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| 1 | Multiple sgRNAs facilitate base editingmediated i-stop to induce complete and precise gene disruption显示文摘Dear Editor,Gene editing is a process to introduce desired changes into targeted loci of genomic DNA.Recently,type II clustered regularly in terspaced short palindromic repeats-associated Cas9 endonuclease(CRISPR/Cas9)system has been demonstrated as a versatile tool for engineering eukaryote genome(Hsu et al.,2014),such as in mice(Zuo et al.,2017). | Kun Jia Zongyang Lu Fei Zhou Zhiqi Xiong Rui Zhang Zhiwei Liu Yu'e Ma Lei He Cong Li Zhen Zhu Dejing Pan Zhengxing Lian | 2019 | Protein & Cell2019，10，11： | 3 |
| 2 | Generation of isogenic single and multiplex gene knockout mice by base editing-induced STOP显示文摘Although CRISPR/Cas9 has been widely used to generate knockout mice, two major limitations remain:the founders usually carry a mixture of genotypes, and mosaicism harboring multiple genotypes.Therefore, it takes a long time to get homozygous mutants. Recently developed base editing(BE) system,which introduces C-to-T conversion without double strand DNA cleavage, has been used to introduce artificial stop codons(i-STOP) to prematurely terminate translation, providing a cleaner strategy for genome engineering. Using this strategy, we generated CD160 KO and VISTA/CD160 double KO mice by microinjection of a single sg RNA targeting CD160 and a mixture of sg RNAs targeting VISTA and CD160,respectively. The BE system induced STOP efficiently in mouse embryos and consequently in founder mice without detectable off-target. Most interestingly, the majority of the mutants harbor same genetic modifications, indicating we generated isogenic single and multiplex gene mutant mice by BE-induced STOP. We also obtained homozygous mutant mouse in F1 mice, demonstrating the accelerated strategy in generating animal models. | Guang Yang Tianyu Zhu Zongyang Lu Guanglei Li Hao Zhang Songjie Feng Yajing Liu Jianan Li Yu Zhang Jia Chen Xuejiang Guo Xingxu Huang | 2018 | Science Bulletin2018，63，17： | 2 |
| 3 | 盐酸羟考酮控释片治疗晚期癌症疼痛的临床应用(英文)显示文摘Objective: The aim of this study was to evaluate the efficacy and adverse reactions of OxyContin hydrochloride controlled release tablets in the treatment of moderate or severe pain in patients with terminal cancer and to observe any improvement on the cancer patients' quality of life. Methods: Sixty-eight patients with moderate or severe cancer pain were treated with OxyContin hydrochloride controlled release tablets. The initial dose was 5 mg/12h, or 1/2 that of the standard morphine regimen. During the course of treatment, the dosage was adjusted according to the patients' condition until the pain completely disappeared or nearly did so. Each patient received a treatment for at least 15 days. At the same time, adverse reactions, the quality of life and scores for the intensity of pain were observed and recorded [1]. Results: The final titrated dosage of OxyContin was as follows: the patients in 30 cases (44.1%) received a dosage of ≤ 30 mg/d, those in 16 cases (23.5%) received a dosage of 31 to 60 mg/d, those in 18 cases (26.5%) received a dosage of 61 to 120 mg/d and those in 4 cases (5.9%) received a dosage of ≥ 120 mg/d. The overall rate of relief from pain was 95.6%, among which the rates of excellent, effective and moderate relief were respectively 39.7%, 48.5% and 7.4%. OxyContin had mild adverse reactions and patients' quality of life was markedly improved. Conclusion: OxyContin is effective in treatment of moderate and severe cancer pain. The adverse reactions of OxyContin are mild, and the drug can significantly improve the quality of life of patients with cancer pain. | Wenwu Wang Xuenong OuYang Zongyang Yu Zhangshu Chen | 2012 | The Chinese-German Journal of Clinical Oncology2012，11，7： | 2 |
