Modulation effects of imagery acupuncture and no-touch double-blinded placebo acupuncture, a cross-over pilot study.

Both imagery and acupuncture are the oldest medical practices. Recently, we have developed a new treatment modality, video-guided acupuncture imagery treatment (VGAIT), which combines acupuncture and imagery. In this crossover study, we investigated the modulation effects of video-guided acupuncture imagery treatment compared with placebo acupuncture using no-touch double-blind placebo acupuncture needles and a no-treatment resting control. Pressure pain threshold and electroencephalogram (EEG) data were collected before and after each intervention. 12 healthy participants completed the study. Results showed that pressure pain thresholds were significantly increased after VGAIT compared to the resting control condition. In addition, we found that VGAIT, but not the no-touch placebo acupuncture or the resting control, significantly increased alpha and beta band power. Our findings demonstrate the potential of VGAIT as a remote therapeutic method (e-health treatment option) for pain and the value of no-touch double-blind placebo acupuncture in acupuncture research.

Comparative Efficacy of Cognitive Training for Post-Stroke Aphasia: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Although cognitive training has shown potential for treating post-stroke aphasia (PSA), its efficacy varies across studies, and the optimal training approaches remain unclear. OBJECTIVE: To evaluate and compare the effects of distinct cognitive training interventions, either combined with or independent of speech and language therapy (SLT), on language function in individuals with PSA. METHODS: A systematic search encompassing PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, VIP, and Chinese Biomedical Databases was conducted for randomized controlled trials (RCTs). A network meta-analysis evaluated interventions, including computer-assisted cognitive training (CCT), conventional cognitive training (CT), virtual reality (VR)-based cognitive training (vrCT), telerehabilitation computer-assisted cognitive training (tCCT), working memory (WM) training, and attention training (AT). RESULTS: Eleven RCTs comprising 501 participants were included. Individuals with PSA who underwent combined WM training with SLT led to significantly enhanced Western Aphasia Battery (WAB) Aphasia Quotient (AQ), as well as in spontaneous speech, auditory comprehension, repetition, and naming, compared to those receiving SLT alone. This combination was more effective than both CCT with SLT and tCCT with SLT in improving WAB AQ. Similarly, it outperformed both CCT with SLT and vrCT with SLT in enhancing WAB spontaneous speech. Additionally, both AT and CT combined with SLT were more effective than SLT alone in enhancing WAB spontaneous speech. Specifically, AT combined with SLT proved more effective than vrCT with SLT in this area. Moreover, vrCT combined with SLT significantly improved auditory comprehension compared with SLT alone. CONCLUSIONS: Combining WM training and SLT and integrating vrCT with SLT both significantly enhance language function in individuals with PSA, compared with SLT alone. Our findings advocate for the use of these cognitive training approaches as promising strategies for language rehabilitation in this population. PROSPERO registration number: CRD42023462361.

