1.Isolation and characterization of bacteriophage against extended-spectrumβ-lactamase-producing Escherichia coli strains
Leijie HUANG ; Xiaoliang LIU ; Rui ZHU ; Fangqi LIN ; Jinhong QIN ; Ping HE ; Xiaokui GUO ; Wei ZHAO
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(8):1069-1073
Objective · To isolate phages which can fight against extended-spectrum β-lactamase (ESBLs)-producing Escherichia coli (E. coli), and provide basic research for establishment of E. coli phage library and treatment of bacterial infection. Methods · Samples collected from sewage were co-cultured with 93 ESBLs-producing E. coli strains. A phage named JDEC001 was isolated by double agar overlay plaque assay. The biological characteristics, complete genome sequence and comparative genome analyses of JDEC001 were studied respectively. Results · JDEC001 belongs to the lytic phage as a member of the Caudovirales order, Podoviridae family. It has high activity at pH from 5 to 11 and with temperature from 0 to 39 ℃ .Whole-genome sequencing of JDEC001 demonstrated double-stranded DNA genome of 38745 bp with GC content of 49.93%, which encoded 46 open reading frames. The comparative genomics also showed that there was no virulent genes or antibiotic resistant genes in its genome. Conclusion · The phage JDEC001 against ESBLs-producing E. coli was isolated and purified, with good stability in a broad range of pH and temperature.
2.Prognostic value and sensitivity to chemotherapy of microsatellite instability in advanced colorectal cancer
Yuchen WU ; Changsheng ZHANG ; Fei LIANG ; Dan HUANG ; Ji ZHU ; Ye XU ; Fangqi LIU
China Oncology 2015;(7):522-528
Background and purpose:Microsatellite instability (MSI) status is commonly applied to predict the prognosis and chemosensitivity in stage Ⅱ and stage Ⅲ colorectal cancer patients. However, researches of its function on metastasis colorectal cancer are limited. This study investigated its value on prognosis and chemosensitivity in metastatic colorectal cancer (CRC) patients.Methods:We retrospectively investigated tumor tissues from metastasis CRC patients who were treated with oxaliplatin and 5-FU-based therapy regimens (FOLFOX and XELOX). Immunostaining of proteins of the mismatch repair genehMLH1,hMSH2,hMSH6 andhPMS2 was performed. Prognostic value and chemosensitivity in patients with MSI status were also determined.Results:Clinical features from 113 patients were analyzed. No cor-relation of overall survival (OS) and chemosensitivity with MSI status was found. We further investigated 79 patients with synchronous metastasis and palliatively tumor resection. Median progression free survival (PFS) from 22 MSI patients was significant longer than that in 57 MSS patients (19.9 monthsvs 7 months,P=0.005). No significant difference was seen in OS comparison (P=0.07). MSI status was also an independent prognostic factors of PFS by Cox multivariate analysis (MSS/MSI,HR=2.079,P=0.043). Moreover, in this group, MSI patients had improved disease control rate (59.1%vs 31.6%, P=0.025) in chemosensitivity analysis than MSS patients.Conclusion:A better PFS in MSI patients with synchronous metastasis and palliative tumor resection was found after treated with oxaliplatin and 5-FU-based therapy and a better chemosensitivity in MSI patients was also found.
3.Advance in research on the correlation between genotypes of susceptible mutations and clinical phenotype of familial adenomatous polyposis.
Shengliang HE ; Jing DU ; Fangqi LIU
Chinese Journal of Medical Genetics 2017;34(6):919-923
Familial adenomatous polyposis (FAP) is one of the most common hereditary colorectal cancers. Its intestinal and extra-intestinal manifestations are correlated with mutation sties of the APC gene. Potential gene modulation sites in patients who have typical clinical manifestations but with unidentified APC mutations are also discussed, which included MUTYH gene, AXIN gene and certain epigenetic changes. With the generalization of Precision Medicine, to offer individualized treatment and surveillance strategy based on the genotype-phenotype correlation will be of great value for FAP patients. This review focuses on the research advance in genotype - phenotype correlation studies of FAP patients.
