Neuroinflammation may disrupt neurotransmitter signaling. This study investigated whether gut microbiota-induced neuroinflammation can regulate glutamate pathways in bipolar disorder (BD). Fecal microbiota transplantation (FMT) was performed to observe behavioral changes in the antibiotic-treated C57BL/6J male mouse model of bipolar depression. Gut microbial structure, circulating, and prefrontal levels of inflammatory factors, microglial activation, and transcription levels of N-methyl-d-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4 isoxazole receptor (AMPAR) genes were measured in the “BD” and control mice. Furthermore, the effects of interleukin-1 (IL-1) receptor antagonist (IL-1RA) on the glutamate pathways were assessed. Compared with the control mice, “BD” mice displayed depression-like behaviors, with a lower diversity of gut bacteria and a decreased abundance of certain species. In addition, “BD” mice showed increased levels of inflammatory factors (e.g., IL-1β) in the serum and prefrontal cortex, microglial activation, and changes in the messenger RNA (mRNA) levels of NMDAR and AMPAR. Treatment with IL-1RA partially reversed the behavioral patterns, neuroinflammation, and transcription levels of glutamate receptors. The findings suggest that gut microbiota may influence glutamate receptor gene expression via an IL-1β-dependent pathway in a mouse model of BD, potentially contributing to neuroinflammatory mechanisms relevant to this disorder.

Background Ginkgo biloba extract (GBE) has been found to be effective in treating neurological diseases. However, whether GBE can be used to treat attention deficit hyperactivity disorder (ADHD) and its potential molecular targets remain unclear. Methods The active components of GBE were screened by the TCMSP database, and the related targets of ADHD were searched by the GENE CARD database. The common target between GBE and ADHD was obtained by Venny platform. The common targets were imported into the STRING database, and the protein interaction network and core target network were constructed by Cytoscape 3.8.0. DAVID database was used to perform GO and KEGG pathway enrichment analysis, and Cytoscape 3.8.0 software was used to construct and analyze the “active ingredient-target-disease” network model. Finally, Autodock tools 1.5.6 and Pymol 2.6.0a0 software were used to analyze the molecular docking results of important components and core targets, and IMDS was used for molecular dynamics simulation. Results A total of 27 active ingredients and 215 targets were screened from GBE, 85 of which were common to ADHD, including 3 core targets (TP53, TNF and IL6). The main related pathways of GBE in the treatment of ADHD were IL-17 signaling pathway, C-type lectin receptor signaling pathway and Toll-like signaling pathway. The results of molecular docking showed that 3 core targets (TP53, TNF and IL6) had a small molecular docking binding free energy with the active components (luteolin and kaempferol), indicating a good affinity. Conclusion GBE may alleviate the progression of ADHD via mediating IL-17 signaling pathway, C-type lectin receptor signaling pathway and Toll-like signaling pathway by regulating TP53, TNF and IL6, which provides a new theoretical basis for the treatment of ADHD.

Introduction: This multicenter, randomized, double-blind, placebo-controlled phase 2 trial compared the efficacy, and safety of adding pyrotinib to trastuzumab, docetaxel, and carboplatin versus placebo, trastuzumab, docetaxel, and carboplatin in Chinese patients with human epidermal receptor 2 (HER2)-positive early or locally advanced breast cancer (ClinicalTrials.gov identifier: NCT03756064). Methods: Sixty-nine women with HER2-positive early (T1-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) were recruited from October 1, 2019, to June 1, 2021. Before surgery, patients received 6 cycles of orally pyrotinib (400 mg once per day), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), docetaxel (75 mg/m2), and carboplatin (AUC = 6 mg/mL·min) or orally placebo, trastuzumab, and docetaxel, and carboplatin every 3 weeks. The primary end point was independent review committee-assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by age, hormone receptor status, tumor stage, nodal status, cTNM stage, and Ki-67 level was used to compare rates between treatment groups. Results: In total, 69 female patients were randomized (pyrotinib, 36; and placebo, 33; median age, 53 [31–69] years). In the intention-to-treat population, total pathologic complete response rates were 65.5% (19/29) in the pyrotinib group and 33.3% (10/30) in the placebo group (difference, 32.2%, p = 0.013). Diarrhea was been reported in 86.1% of patients (31/36) in the pyrotinib group as the most common adverse events (AEs) and 15.2% of patients (5/33) in the placebo group. But no grade 4 or 5 AEs were reported. Conclusion: Treatment with pyrotinib, trastuzumab, docetaxel, and carboplatin resulted in a statistically significant improvement in the total pathologic complete response rate versus placebo, trastuzumab, docetaxel, and carboplatin for the neoadjuvant treatment of HER2-positive early or locally advanced breast cancer in Chinese patients. Safety data were in line with the known pyrotinib safety profile and generally comparable between treatment groups.

