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Structural basis of negative regulation of CRISPR-Cas7-11 by TPR-CHAT

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2716-2725页

作者： Tian Hong qinghua luo Haiyun Ma Xin Wang Xinqiong Li Chongrong Shen Jie Pang Yan Wang Yuejia Chen Changbin Zhang Zhaoming Su Haohao Dong Xiaodi Tang Department of Laboratory Medicine State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduChina Frontiers Medical Center Tianfu Jincheng LaboratoryWest China HospitalSichuan UniversityChengduChina

CRISPR‒Cas7-11 is a Type Ⅲ-E CRISPR-associated nuclease that functions as a potent RNA editing ***-peptide repeat fused with Cas/HEF1-associated signal transducer(TPR-CHAT)acts as a regulatory protein that interacts with CRISPR RNA(crRNA)-bound Cas7-11 to form a CRISPR-guided caspase complex(Craspase).However,the precise modulation of Cas7-11’s nuclease activity by TPR-CHAT to enhance its utility requires further ***,we report cryo-electron microscopy(cryo-EM)structures of Desulfonema ishimotonii(Di)Cas7-11-crRNA,complexed with or without the full length or the N-terminus of *** structures unveil the molecular features of the Craspase *** analysis,combined with in vitro nuclease assay and electrophoretic mobility shift assay,reveals that DiTPR-CHAT negatively regulates the activity of DiCas7-11 by preventing target RNA from binding through the N-terminal 65 amino acids of DiTPR-CHAT(DiTPR-CHAT_(NTD)).Our work demonstrates that DiTPRCHAT_(NTD) can function as a small unit of DiCas7-11 regulator,potentially enabling safe applications to prevent overcutting and offtarget effects of the CRISPR‒Cas7-11 system.

关键词： CRISPR crRNA TPR

Preprocessing and Efficacy Analysis of Comprehensive Anti-Inflammatory Treatment for Lymphedema in Patients with Irritating Contact Dermatitis

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Journal of Cosmetics, Dermatological Sciences and Applications 2024年第2期14卷 188-199页

作者： Qiaoling Zhong Feng Liu Huiting Zhang Liping Zhang Jinlan Li Lijuan Zhang Na Li qinghua luo Cancer Prevention and Treatment Center Affiliated to Sun Yat-Sen University State Key Laboratory of South China Oncology Guangzhou China

Objective: To explore the pre-treatment and efficacy analysis of comprehensive anti-inflammatory treatment for lymphedema in patients with irritating contact dermatitis. Method: Convenience sampling method was used to observe the skin of 160 patients with upper limb lymphedema admitted to the lymphedema outpatient department of our hospital. They were divided into an observation group (80 cases) and a control group (80 cases), and both groups received a course of comprehensive anti-inflammatory treatment (20 treatments). The control group received routine skin care;On the basis of the control group, the observation group received pre-treatment of the affected limb skin: Laofuzi herbal ointment was applied externally to the prone areas of irritating contact dermatitis (such as the upper arm, inner forearm, and cubital fossa). Result: The incidence of irritating contact dermatitis in the observation group was significantly lower than that in the control group (P 0.05). Patients in the observation group felt significantly better in terms of comfort, skin moisture, and itching relief after being wrapped with low elasticity bandages than those in the control group (P Conclusion: Preventive treatment can effectively reduce the incidence of irritating contact dermatitis, prolong the time of stress treatment, thereby increasing efficacy and improving patient compliance.

关键词： Comprehensive Anti-Inflammatory Treatment Upper Limb Lymphedema Irritating Contact Dermatitis Effect

孟德尔随机化研究首次性行为年龄与双相障碍的关系

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中华精神科杂志 2024年第4期57卷 199-206页

作者：张郑罗庆华重庆医科大学附属第一医院精神科重庆400016

目的通过孟德尔随机化(Mendelian randomization,MR)方法探索首次性行为年龄(age at first sexual intercourse,AFS)与双相障碍发病风险之间的潜在因果关系。方法利用来自欧洲血统人群的大规模全基因组关联研究(Genome-Wide Association... 详细信息