| 4 | Allele-specific genome editing of imprinting genes by preferentially targeting non-methylated loci using Staphylococcus aureus Cas9(SaCas9)显示文摘Allele-specific DNA methylation is the most important imprinting marker localized to differentially methylated regions(DMRs),and aberrant genomic imprinted DNA methylation is associated with some human diseases,including Prader-Willi syndrome and cancer.Thus,the development of an effective strategy for the precise editing of allele-specific methylated genes is essential for the functional clarification of imprinting elements and the correction of imprinting disorders in human diseases.To discover a feasible allele-specific genome editing tool based on the CRISPR/Cas system,which is an efficient genetargeting technique in various organisms,we examined the targeting efficiency of Staphylococcus aureus Cas9(SaCas9)and Streptococcus pyogenes Cas9(SpCas9)in response to DNA methylation interference.We found that the targeting efficiency of SaCas9,but not SpCas9,was enhanced by targeted DNA demethylation using the d Cas9-Tet1 catalytic domain(CD)but suppressed by targeted DNA methylation using Dnmt3l-Dnmt3a-d Cas9.An in vitro cleavage assay further demonstrated that SaCas9 nuclease activity was inhibited by 5-methylcytosine(5mC)in a synthesized Cp G-containing context.Further analysis with Ch IP-Q-PCR demonstrated that the non-methylated sequence targeting of Sa Cas9 depends on the binding preference of SaCas9 to non-methylated sequences.Taking advantage of this feature of SaCas9,we have successfully obtained non-methylated allele-biased targeted embryos/mice for two imprinting genes,H19 and Snrpn,with relatively high efficiencies of 28.6%and 47.4%,respectively.These results indicate that the targeting efficiency of SaCas9 was strongly reduced by DNA methylation.By using SaCas9,we successfully achieved allele-specific genome editing of imprinting genes by preferentially targeting non-methylated loci. | Yajing Liu Jianan Li Changyang Zhou Bin Meng Yu Wei Guang Yang Zongyang Lu Qingmei Shen Yu Zhang Hui Yang Yunbo Qiao | 2019 | Science Bulletin2019，64，21： | 1 |
| 5 | Stable Inheritance of the Antisense Waxy Gene in Transgenic Rice with Reduced Amylose Level and Improved Quality显示文摘 | Qiaoquan Liu Zongyang Wang Xiuhua Chen Xiuling Cai Shuzhu Tang Hengxiu Yu Jinliu Zhang Menming Hong Minghong Gu | 2003 | Transgenic Research2003，，1： | 1 |
| 6 | Applied research on serum protein fingerprints for prediction of Qi deficiency syndrome and phlegm and blood stasis in patients with non-small cell lung cancer显示文摘OBJECTIVE:This study screened serum tumor biomarkers by surface enhanced laser desorption/ionization time-of-flight mass spectrometry(SELDI-TOF-MS) to establish a subset which could be used for the prediction of Qi deficiency syndrome and phlegm and blood stasis in patients with non-small cell lung cancer;and as diagnostic model of Chinese medicine.METHODS:Serum samples from 63 lung cancer patients with Qi deficiency syndrome and phlegm and blood stasis,and 28 lung cancer patients with non-Qi deficiency syndrome and phlegm and blood stasis were analyzed using SELDI-TOF-MS with a PBS II-C protein chip reader.Protein profiles were generated using immobilized metal affinity capture(IMAC3) protein chips.Differentially-expressed proteins were screened.Protein peak clustering and classification analyses were performed using Biomarker Wizard and Biomarker Pattern software packages,respectively.RESULTS:A total of 268 effective protein peaks were detected in the 1,000-10,000 Da molecular range for the 15 serum proteins screened(P<0.05).The decision tree model was M 2284.97,with a sensitivity of 96.2% and a specificity of 66.7%.CONCLUSION:SELDI-TOF-MS techniques,combined with a decision tree model,can help identify serum proteomic biomarkers related to Qi deficiency syndrome and phlegm and blood stasis in lung cancer patients;and the predictive model can be used to discriminate between Chinese medicine diagnostic models of disease. | Zhizhen Liu Zongyang Yu Xuenong OuYang Jian Du Xiaopeng Lan Meng Zhao | 2012 | Journal of Traditional Chinese Medicine2012，32，3： | 1 |