Background:The standard recommendation for neoadjuvant therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients is trastuzumab in combination with chemotherapy, but there is no current standard recommendation for appropriate chemotherapy regimens. This meta-analysis evaluated the efficacy and cardiac safety of the concurrent use of anti-HER2 targeted drugs and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancers.Methods:The pooled odds ratio (OR) rate for pathologic complete response (pCR), the pooled hazard ratio (HR) of overall survival (OS), and the left ventricular ejection fraction (LVEF) decline events were all calculated. Differences in efficacy, prognosis, and cardiac safety were compared between patients receiving an anthracycline-containing regimen (AB) and those treated with non-anthracycline-based (nAB) NAC.Results:A total of 1366 patients in 4 prospective and 3 retrospective studies were included in the meta-analysis. The pooled OR for pCR rate was 0.73 with a 95% confidence interval (CI) of 0.43 to 1.24 (P = .246). Subgroup analysis of low tumor burden cases showed no improvement in pCR rate for patients in the AB group compared with nAB, with the pooled OR rate being 0.73 with a 95% CI of 0.37 to 1.44 (P= .357). The 3-year OS rate was 95.63% and 95.54% in the AB and nAB groups, respectively, with no statistical difference (P= .157). There was a significant increase in the rate of LVEF decline of 19.07% in the AB group compared with 13.33% for the nAB group, with an HR of 1.62 and a 95% CI of 1.11 to 2.36 (P = .013).Conclusions:The addition of anthracyclines did not improve pCR rates and survival after neoadjuvant and the increased cardiotoxicity of anthracyclines further limited their application. This study showed that it was feasible to use anti-HER2 drugs without anthracyclines in neoadjuvant therapy for HER2-positive breast cancer patients.

BACKGROUND:Breast cancer (BC) is a prevalent malignancy with complex etiology and varied clinical behavior. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancer progression, including BC. Among these, lncRNA TDRKH-AS1 has been implicated in several cancers, but its role in BC remains unclear.METHODS:We conducted a comprehensive investigation to elucidate the role of TDRKH-AS1 in BC. Clinical samples were collected from BC patients, and BC cell lines were cultured. Bioinformatics analysis using the starBase database was carried out to assess TDRKH-AS1 expression levels in BC tissue samples. Functional experiments, including knockdown, colony formation, CCK-8, Transwell, and wound-healing assays, were conducted to determine the role of TDRKH-AS1 in BC cell proliferation and invasion. Luciferase reporter and RIP assays were used to examine the interactions between TDRKH-AS1 and miR-134-5p. In addition, the downstream target gene of miR-134-5p, cAMP response element-binding protein 1 (CREB1), was identified and studied using various methods, including RT-qPCR, immunoprecipitation, and rescue experiments. In vivo experiments using mouse tumor xenograft models were conducted to examine the role of TDRKH-AS1 in BC tumorigenesis.RESULTS:TDRKH-AS1 was found to be significantly upregulated in BC tissues and cell lines. High TDRKH-AS1 expression correlated with advanced BC stages and worse patient outcomes. Knockdown of TDRKH-AS1 led to decreased BC cell proliferation and invasion. Mechanistically, TDRKH-AS1 acted as a sponge for miR-134-5p, thereby reducing the inhibitory effects of miR-134-5p on CREB1 expression. Overexpression of CREB1 partially rescued the effects of TDRKH-AS1 knockdown in BC cells. In vivo studies further confirmed the tumor-promoting role of TDRKH-AS1 in BC.CONCLUSIONS:Our study unveiled a novel regulatory axis involving TDRKH-AS1, miR-134-5p, and CREB1 in BC progression. TDRKH-AS1 functioned as an oncogenic lncRNA by promoting BC cell proliferation and invasion through modulation of the miR-134-5p/CREB1 axis. These findings highlighted TDRKH-AS1 as a potential diagnostic biomarker and therapeutic target for BC treatment.