Adenomatous Polyposis Coli
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genetics
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Axin Protein
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genetics
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DNA Glycosylases
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genetics
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Genes, APC
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Genetic Association Studies
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Genetic Predisposition to Disease
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Humans
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Mutation
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beta Catenin
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genetics
4.Analysis of thalassemia-related mutations in Pingxiang area of Jiangxi.
Jianling GAN ; Fangqi DING ; Hongyu LIU
Chinese Journal of Medical Genetics 2020;37(10):1101-1103
OBJECTIVE:
To study the distribution of α- and β -thalassemia-related mutations in Pingxiang area of Jiangxi Province, China.
METHODS:
PCR and reverse dot blotting (PCR-RDB) were carried out to detect common mutations of α and β globin genes among 2558 individuals with positive results of primary screening.
RESULTS:
The PCR-RDB assay has identified 1222 carriers of thalassemia-related mutations, which yielded a detection rate of 47.8%. Among these, 645 individuals (including homozygous patients) have carried α globin gene mutations, with the common types including -αSEA/αα, -α/αα and -α/αα. 539 individuals have carried β globin gene mutations, with the common types including IVS-Ⅱ-654, CD41-42, CD17, CD28, CD27-28, βE, and CD71-72. Thirty eight individuals (1.5%) have carried α and β globin gene mutations simultaneously.
CONCLUSION
The carrier rate for α and β globin gene mutations in Jiangxi is high. Attention should be paid to newborn screening as part of the birth defect prevention and control program in order to reduce the birth rate of thalassemia in this region.
5.Colorectal cancer heterogeneity: genotype, phenotype and clinical manifestation.
Sanjun CAI ; Junjie PENG ; Fangqi LIU
Chinese Journal of Gastrointestinal Surgery 2017;20(10):1099-1103
Colorectal cancer is the third high-incidence of malignant tumors in the world, and also a kind of tumor with good biological behavior and good efficacy. Colorectal cancer heterogeneity is a very important trait of its biological behavior, which can be reflected in many different aspects, including tumor type, pathogenesis, molecular phenotyping and time-space heterogeneity. Different pathogenesis produces different tumor phenotypes, which are generated in the process of natural evolution and intervention. Various phenotypes show the difference among different individuals of colorectal cancer, in terms of clinical characteristics, treatment response and prognosis. Understanding the heterogeneity of colorectal cancer has important clinical value for individualized treatment.
6. Adjuvant and perioperative neoadjuvant therapy for colorectal cancer
Chinese Journal of Gastrointestinal Surgery 2019;22(4):315-320
Colorectal cancer is one of the most common malignant tumors in the world, threatening human health. The treatment strategy of stage II and stage III colorectal cancer has changed from surgery alone to multidisciplinary mode emphasizing perioperative treatment. The indication of adjuvant chemotherapy for stage II colon cancer is still defined by high-risk factors, but only microsatellite status and
7.The differences between three distinct locations of colorectal cancers based on clinicopathological characteristics and molecular features.
Cong LI ; Zhimin WANG ; Jiang ZHAO ; Sanjun CAI ; Ye XU ; Fangqi LIU
Chinese Journal of Preventive Medicine 2014;48(12):1078-1082
OBJECTIVETo investigate the differences of clinical characteristics and molecular features among colorectal cancer subsides and provide evidence for colorectal cancer protection, diagnosis and treatment.
METHODSAll of 4 316 colorectal patients from Shanghai cancer center were selected for clinical character analysis, among which, 2 224 subjects for molecular feature analysis. Clinic pathological characteristics like age, gender, tumor types, histological types, differentiation and T-stage, as well as molecular features like hMLH1, hMSH2, CD44, p21, p53, COX2,E-cadherin, Her2 and Ki-67, were involved into this research.