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OBJECTIVES: Scalp acupuncture is a method of treating diseases by dividing and stimulating the corresponding function-oriented cortical scalp areas. It is a commonly used therapy for neurological disorders. However, the specific target selection for scalp acupuncture remains to be explored. This manuscript aims to initiate an attempt to develop/identify scalp acupuncture targets based on neuroimaging findings and noninvasive brain stimulation. METHODS: Neurosynth-based meta-analysis of neuroimaging studies was conducted to identify brain stimulation targets of neurological disorders. The identified target regions were further projected to the scalp. The traditional acupoints and 10-20 EEG system were referenced for the localization of these targets. In this study, the "mild cognitive impairment" (MCI), "Alzheimer's disease" (AD) and "dementia" were used as the retrieval terms respectively, and a unity detection method was used to generate brain maps, with the default FDR (false discovery rate, P<0.01) threshold of Neurosynth set for subsequent exploration of various disease-related brain regions. The literature search was conducted on July 30, 2022. RESULTS: The localization and manipulation suggestions of neuroimage-based scalp acupuncture targets for MCI, AD, and dementia were introduced in the present paper (part 2). Here are 3 target examples for each of these 3 diseases due to word limitation. 1) MCI：Based on the 81 papers retrieved, we identified 6 potential scalp acupuncture points for MCI, their corresponding brain regions, brain functions and the possible resultant effects of the scalp target acupoint stimulation respectively are as below. MCI1：the orbital part of the left inferior frontal gyrus (left Brodmann area ［BA］47), related to semantic coding, working memory and episodic memory, improving semantic coding and memory function；MCI2：the anterior motor area/left anterior central gyrus (left BA6), the motor center area, improving MCI motor function；MCI3：the left medial temporal gyrus (left BA21), related to the processing of speech, visual space, language and word understanding, improving language and memory. 2) AD：Based on the 196 papers retrieved, we found 6 potential scalp acupuncture targets for AD, their corresponding brain regions and brain functions of the 3 example targets respectively are as below. AD1：the left medial temporal gyrus (left BA21), participating in language and semantic processing, sentence and word generation, intent expression, deductive reasoning；AD2：the left angular gyrus (left BA39), related to semantic processing, word reading and comprehension, memory retrieval, attention and spatial cognition, reasoning, etc.；AD3：the left fusiform/suboccipital gyrus (left BA37), related to semantic classification, text generation, sign language, phonology processing, etc. 3) Dementia：Based on the 142 papers retrieved, we found 4 potential scalp acupuncture targets for dementia, their corresponding brain regions, brain functions and the possible targets of the proposed scalp stimulation respectively are as below. D1 and D2：the left inferior frontal gyrus (i.e., left BA46, and left BA47, respectively), being closely related to working memory, emotional response regulation, melody and other processing processes, may be suitable for treating memory decline and advanced executive dysfunction in patients with dementia；D3：the left medial temporal gyrus (left BA21), an important brain region for various sensory integration, cognitive processing and memory functions, and emotional processing, may be suitable for temporal dementia. CONCLUSIONS: We identified scalp acupuncture targets for several common neurological disorders based on neuroimaging findings and noninvasive brain stimulation. The proposed targets may also be used for treating these disorders using nerve/brain stimulation methods.