目的 探讨miR-4763-3p在注意缺陷多动障碍(ADHD)儿童血清中的表达及临床意义.方法 选取2019年6月—2022年6月浙江大学医学院附属精神卫生中心收治的ADHD儿童120例纳入观察组,另选取体检的健康儿童100例纳入对照组.采用Conners父母症状问卷评估患儿的行为症状,采集血清样本,应用RT-qPCR法检测样本中miR-4763-3p的表达水平,并比较两组血清miR-4763-3p水平,分析血清miR-4763-3p与ADHD患儿行为症状的相关性,采用ROC曲线分析miR-4763-3p诊断ADHD的临床价值.结果 ADHD患儿血清中miR-4763-3p的相对表达量为(6.75±0.97),对照组血清中miR-4763-3p的相对表达量为(9.12±1.84),两组比较差异有统计学意义(t=12.222,P＜0.001);ADHD-AI型、ADHD-HI型及ADHD-C 型 ADHD 患儿血清 miR-4763-3p 的相对表达量分别为(6.83±0.94)、(7.02±1.38)及(4.73±0.81),3 组 miR-4763-3p相对表达量比较差异有统计学意义(F=4.057,P＜0.05);ADHD-C混合型ADHD患儿血清miR-4763-3p的相对表达量明显低于 ADHD-AI 型和 ADHD-HI 型(t=11.657、9.168,P＜0.001),但 ADHD-AI 型和 ADHD-HI 多型 ADHD 患儿血清miR-4763-3p的相对表达量比较差异无统计学意义(t=0.595,P＞0.05);ADHD患儿血清miR-4763-3p的表达量与学习问题、品行问题、多动、冲动、焦虑及身心障碍评分呈负相关(P＜0.05);血清miR-4763-3p诊断ADHD的曲线下面积为0.834(95％CI:0.791-0.892,P＜0.001),诊断截断值为7.58,诊断灵敏度和特异度分别为91.03％和83.75％.结论 miR-4763-3p在ADHD患儿血清中呈低表达,且其表达水平与患儿行为症状有关,其可能成为ADHD临床诊断的辅助指标.

目的 探讨GRIN2A基因和GRIN2B基因单核苷酸多态性与哌甲酯治疗注意缺陷多动障碍(ADHD)疗效的关系.方法 选择2016年2月至2019年2月杭州市第七人民医院儿童心理科门诊及住院的6～15岁ADHD患儿80例,治疗前抽取外周血3 ml,用试剂盒提取DNA后-80℃冷冻备用.其中74例患儿完成8周的哌甲酯治疗随访,并于治疗前及治疗8周后进行SNAP-IV、中国韦氏儿童智力测试(C-WISC)、Conners父母评症状量表(PSQ)、注意力竞量测验(T.O.V.A.)和神经心理测评.以GRIN2A基因rs2229193和GRIN2B基因rs2284411作为候选基因位点,采用PCR扩增并结果判读.结果 GRIN2A基因G/A+A/A基因型患儿的SNAP-IV对立违抗分量表得分、PSQ品行问题项目得分均较G/G基因型高(均P＜0.01).GRIN2B基因T/C+T/T基因型患儿的SNAP-IV注意缺陷分量表得分较C/C基因型更高(P＜0.05).治疗有效和治疗无效患儿间GRIN2A基因G/A+A/A基因型频率与G/G基因型频率、GRIN2B基因T/C+T/T基因型频率与C/C基因型频率比较差异均无统计学意义(均P＞0.05);对立违抗改善与未改善患儿的GRIN2A基因G/A+A/A基因型频率与G/G基因型频率比较差异有统计学意义(P＜0.05),而GRIN2B基因T/C+T/T基因型频率和C/C基因型频率比较差异无统计学意义(P＞0.05).结论 GRIN2A基因中A等位基因携带组在接受哌甲酯治疗后,对立违抗行为显著减少,提示GRIN2A基因多态性可能与哌甲酯改善ADHD患儿对立违抗行为的疗效相关.

