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Impact of twice-a-day transcranial direct current stimulation intervention on cognitive function and motor cortex plasticity in patients with Alzheimer’s disease 每日两次经颅直流电刺激干预对阿尔茨海默病患者认知功能和运动皮质可塑性的影响
IF 11.9 3区 医学 Q1 PSYCHIATRY Pub Date : 2023-11-01 DOI: 10.1136/gpsych-2023-101166
Xingxing Li, Lei Chen, Kunqiang Yu, Wenhao Zhuang, Hui Zhu, Wenqiang Xu, Hui Yan, Gangqiao Qi, Dongsheng Zhou, Shaochang Wu
Background Non-invasive brain stimulation has improved cognitive functions in patients with Alzheimer’s disease (AD), and some studies suggest a close relationship between cognition and plasticity. However, the clinical benefits of transcranial direct current stimulation (tDCS) in patients still need to be evaluated. Aims This study examined the role of tDCS in improving cognition and whether the improved cognition is related to altered cortical plasticity. Methods 124 patients with AD were randomly assigned to active tDCS (n=63) or sham tDCS (n=61). The tDCS was applied at the dorsolateral prefrontal cortex for 30 treatment sessions across 6 weeks (5 days per week, 2 days off). The Mini-Mental State Examination and the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) were used for cognition evaluation at baseline, week 2 and week 6. The cortical plasticity was represented by motor-evoked potential (MEP) measured with an electromyogram. Results The results showed that multiple courses of active tDCS can improve the cognitive functions of patients with AD, especially in the memory domain (word recall, recall of test instructions and word recognition). In addition, the damaged MEP level was enhanced following active treatment. In the active tDCS group, the improvements in ADAS-Cog total and subitem (word recall and word recognition) scores were negatively correlated with the enhancement of MEP. Conclusions Our research indicates for the first time that twice-a-day tDCS may improve the cognitive function of patients with AD. This study also suggests that cognitive dysfunction may be related to impaired cortical plasticity, which warrants mechanistic investigations of the relationship between cognition and plasticity in the future. Trial registration number ChiCTR1900021067. Data are available upon reasonable request.
无创脑刺激可改善阿尔茨海默病(AD)患者的认知功能,一些研究表明认知与可塑性之间存在密切关系。然而,经颅直流电刺激(tDCS)对患者的临床益处仍需评估。目的探讨tDCS在认知改善中的作用,以及认知改善是否与大脑皮层可塑性改变有关。方法124例AD患者随机分为活动性tDCS组(63例)和假性tDCS组(61例)。tDCS应用于背外侧前额皮质,共30次治疗,为期6周(每周5天,休息2天)。在基线、第2周和第6周使用认知能力评估量表(ADAS-Cog)和简易精神状态检查(Mini-Mental State Examination)。用肌电图测量运动诱发电位(MEP)表征皮层可塑性。结果表明,多疗程的tDCS活动可改善AD患者的认知功能,特别是在记忆领域(单词回忆、测试说明回忆和单词识别)。此外,在积极治疗后,受损的MEP水平有所提高。在活跃tDCS组,ADAS-Cog总分和子项(单词回忆和单词识别)得分的改善与MEP的增强呈负相关。我们的研究首次表明,每天两次的tDCS可以改善AD患者的认知功能。该研究还表明认知功能障碍可能与大脑皮层可塑性受损有关,这为未来认知和可塑性之间关系的机制研究提供了依据。试验注册号ChiCTR1900021067。如有合理要求,可提供资料。
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引用次数: 0
Repeated methamphetamine exposure decreases plasma brain-derived neurotrophic factor levels in rhesus monkeys. 反复接触甲基苯丙胺可降低恒河猴血浆脑源性神经营养因子水平。
IF 11.9 3区 医学 Q1 PSYCHIATRY Pub Date : 2023-10-31 eCollection Date: 2023-01-01 DOI: 10.1136/gpsych-2023-101127
Wenlei Zhang, Jiahui Zhou, Hang Su, Xiaocheng Zhang, Weichen Song, Zijing Wang, Chengjie Tang, Kadir Uludağ, Min Zhao, Zhi-Qi Xiong, Rongwei Zhai, Haifeng Jiang

Background: Brain-derived neurotrophic factor (BDNF) is known to prevent methamphetamine (METH)-induced neurotoxicity and plays a role in various stages of METH addiction. However, there is a lack of research with longitudinal design on changes in plasma BDNF levels in active METH-dependent individuals.

