastases, especially for those with lesions from lung cancer and the radiation dose should be selected as BED ≥100 Gy.

The feather degradation mechanisms of a new Streptomyces sp. isolate SCUT-3.

Feather waste is the highest protein-containing resource in nature and is poorly reused. Bioconversion is widely accepted as a low-cost and environmentally benign process, but limited by the availability of safe and highly efficient feather degrading bacteria (FDB) for its industrial-scale fermentation. Excessive focuses on keratinase and limited knowledge of other factors have hindered complete understanding of the mechanisms employed by FDB to utilize feathers and feather cycling in the biosphere. Streptomyces sp. SCUT-3 can efficiently degrade feather to products with high amino acid content, useful as a nutrition source for animals, plants and microorganisms. Using multiple omics and other techniques, we reveal how SCUT-3 turns on its feather utilization machinery, including its colonization, reducing agent and protease secretion, peptide/amino acid importation and metabolism, oxygen consumption and iron uptake, spore formation and resuscitation, and so on. This study would shed light on the feather utilization mechanisms of FDBs.

Prognostic analysis of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgical treatment / 中华放射肿瘤学杂志

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.

Analysis of recurrence pattern of neoadjuvant therapy combined with surgical treatment for esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

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.

The role of salvage radiotherapy in re-treatment of esophageal squamous cell carcinoma with regional lymph node oligo-recurrence after surgery / 中华放射肿瘤学杂志

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.

Analysis of clinical outcomes and prognostic factors in 109 patients with early-stage non-small cell lung cancer treated with stereotactic ablation radiotherapy / 中华放射肿瘤学杂志

Objective:To evaluate the long-term survival and identify prognostic factors of patients diagnosed with early-stage non-small cell lung cancer (ES-NSCLC) receiving stereotactic ablation radiotherapy (SABR).Methods:Clinical data of 109 ES-NSCLC patients treated with SABR in Henan Cancer Hospital from 2011 to 2018 were retrospectively analyzed. The overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) were calculated by Kaplan- Meier method and log-rank test. Multivariate prognostic analysis was performed by Cox regression model. Results:The median follow-up time was 44 months (2-93 months). The median OS, CSS and PFS were 78 months, 78 months and 44 months, respectively. The 1-year OS, CSS and PFS were 95.4%, 97.2% and 84.1%, and 75.6%, 79.1% and 56.6% for the 3-year OS, CSS and PFS, and 55.6%, 60.7% and 37.3% for the 5-year OS, CSS and PFS, respectively. Univariate analysis showed that ECOG score, age, smoking history and derived-neutrophil/lymphocyte ratio (dNLR) were the influencing factors of OS ( P=0.03, 0.02, 0.04, 0.001). Age, smoking history and dNLR were the influencing factors of CSS ( P=0.02, 0.03, 0.001). Multivariate analysis demonstrated that dNLR was an independent prognostic factor for OS and CSS ( P=0.001, 0.001). Conclusions:ES-NSCLC patients treated with SABR can achieve favorable survival. The dNLR is an independent prognostic factor of OS and CSS, which can be considered in clinical application.

Prognostic analysis of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgical treatment / 中华放射肿瘤学杂志

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.

Reply to: Comments on "Nomograms based on inflammatory biomarkers for predicting tumor grade and micro-vascular invasion in stage I/II hepatocellular carcinoma".

We appreciate to receive commentary from Dr Guangtong Deng and Dr Liang Xiao to our article, "Nomograms based on inflammatory biomarkers for predicting tumor grade and micro-vascular invasion in stage I/II hepatocellular carcinoma". First, neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR) are two different parameters. Some studies show that NLR is inconsistent with dNRL in prognostic value through multivariate Cox regression, therefore, it is reasonable that both NLR and dNLR entered into multivariate analysis simultaneously. Second, it is common that articles of predictive nomograms turned continuous variables into categorical variables. The reason is that the categorization of patient clinical variables is beneficial to doctors to make decisions based on the risk level of individual patients in clinical. At last, multicenter validation is quite difficult and we have listed the shortcomings in the limitations of our article. Further validation will need the joint efforts by other institutions.

Enzymatic characteristics of a recombinant protease (rPepD) from Aspergillus niger expressed in Pichia pastoris.

The Aspergillus niger AS3.350 protease gene (pepD) was successfully cloned and expressed in Pichia pastoris KM71. The rPepD activity was 331.5 U/ml, and the optimum temperature and pH were 45 °C and 8-9 respectively. In addition, enzyme activity was significantly inhibited by PMSF, EDTA, Mg2+, Fe2+ and Zn2+ ions, and stimulated by Ca2+ which selectively bound to the T302 and D323 residues. Mutation in either or both of the residues inhibited rPepD expression, indicating that binding to Ca2+ is necessary for PepD expression and activity. The rPepD showed a wide substrate range, and was particularly selective to those with hydrophobic amino acids. The degree of rPepD-mediated hydrolysis of soy protein isolate, corn flour and gluten meal were 8.7%, 38.1% and 33.6% respectively, which was higher than that by Alcalase, indicating that rPepD has potential applications in the food processing industry.