目的通过孟德尔随机化(Mendelian randomization,MR)方法探索首次性行为年龄(age at first sexual intercourse,AFS)与双相障碍发病风险之间的潜在因果关系。方法利用来自欧洲血统人群的大规模全基因组关联研究(Genome-Wide Association Studies,GWAS)汇总数据,选择与AFS和双相障碍相关、相互独立的遗传位点作为暴露和结局的工具变量。AFS的数据来源包括医学研究委员会整合流行病学单位(Medical Research Council Integrative Epidemiology Unit,MRC-IEU)的406457名个体(AFS1数据)和英国生物库(UK Biobank,UKB)的397338名个体(AFS2数据)。双相障碍的GWAS数据来源于精神病基因组学联盟(Psychiatric Genomics Consortium,PGC)2019年和2021年的研究,分别包括20352例患者与31358名对照者(BD1数据)和41917例患者与371549名对照者(BD2数据)。通过逆方差加权法(inverse variance weighting,IVW)评估AFS与BD的因果效应,此外采用MR-Egger回归、加权中位数法(weighted median,WM)、基于众数的简单估计和基于众数的加权估计法检验结果稳定性,以优势比(odds ratio,OR)和效应系数(beta coefficient,β)作为效应大小的评价指标。结果正向MR分析显示,AFS与双相障碍发病风险存在因果关系(IVW:OR=0.69,95%CI=0.57~0.82,P<0.001)。反向MR分析显示,双相障碍与AFS未见因果关系(IVW:β=0.01,95%CI=-0.01~0.03,P=0.159)。结论AFS与双相障碍发病风险之间有因果关系,而双相障碍对AFS的影响不显著。

关键词：双相情感障碍性行为孟德尔随机化因果推断

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The Role of Body Composition Analyzer in the Preoperative Assessment of Breast Cancer Patients

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Journal of Cancer Therapy 2024年第9期15卷 320-329页

作者： Lijuan Zhang Qiaoling Zhong Yun Ding Jinlan Li qinghua luo Liping Zhang Yuezhou Guo Na Li Huizhen Zhang State Key Laboratory of South China Oncology Cancer Prevention and Treatment Center Affiliated to Sun Yat-sen University Guangzhou China

Background: The segmental multi-frequency bioelectrical impedance analysis (SMF-BIA) is a useful method for evaluating physical health and nutritional status in various clinical settings. But less is known about its role in the preoperative assessment of breast cancer patients. Herein, we try to monitor the changes in body composition of preoperative patients by SMF-BIA and figure out its association with clinical features. Methods: The changes in body composition were monitored by SMF-BIA in 563 female patients with breast cancer. Monitor body moisture and collect relevant data on the day before surgery as a prospective study. Retrospective analysis will be conducted based on preoperative data and pathological results after lymph node resection, Spearman’s correlation coefficients were calculated to investigate the correlation among parameters. Results: We found that the body water, extracellular water ratio, and bioelectrical impedance of the affected upper limbs of patients with different tumor stages or different numbers of lymph node metastases were significantly different from those of their healthy upper limbs (P P P P P Conclusion: SMF-BIA can help monitor the changes in body composition of breast cancer patients and provide detailed information for making a personalized treatment plan and individual nursing schedule. However, the value of SMF-BIA in preoperative assessment still needs to be validated in large prospective clinical trials.

关键词： Breast Cancer Body Composition Tumor Stages Lymphatic Metastasis Multi-Frequency Bioelectrical Impedance Analysis

Observation of Curative Effect of Surgical Nursing in Patients with Grade III Hand-Foot Syndrome

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Journal of Cancer Therapy 2024年第8期15卷 280-286页

作者： Liping Zhang Lijuan Zhang Yun Ding Lili Han Jiamin Kuang qinghua luo Xinhua Xie Zeyu Shuang Qiaoling Zhong State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer Center Guangzhou China