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OBJECTIVES: Scalp acupuncture is a unique acupuncture method developed based on brain functional and pathophysiological knowledge. In past decades, there has been significant development in the understanding of the brain pathology of many neurological disorders through cutting-edge brain imaging techniques. Yet, these findings have not been incorporated into scalp acupuncture. In the present paper, we aimed to initiate an attempt to develop/identify scalp acupuncture targets based on neuroimaging findings. METHODS: Based on the meta-analysis of neuroimaging studies in the Neurosynth database platform (http：//neurosynth.org/), the brain clusters related to neurological disorders were automatically identified according to the search terms "Parkinson's disease"(PD), "chronic pain"(CP), "aphasia"(APH), "dyslexia"(DYS), "mild cognitive impairment", "Alzheimer's disease" and "dementia". Subsequently, the discovered brain region clusters projected onto the brain surface and scalp surface were listed, and the peak points of the clusters projected to the scalp surface were proposed as the potential stimulation targets for the corresponding diseases. Further, by combining the traditional scalp acupoints (including the scalp acupuncture lines) with 10-20 EEG system sites, we made localization suggestions for scalp stimulation targets and made acupuncture operation suggestions by combining with the shape of the brain region clusters. The literature search was conducted on July 30, 2022. RESULTS: The localization and manipulation suggestions of neuroimage-based scalp acupuncture targets were introduced in two parts. This part (part 1) includes PD, CP, APH, and DYS. Here are 3 target examples of each of these 4 diseases simply introduced due to word limitation. 1) PD. Based on the 175 articles retrieved from Neurosynth, we identified 7 potential scalp acupuncture targets for PD, the locations of the acupuncture stimulation and the recommended acupuncture needle operation (RANO) as well as the corresponding brain regions (CBRs) respectively are as below. PD1：about 0.5 cun (1 cun≈33.3 mm) superior-posterior to the left Xuanlu (GB5)；puncturing subcutaneously and forward-upward；the left premotor area, subfrontal cortex of the island, inferior frontal gyrus and middle frontal gyrus. PD2：about 1 cun lateral-inferior to the left Chengling (GB18)；puncturing subcutaneously and backward-upward；the inferior parietal lobule and postcentral gyrus. PD3：about 0.5 cun lateral-anterior to the left GB18；puncturing subcutaneously and inward-backward；left anterior central gyrus and posterior central gyrus. 2) CP. Based on the retrieved 92 articles, we identified 8 potential scalp acupuncture targets, the location of the acupuncture stimulation and the RANO, and CBRs respectively are as below. CP1：about 1 cun anterior-inferior to the left Xuanli (GB8)；puncturing subcutaneously and backward-inwards；the left inferior frontal gyrus orbitalis and pars triangularis. CP2：about 0.5 cun posterior-superior to the left GB5；puncturing subcutaneously and forward-upward；the left anterior central gyrus and premotor area. CP3：about 0.5 cun posterior-superior to the left GB8；puncturing subcutaneously and forward；left inferior central area/central sulci operculum (second somatosensory area). 3) APH. Based on the retrieved 82 papers, we identified 7 potential scalp acupuncture targets for APH, their locations, RANO, and CBRs respectively are as below. APH1：close to the left GB5；puncturing subcutaneously and forward-downward；left subfrontal gyrus operculi/triangularis. APH2：about 0.5 cun posterior to the left Hanyan (GB4)；puncturing subcutaneously and backward-upward；the left anterior central gyrus and posterior central gyrus. APH3：about 0.5 cun anterior-inferior to the left Qubin (GB7)；puncturing subcutaneously and backward-downward；left medial/superior temporal gyrus. 4) DYS. Based on the retrieved 76 researches, we identified 8 potential scalp acupuncture targets for DYS, their locations, RANO and CBRs respectively are as below. DYS1：about 1 cun anterior-inferior to the left GB5；puncturing subcutaneously and forward-upward；the pars triangularis of the left inferior frontal gyrus. DYS2：about 0.5 cun posterior-superior to the left GB5；puncturing subcutaneously and forward-downward；the left subfrontal gyrus operculum, pars triangularis and anterior central gyrus. DYS3：the midpoint between the left GB5 and GB18；puncturing subcutaneously and forward；the left anterior central gyrus and posterior central gyrus. CONCLUSIONS: We identified scalp acupuncture targets for several common neurological disorders based on neuroimaging evidence for clinical application and research. The proposed targets may also be used for treating these disorders using brain stimulation methods.

[Neuroimaging-based study of scalp acupuncture targets for common psychiatric diseases (Part 2)].

In this study, based on the neuroimaging literature Meta analysis retrieved from Neurosynth platform, the scalp stimulation targets for common psychiatric diseases are developed, which provided the stimulation target protocols of scalp acupuncture for attention deficit hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder and schizophrenia. The paper introduces the functions of the brain areas that are involved in each target and closely related to the diseases, and lists the therapeutic methods of common acupuncture/scalp acupuncture and common neuromodulation methods for each disease so as to provide the references for clinical practice. Based on the study results above, the paper further summarizes the overlapped stimulation targets undergoing the intervention with scalp acupuncture for common psychiatric diseases, and the potential relationship between these stimulation targets and treatments with acupuncture and moxibustion.

[Neuroimaging-based study of scalp acupuncture targets for common psychiatric diseases].

Scalp acupuncture is a unique acupuncture method, developed based on the cerebral cortex localization. Neuroimaging technology enables the combination of contemporary brain science findings with the studies of scalp stimulation sites. In this study, based on the neuroimaging literature retrieved from Neurosynth platform, the scalp stimulation targets of common psychiatric diseases are developed, which provides the stimulation target protocol of scalp acupuncture for anxiety, bipolar disorder, major depressive disorder and post-traumatic stress disorder. The paper introduces the functions of the brain areas that are involved in each target and closely related to the diseases, and lists the therapeutic methods of common acupuncture and scalp acupuncture for each disease so as to provide the references for clinical practice. These targets can be used not only for the stimulation of scalp acupuncture, but also for the different neuromodulation techniques to treat related diseases.