RESULTSIt showed that compared with left-sided colon and rectal cancers, right-sided cancers occurred more in women (46.0% (541/1 176); 39.2% (424/1 083); 41.2% (848/2 057), respectively, χ² = 11.85, P < 0.01), had more mucinous or signet-ring carcinoma (12.0% (128/1 064), 5.8% (56/960), 4.0% (75/1 859), respectively, χ² = 31.27, P < 0.01), poor differentiated carcinoma (32.1% (343/1 069), 19.5% (201/1 033), 19.3% (380/1 967), respectively, χ² = 72.66, P < 0.01) , and advanced T stage (87.9% (992/1 129), 83.2% (869/1 045), 72.2% (1 486/2 057), respectively, χ² = 121.44, P < 0.01). Meanwhile, the rates of hMLH1 were higher in right-sided colon cancers when compared with rectal cancers (13.4% (59/439) vs 8.5% (88/1 035), OR (95%CI): 1.67 (1.18-2.37)), as well as the rates of hMSH2 negative expression (4.9% (22/452) vs 2.4% (26/1 083), OR (95% CI): 2.08(1.17-3.71)). The rates of p53 positive expression were higher in right-sided colon cancers when compared with rectal cancers (76.2% (321/421) vs 68.4%, (776/1 134), OR (95% CI): 0.68 (0.52-0.87)). Compared with right-sided colon cancers, the rates of Her2 positive expression were higher in rectal cancers (19.3% (176/913) vs 13.2% (45/340), OR (95% CI): 1.57 (1.10-2.23)) , as well as the rates of Ki-67 expression which was positive in more than 50% cells (73.6% (840/1 141) vs 65.6% (299/456), OR (95% CI): 0.68 (0.54-0.86)).
CONCLUSIONThere are specific characteristics in right-sided colon cancers. The difference of molecular features between right-sided colon and rectal cancers are more significant.
Adenocarcinoma, Mucinous ; Cadherins ; Carcinoma ; Carcinoma, Signet Ring Cell ; China ; Colonic Neoplasms ; Colorectal Neoplasms ; Female ; Humans ; Neoplasm Grading ; Neoplasm Staging ; Rectal Neoplasms ; Sex Factors
8. Analysis of risk factors for postsurgical gastroparesis syndrome (PGS) after operation for gastric cancer
Delian LIU ; Xuewei ZHANG ; Fangqi LYU
Chinese Journal of Oncology 2017;39(2):150-153
Objective:
To investigate the risk factors for postsurgical gastroparesis syndrome (PGS) after surgery for stomach cancer.
Methods:
A total of 684 patients with gastric cancer who underwent surgery for stomach cancer from Jan. 1, 2010 to Dec. 31, 2014 in Tai′an Tumor Prevention and Treatment Hospital, including 475 males and 209 females, with an average age of 59.9 years were identified and included in this study. There were 206 cases of gastric cardia and gastric fundus cancers and 478 cases of gastric antrum cancer. 206 cases underwent proximal radical subtotal gastrectomy and D2 lymph node dissection, 478 distal radical subtotal gastrectomy, 206 residual esophagogastric anastomosis, 311 Billroth-Ⅰ anastomosis, 99 Billroth-Ⅱ anastomosis, and 68 Billroth-Ⅱ plus Roux-en-y anastomosis. The incidence and risk factors of PGS were analyzed.