Objective: To investigate the effect of surgical nursing on grade III Hand-Foot Syndrome (HFS) induced by Doxorubicin hydrochloride liposome chemotherapy after breast cancer surgery. Method: From January 2019 to December 2019, 10 patients with HFS grade III caused by Doxorubicin hydrochloride liposome chemotherapy after breast cancer surgery in the Breast Department of Cancer Prevention and Treatment Center of Sun Yat-sen University were selected, and surgical nursing methods were used to intervene and observe the therapeutic effects of the patients. Results: One patient was cured within 7 days, the cure rate was 10% in 7 days, 8 patients were cured within 10 days, the cure rate was 80% in 10 days, 10 patients were cured within 15 days, the cure rate was 100% in 15 days. Conclusion: The surgical nursing method is effective for patients with grade III HFS caused by Doxorubicin hydrochloride liposome chemotherapy after breast cancer surgery, shortening the treatment time of HFS, and is worthy of clinical promotion.

关键词： Surgical Nursing Methods Breast Cancer Chemotherapy Grade III Hand-Foot Syndrome

Effects of Alexithymia to Stigma of Patients with Lymphedema

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Journal of Cancer Therapy 2024年第4期15卷 201-211页

作者： Qiaoling Zhong Huizhen Zhang Liping Zhang qinghua luo Huiting Zhang Feng Liu Hailin Tang Na Li Lijuan Zhang State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer Center Guangzhou China

BACKGROUND: Secondary lymphedema is one of the common complications after malignant tumor surgery. It is a chronic and complex disease. Once lymphedema occurs, there will be discomfort such as limb swelling, pain, numbness and tension, which will eventually lead to changes in the appearance of the affected limb and will seriously affect the quality of life and require lifelong treatment and psychosocial support. This study investigated the current situation of stigma and alexithymia in patients with lymphedema, and discussed the impact of alexithymia on stigma in patients with lymphedema. AIMS: To understand the current situation of stigma and alexithymia in patients with lymphedema, and to analyze the influence of alexithymia on stigma. METHODS: 195 patients with lymphedema in a hospital were selected by convenient sampling. General information questionnaire, Toronto Alexithymia Scale and social impact scale were used to investigate respectively, to study the general situation, stigma and alexithymia of the respondents. RESULTS: The results showed that the total score of stigma in 195 patients with lymphedema was (60.36 ± 11.08), and the total score of alexithymia was (56.53 ± 8.43). Multiple linear regression analysis showed that alexithymia and family relationship were the influencing factors of stigma in patients with lymphedema. CONCLUSIONS: The patients with lymphedema have obvious stigma, and alexithymia and family relationship are the influencing factors.

关键词： Alexithymia Lymphedema Stigma Influence Factor

禽腺病毒4型GZ-B1毒株的Hexon基因序列分析

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贵州畜牧兽医 2024年第1期48卷 54-56页

作者：罗青华罗东还温贵兰徐飞贵州大学动物科学学院贵州贵阳550025

为了解禽腺病毒4型(FAdV-4)GZ-B1株的遗传进化情况,试验设计合成FAdV-4 Hexon基因的特异引物,对GZ-B1株Hexon基因进行PCR扩增并克隆至pMD-19T载体,基因测序和遗传进化分析。结果:扩增的Hexon基因长度为327 bp,与预期相符。GZ-B1株与国内... 详细信息

为了解禽腺病毒4型(FAdV-4)GZ-B1株的遗传进化情况,试验设计合成FAdV-4 Hexon基因的特异引物,对GZ-B1株Hexon基因进行PCR扩增并克隆至pMD-19T载体,基因测序和遗传进化分析。结果:扩增的Hexon基因长度为327 bp,与预期相符。GZ-B1株与国内外13株FAdV参考毒株中的7株FAdV-C毒株同源性较高(95.8%~98.5%),其中与国内强毒株GDMZ、LC1611、SDSG、SDXL同源性最高(均为98.5%),与基因型A、B、D、E的6株参考毒株同源性较低(73.0%~77.5%)。遗传进化树显示,GZ-B1株与基因型A、B、D、E毒株处于不同进化分支,与国内外C基因型毒株处于同一进化分支,表明该毒株与C基因型毒株遗传差异较小,其中与国内C型强毒株LC1611的遗传差异最小,亲缘关系最近。结论:FAdV-4 GZ-B1株属于C基因型、血清4型,与国内流行株FAdV-4 LC1611亲缘关系最近,同源性最高。