Brain stimulation targets for chronic pain: Insights from meta-analysis, functional connectivity and literature review.

Noninvasive brain stimulation (NIBS) techniques have demonstrated their potential for chronic pain management, yet their efficacy exhibits variability across studies. Refining stimulation targets and exploring additional targets offer a possible solution to this challenge. This study aimed to identify potential brain surface targets for NIBS in treating chronic pain disorders by integrating literature review, neuroimaging meta-analysis, and functional connectivity analysis on 90 chronic low back pain patients. Our results showed that the primary motor cortex (M1) (C3/C4, 10-20 EEG system) and prefrontal cortex (F3/F4/Fz) were the most used brain stimulation targets for chronic pain treatment according to the literature review. The bilateral precentral gyrus (M1), supplementary motor area, Rolandic operculum, and temporoparietal junction, were all identified as common potential NIBS targets through both a meta-analysis sourced from Neurosynth and functional connectivity analysis. This study presents a comprehensive summary of the current literature and refines the existing NIBS targets through a combination of imaging meta-analysis and functional connectivity analysis for chronic pain conditions. The derived coordinates (with integration of the international electroencephalography (EEG) 10/20 electrode placement system) within the above brain regions may further facilitate the localization of these targets for NIBS application. Our findings may have the potential to expand NIBS target selection beyond current clinical trials and improve chronic pain treatment.

Herbal formulas for detoxification and dredging collaterals in treating carotid atherosclerosis: a systematic review and meta-analysis.

Objective: To systematically evaluate the efficacy and safety of the Chinese medicine detoxification and dredging collaterals in treating carotid atherosclerosis (CAS). Methods: A systematic and comprehensive search of nine relevant domestic and international databases were conducted from their inception until June 2022. The methodological quality of the included trials was evaluated, and the efficacy and safety were comprehensively analyzed. After applying the inclusion and exclusion criteria to the randomized controlled trials (RCTs), the research quality evaluation and data extraction were conducted, followed by a meta-analysis of the selected articles. The Cochrane's Bias risk assessment was utilized to evaluate the quality of the evidence. Results: Of the 2,660 studies initially retrieved, 14 studies were included, involving a total of 1,518 patients. The results of the meta-analysis indicated that the clinical efficacy of the Detoxification and Collateral Dredging method in the treatment of CAS was superior to that of western medicine treatment alone, and the difference was statistically significant [RR = 1.23, 95% CI (1.13, 1.34)] Furthermore, carotid intima-media thickness [Mean Difference (MD) = -0.10, 95% CI (-0.13, -0.08)] and Crouse plaque score [MD = -0.54, 95% CI (-0.75, -0.32)] were significantly lower in the Detoxification and Collateral Dredging group compared to the pure western medicine treatment group. The difference was statistically significant. In addition, serum total cholesterol [MD = -0.70, 95% CI (-0.85, -0.55)] and low-density lipoprotein cholesterol [MD = -0.70, 95% CI (-0.85, -0.55)] were lower in the Detoxification and Collateral Dredging group than in the Western medicine group, with all differences being statistically significant. Serum high-density lipoprotein cholesterol was higher in the Detoxification and Collateral Dredging group compared to the pure western medicine group, and the difference was statistically significant [MD = 0.17, 95% CI (0.11, 0.23)]. Conclusion: The use of Chinese medicine Detoxification and Collateral Dredging approach in the treatment of CAS may offer benefits in improving carotid atherosclerotic plaque and reducing blood lipid levels, with a safety profile superior to that of western medicine treatment alone.

Anatomical and Functional Connectivity of Critical Deep Brain Structures and Their Potential Clinical Application in Brain Stimulation.

