Shuyu capsule alleviates premenstrual depression via allopregnanolone metabolic pathway targeting GABA (A) receptors δ subunit in the hippocampus.

To reveal the exact changes of allopregnanolone-mediated γ-aminobutyric acid A receptor pathways and its specific therapeutic targets by Shuyu Capsule treating premenstrual depression, female Wistar rat models of premenstrual depression was established by Forced swimming test (FST). Behavioral tests, enzyme-linked immunosorbent assay (ELISA), interference knockdown adenovirus, and overexpressed vector adenovirus of GABAARδ, RT-qPCR, Western-Blot, and immunohistochemical detecting expressions were applied to identify the therapeutic targets. FST-based rat model indicated that Shuyu capsules alleviated typical premenstrual depression and may regulate alternations of 5α-reductase and 3α-steroid dehydrogenase, enhancing the metabolic pathway of progesterone to allopregnanolone, as well as targeting the GABAARδ subunit, thereby alleviating premenstrual depression of PMDD rat models.

Abnormal eye movement features in patients with depression: Preliminary findings based on eye tracking technology.

BACKGROUND: Saccadic eye movement (SEM) has been considered a non-invasive potential biomarker for the diagnosis of depression in recent years, but its application is not yet mature. In this study, we used eye-tracking technology to identify the eye movements of patients with depression to develop a new method for objectively identifying depression. METHODS: Thirty-six patients with depression as the depression group, while thirty-six matched healthy individuals as the control group were recruited and completed eye movement tests, including two tasks: the prosaccade task and the antisaccade task. iViewX RED 500 eye-tracking instruments from SMI were used to collect eye movement data for both groups. RESULTS: In the prosaccade task, there was no difference between the depression and control groups(t = 0.019， P > 0.05). In general, with increasing angle, both groups showed significantly higher peak velocity (F = 81.72， P < 0.0001), higher mean velocity (F = 32.83, P = 0.000), and greater SEM amplitude (F = 24.23, P < 0.0001). In the antisaccade task, there were significant differences in correct rate (t = 3.219, P = 0.002) and mean velocity (F = 3.253， P < 0.05) between the depression group and the control group. In the anti-effect analysis, there were significant differences in correct rate (F = 67.44, P < 0.0001) and accuracy (F = 79.02, P < 0.0001) between the depression group and the control group. Both groups showed longer latency and worse correct rate and precision in the antisaccade task compared with the prosaccade task. CONCLUSION: Patients with depression showed different eye movement features, which could be potential biomarkers for clinical identification. Further studies must validate these results with larger sample sizes and more clinical populations.

Bibliometric Analysis on GABA-A Receptors Research Based on CiteSpace and VOSviewer.

Background: GABA-A receptors are the primary mediators of brain inhibitory neurotransmission. In the past years, many studies focused on this channel to decipher the pathogenesis of related diseases but lacked bibliometric analysis research. This study aims to explore the research status and identify the research trends of GABA-A receptor channels. Methods: Publications related to GABA-A receptor channels were retrieved from the Web of Science Core Collection from 2012 to 2022. After screening, the VOSviewer 1.6.18 and Citespace 5.8 R3 were used for bibliometric analysis from journals, countries, institutions, authors, co-cited references and keywords. Results: We included 12,124 publications in the field of GABA-A receptor channels for analysis. The data shows that although there was a slight decrease in annual publications from 2012 to 2021, it remained at a relatively high level. Most publications were in the domain of neuroscience. Additionally, the United States was the most prolific country, followed by China. Univ Toronto was the most productive institution, and James M Cook led essential findings in this field. Furthermore, brain activation, GABAAR subunits expression, modulation mechanism in pain and anxiety behaviors and GABA and dopamine were paid attention to by researchers. And top research frontiers were molecular docking, autoimmune encephalitic series, obesity, sex difference, diagnosis and management, EEG and KCC2. Conclusion: Taken together, academic attention on GABA-A receptor channels was never neglected since 2012. Our analysis identified key information, such as core countries, institutions and authors in this field. Molecular docking, autoimmune encephalitic series, obesity, sex difference, diagnosis and management, EEG and KCC2 will be the future research direction.

Scientometric analysis of post-stroke depression research based on CiteSpace.