关键词：禽腺病毒4型 GZ-B1毒株 Hexon基因序列分析

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基于孟德尔随机化的DHA水平与ADHD的关系研究

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重庆医学 2024年第8期53卷 1151-1156页

作者：张郑谭景蓝罗庆华重庆医科大学附属第一医院精神科重庆400016

目的基于孟德尔随机化(MR)探讨二十二碳六烯酸(DHA)水平与注意缺陷与多动障碍(ADHD)发病的关系。方法从已发表的全基因组关联研究数据(GWAS)中提取了DHA和ADHD的工具变量,为了确保研究结果的稳定性,ADHD数据集选自两个不同的研究。DHA... 详细信息

目的基于孟德尔随机化(MR)探讨二十二碳六烯酸(DHA)水平与注意缺陷与多动障碍(ADHD)发病的关系。方法从已发表的全基因组关联研究数据(GWAS)中提取了DHA和ADHD的工具变量,为了确保研究结果的稳定性,ADHD数据集选自两个不同的研究。DHA水平的数据集包括115006例个体,ADHD1数据集共55374例个体涵盖20183例病例和35191例对照,ADHD2共225534例个体涵盖38691例病例和186843例对照,进行全面MR分析和敏感性分析。应用逆方差加权法(IVW)、MR-Egger回归分析及加权中位数法(WM)进行MR分析,以优势比(OR)和回归系数(β)作为评价指标,对DHA与ADHD的双向因果关系进行探讨。结果DHA与ADHD发病存在因果关系(ADHD1的IVW:OR=0.833,95%CI:0.719~0.964,P=0.014;ADHD2的IVW:OR=0.895,95%CI:0.808~0.992,P=0.034)。此外,发现ADHD与DHA存在反向因果关系(IVW:β=-0.073,95%CI:-0.103~-0.043,P<0.001)。结论DHA水平与ADHD存在潜在的双向因果关系。

关键词：二十二碳六烯酸注意缺陷与多动障碍孟德尔随机化因果推断儿童心理

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右单侧刺激电休克治疗对重性抑郁障碍的干预研究

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中国神经精神疾病杂志 2024年第6期50卷 337-342页

作者：谭佩傅一笑罗庆华杜莲邱田邱海棠重庆医科大学附属第一医院精神科重庆400016 重庆市精神卫生中心

目的探索右单侧刺激电休克治疗(right unilateral modified electroconvulsive therapy,RUL-MECT)对重性抑郁障碍(major depressive disorder,MDD)患者的疗效及安全性。方法采用随机双盲对照研究设计。纳入70例MDD患者,随机分为研究组、对照组,每组35例,研究组进行基于年龄法的RUL-MECT,对照组进行双侧颞叶刺激MECT,每组分别进行8次治疗。采用17项汉密尔顿抑郁量表(17-item Hamilton depression scale,HAMD-17)、成套认知功能测验(MATRICS consensus cognitive battery,MCCB)、定向力测验(orientation recovery tests,ORT)对被试抑郁症状和认知功能进行评估,记录干预过程中患者出现的不良反应。结果干预前研究组与对照组HAMD-17得分(32.89±5.68 vs.33.54±4.78)差异无统计学意义(P>0.05),经过8次干预,研究组HAMD-17得分为(6.83±4.68)分,对照组得分为(7.20±4.60)分,重复测量方差分析显示,时间效应有统计学意义(P0.05)。MCCB得分上,连线测试、符号编码、语言记忆、空间广度、数字序列、迷宫测验、视觉记忆、情绪管理、持续操作时间主效应有统计学意义(P0.05)。结论RUL-MECT与双侧刺激MECT相比,抗抑郁疗效相当,对认知功能改善及定向力恢复要优于双侧刺激组MECT。

关键词：重性抑郁障碍无抽搐电休克治疗右单侧刺激电休克治疗认知功能定向力临床疗效安全性

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