Subcortical structures, such as the hippocampus, amygdala, and nucleus accumbens (NAcc), play crucial roles in human cognitive, memory, and emotional processing, chronic pain pathophysiology, and are implicated in various psychiatric and neurological diseases. Interventions modulating the activities of these deep brain structures hold promise for improving clinical outcomes. Recently, non-invasive brain stimulation (NIBS) has been applied to modulate brain activity and has demonstrated its potential for treating psychiatric and neurological disorders. However, modulating the above deep brain structures using NIBS may be challenging due to the nature of these stimulations. This study attempts to identify brain surface regions as source targets for NIBS to reach these deep brain structures by integrating functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). We used resting-state functional connectivity (rsFC) and probabilistic tractography (PTG) analysis to identify brain surface stimulation targets that are functionally and structurally connected to the hippocampus, amygdala, and NAcc in 119 healthy participants. Our results showed that the medial prefrontal cortex (mPFC) is functionally and anatomically connected to all three subcortical regions, while the precuneus is connected to the hippocampus and amygdala. The mPFC and precuneus, two key hubs of the default mode network (DMN), as well as other cortical areas distributed at the prefrontal cortex and the parietal, temporal, and occipital lobes, were identified as potential locations for NIBS to modulate the function of these deep structures. The findings may provide new insights into the NIBS target selections for treating psychiatric and neurological disorders and chronic pain.

Thalamocortical Mechanisms Underlying Real and Imagined Acupuncture.

Both acupuncture and imagery have shown potential for chronic pain management. However, the mechanisms underlying their analgesic effects remain unclear. This study aims to explore the thalamocortical mechanisms underlying acupuncture and video-guided acupuncture imagery treatment (VGAIT), a combination of acupuncture and guided imagery, using the resting-state functional connectivity (rsFC) of three thalamic subdivisions-the ventral posterolateral thalamus (VPL), mediodorsal thalamus (MD), and motor thalamus subregion (Mthal)-associated with somatosensory, limbic, and motor circuity. Twenty-seven healthy individuals participated in a within-subject randomized crossover design study. Results showed that compared to sham acupuncture, real acupuncture altered the rsFC between the thalamus and default mode network (DMN) (i.e., mPFC, PCC, and precuneus), as well as the prefrontal and somatosensory cortex (SI/SII). Compared to the VGAIT control, VGAIT demonstrated greater rsFC between the thalamus and key nodes within the interoceptive network (i.e., anterior insula, ACC, PFC, and SI/SII), as well as the motor and sensory cortices (i.e., M1, SMA, and temporal/occipital cortices). Furthermore, compared to real acupuncture, VGAIT demonstrated increased rsFC between the thalamus (VPL/MD/Mthal) and task-positive network (TPN). Further correlations between differences in rsFC and changes in the heat or pressure pain threshold were also observed. These findings suggest that both acupuncture- and VGAIT-induced analgesia are associated with thalamocortical networks. Elucidating the underlying mechanism of VGAIT and acupuncture may facilitate their development, particularly VGAIT, which may be used as a potential remote-delivered pain management approach.

The outcomes of endoscopic orbital decompression combined with fat decompression for thyroid-associated ophthalmopathy.

PURPOSE: To present the clinical features of thyroid-associated ophthalmopathy (TAO) with different CT types, and to report the outcomes of endoscopic orbital decompression combined with fat decompression (EOD-FD). PATIENTS AND METHODS: Thirty-four patients with TAO who underwent EOD-FD between December 2020 and March 2022 in the Ophthalmology Department of Li Huili Hospital Affiliated with Ningbo University, were included in this retrospective interventional case series. Patients were categorized into two groups based on the results of computerized tomography (CT) scans: muscle expansion type and fat hyperplasia type. RESULTS: Thirty-four TAO patients (55 eyes) were included in this study, and the mean age was 38.62 years (range 22-60 years). The average eye protrusion (EP) reduced from preoperative 23.20 mm to postoperative 19.66 mm (p < 0.0001). Mean intraocular pressure (IOP) decreased from 20.11 mmHg at baseline to 17.29 mmHg postoperatively (p < 0.0001), with a reduction of 2.84 mmHg (14.12%). Twenty cases of muscle expansion and fourteen cases of fat hyperplasia were definite by CT imaging. The mean IOP in the muscle expansion group was higher than that in the fat hyperplasia group (p < 0.05). Elevated intraocular pressure (IOP) occurred in 23 eyes (36.11%), and it was associated with extraocular muscle involvement, gender, and EP. In 3 cases of impaired vision, the mean best corrected visual acuity (VA) improved from 0.4 preoperatively to 0.84 postoperatively (p < 0.01). There were 8 cases with visual field (VF) damage and/or corneal epithelium damage, and all these damages were reversible. CONCLUSION: In this study, we describe the clinical features and experience of EOD-FD in patients with TAO. EOD-FD is an effective technique in reducing IOP and proptosis, with a low incidence of postoperative diplopia.