目的 系统评价经颅磁刺激(TMS)联合康复训练治疗孤独谱系障碍(ASD)的疗效.方法 检索PubMed、Web of Science、Google Scholar、EMBASE、Cochrane Library、知网、维普及万方数据库,检索时间为各数据库建库至2020年12月31日,收集TMS联合康复训练治疗ASD患者的随机对照研究,选取治疗后临床症状的量表评分为疗效指标.由2名研究者独立筛选文献,提取信息,评价纳入文献的方法学质量,进行Meta分析.结果 纳入10篇随机对照研究.TMS联合康复训练治疗ASD患者的临床效果优于单用康复治疗,包括儿童孤独症评定量表评分(OR=-1.06,95％CI:-1.50～-0.61,P＜0.05)、孤独症行为量表评分(OR=-0.95,95％CI:-1.46～-0.43,P＜0.05)、发育商评分(OR=0.74,95％CI:0.49～-0.98,P＜0.05).TMS联合康复治疗ASD患者刺激背外侧前额叶皮层、高频、低频等不同参数的效果均优于单用康复治疗(均P＜0.05).结论 TMS联合康复治疗ASD患者效果优于单用康复治疗.

Background. To date, around 4 per 100,000 adolescents committed suicide within the 29 OECD countries. The suicidal behavior is related to psychological factors, genetics, neurobiology, and other biomarkers. The aim of this study was to examine risk factors for the development of suicidal ideation in adolescent females with depression, focusing on the relationship between different testosterone levels and suicidal ideation, in order to help develop strategies to intervene in suicidal behavior in female adolescents with depression. Method. In this single-center prospective cohort study, we enrolled adolescent females with depression. We collected information on their baseline data, testosterone levels, symptom self-rating scale scores, suicidal ideation, non-suicidal self-injurious (NSSI) behaviours, and suicide attempts. We used multivariate logistic regression to identify risk factors for the development of suicidal ideation in adolescent females with depression. Results. A total of 113 hospitalized adolescent females were enrolled with a mean age of 13.5 (1.20). Among these patients, there were 86 (76.11%) subjects who suffered from suicidal ideation, 59 (52.21%) had NSSI and 23 (20.35%) had suicide attempt behavior. In the final model, higher level of testosterone (p=0.04) and higher age (p=0.02) were associated with the higher odds of having suicidal ideation. Conclusion. In this exploratory cohort study, the emergence of suicidal ideation was common among adolescent females with depression. This study is consistent with the other studies. It shows that the age is a potential predictor for suicidal ideation in hospitalized adolescent females with depression.

目的 比较加味酸枣仁汤与劳拉西泮治疗高中生焦虑症的疗效以及安全性.方法 高中生焦虑症患者68例随机分为加味酸枣仁汤组和劳拉西泮组,并给予相应的治疗.于0,1,2周测定汉密尔顿焦虑量表(Hamilton Anxiety Scale,HAMA)得分评价其疗效,第2周测定副反应量表(Treatment Emergent Symptom Scale,TESS)评价其不良反应.比较2组间HAMA减分率、治疗有效率、起效时间、不良反应发生率的差异.结果 1,2周,2组HAMA得分均显著下降(P＜0.001).虽然2组总有效率无统计学差异(90.91％vs90.63％),但是加味酸枣仁汤组疗效显著的比例(57.58％)明显高于对照组(31.25％)(P＜0.05),且HAMA得分(10.82±5.80)显著低于对照组(14.88±5.50)(P＜0.05).加味酸枣仁汤组起效时间(3 d)则稍晚于对照组(1 d)(P＜0.01).加味酸枣仁汤组乏力和头痛的反应发生率显著低于劳拉西泮组(P＜0.05).结论 在高中生焦虑症的治疗中,加味酸枣仁汤比劳拉西泮更安全、有效.