Post-stroke depression (PSD) has served as a severe and common complication leading to a higher level of mortality. Though various studies have been focused on PSD, limited research endeavor has been dedicated to bibliometric analysis in the past. In view of this, the current analysis serves to elucidate the latest status of global research and pinpoint the emerging area of interest for PSD, in order to support further investigation of the field. Publications related to PSD were retrieved from the Web of Science Core Collection database on September 24, 2022, and included in the bibliometric analysis. VOSviewer and CiteSpace software were used to visually analyze publication outputs, scientific cooperation, highly-cited references, and keywords to identify the current status and future trends in PSD research. A total of 533 publications were retrieved. The annual number of publications showed an increasing trend from 1999 to 2022. In terms of country and academic institution, the USA and Duke University have topped the list of PSD research respectively. Meanwhile, Robinson RG and Alexopoulos GS have been the most representative investigators of the field. In the past, researchers focused on the risk factors of PSD, late-life depression, and Alzheimer disease. In recent years, further research effort has been placed on meta-analysis, ischemic stroke, predictor, inflammation, mechanism, and mortality. In conclusion, in the past 20 years, PSD research has been progressing and gaining more attention. The bibliometric analysis successfully unveiled the field's major contributing countries, institutions, and investigators. Furthermore, current hot spots and future trends in the field of PSD were identified, which included meta-analysis, ischemic stroke, predictor, inflammation, mechanism, and mortality.

Profiling GABA(A) Receptor Subunit Expression in the Hippocampus of PMDD Rat Models Based on TCM Theories.

γ-Aminobutyric acid type A receptors (GABAARs) play an important role in cognitive and emotional regulation and are related to the hippocampus. However, little is known regarding patterns of hippocampal GABAAR subunit expression in rat models of premenstrual dysphoric disorder (PMDD). This study investigated the above changes by establishing two PMDD rat models based on Traditional Chinese Medicine (TCM) theories, namely, PMDD liver-qi invasion syndrome (PMDD-LIS) and PMDD liver-qi depression syndrome (PMDD-LDS). Behavioral tests were used to detect depression and irritability emotion. Western blot analysis was used to investigate protein levels of GABAAR α1, α2, α4, α5, ß2, ß3, and δ subunits, whereas ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis was performed to determine gamma-aminobutyric acid (GABA) and glutamate (Glu) levels in the hippocampus across each group. Concurrently, behavioral data indicated that the PMDD-LDS and PMDD-LIS rat models had been successfully established. GABAAR α2, α5, ß2, and δ subunit was significantly upregulated, whereas α4 was significantly downregulated (P < 0.05) in PMDD-LDS rat models relative to controls. On the other hand, GABAAR α1, α2, and ß3 were significantly downregulated while α4 and ß2 were significantly upregulated in PMDD-LIS rat models relative to the control group (P < 0.05). Moreover, GABA levels significantly decreased, while Glu and the ratio of glutamate to GABA increased in PMDD-LIS rat models (P < 0.05). Conversely, GABA and Glu levels significantly decreased, whereas the ratio of glutamate to GABA increased in PMDD-LIS rat models (P < 0.05). Conclusively, our results revealed differential expression of GABAAR α1, α2, α4, α5, ß2, ß3, and δ subunits between PMDD-LIS and PMDD-LDS rat models, suggesting that they may be biomarkers in the pathogenesis of PMDD.

Allopregnanolone-mediated GABAA-Rα4 function in amygdala and hippocampus of PMDD liver qi-invasion syndrome model rats.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a common mental health challenge among women of reproductive age. Allopregnanolone (3α, 5α-THP; ALLO) mediated functional alterations of GABAA receptors (GABAA-R) are involved in PMDD pathogenesis, however, the specific mechanism remains unknown. Therefore, we investigated the role of ALLO mediated GABAA-Rα4 in the pathophysiology of PMDD. PURPOSE: We determined whether the pathogenesis of PMDD is associated with ALLO mediated GABAA-Rα4 expression changes in different brain regions. METHODS: Rat models of PMDD liver-qi invasion syndrome (PMDD-LIS) were established via the resident intruder paradigm. Behavioral changes of rats were assessed by aggressive behavior tests, EPM and OFT. The levels of progesterone and ALLO in serum as well as brain areas were determined by ELISA. Variations in GABAA-Rα4 levels in brain regions were assessed by immunofluorescence and RT-PCR. Medicated serum was used to interfere with rat hippocampal neurons, and changes in Cl- current were recorded through electrophysiology. RESULTS: Premenstrual anxiety and irritability of PMDD-LIS patients can be simulated in PMDD-LIS rat models. Exogenous ALLO significantly improved the anxiety behaviors of PMDD-LIS rats. Changes in ALLO among different brain regions varied. GABAA-Rα4 expressions were low in the amygdala and abnormally high in the hippocampus, however, ALLO alleviated these deviations. Whole-cell patch clamp recording technique showed a weaker Cl- current intensity of PMDD-LIS rats, reduced neuroinhibitory functions and increased Cl- current intensity in the ALLO group drug serum intervention and enhanced emotional inhibition function. CONCLUSION: We established that ALLO regulation of the GABAA-Rα4 subunit in the amygdala and hippocampus is involved in PMDD-LIS pathogenesis.