Corrigendum: Modulations of static and dynamic functional connectivity among brain networks by electroacupuncture in post-stroke aphasia.

[This corrects the article DOI: 10.3389/fneur.2022.956931.].

Modulations of static and dynamic functional connectivity among brain networks by electroacupuncture in post-stroke aphasia.

Introduction: Post-stroke aphasia (PSA) is a language disorder caused by left hemisphere stroke. Electroacupuncture (EA) is a minimally invasive therapeutic option for PSA treatment. Tongli (HT5) and Xuanzhong (GB39), two important language-associated acupoints, are frequently used in the rehabilitation of patients with PSA. Preliminary evidence indicated functional activation in distributed cortical areas upon HT5 and GB39 stimulation. However, research on the modulation of dynamic and static functional connectivity (FC) in the brain by EA in PSA is lacking. Method: This study aimed to investigate the PSA-related effects of EA stimulation at HT5 and GB39 on neural processing. Thirty-five participants were recruited, including 19 patients with PSA and 16 healthy controls (HCs). The BOLD signal was analyzed by static independent component analysis, generalized psychophysiological interactions, and dynamic independent component analysis, considering variables such as age, sex, and years of education. Results: The results revealed that PSA showed activated clusters in the left putamen, left postcentral gyrus (PostCG), and left angular gyrus in the salience network (SN) compared to the HC group. The interaction effect on temporal properties of networks showed higher variability of SN (F = 2.23, positive false discovery rate [pFDR] = 0.017). The interaction effect on static FC showed increased functional coupling between the right calcarine and right lingual gyrus (F = 3.16, pFDR = 0.043). For the dynamic FC, at the region level, the interaction effect showed lower variability and higher frequencies of circuit 3, with the strongest connections between the supramarginal gyrus and posterior cingulum (F = 5.42, pFDR = 0.03), middle cingulum and PostCG (F = 5.27, pFDR = 0.036), and triangle inferior frontal and lingual gyrus (F = 5.57, pFDR = 0.026). At the network level, the interaction effect showed higher variability in occipital network-language network (LN) and cerebellar network (CN) coupling, with stronger connections between the LN and CN (F = 4.29, pFDR = 0.042). Dynamic FC values between the triangle inferior frontal and lingual gyri were anticorrelated with transcribing, describing, and dictating scores in the Chinese Rehabilitation Research Center for Chinese Standard Aphasia Examination. Discussion: These findings suggest that EA stimulation may improve language function, as it significantly modulated the nodes of regions/networks involved in the LN, SN, CN, occipital cortex, somatosensory regions, and cerebral limbic system.

Novel hydroxymethylbilane synthase gene mutation identified and confirmed in a woman with acute intermittent porphyria: A case report.

BACKGROUND: Acute intermittent porphyria (AIP) is a rare autosomal dominant porphyrin metabolic disease caused by a mutation in the hydroxymethylbilane synthase (HMBS) gene. This study aimed to explore the clinical manifestations of a patient with AIP, to identify a novel HMBS gene mutation in the proband and some of her family members, and to confirm the pathogenicity of the variant. CASE SUMMARY: A 22-year-old Chinese woman developed severe abdominal pain, lumbago, sinus tachycardia, epileptic seizure, hypertension, and weakness in lower limbs in March, 2018. Biochemical examinations indicated hypohepatia and hyponatremia. Her last menstrual period was 45 d prior to admission, and she was unaware of the pregnancy, which was confirmed by a pregnancy test after admission. Sunlight exposure of her urine sample for 1 h turned it from yellow to wine red. Urinary porphyrin test result was positive. Based on these clinical manifestations, AIP was diagnosed. After increasing her daily glucose intake (250-300 g/d), abdominal pain was partially relieved. Three days after hospitalization, spontaneous vaginal bleeding occurred, which was confirmed as spontaneous abortion; thereafter, her clinical symptoms completely resolved. Genetic testing revealed a novel heterozygous splicing variant of the HMBS gene in exon 10 (c.648_651+1delCCAGG) in the proband and four other family members. The pathogenicity of the variant was verified through bioinformatic methods and a minigene assay. CONCLUSION: We identified a novel HMBS gene mutation in a Chinese patient with AIP and confirmed its pathogenicity.