Heterologous expression and characterization of an antifungal chitinase (Chit46) from Trichoderma harzianum GIM 3.442 and its application in colloidal chitin conversion.

In this study, a chitinase gene, Chit46 from a mycoparasitic fungus Trichoderma harzianum was successfully expressed in Pichia pastoris with a high heterologous chitinase production of 31.4 U/mL, much higher than the previous reports. The active center and substrate binding pocket of the recombinant Chit46 (rChit46) were analyzed and the effects of pH, temperature, metal ions and glycosylation on its activity were tested. rChit46 effectively hydrolyzed colloidal chitin with a high conversion rate of 80.5% in 3 h and the chitin hydrolysates were mainly composed of (GlcNAc)2 (94.8%), which make it a good candidate for the green recycling of chitinous waste. rChit46 could also significantly inhibit growth of the phytopathogenic fungus Botrytis cinerea, which endowed it with the potential as a biocontrol agent.

Ilexgenin A inhibits mitochondrial fission and promote Drp1 degradation by Nrf2-induced PSMB5 in endothelial cells.

Atherosclerosis (AS) is one of important events involving in the pathological process of coronary artery disease. Many traditional Chinese medicines have been widely used for the treatment of AS. Previous studies have demonstrated that Ilexgenin A (IA) obtained from Ilex hainanensis Merr. could improve AS development. However, its underlying mechanism is still unknown. This study was conducted to explore the possible targets and mechanisms involving in the anti-atheroclerosis effect of IA. The results showed IA significantly promoted NO production, reduced reactive oxygen species (ROS) generation, and inflammatory cytokine production induced by palmitate (PA) in endothelial cells, demonstrating IA could improve endothelial dysfunction. Meanwhile, IA dramatically inhibited dynamin-related protein 1 (Drp1) expression and mitochondrial fission induced by PA whereas proteasome inhibitor epoxomicin attenuated its effect on Drp1 expression, indicating IA decreased Drp1 expression with regulation of proteasome. Furthermore, IA also could increase the expression of proteasome subunit beta type5 (PSMB5) and activate nuclear factor-like 2 (Nrf2). Nrf2 knockdown eliminated the induction effect of IA on PSMB5 expression while abrogated its inhibition on ROS generation and mitochondrial fission stimulated by PA. These results demonstrated that IA could promote PSMB5 expression in an Nrf2-dependent manner, resulting in the suppression of mitochondrial fission, and thus improve endothelial dysfunction. These findings laid a foundation to the future development of IA as an agent to the prevention and treatment of AS.

Overexpressing miR-29c targeting AKT2 enhances the radiosensitivity of human hepatocellular carcinoma cell line HepG2 / 中华放射医学与防护杂志

Objective To investigate the effect of miR-29c on radiosensitivity of hepatoma HepG2 cells by targeting AKT2 gene.Methods The expression of miR-29c in human normal hepatocytes THLE-3 and hepatoma cell HepG2 was detected by RT-PCR.The relationship between miR-29c and AKT2 were predicted by predicted by informative analysis and verified by dual luciferase reporter gene test and Western blot.miR-29c mimic/AKT2 gene recombinant plasmid and miR-29c inhibitor/ lentivirus vector AKT2 shRNA were transfected into HepG2 cells by Liposome 2000.The cells were irradiated with different doses (0,2,4,6 and 8 Gy) of X-rays,and the effects of miR-29/AKT2 on the survival and cell viability of HepG2 cells were detected by cloning and MTT assays.Results Compared with THLE-3 cells,the expression of miR-29c in HepG2 cells was significantly lower (t=17.816,P＜0.05).After 2,4,6 and 8 Gy X-ray irradiation,the survival of HepG2 cells was significantly lower than that of THLE-3 cells (t =4.541,6.823,7.218,9.363,P＜0.05),and the expression of miR-29c in HepG2 cells was significantly decreased (t =5.599,9.262,10.470,10.873,P＜0.05).The survival and viability of HepG2 cells were decreased by miR-29c overexpression (tsurvival rate =4.307,7.668,7.668,6.894,P＜0.05;tcell viability =3.443,8.116,13.434,P ＜ 0.05) but they were increased by miR-29c inhibition (tsurvival rate =4.003,6.713,7.141,P＜0.05;tcell viability =4.282,5.113,P＜0.05).Double luciferase reporter gene experiments showed that AKT2 was the target gene of miR-29c since the expression of AKT2 was negatively regulated by miR-29c.After the silence of AKT2 or overexpression of AKT2,the survival and viability of HepG2 cells were consistent with the overexpression of miR-29c or the inhibition of miR-29c,respectively.Conclusions MiR-29c increases the radiosensitivity of hepatoma cell HepG2 by targeting AKT2.

Prognostic significance of fibrinogen concentration combined with neutrophil-to-lymphocyte ratio in esophageal squamous cell carcinoma patients receiving neoadjuvant therapy / 中华放射肿瘤学杂志

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.

Comparison of survival between neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy followed by surgery for esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

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.