Research progress of traditional Chinese medicine compound "Xiaochaihu Decoction" in the treatment of depression.

Depression is a common psychiatric disorder under the category of depression syndrome in Traditional Chinese Medicine (TCM) theory. Meanwhile, Xiaochaihu Decoction is a classical TCM formulation regulating Qi, resolving and dissipating stagnation. Clinically, the formulation has long been adopted to treat Shaoyang stagnation syndrome for depression syndrome. In this review, potential targets of action and the corresponding pathways of Xiaochaihu Decoction are explored for depression treatment via network pharmacology. The article also systematically summarizes the active components and pharmacological mechanisms of seven Chinese herbal medicine components in Xiaochaihu Decoction and guides the future study direction of Xiaochaihu Decoction, which may serve a promising treatment for depression.

Mechanism Study on Chinese Medicine in Treatment of Nodular Goiter.

Nodular goiter has become increasingly prevalent in recent years. Clinically, there has been a burgeoning interest in nodular goiter due to the risk of progression to thyroid cancer. This review aims to provide a comprehensive summary of the mechanisms underlying the therapeutic effect of Chinese medicine (CM) in nodular goiter. Articles were systematically retrieved from databases, including PubMed, Web of Science and China National Knowledge Infrastructure. New evidence showed that CM exhibited multi-pathway and multi-target characteristics in the treatment of nodular goiter, involving hypothalamus-pituitary-thyroid axis, oxidative stress, blood rheology, cell proliferation, apoptosis, and autophagy, especially inhibition of cell proliferation and promotion of cell apoptosis, involving multiple signal pathways and a variety of cytokines. This review provides a scientific basis for the therapeutic use of CM against nodular goiter. Nonetheless, future studies are warranted to identify more regulatory genes and pathways to provide new approaches for the treatment of nodular goiter.

Resident intruder paradigm-induced PMDD rat model of premenstrual irritability: behavioral phenotypes, drug intervention, and biomarkers.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is high in women of childbearing age with obvious premenstrual irritability. However, reliable animal models are still lacking. MATERIALS AND METHODS: PMDD rat model of premenstrual irritability was induced by the resident-intruder paradigm (RIP). Behavioral characteristics were determined by the aggressive behavior test, elevated plus maze, open-field test, and breast width measurement. The estrous cycle in rats was artificially manipulated by bilateral ovariectomy and exogenous hormone injection to verify the model phenotype's dependence on the estrous cycle. Fluoxetine and Baixiangdan capsules were administered by gavage to determine the symptom improvement effect of PMDD irritability. Biomarkers in serum and brain were detected using ELISA, and GABRA4 was detected in the brain by RT-PCR and Western blot. RESULTS: Rat models demonstrated similar clinical characteristics as PMDD, such as premenstrual irritability and anxiety, and the above symptoms were estrous cycle-dependent. In addition, the levels of progesterone (P) and ALLO hormones decreased in the serum, hippocampus, amygdala, and frontal lobe in the NR phase. The contents of 5-HT in the brain were significantly increased, while NE and GABA contents were considerably reduced. Moreover, mRNA and protein expression of GABRA4 levels in model rats' amygdala, hippocampus, and frontal lobe were significantly increased, while drug intervention downregulated its expression in these tissues. CONCLUSION: Premenstrual irritability rat model of PMDD demonstrates a behavioral phenotype consistent with the clinical symptoms of PMDD and micro index. The increased levels of 5-HT, NE, and expression of GABRA4, as well as the decrease of GABA, P, and ALLO levels, may be critical biomarkers of the abnormal changes that occur during the pathogenesis of PMDD.