Restraint stress of female mice during oocyte development facilitates oocyte postovulatory aging.

Studies suggest that psychological stress on women can impair their reproduction and that postovulatory oocyte aging (POA) might increase the risk of early pregnancy loss and affect offspring's reproductive fitness and longevity. However, whether psychological stress during oocyte development would facilitate POA is unknown but worth exploring to understand the mechanisms by which psychological stress and POA damage oocytes. This study observed effects of female restraint stress during oocyte development (FRSOD) on oocyte resistance to POA. Female mice were restrained for 48 h before superovulation, and they were sacrificed at different intervals after ovulation to recover aging oocytes for analyzing their early and late aged characteristics. The effects of FRSOD on aging oocytes included: (1) increasing their susceptibility to activation stimulus with elevated cytoplasmic calcium; (2) impairing their developmental potential with downregulated expression of development-beneficial genes; (3) facilitating degeneration, cytoplasmic fragmentation and apoptosis; (4) worsening the disorganization of cortical granules and spindle/chromosomes; and (5) impairing redox potential with increased oxidative stress. In conclusion, FRSOD impairs oocyte resistance to POA, so that stressed oocytes become aged significantly quicker than unstressed controls. Thus, couples wishing to achieve pregnancy should take steps to avoid not only fertilization of aged oocytes but also pregestational stressful life events.

Glucocorticoid Exposure of Preimplantation Embryos Increases Offspring Anxiety-Like Behavior by Upregulating miR-211-5p via Trpm1 Demethylation.

Most studies on mechanisms by which prenatal stress affects offspring behavior were conducted during late pregnancy using in vivo models; studies on the effect of preimplantation stress are rare. In vivo models do not allow accurate specification of the roles of different hormones and cells within the complicated living organism, and cannot verify whether hormones act directly on embryos or indirectly to alter progeny behavior. Furthermore, the number of anxiety-related miRNAs identified are limited. This study showed that both mouse embryculture with corticosterone (ECC) and maternal preimplantation restraint stress (PIRS) increased anxiety-like behavior (ALB) while decreasing hippocampal expression of glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) in offspring. ECC/PIRS downregulated GR and BDNF expression by increasing miR-211-5p expression via promoter demethylation of its host gene Trpm1, and this epigenetic cell fate determination was exclusively perpetuated during development into mature hippocampus. Transfection with miR-211-5p mimic/inhibitor in cultured hippocampal cell lines confirmed that miR-211-5p downregulated Gr and Bdnf. Intrahippocampal injection of miR-211-5p agomir/antagomir validated that miR-211-5p dose-dependently increased ALB while decreasing hippocampal GR/BDNF expression. In conclusion, preimplantation exposure to glucocorticoids increased ALB by upregulating miR-211-5p via Trpm1 demethylation, and miR-211-5p may be used as therapeutic targets and biomarkers for anxiety-related diseases.

Effects of postovulatory oviduct changes and female restraint stress on aging of mouse oocytes.