Results:
All of the 684 patients were successfully operated.Among them, 48 (7.0%)encountered PGS. The univariate analysis showed that age, smoking index, alcohol consumption index,
9.A study on multiparametric MRI-based radiomics approach to preoperatively estimating tumor-stroma ratio in rectal cancer
Chongpeng CAI ; Tingdan HU ; Jing GONG ; Dan HUANG ; Fangqi LIU ; Tong TONG
Chinese Journal of Radiology 2021;55(11):1135-1140
Objective:To develop and validate a radiomics biomarker for the preoperative estimation of the tumor-stroma ratio (TSR) in rectal cancer.Methods:From January 2016 to March 2019, totally 149 patients with rectal cancer were enrolled retrospectively at Fudan University Shanghai Cancer Center. The patients were divided into two cohorts using a random number table, 119 in the training and 30 in validation cohorts. The patients were classified into the TSR-high group (TSR>50%) and TSR-low group (TSR≤50%) according to the content of tumor stroma in pathology. All patients underwent T 2WI, enhanced T 1WI and DWI. The lesions on the T 2WI, enhanced T 1WI, DWI and ADC images were delineated and radiomics features were extracted. A radiomics signature (rad-score) was generated by using the least absolute shrinkage and selection operator (LASSO) algorithm. The Spearman correlation coefficients were used to determine the association between rad-score and TSR. The area under the ROC curve (AUC) was used to assess the diagnostic performance of the rad-score. The reliability of the rad-score was quantified by calculating the sensitivity, specificity and accuracy of TSR. Results:With LASSO, a rad-score with 13 radiomics parameters was successfully constructed and was positively correlated with TSR score in the training ( r=0.72, P<0.001) and validation cohorts ( r=0.46, P=0.011). In the training cohort, the AUC of the rad-score was 0.940, with the sensitivity, specificity, accuracy of 100%, 87.3%, 92.4%. In the validation cohort, the AUC was 0.796, with the sensitivity, specificity, accuracy of 83.3%, 67.7%, 73.3%. Conclusions:The rad-score is of promising value for TSR estimation in rectal cancer. It is a promising supplement for patient stratification and may inform decision-making.
10.Study on protective effect and mechanism of Modified Yupingfeng nasal spray on nasal mucosal injury in AR model rats
Yuan XI ; Xinning HE ; Yuyin LIU ; Na ZHANG ; Ting LIU ; Fangqi LIANG ; Li TIAN
China Pharmacy 2023;34(10):1204-1210
OBJECTIVE To study protective effect and potential mechanism of Modified yupingfeng nasal spray (YPF+) on nasal mucosal injury in allergic rhinitis (AR) model rats. METHODS AR model was induced by ovalbumin (OVA) and randomly divided into model group, YPF+group (50 µg/side,twice a day), positive control group (Mometasone furoate aqueous nasal spray, 50 µg/side,once a day); the blank group was set up, with 10 rats in each group. Administration groups were given relevant medicine, and blank group and model group were given equivalent normal saline for consecutive 4 weeks. Thirty minutes after last medication, the behavioral scores of rats were recorded, and the pathological changes of their nasal mucosa tissue were observed. The level of reactive oxygen species (ROS) in nasal mucosa tissue was detected. The protein and mRNA expressions of nucleotide- binding oligomerization domain-like receptor protein 3 (NLRP3),caspase-1,gasdermin D (GSDMD) were detected; the contents of interleukin-1β (IL-1β) and IL-18 in serum were also determined. RESULTS Compared with blank group, in model group, the nasal mucosa tissue structure was disordered, inflammatory cells infiltrated seriously, and lamina propria vascular dilation was visible; its behavioral score and pathological score, the level of ROS, protein and mRNA expressions of NLRP3, caspase-1 and GSDMD, serum contents of IL-1β and IL-18 in nasal mucosa tissue were increased significantly (P<0.05). Compared with model group, the symptoms of nasal mucosal injury in rats of each drug group were improved to varying degrees, and the above indicators were significantly reduced (P<0.05). CONCLUSIONS YPF+ may improve nasal mucosal injury of rats, relieve AR symptoms such as sneezing, itchy nose, runny nose, the mechanism of which may be associated with reducing the production of ROS in nasal mucosa and downregulating NLRP3/caspase-1/ GSDMD pathway.