Gabrb2 knock-out mice exhibit double-directed PMDD-like symptoms: GABAAR subunits, neurotransmitter metabolism disruption, and allopregnanolone binding.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a severe mood disorder with pathological changes rooted in GABRB2 copy number variation. Here, we aimed to elucidate the gene dose effect and allopregnanolone binding mechanism of Gabrb2 on possible PMDD-like and comorbid phenotypes in knockout mice. METHODS: PMDD-like behaviors of Gabrb2-knockout mice were measured through various tests. Western Blot and ELISA were used to detect changes in the GABAAR subunits and related neurotransmitter changes in mice respectively for the internal mechanism. The response of mice to allopregnanolone (ALLO) was examined through an exogenous ALLO injection, then validated by the patch-clamp technique to elaborate the potential mechanism of ALLO-mediated GABAAR. RESULTS: Gabrb2-knockout mice displayed changes in anxiety-like and depression-like emotions opposite to PMDD symptoms, changes in social, learning, and memory capacities similar to PMDD symptoms, and pain threshold changes opposite to PMDD symptoms. GABAAR δ subunit expression in the brains of the Gabrb2-knockout mice was significantly higher than that of Wild-type mice (P<0.05). Gabrb2-knockout mice demonstrated neurotransmitter metabolism disturbance of GABA, Glu, acetylcholine, DA, norepinephrine, and epinephrine. Moreover, Gabrb2-knockout mice did not display the expected phenotypic effect after ALLO injection. Relative to WT mice, the knockout of the ß2 subunit gene enhanced the agonistic effect of ALLO on GABAA receptors in cortical neuronal cells. CONCLUSIONS: GABAAR ß 2 regulates PMDD-like behaviors. The ALLO binding site may not be located on ß two subunits, abnormal δ and ε subunit expression in the mouse brain and the disturbance of neurotransmitters may result in ALLO sensitivity.

Global hotspots and prospects of perimenopausal depression: A bibliometric analysis via CiteSpace.

Background: Perimenopausal depression (PMD) is characterized by affective symptoms as well as menopause-specific somatic complaints and has attracted increasing attention over the past few decades. Using a bibliometric tool, this study aims to evaluate the origin, current hotspots, and research trends on PMD. Methods: Articles with research on PMD were retrieved from Web of Science Core Collection (WoSCC). We used the bibliometric method to analyze publication years, journals, countries, institutions, authors, research hotspots, and trends. We plotted the reference co-citation network and used keywords to analyze the research hotspots and trends. Results: A total of 209 publications related to PMD were identified from WoSCC on May 8, 2022. The number of publications concerning PMD every year shows an upward trend. Further analysis indicated that 209 articles were contributed by 45 countries, 288 institutions, and 501 authors. The United States contributed the most significant number of publications, followed by China. Harvard University is the core institution of PMD research, and Cohen's work has had an important impact on another research. The occurrence and pathological mechanisms of depression during the menopausal transition from the knowledge base of PMD. All of them belong to the category of gynecology and psychosis, which reflects the focus of the research topics. Major depression, postmenopausal women, symptoms like hot flashes, and prevalence and risk factors are research hotspots in the PMD field. The frontiers in PMD field that will impact future research are anxiety, meta-analysis, association, and Beck Depression Inventory-II (BDI-II). Conclusion: These findings provide us with the core countries, institutions, and authors in PMD research and point out the direction of attention in this field. The current research focuses on depression, postmenopausal women, hot flashes, and other symptoms, as well as the prevalence and risk factors. The frontiers will be anxiety, meta-analysis, related factors, and depression assessment in future research.

Tubeimoside-1: A review of its antitumor effects, pharmacokinetics, toxicity, and targeting preparations.