Aims: The aim of the study was to investigate changes in BDNF levels during METH self-administration in monkeys.

Methods: This study measured plasma BDNF levels in three male rhesus monkeys with continuous METH exposure and four male control rhesus monkeys without METH exposure. Changes in plasma BDNF levels were then assessed longitudinally during 40 sessions of METH self-administration in the three monkeys.

Results: Repeated METH exposure decreased plasma BDNF levels. Additionally, plasma BDNF decreased with long-term rather than short-term accumulation of METH during METH self-administration.

Conclusions: These findings may indicate that the changes in peripheral BDNF may reflect the quantity of accumulative METH intake during a frequent drug use period.

背景:脑源性神经营养因子(BDNF)可预防甲基苯丙胺(METH)诱导的神经毒性,并在甲基苯丙胺成瘾的各个阶段发挥作用。然而,缺乏对活性METH依赖个体血浆BDNF水平变化的纵向设计研究。目的:本研究的目的是研究猴子在自行给药METH期间BDNF水平的变化。方法:本研究测定了三只持续暴露于甲基安非他明的雄性恒河猴和四只未暴露于甲基麻黄碱的雄性对照恒河猴的血浆BDNF水平。然后在三只猴子自我给药METH的40个疗程中纵向评估血浆BDNF水平的变化。结果:反复接触甲基安非他明可降低血浆BDNF水平。此外,在METH自我给药期间,血浆BDNF随着METH的长期而非短期积累而降低。结论:这些发现可能表明外周BDNF的变化可能反映了频繁用药期间累积的METH摄入量。
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引用次数: 0
Cost-benefit and discriminant validity of a stepwise dementia case-finding approach in an Asian older adult community. 亚洲老年人社区逐步痴呆病例发现方法的成本效益和判别有效性。
IF 11.9 3区 医学 Q1 PSYCHIATRY Pub Date : 2023-10-30 eCollection Date: 2023-01-01 DOI: 10.1136/gpsych-2023-101049
Ting Pang, Binte Xia, Xuhao Zhao, Yaping Zhang, Cheuk Ni Kan, Saima Hilal, Christopher Chen, Narayanaswamy Venketasubramanian, Wong Tien Yin, Ching-Yu Cheng, Changzheng Yuan, Xin Xu

Background: Case-finding is a recommended approach for dementia early detection in the community.

Aims: To investigate the discriminant validity and cost-effectiveness of a stepwise dementia case-finding approach in a Singaporean older adult community.

Methods: The two-phase study was conducted in the community from 2009 to 2015 in Singapore. A total of 3780 participants (age ≥60 years) completed phase I (a brief cognitive screening); 918 completed phase II and were included in the final analysis. In phase I, all participants were administered the Abbreviated Mental Test (AMT) and the Progressive Forgetfulness Question (PFQ). Those who screened positive on either test were invited to phase II, whereby the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a formal neuropsychological battery were administered, followed by the research diagnosis of no cognitive impairment, cognitive impairment no dementia (CIND)-Mild (≤2 impaired cognitive domains), CIND-Moderate (>2 impaired domains) or dementia. Receiver operating characteristic curve analyses were conducted for the different cognitive instruments. All discriminant indices were calculated, including sensitivity, specificity, positive and negative predictive values (NPV) and accuracy. Cost-effectiveness analysis was conducted by estimating the amount of screening time needed and the number of older adults requiring re-evaluation in two case-finding scenarios, ie, with or without preselection by the PFQ.