目的 探讨儿童青少年抑郁障碍患者合并拒绝上学行为的相关因素.方法 选取2019年3—12月在我院诊断抑郁障碍的儿童青少年患者共84例为研究对象,采用自制的一般情况量表、抑郁自评量表(SDS)、焦虑自评量表(SAS)及家庭亲密度与适应性量表(FACESⅡ)评估患者的人口学特征、临床症状严重程度及家庭功能.单因素及多因素分析儿童青少年抑郁障碍患者合并拒绝上学行为的影响因素.结果 单因素分析显示,女性、同伴关系紧张、父母受教育水平低、非独生子女、抑郁焦虑程度严重的儿童青少年抑郁障碍患者合并拒绝上学行为率更高,差异有统计学意义(P<0.05);多因素分析显示,同伴关系紧张、父亲受教育水平低、非独生子女、抑郁程度高是儿童青少年抑郁障碍患者出现拒绝上学行为的危险因素(P<0.05).结论 儿童青少年抑郁障碍患者合并拒绝上学行为较普遍,而同伴关系紧张、父亲受教育水平低、非独生子女、抑郁程度高是儿童青少年抑郁障碍患者出现拒绝上学行为的危险因素.

目的 探讨N-甲基-D-天冬氨酸受体(NMDAR)亚基NMDA2A基因(GRIN2A)和NMDA2B基因(GRIN2B)单核苷酸多态性与注意缺陷多动障碍(ADHD)的关系.方法 选择2016年2月至2018年4月就诊于浙江大学医学院附属精神卫生中心(杭州市第七人民医院)儿童心理科门诊及住院的ADHD患儿(ADHD组)49例及同时期健康体检儿童(健康对照组)50例,抽取外周血样本,提取DNA,根据dbSNP数据库及既往文献选取GRIN2A的rs2229193和GRIN2B的rs2284411作为候选基因位点,设计引物序列,行PCR扩增及结果判读.比较两组GRIN2A基因型频率G/G和G/A,GRIN2B基因型频率C/C和(T/C+T/T)的分布差异.结合ADHD症状评定量表和神经心理测评[SNAP-Ⅳ儿童注意力量表(包含注意缺陷分量表、多动冲动分量表、对立违抗分量表)、中国韦氏儿童智力量表(C-WISC)、Conners父母评症状量表(PSQ)、注意力竞量测验(T.O.V.A.)]得分,比较GRIN2A、GRIN2B不同基因型ADHD患儿的症状.结果 两组GRIN2A基因型频率、GRIN2B基因型频率分布比较,差异无统计学意义(P>0.05).GRIN2A为G/A+A/A基因型的患儿较G/G基因型的患儿有更高的SNAP-IV对立违抗分量表得分以及更高的PSQ品行问题得分,差异均有统计学意义(均P<0.05).两者SNAP-IV其他分量表得分、C-WISC、PSQ、T.O.V.A.比较,差异均无统计学意义(均P>0.05).GRIN2B为C/C基因型和T/C+T/T基因型的两种患儿SNAP-IV、C-WISC、PSQ、T.O.V.A.比较,差异均无统计学意义(均P>0.05).结论 GRIN2A中A等位基因携带患儿可能有更多的对立违抗行为和品行问题,提示GRIN2A基因多态性可能与ADHD患儿对立违抗障碍及品行障碍相关.