Tubeimoside-1 (TBMS-1), a natural triterpenoid saponin found in traditional Chinese herbal medicine Bolbostemmatis Rhizoma, is present in numerous Chinese medicine preparations. This review aims to comprehensively describe the pharmacology, pharmacokinetics, toxicity and targeting preparations of TBMS-1, as well the therapeutic potential for cancer treatement. Information concerning TBMS-1 was systematically collected from the authoritative internet database of PubMed, Web of Science, and China National Knowledge Infrastructure applying a combination of keywords involving "tumor," "pharmacokinetics," "toxicology," and targeting preparations. New evidence shows that TBMS-1 possesses a remarkable inhibitory effect on the tumors of the respiratory system, digestive system, nervous system, genital system as well as other systems in vivo and in vitro. Pharmacokinetic studies reveal that TBMS-1 is extensively distributed in various tissues and prone to degradation by the gastrointestinal tract after oral administration, causing a decrease in bioavailability. Meanwhile, several lines of evidence have shown that TBMS-1 may cause adverse and toxic effects at high doses. The development of liver-targeting and lung-targeting preparations can reduce the toxic effect of TBMS-1 and increase its efficacy. In summary, TBMS-1 can effectively control tumor treatment. However, additional research is necessary to investigate in vivo antitumor effects and the pharmacokinetics of TBMS-1. In addition, to reduce the toxicity of TBMS-1, future research should aim to modify its structure, formulate targeting preparations or combinations with other drugs.

Top 100 Cited Papers on Premenstrual Syndrome/Premenstrual Dysphoric Disorder: A Bibliometric Study.

Background: Premenstrual syndrome/premenstrual dysphoric disorder is a serious condition affecting women worldwide, causing clinically significant distress or interference. Therefore, solving these diseases has become the utmost concern worldwide, culminating in numerous studies. In this study, we performed bibliometric analysis on the 100 most cited papers with the aim of identifying research hot spots and trends in this field. Methods: We screened the Science Citation Index Expanded (SCIE) of Web of Science (WOS) to identify the top 100 cited studies on PMS/PMDD. Next, we analyzed relevant literature from various journals, countries/regions, institutions, authors, and keywords. Finally, we used VOSviewer and Citespace software to generate knowledge maps and identify hot spots and trends. Results: The top 100 highly cited studies were published in 55 journals, between 1999 and 2017, across 24 countries/regions around the world. Most articles were published in Obstetrics and Gynecology, whereas Psych neuroendocrinology had the largest average number of citations per paper. The United States had the highest number of publications, followed by England, Canada, and Sweden. The top three institutions that published the highly cited literature were the University of Pennsylvania, Yale University, and National Institute of Mental Health (NIMH). Obstetrics, Gynecology, Psychiatry, and Reproductive Biology were the main research directions, whereas the top 10 Co-occurrence of Keywords included double-blind, fluoxetine, efficacy, prevalence, epidemiology, phase sertraline treatment, depression, progesterone, placebo, and placebo-controlled trial. Results from cluster analysis indicated that more comprehensive epidemiology and steroid pathogenesis have gradually become the hot spots and trends. Conclusion: These findings demonstrated that bibliometric analysis can intuitively and rapidly reveal the frontiers and hot spots of research in PMS/PMDD. Notably, epidemiology, steroid pathogenesis, GABAA receptor delta subunits, and double-blind placebo-controlled trials are potential areas of focus for future research.

Network Pharmacology and Data Mining Approach Reveal the Medication Rule of Traditional Chinese Medicine in the Treatment of Premenstrual Syndrome/Premenstrual Dysphoric Disorder.

Premenstrual syndrome (PMS) is a common disorder that affects women of reproductive age. It is characterized by periodic mental and somatic symptoms such as irritability, depression, and breast pain during the luteal phase. Premenstrual dysphoric disorder (PMDD) is the most severe form of PMS. In recent years, the incidence of PMS/PMDD has been increasing year after year. However, due to the complex symptoms and ambiguous classification of PMS/PMDD, the limitations of present treatments, such as their poor efficacy rate, have become increasingly apparent. With its unique benefits such as syndrome differentiation and high cure rate, traditional Chinese medicine (TCM) has sparked new diagnosing and treating of PMS/PMDD. This study uses data mining methods, and statistical analysis revealed that Xiaoyao San and Chaihu Shugan San were the commonly used TCM to treat PMS/PMDD. A detailed investigation of regularly used single herbs revealed that most TCM is used as cold herbs that penetrate the liver meridian, with predominant bitter, sweet, and pungent flavors. The network pharmacology method analyzes the interactions between diseases, targets, and herbs. Meanwhile, the deep action targets and molecular mechanisms of 10 commonly used herbs for the treatment of PMS/PMDD are studied, revealing that it involves several ingredients, many targets, and different pathways. This interaction provides insight into the mechanism of action of TCM in the synergistic treatment of PMS/PMDD. It is now clear that we can begin treating PMS/PMDD with TCM using the target and mechanism revealed by the abovementioned findings in the future. This serves as an essential reference for future research and clinical application of TCM in the treatment of PMS/PMDD.