Results: The stepwise case-finding approach (preselection by the PFQ, then MMSE or MoCA or AMT) showed an excellent NPV (>99%) and accuracy (>86%) for excluding dementia-free cases. Without preselection by the PFQ, screening time for the three cognitive tools were 317.5, 317.5 and 254 hours, with 159, 302 and 175 screen-positive older adults involved in further evaluation. By adopting the stepwise case-finding approach, total screening time were 156.5, 156.5 and 126.2 hours, which decreased by 50.7%, 50.7% and 50.3% as compared with those without preselection. Furthermore, after preselection, only 98, 167 and 145 screen-positive older adults required further evaluation, corresponding to a reduction of 38.4%, 44.7% and 17.1% in the numbers compared with those without preselection.

Conclusions: A stepwise approach for dementia case-finding should be implemented in the community to minimise the time and resources needed for large-scale early detection of dementia.

背景:病例发现是社区早期发现痴呆症的推荐方法。目的:研究新加坡老年人社区逐步痴呆病例发现方法的判别有效性和成本效益。方法:该研究于2009年至2015年在新加坡社区进行。共有3780名参与者(年龄≥60岁)完成了第一阶段(简短的认知筛查);918人完成了第二阶段,并被纳入最终分析。在第一阶段,所有参与者都接受了简短心理测试(AMT)和渐进遗忘问题(PFQ)。那些在任何一项测试中均呈阳性的人被邀请进入第二阶段,进行迷你精神状态检查(MMSE)、蒙特利尔认知评估(MoCA)和正式的神经心理测试,然后进行无认知障碍、无痴呆(CIND)-轻度(≤2个认知域受损)的研究诊断,CIND中度(>2个受损结构域)或痴呆。对不同的认知工具进行受试者操作特征曲线分析。计算所有判别指标,包括敏感性、特异性、阳性和阴性预测值(NPV)和准确性。成本效益分析是通过估计两种病例发现情况下所需的筛查时间和需要重新评估的老年人数量来进行的,结果:逐步病例发现方法(通过PFQ预选,然后是MMSE或MoCA或AMT)在排除无痴呆病例方面显示出优异的NPV(>99%)和准确率(>86%)。在没有PFQ预选的情况下,三种认知工具的筛查时间分别为317.5、317.5和254小时,其中159302和175名筛查呈阳性的老年人参与了进一步评估。采用逐步病例发现法,总筛查时间分别为156.5、156.5和126.2 小时,与未预选组相比分别下降了50.7%、50.7%和50.3%。此外,在预选后,只有98167和145名筛查呈阳性的老年人需要进一步评估,与未经预选的老年人相比,这一数字分别减少了38.4%、44.7%和17.1%。结论:应在社区中实施逐步发现痴呆症病例的方法,以最大限度地减少大规模早期发现痴呆症所需的时间和资源。
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引用次数: 0
Promising applications of non-invasive brain stimulation on military cognition enhancement: a long way to go. 无创大脑刺激在军事认知增强方面的应用前景广阔:还有很长的路要走。
IF 11.9 3区 医学 Q1 PSYCHIATRY Pub Date : 2023-10-29 eCollection Date: 2023-01-01 DOI: 10.1136/gpsych-2023-101264
Xiaolong Sun, Hua Yuan
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引用次数: 0
Deciphering the 'gut-brain axis' through microbiome diversity. 通过微生物组多样性解读“肠脑轴”。
IF 11.9 3区 医学 Q1 PSYCHIATRY Pub Date : 2023-10-29 eCollection Date: 2023-01-01 DOI: 10.1136/gpsych-2023-101090
Jinyuan Liu, Ke Xu, Tsungchin Wu, Lydia Yao, Tanya T Nguyen, Dilip Jeste, Xinlian Zhang

Incentivised by breakthroughs and data generated by the high-throughput sequencing technology, this paper proposes a distance-based framework to fulfil the emerging needs in elucidating insights from the high-dimensional microbiome data in psychiatric studies. By shifting focus from traditional methods that focus on the observations from each subject to the between-subject attributes that aggregate two or more subjects' entire feature vectors, the described approach revolutionises the conventional prescription for high-dimensional observations via microbiome diversity. To this end, we enrich the classical generalised linear models to articulate the multivariable regression relationship between distance-based variables. We also discuss a robust and computationally feasible semiparametric inference technique. Benefitting from the latest advances in the semiparametric efficiency theory for such attributes, the proposed estimators enjoy robustness and good asymptotic properties that guarantee sensitivity in detecting signals between clinical outcomes and microbiome diversity. It offers a readily implementable and easily interpretable solution for deciphering the gut-brain axis in mental health research.