PurposeNeoadjuvant chemotherapy (NCT) is typically the initial treatment for non-early breast cancer patients. We thereby conducted a meta-analysis to explore whether dose-dense neoadjuvant chemotherapy (ddNCT) improved the long-term prognosis of patients compared to the standard NCT regimen.MethodsWe compared the differences in efficacy and prognosis between patients receiving standard NCT and ddNCT. We also calculated the pooled odds ratio (OR) of pathological complete response (pCR) and the pooled hazard ratio (HR) of overall survival (OS) and disease-free survival (DFS).ResultsNine randomized controlled trials involving 3,724 patients from 10 published studies were included in the meta-analysis. The pooled OR for ddNCT was 1.18 (95% confidence interval (CI): 0.83-1.67, P = 0.356). A subgroup analysis in the cases with low hormone receptor expression levels showed the pCR in patients undergoing ddNCT was significantly higher than the pCR in patients undergoing standard NCT (OR = 1.36, 95% CI: 1.09-1.69, P = 0.007). There was no significant difference in DFS and OS between ddNCT and standard NCT (DFS: HR = 0.90, 95% CI: 0.79-1.02, P = 0.095; OS; HR = 0.91, 95% CI: 0.81-1.04, P = 0.160), regardless of hormone receptor expression levels. These data suggested the higher pCR rate in patients receiving ddNCT did not result in a survival benefit.ConclusionsThe meta-analysis demonstrated that ddNCT can significantly improve the pCR rate in patients with low hormone receptor expression levels, although patient survival was not significantly improved. The ddNCT can increase the breast-conserving rate and reduced preoperative waiting time without increasing adverse reactions. This regimen can be considered when developing an NCT plan.

Purpose Neoadjuvant chemotherapy (NCT) is typically the initial treatment for non-early breast cancer patients. We thereby conducted a meta-analysis to explore whether dose-dense neoadjuvant chemotherapy (ddNCT) improved the long-term prognosis of patients compared to the standard NCT regimen. Methods We compared the differences in efficacy and prognosis between patients receiving standard NCT and ddNCT. We also calculated the pooled odds ratio (OR) of pathological complete response (pCR) and the pooled hazard ratio (HR) of overall survival (OS) and disease-free survival (DFS). Results Nine randomized controlled trials involving 3,724 patients from 10 published studies were included in the meta-analysis. The pooled OR for ddNCT was 1.18 (95% confidence interval (CI): 0.83–1.67, P = 0.356). A subgroup analysis in the cases with low hormone receptor expression levels showed the pCR in patients undergoing ddNCT was significantly higher than the pCR in patients undergoing standard NCT (OR = 1.36, 95% CI: 1.09‒1.69, P = 0.007). There was no significant difference in DFS and OS between ddNCT and standard NCT (DFS: HR = 0.90, 95% CI: 0.79‒1.02, P = 0.095; OS; HR = 0.91, 95% CI: 0.81‒1.04, P = 0.160), regardless of hormone receptor expression levels. These data suggested the higher pCR rate in patients receiving ddNCT did not result in a survival benefit. Conclusions The meta-analysis demonstrated that ddNCT can significantly improve the pCR rate in patients with low hormone receptor expression levels, although patient survival was not significantly improved. The ddNCT can increase the breast-conserving rate and reduced pre-operative waiting time without increasing adverse reactions. This regimen can be considered when developing an NCT plan.

Long non-coding RNA (lncRNA) lung cancer associated transcript 1 (LUCAT1) plays an important regulatory role in a variety of cancers, but its role in breast cancer is still unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to investigate the expression of LUCAT1, miR-199a-5p, HIF-1α in breast cancer tissues and cell lines; CCK8 method was used to detect the proliferation of breast cancer cells; Transwell assay was adopted to evaluate the migration and invasion of breast cancer cells; luciferase reporter gene assay was used to validate the interaction between LUCAT1 and miR-199a-5p. Western blot was utilized to analyze the effects of LUCAT1 and miR-199a-5p on the expression of HIF-1α. LUCAT1 was significantly up-regulated in breast cancer and cell lines; overexpression of LUCAT1 promoted the proliferation, migration and invasion of breast cancer cells. Additionally, LUCAT1 functioned as “ceRNA” to modulate the expression of miR-199a-5p, in turn regulated the expression of HIF-1α. LUCAT1 is an oncogenic lncRNA in breast cancer, and it can inhibit the function of miR-199a-5p and increase the expression of HIF-1α, promoting the proliferation, migration and invasion of cancer cells.