Brain Activation During Processing of Depression Emotion in College Students With Premenstrual Syndrome in China: Preliminary Findings.

Background: This study aimed to investigate the neural substrates of processing depression emotion in premenstrual syndrome (PMS) and healthy subjects of college students using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI). Methods: During BOLD-fMRI scanning, 13 PMS patients and 15 healthy controls (HC) performed a picture visual stimulation task during luteal and follicular phases, in which participants and HC were asked to see pictures containing depression and non-depression emotions. Simultaneously, self-rating depression scales (SDS) were employed to evaluate the emotional status of participants. Results: Compared to HC, right inferior occipital gyrus, right middle occipital gyrus, right lingual gyrus, right fusiform gyrus, right inferior temporal gyrus, cerebelum_crus1_R, cerebelum_6_R, culmen, the cerebellum anterior lobe, tuber, and cerebellar tonsil of PMS patients showed enhanced activation. In contrast, sub-lobar, sub-gyral, extra-nuclear, right orbit part of superior frontal gyrus, right middle temporal gyrus, right orbit part of inferior frontal gyrus, limbic lobe, right insula, bilateral anterior and adjacent cingulate gyrus, bilateral caudate, caudate head, bilateral putamen, and left globus pallidus exhibited decreased activation. Conclusion: The findings indicate that abnormal functional regulation of brain regions such as occipital lobe and cerebellum leads to abnormal changes in emotional regulation, cognitive ability, and attention distribution in PMS patients, implying significant central pathogenesis.

Radix Ranunculi ternati: review of its chemical constituents, pharmacology, quality control and clinical applications.

OBJECTIVES: Radix ranunculi ternati (RRT) is widely used as traditional and folk medicine distributed in China, as well as in Kyushu and Shikoku in Japan. Although RRT has a short history of use as medicine, it has a high medicinal value. This study summarizes the research progress on the chemical constituents, pharmacological activity, quality control measures and clinical applications to provide a valuable and exhaustive reference for the development and application of RRT. KEY FINDINGS: Phytochemical studies showed that this plant mainly contains glycosides, organic acids, esters, sterols, flavonoids, alkaloids and volatile oils. The pharmacological activity of RRT includes immune regulation, anti-tumour, anti-tuberculosis, antioxidant, antibacterial, hepatoprotective and anti-inflammatory effects. This plant is especially effective in the treatment of cancer, tuberculosis, thyroid and nasopharynges disorders.

Acupuncture combined with SSRIs in the treatment of perimenopausal depressive disorder: A protocol for systematic review and meta-analysis.

BACKGROUND: Perimenopausal depressive disorder (PDD) is an affective disorder involving endocrine, neurological, immune, which seriously endangers the physical and mental health of human. Selective serotonin reuptake inhibitors (SSRIs) are the current first-line clinical treatment, have limited efficacy and serious side effects. Acupuncture combined with SSRIs therapy has been widely used clinically because it increases efficacy and reduces side effects. There is a lack of high-quality evidence to assess its efficacy and safety. This study evaluated the effectiveness and safety of acupuncture combined with SSRIs in the treatment of PDD by meta-analysis. METHODS: All randomized controlled trials articles about acupuncture combined with SSRIs treatment of PDD will be searched in databases, such as PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang, Wei Pu from the construction of the library to December 16, 2021. According to Cochrane 5.1 Handbook criteria, two researchers independently screened the literature, extracted data, and evaluated the quality of included studies. Meta-analysis was performed by using RevMan 5.4 and STATA 16.0 software. RESULTS: This study will summarize the current evidence to evaluate the effectiveness and safety of acupuncture combined with SSRIs for the treatment of PDD. CONCLUSION: The results of this study will provide clinicians with new treatment ideas and bring benefits to most patients. REGISTRATION NUMBER: INPLASY2021120080 (DOI number: 10.37766/inplasy2021.12.0080).

Global and regional prevalence and burden for premenstrual syndrome and premenstrual dysphoric disorder: A study protocol for systematic review and meta-analysis.