Postovulatory oocyte aging is one of the major causes for human early pregnancy loss and for a decline in the population of some mammalian species. Thus, the mechanisms for oocyte aging are worth exploring. While it is known that ovulated oocytes age within the oviduct and that female stresses impair embryo development by inducing apoptosis of oviductal cells, it is unknown whether the oviduct and/or female stress would affect postovulatory oocyte aging. By comparing aging characteristics, including activation susceptibility, maturation-promoting factor activity, developmental potential, cytoplasmic fragmentation, spindle/chromosome morphology, gene expression, and cumulus cell apoptosis, this study showed that oocytes aged faster in vivo in restraint-stressed mice than in unstressed mice than in vitro. Our further analysis demonstrated that oviductal cells underwent apoptosis with decreased production of growth factors with increasing time after ovulation, and female restraint facilitated apoptosis of oviductal cells. Furthermore, mating prevented apoptosis of oviductal cells and alleviated oocyte aging after ovulation. In conclusion, the results demonstrated that mouse oviducts underwent apoptosis and facilitated oocyte aging after ovulation; female restraint facilitated oocyte aging while enhancing apoptosis of oviductal cells; and copulation ameliorated oviductal apoptosis and oocyte aging.

A next-generation sequencing study on mechanisms by which restraint and social instability stresses of male mice alter offspring anxiety-like behavior.

Pathophysiological mechanisms for depression/anxiety are largely unknown. Evidence for transgenerational transmission of acquired epigenetic marks remains limited. We bred unstressed (US) female mice with adolescently restraint-stressed (RS), social instability-stressed (SI) or US males to produce RS, SI and control F1 offspring, respectively. Compared to controls, while paternal RS decreased anxiety-like behavior (ALB) in both female and male offspring, paternal SI increased ALB only in female offspring. Next-generation sequencing and bioinformatics using RS and SI female offspring identified 5 candidate anxiety-transmitting (CAT) genes; each showed a consistent pattern of DNA methylation from F0 spermatozoa through F1 blastocysts to fetal and adult hippocampi. Further analyses validated 4 CAT genes, demonstrated that paternal SI caused ALB differences between male and female offspring through modifying the CAT genes, and indicated a strong correlation between inflammation and ALB pathogenesis and an important function for intronic DNA methylation in regulating ALB-related genes. In conclusion, this study identified important CAT genes and suggested the possibility that stresses on males might alter offspring's ALB by modifying sperm DNA methylation.

Evaluating the Long-Term Efficacy of Acupuncture Therapy for Subacute Poststroke Aphasia: Study Protocol for a Randomized, Blinded, Controlled, Multicentre Trial.

BACKGROUND: Poststroke aphasia (PSA) is a disabling condition that decreases the quality of life, and the duration of the disease harms the quality of life of PSA patients. Acupuncture has been widely employed for PSA. There is some evidence for the immediate treatment efficacy of acupuncture for PSA; however, long-term results after acupuncture may be poorer. METHODS: This is a multicentre, randomized, blinded, nonacupoint (NA) acupuncture controlled, multimodal neuroimaging clinical trial. A total of 48 subjects with subacute PSA will be randomly assigned to an acupoint group or an NA control group. The acupoint group will receive acupuncture with normal needling at DU20, EX-HN1, HT5, GB39, EX-HN12, EX-HN13, and CV23. The NA control group will receive acupuncture in locations not corresponding to acupuncture points as sham acupoints. Both groups will receive identical speech and language therapy thrice a week for four weeks. The primary outcome will be the change in the aphasia quotient (AQ) score measured by the Western Aphasia Battery (WAB) test during the 12th week after randomization. Participants will be blindly assessed at prerandomization (baseline) and 4 weeks, 12 weeks, and 24 weeks after randomization. The secondary outcomes include the Boston Diagnostic Aphasia Examination (BDAE) score, the Disease Prognosis Scale score for ischaemic stroke, etc. Magnetic resonance imaging (MRI) and electroencephalogram (EEG) will also be performed at 4-time intervals as secondary outcomes. All scores and image evaluations will be taken at the same point as the linguistic evaluation. The multilevel evaluation technique will be used to assess the long-term efficacy of acupuncture therapy. MRI scans and EEG will be used to assess acupuncture-related neuroplasticity changes. Discussion. The results from our trial will help to supply evidence for the long-term acupuncture effects for PSA over a long follow-up period. It will provide valuable information for future studies in the field of PSA treatment. The trial was registered at the Chinese Clinical Trial Registry on 16 March 2020 (ChiCTR2000030879).