Purpose Neoadjuvant chemotherapy (NCT) is typically the initial treatment for non-early breast cancer patients. We thereby conducted a meta-analysis to explore whether dose-dense neoadjuvant chemotherapy (ddNCT) improved the long-term prognosis of patients compared to the standard NCT regimen. Methods We compared the differences in efficacy and prognosis between patients receiving standard NCT and ddNCT. We also calculated the pooled odds ratio (OR) of pathological complete response (pCR) and the pooled hazard ratio (HR) of overall survival (OS) and disease-free survival (DFS). Results Nine randomized controlled trials involving 3,724 patients from 10 published studies were included in the meta-analysis. The pooled OR for ddNCT was 1.18 (95% confidence interval (CI): 0.83–1.67, P = 0.356). A subgroup analysis in the cases with low hormone receptor expression levels showed the pCR in patients undergoing ddNCT was significantly higher than the pCR in patients undergoing standard NCT (OR = 1.36, 95% CI: 1.09‒1.69, P = 0.007). There was no significant difference in DFS and OS between ddNCT and standard NCT (DFS: HR = 0.90, 95% CI: 0.79‒1.02, P = 0.095; OS; HR = 0.91, 95% CI: 0.81‒1.04, P = 0.160), regardless of hormone receptor expression levels. These data suggested the higher pCR rate in patients receiving ddNCT did not result in a survival benefit. Conclusions The meta-analysis demonstrated that ddNCT can significantly improve the pCR rate in patients with low hormone receptor expression levels, although patient survival was not significantly improved. The ddNCT can increase the breast-conserving rate and reduced pre-operative waiting time without increasing adverse reactions. This regimen can be considered when developing an NCT plan.

Purpose To investigate whether estrogen receptor (ER), progesterone receptor (PR) and Ki-67 expression discordance before and after neoadjuvant chemotherapy (NAC) correlates with prognosis and treatment of breast cancer patients. Methods The study cohort included 482 breast cancer patients at the Zhejiang Cancer Hospital from January 1, 2008, to December 31, 2018. Core needle biopsies and excised tissue biopsies pre- and post-NAC were obtained. Immunohistochemistry was used to determine ER, PR and Ki-67 status. The relationship between biomarker discordance before and after NAC and clinicopathological features was compared retrospectively. Results ER (n = 482), PR (n = 482) and Ki-67 (n = 448) expression was assessed in the same lesion pre- and post-NAC. Discordance in the three markers pre- and post-NAC was observed in 50 (10.4%), 82 (17.0%) and 373 (77.4%) cases, respectively. Positive-to-negative PR expression changes were the most common type of discordance observed. The risk of death in patients with a PR positive-to-negative conversion was 6.58 times greater than for patients with stable PR expression. The risk of death in patients with increased Ki-67 expression following NAC treatment was 2.05 times greater than for patients with stable Ki-67 expression. Conclusion Breast cancer patients showed changes in ER, PR and/or Ki-67 status throughout NAC, and these changes possibly influenced disease-free survival and overall survival. A switch to negative hormone receptor expression with increased Ki-67 expression following NAC could be indicators of a worse prognosis. Biomarker expression investigations following NAC may potentially improve patient management and survival.