在高通量测序技术的突破和数据的激励下,本文提出了一个基于距离的框架,以满足在精神病研究中从高维微生物组数据中阐明见解的新需求。通过将重点从关注每个受试者观察结果的传统方法转移到聚合两个或多个受试者整个特征向量的受试者间属性,所描述的方法彻底改变了通过微生物组多样性进行高维观察的传统处方。为此,我们丰富了经典的广义线性模型,以阐明基于距离的变量之间的多变量回归关系。我们还讨论了一种稳健且计算可行的半参数推理技术。得益于此类属性的半参数效率理论的最新进展,所提出的估计量具有鲁棒性和良好的渐近性质,保证了检测临床结果和微生物组多样性之间信号的敏感性。它为解读心理健康研究中的肠脑轴提供了一个易于实施和解释的解决方案。
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引用次数: 0
Time to treat the climate and nature crisis as one in divisible global health emergency. 是时候将气候和自然危机视为可分割的全球卫生紧急事件了。
IF 11.9 3区 医学 Q1 PSYCHIATRY Pub Date : 2023-10-20 eCollection Date: 2023-01-01 DOI: 10.1136/gpsych-2023-101395
Chris Zielinski
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引用次数: 0
High-definition transcranial direct current stimulation over the right dorsolateral prefrontal cortex reduces risk-taking. 右背外侧前额叶皮层的高清经颅直流电刺激可以减少冒险行为。
IF 11.9 3区 医学 Q1 PSYCHIATRY Pub Date : 2023-10-19 eCollection Date: 2023-01-01 DOI: 10.1136/gpsych-2023-101182
Wei Li, Shuyue Zhang, Xinyu He, Jiawen Hu, Jia Shi, Qinghua He
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引用次数: 0
Targeting the ferroptosis crosstalk: novel alternative strategies for the treatment of major depressive disorder. 针对脱铁性串扰:治疗重度抑郁症的新的替代策略。
IF 11.9 3区 医学 Q1 PSYCHIATRY Pub Date : 2023-10-19 eCollection Date: 2023-01-01 DOI: 10.1136/gpsych-2023-101072
Luyao Wang, Rongyang Xu, Chengying Huang, Guozhong Yi, Zhiyong Li, Huayang Zhang, Rongxu Ye, Songtao Qi, Guanglong Huang, Shanqiang Qu

Depression is a major contributor to poor global health and disability, with a recently increasing incidence. Although drug therapy is commonly used to treat depression, conventional antidepressant drugs have several disadvantages, including slow onset, low response rates and severe adverse effects. Therefore, developing effective therapies for depression remains challenging. Although various aetiological theories of depression exist, the underlying mechanisms of depression are complex, and further research is crucial. Moreover, oxidative stress (OS)-induced lipid peroxidation has been demonstrated to trigger ferroptosis. Both OS and ferroptosis are pivotal mechanisms implicated in the pathogenesis of neurological disorders, and investigation of the mediators involved in these processes has emerged as a prominent and active research direction. One previous study revealed that regulatory proteins involved in ferroptosis are implicated in the pathogenesis of depression, and antidepressant drugs could reverse depressive symptoms by inhibiting ferroptosis in vivo, suggesting an important role of ferroptosis in the pathogenesis of depression. Hence, our current comprehensive review offers an up-to-date perspective on the intricate mechanisms involved, specifically concerning ferroptosis and OS in the context of depression, along with promising prospects for using molecular mediators to target ferroptosis. We delineate the key targets of molecular mediators involved in OS and ferroptosis implicated in depression, most notably reactive oxygen species and iron overload. Considering the pivotal role of OS-induced ferroptosis in the pathogenesis of neurological disorders, delving deeper into the underlying subsequent mechanisms will contribute significantly to the identification of novel therapeutic targets for depression.