INTRODUCTION: Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are becoming common mental diseases in women impairing daily functioning. Estimation of the epidemiological burden of PMS/PMDD can serve as scientific basis for prevention and management of premenstrual disorders. Herein, we firstly provide a protocol to perform estimation on the prevalence and risk factors for PMS/PMDD in the general population globally and regionally. METHODS/DESIGN: The PubMed, Web of Science, Chinese National Knowledge Infrastructure, the Cochrane Central Register of Controlled Trials (Cochrane Library), Chinese VIP Information, EMBASE, Wanfang Database, as well as the Chinese Biomedical Literature Database will be queried to find related studies containing information on the prevalence of PMDD (2011-2021). Two independent reviewers will comb the literature and abstract the data characteristics. Disparities will be reconciled via consents. The primary outcome will be the global prevalence. The random-effect model will be employed to pool the assessments. The standard χ2 tests, as well as the I2 statistic will be used to determine heterogeneity. Furthermore, the meta-regression analysis will be employed to estimate the differences in study-level characteristics. All the statistical analyses will be carried out in the software Stata v 15.0 (Stata Corporation, College Station, TX), as well as the R (v R 3.5.1, R Foundation for Statistical Computing, Vienna, Austria) software. DISCUSSION: Based on existing evidence, our study will offer a high-quality synthesis for global and regional prevalence, burden, and risk factors of PMS/PMDD. Effective strategies will be made for prevention and management of epidemiological burden on the PMS/PMDD, even premenstrual disorders. ETHICS AND DISSEMINATION: This study does not involve the specific patients, and all research data comes from publicly available professional literature, so an ethics committee is not required to conduct an ethical review and approval of the study. INPLASY REGISTRATION NUMBER: INPLASY2021120065.

Alzheimer disease effects of different stages on intestinal flora: A protocol for systematic review and meta-analysis.

BACKGROUND: Alzheimer disease (AD) is a common degenerative disease of the central nervous system that can be divided into 3 stages, according to the degree of cognitive impairment. The clinical manifestations are cognitive dysfunction and memory loss, impacting the daily activities of the affected individuals. In recent years, studies have demonstrated a relationship between intestinal flora and AD. However, no meta-analysis has documented the correlation between AD and intestinal flora, to the best of our knowledge. Herein, we sought to assess the correlation between different stages of AD and intestinal flora. A systematic and comprehensive understanding of this relationship is of great significance for developing prevention and treatment strategies against AD. METHODS: A comprehensive search of the medical literature in Chinese and English language was performed in databases, such as PubMed, EBSCO, CNKI, web of science, WanFang, Cochrane Library, and CBM databases. Pre-defined search strategies were used to retrieve clinical studies of Alzheimer disease and gut microbiota. The included studies were independently analyzed by the 2 researchers who extracted the data. The quality of the data was evaluated according to the "Cochrane system evaluator manual." Finally, Endnote and RevMan software were used for systematic regression and meta-analysis of evidence. RESULTS: We documented the intestinal flora changes in the 3 stages of Alzheimer disease, according to currently available clinical evidence, and revealed the correlation between the abundance and diversity of flora and treatment efficacy. These findings are essential for developing new strategies for the prevention and treatment of Alzheimer disease. INPLASY REGISTRATION NUMBER: INPLASY2021100093. ETHICS AND DISSEMINATION: Since all data utilized in this systematic review and meta-analysis are published, ethical approval was not needed.

Copy number variation profile-based genomic typing of premenstrual dysphoric disorder in Chinese.

Premenstrual dysphoric disorder (PMDD) affects nearly 5% of women of reproductive age. Symptomatic heterogeneity, together with largely unknown genetics, has greatly hindered its effective treatment. In the present study, analysis of genomic sequencing-based copy number variations (CNVs) called from 100 kb white blood cell DNA sequence windows by means of semisupervized clustering led to the segregation of patient genomes into the D and V groups, which correlated with the depression and invasion clinical types, respectively, with 89.0% consistency. Application of diagnostic CNV features selected using the correlation-based machine learning method enabled the classification of the CNVs obtained into the D group, V group, total patient group, and control group with an average accuracy of 83.0%. The power of the diagnostic CNV features was 0.98 on average, suggesting that these CNV features could be used for the molecular diagnosis of the major clinical types of PMDD. This demonstrated concordance between the CNV profiles and clinical types of PMDD supported the validity of symptom-based diagnosis of PMDD for differentiating between its two major clinical types, as well as the predominantly genetic nature of PMDD with a host of overlaps between multiple susceptibility genes/pathways and the diagnostic CNV features as indicators of involvement in PMDD etiology.