The mechanism of bipolar disorder is unclear. Growing evidence indicates that gut microbiota plays a pivotal role in mental disorders. This study aimed to find out changes in the gut microbiota in bipolar depression (BD) subjects following treatment with quetiapine and evaluate their correlations with the brain and immune function. Totally 36 subjects with BD and 27 healthy controls (HCs) were recruited. The severity of depression was evaluated with the Montgomery-Asberg depression rating scale (MADRS). At baseline, fecal samples were collected and analyzed by quantitative polymerase chain reaction (qPCR). T lymphocyte subsets were measured to examine immune function. Near-infrared spectroscopy (NIRS) was used to assess brain function. All BD subjects received quetiapine treatment (300 mg/d) for four weeks, following which the fecal microbiota and immune profiles were reexamined. Here, we first put forward the new concept of brain-gut coefficient of balance (B-GCB), which referred to the ratio of [oxygenated hemoglobin]/(Bifidobacteria to Enterobacteriaceae ratio), to analyze the linkage between the gut microbiota and brain function. At baseline, the CD3+ T cell proportion was positively correlated with log10 Enterobacter spp count, whereas the correlativity between the other bacteria and immune profiles were negative. Log10 B-GCB was positively correlated with CD3+ T cell proportion. In subjects with BD, counts of Faecalibacterium prausnitzii, Bacteroides-Prevotella group, Atopobium Cluster, Enterobacter spp, and Clostridium Cluster IV were higher, whereas the log10 (B/E) were lower than HCs (B/E refers to Bifidobacteria to Enterobacteriaceae ratio and represents microbial colonization resistance). After treatment, MADRS scores were reduced, whereas the levels of Eubacterium rectale, Bifidobacteria, and B/E increased. The composition of the gut microbiota and its relationship to brain function were altered in BD subjects. Quetiapine treatment was effective for depression and influenced the composition of gut microbiota in patients. Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR-COC-17011401, URL: http://www.chictr.org.cn/listbycreater.aspx.

<span id="ChDivSummary" name="ChDivSummary" class="abstract-text">目的:了解注意缺陷多动障碍儿童盐酸哌甲酯治疗后照料者的育儿压力变化。方法:对符合DSM-IV诊断标准的93例ADHD儿童使用盐酸哌甲酯治疗6周,使用ADHD症状分级父母评定量表、Conners父母评症状量表（PSQ）评估ADHD儿童症状,使用CGSQ评估儿童照料者的育儿压力。结果:盐酸哌甲酯治疗6周后ADHD儿童照料者的CGSQ总分（46.7±16.9 vs.40.6±13.6）及三个维度评分均下降（均P&lt;0.05）;多重线性回归分析显示,基线ADHD儿童PSQ总分及照料者对孩子的期待越高,照料者基线CGSQ总分越高（β=0.61、0.29,P&lt;0.05）。经过治疗ADHD儿童的PSQ减分率、母亲年龄越大及儿童年级越低,照料者的CGSQ减分率越大（β=0.71、0.41、-0.31,P&lt;0.05）。结论:盐酸哌甲酯治疗可减轻照料者的育儿压力,症状改善好、母亲年龄大及年级低的儿童照料者育儿压力减轻明显。</span>

e12079 Background: The expression status of estrogen receptor (ER), progesterone receptor (PR), and Ki-67 antigen (Ki-67) divides breast cancer into different subtypes. Changes in these biomarkers during treatment alter the overall treatment decision and affect prognosis. To date, few studies have investigated the effects of changes in these biomarkers throughout neoadjuvant chemotherapy (NAC) on patient prognosis. Methods: A total of 482 patients who received NAC were enrolled. The expression of ER, PR and Ki-67 between pre- and posttherapy specimens was studied by immunohistochemical methods. Physical and imaging examinations based on the Response Evaluation Criteria in Solid Tumors guidelines version 1.1 were utilized to assess the treatment response. The impact of these biomarkers status changes on survival was then tested for statistical significance using a Cox proportional hazards regression model for univariate and multivariate analyses. Results: The rate of discordance for ER, PR and Ki-67 was 10.37%, 17.01% and 77.39%, respectively, in which the PR positive-to-negative conversion was the most common change. A statistically significant differential overall survival (OS) related to biomarkers status throughout NAC (P<.01) was noted. The risk of death in patients with a PR positive-to-negative conversion was 6.58 times greater than that of stable PR expression (P=.002). The risk of disease recurrence in patients with increased Ki-67 expression was 1.91 times greater than that of stable Ki-67 expression (P=.02). Furthermore, we validated both of them as independent predictors of poor prognosis. Conclusions: We concluded that inconsistent expression of biomarkers can significantly affect patient prognosis. We suggest that biomarkers investigations during NAC may potentially improve patient management and survival. Survival result that compared with concordance and discondance in ER, PR and Ki-67. (N=482).*P<.05. [Table: see text]