抑郁症是导致全球健康状况不佳和残疾的主要原因,最近发病率不断上升。尽管药物治疗通常用于治疗抑郁症,但传统的抗抑郁药物有几个缺点,包括起效慢、反应率低和严重的不良反应。因此,开发有效的抑郁症治疗方法仍然具有挑战性。尽管抑郁症的病因理论多种多样,但抑郁症的潜在机制是复杂的,进一步的研究至关重要。此外,氧化应激(OS)诱导的脂质过氧化已被证明可引发脱铁性贫血。OS和脱铁性贫血都是神经系统疾病发病机制中的关键机制,研究参与这些过程的介质已成为一个突出而活跃的研究方向。先前的一项研究表明,参与脱铁症的调节蛋白与抑郁症的发病机制有关,抗抑郁药物可以通过在体内抑制脱铁症来逆转抑郁症状,这表明脱铁症在抑郁症的发病机理中发挥着重要作用。因此,我们目前的全面综述为所涉及的复杂机制提供了一个最新的视角,特别是关于抑郁症背景下的脱铁性贫血和OS,以及使用分子介质靶向脱铁性高血压的前景。我们描述了参与OS和与抑郁症相关的脱铁性贫血的分子介质的关键靶点,最显著的是活性氧和铁过载。考虑到OS诱导的脱铁性贫血在神经系统疾病发病机制中的关键作用,深入研究潜在的后续机制将有助于确定抑郁症的新治疗靶点。
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引用次数: 0
Development of the Life Gatekeeper suicide prevention training programme in China: a Delphi study. 中国“生命守护者”自杀预防培训项目的发展:德尔菲研究。
IF 11.9 3区 医学 Q1 PSYCHIATRY Pub Date : 2023-10-17 eCollection Date: 2023-01-01 DOI: 10.1136/gpsych-2023-101133
Chengxi Cai, Chen Yin, Yongsheng Tong, Diyang Qu, Yunzhi Ding, Daixi Ren, Peiyu Chen, Yi Yin, Jing An, Runsen Chen

Background: Youth suicide has been a pressing public mental health concern in China, yet there is a lack of gatekeeper intervention programmes developed locally to prevent suicide among Chinese adolescents.

Aims: The current Delphi study was the first step in the systematic development of the Life Gatekeeper programme, the first gatekeeper programme to be developed locally in China that aims to equip teachers and parents with the knowledge, skills and ability to identify and intervene with students at high risk of suicide.

Methods: The Delphi method was used to elicit a consensus of experts who were invited to evaluate the importance of training content, the feasibility of the training delivery method, the possibility of achieving the training goals and, finally, the appropriateness of the training materials. Two Delphi rounds were conducted among local experts with diversified professional backgrounds in suicide research and practice. Statements were accepted for inclusion in the adjusted training programme if they were endorsed by at least 80% of the panel.

Results: Consensus was achieved on 201 out of 207 statements for inclusion into the adapted guidelines for the gatekeeper programme, with 151 from the original questionnaire and 50 generated from comments of the panel members. These endorsed statements were synthesised to develop the content of the Life Gatekeeper training programme.

Conclusions: This Delphi study provided an evidence base for developing the first gatekeeper training programme systematically and locally in China. We hope that the current study can pave the way for more evidence-based suicide prevention programmes in China. Further study is warranted to evaluate the effectiveness of the Life Gatekeeper training programme.