| 7 | Stable Inheritance of the Antisense Waxy Gene in Transgenic Rice with Reduced Amylose Level and Improved Quality显示文摘 | Qiaoquan Liu Zongyang Wang Xiuhua Chen Xiuling Cai Shuzhu Tang Hengxiu Yu Jinliu Zhang Menming Hong Minghong Gu | 2003 | Transgenic Research2003，，1： | 1 |
| 8 | DICE方案与CHOP方案治疗中高度恶性非霍奇金淋巴瘤的随机对照研究(英文)显示文摘Objective: To compare efficacies and safeties of DICE and CHOP regimens in treating intermediate and high grade non-Hodgkin's lymphoma (NHL), and indicate the standard treatment for it. Methods: A total of 74 patients with moder- ately or highly malignant NHL, verified by pathology or histology, were randomized into the trial group (37 patients treated with DICE regimen) and the control group (37 patients treated with CHOP regimen). Survival rate was analyzed by Kaplan-Meier method. Chi-square test was performed between groups. Results: The complete response rate, partial response rate, and response rate were significantly higher in DICE group than in CHOP group (40.5% vs. 29.7%, 37.8% vs. 27.0%, and 78.3% vs. 56.7%, respectively, P < 0.05). The 1-, 3-, and 5-year survival rates were significantly higher in DICE group than in CHOP group (89.2% vs. 81.2%, 76.0% vs. 52.6%%, and 46.7% vs. 36.4%, respectively, P < 0.05). The major side effects, appeared with no differences (P > 0.05) in incidences between the two groups, were leukopenia, thrombocytopenia, and nausea. There were only three episodes of clinical cystitis or gross haematuria in DICE regimen. Conclusion: The results showed higher efficacy of DICE regimen over CHOP regimen. DICE regimen may prolong the survival time of patients with moderately and highly malignant NHL. | Wenwu Wang Xuenong OuYang Zhangshu Cheng Yonghai Peng Fangwei Xie Zongyang Yu | 2008 | The Chinese-German Journal of Clinical Oncology2008，7，2： | 0 |
| 9 | 诱导化疗后同期放化疗治疗不能手术的Ⅲ期非小细胞肺癌的初步结果(英文)显示文摘Objective: The aim of our study was to evaluate the toxicity and efficacy of induction chemotherapy (ICT) followed by three-dimensional conformal radiotherapy (3D CRT) and concurrent weekly paclitaxel on unresectable non-small cell lung cancer (NSCLC). Methods: Stage Ⅲ NSCLC patients with favorable conditions were treated with 2 to 4 cycles of carboplatin (AUC = 5-6, d1) combined with paclitaxel (175 mg/m2 , d1), then followed by weekly paclitaxel (40 mg/m2 ) and concurrent 3D CRT within 3-4 weeks. The prescription dose was given as high as possible under the condition that V20 ≤ 31% and spinal cord dose ≤ 50 Gy. Results: Thirty-one patients were enrolled. ICT was well tolerated. During the concurrent chemoradiotherapy, the treatment of 3 patients was ended ahead of the schedule because of severe pulmonary and heart toxicities; the treatment of 2 patients was delayed for 7 and 12 days because of fatigue. Myelosuppression was mild (16/31): all were grade 1-2 except 1 was grade 3. Lymphocytopenia was more obvious (29/31, grade 3 in 21). Three patients developed grade 3 radiation-induced esophagitis, and 2 developed grades 3-4 radiation-induced pneumonitis. Two developed grade 3 esophageal stricture. No grades 3-4 pulmonary fibrosis was observed. The overall response rate was 74.1%. The 1-, 2-, 3-year overall survival rates were 74.2%, 41.9%, and 34.6%, respectively, with the median survival time of 18.5 months. The 1-, 2-, 3-year local progression-freely survival rates were 64.5%, 32.3%, and 20.5%, respectively, with the median local progression-freely survival time of 14.3 months. Conclusion: The program of ICT followed by weekly paclitaxel and 3D CRT is accomplished in most of the favorable stage Ⅲ NSCLC patients. The toxicity is tolerable, and the response rate is inspiriting. | Wenwu Wang Xuenong Ou-Yang Xi Chen Zongyang Yu | 2013 | The Chinese-German Journal of Clinical Oncology2013，12，7： | 0 |
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