背景:在中国,青少年自杀一直是一个紧迫的公共心理健康问题,但缺乏当地制定的预防青少年自杀的看门人干预计划。目的:目前的德尔菲研究是系统开发“生活看门人”计划的第一步,这是中国当地开发的第一个看门人计划,旨在使教师和家长具备识别和干预高自杀风险学生的知识、技能和能力。方法:采用德尔菲法征求专家的一致意见,邀请专家评估培训内容的重要性、培训实施方法的可行性、实现培训目标的可能性,以及培训材料的适当性。在自杀研究和实践方面,在具有不同专业背景的当地专家中进行了两轮德尔菲调查。如果得到至少80%的小组成员的认可,这些声明将被纳入调整后的培训计划。结果:207份声明中有201份达成共识,纳入看门人方案的修订指南,其中151份来自原始问卷,50份来自小组成员的评论。这些认可的声明被综合起来,以制定“生命守护者”培训计划的内容。结论:这项德尔菲研究为在中国系统地、本地地制定第一个看门人培训计划提供了证据基础。我们希望目前的研究能够为中国更多基于证据的自杀预防计划铺平道路。有必要进行进一步的研究,以评估救生员培训方案的有效性。
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引用次数: 0
Chinese herbal medicine combined with cognitive-behavioural therapy for avoidant paruresis: a controlled trial. 中草药联合认知行为疗法治疗回避型遗尿:一项对照试验。
IF 11.9 3区 医学 Q1 PSYCHIATRY Pub Date : 2023-10-12 eCollection Date: 2023-01-01 DOI: 10.1136/gpsych-2023-101014
Shijie Liang, Ying Zhou, Chao Yu, Xiang Gao, Fangbin Ji, Qianyuan Fang, Zhihang Zhang, Libin Yang, Youkang Zhao, Yuhui Zhao, Renwu Yin, Kaimin Chen, Zheng Lu

Background: Avoidant paruresis is a common clinical condition in urology and psychosomatic medicine. However, it has limited treatment options that are safe and effective with few side effects.

Aims: Our study aimed to investigate the effectiveness and safety of the Chinese herbal Yangxin Tongquan decoction combined with cognitive-behavioural therapy (CBT) for avoidant paruresis.

Methods: Sixty-eight patients with avoidant paruresis were divided into a treatment group (33 patients) and a control group (35 patients). The control group was assigned 10 weeks of CBT and systematic desensitisation. In addition to CBT and systematic desensitisation, the treatment group was given the Chinese herbal Yangxin Tongquan decoction during the 10-week study. The Shy Bladder Syndrome Scale (SBS) and the Self-rating Anxiety Scale (SAS) were administered before and after treatment to measure any change.

Results: The overall efficacy in the treatment group (n=30) was 80.0% vs 62.5% in the control group (n=33). Comparing pretreatment and post-treatment measures, both groups showed improvement in SBS scores and SAS scores (treatment group: t(SBS) =8.397, p(SBS) <0.001, t(SAS) =8.216, p(SAS)<0.001; control group: t(SBS) =6.802, p(SBS) <0.001, t(SAS)=5.171, p(SAS) <0.001). Moreover, both groups' SBS and SAS scores changed significantly over time (SBS scores: Ftime =118.299, p<0.001; SAS scores: Ftime =92.114, p<0.001). However, the treatment group performed better than the control group (SBS scores: Ftime*group =5.709, p=0.020; SAS scores: Ftime*group =7.235, p=0.009).

Conclusions: The Chinese herbal Yangxin Tongquan decoction combined with cognitive-behavioural psychotherapy positively affects the treatment of avoidant paruresis without significant adverse effects.

背景:遗尿症是泌尿外科和心身医学中常见的临床疾病。然而,它的治疗选择有限,安全有效,副作用很少。目的:本研究旨在探讨养心通泉汤联合认知行为疗法(CBT)治疗遗尿的有效性和安全性。方法:将68例回避型遗尿患者分为治疗组(33例)和对照组(35例)。对照组被分配10周的CBT和系统脱敏。在为期10周的研究中,除了CBT和系统脱敏外,治疗组还服用了中药养心通泉汤。在治疗前后使用害羞膀胱综合征量表(SBS)和焦虑自评量表(SAS)来测量任何变化。结果:治疗组(n=30)的总有效率为80.0%,对照组(n=33)为62.5%。比较治疗前和治疗后的测量,两组的SBS评分和SAS评分均有改善(治疗组:t(SBS)=8.397,p(SBS)0.001,t(SAS)=8.216,p(SAS)=6.802,p(SBS)0.001,t(SAS)=5.171,p(SAS)0.001)。此外,两组SBS和SAS评分随时间变化显著(SBS评分:Ftime=118.299,p0.001;SAS评分:Ftime=92.114,p0.001)。然而,治疗组疗效优于对照组(SBS评分:Ftime*组=5.709,p=0.020;SAS评分:Ftime*组=7.235,p=0.009)。
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引用次数: 0
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General Psychiatry
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