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.

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.

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.

Efficacy and safety of Shugan Jieyu Decoction in the treatment of coronary heart disease complicated with depression.

BACKGROUND: Coronary heart disease combined with depression is 1 of the 2 major diseases affecting physical and mental health. It has become a hot spot at the intersection of psychiatry and internal medicine. Most doctors call double heart medicine, which has a high incidence rate and a low diagnostic rate. Clinical research shows that Shugan Jieyu Decoction (SJD) has a better curative effect, increased safety, and fewer adverse reactions, but it lacks systematic evaluation. This study aims to integrate clinical data through network meta-analysis and provide more evidence-based medical evidence for clinical medication. METHODS: We searched 8 electronic databases: China knowledge network database, Wanfang, VIP, SinoMed, PubMed, Embase, WebofScience, Cochrane Library, and selected 22 randomized controlled trials from January 2012 to January 2022. The common primary endpoint was the relief of angina pectoris and the improvement of depression. Two researchers used Endnote9.1 software to conduct literature screening and information extraction according to the developed nano-passage standard, used Cochrane collaborative tool to evaluate the bias risk in the experiment, and then used RevMan5.3 software to assess the literature and data analysis synthesis. RESULTS: In 1908 patients with coronary heart disease and depression, the total effective rate of SJD in the treatment of angina pectoris was 3.49 (95% confidence interval, 1.93-6.29), as well as the network meta-analysis of improving depressive symptoms, anxiety, depression scores (SAS, SDS) and quality of life scores (HAMD), and reducing the indicators related to CPR and homocysteine. CONCLUSION: The analysis of this study shows that SJD can reduce the frequency of angina pectoris in patients with coronary heart disease and depression, alleviate anxiety and depression, provide a reference basis for clinical treatment, and select more effective intervention therapy.

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.

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.

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.

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.

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.

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).

Network meta-analysis of 6 kinds of Chinese patent medicines combined with mifepristone in the treatment of uterine fibroids: A protocol for systematic review and network meta-analysis.

BACKGROUND: Uterine fibroids are benign. They belong to the category of "abdominal mass" in traditional Chinese medicine, and pathogenesis is mainly caused by weakness of the body, qi stagnation, and blood stasis. Drug therapy is the preferred treatment of uterine fibroids in clinical practice, and mifepristone is the most commonly used drug. In the past decade, a large number of clinical randomized controlled trials have proven that Chinese patent medicine combined with mifepristone in the treatment of uterine fibroids has a better curative effect, fewer adverse reactions, and higher safety than mifepristone alone. However, there is a lack of evidence-based research. This study aims to integrate clinical data through network meta-analysis to provide more evidence-based medical evidence for clinical medication. METHODS: The comprehensive search included Chinese and other-language databases, such as MEDLINE (PubMed), Web of Science, The Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Scientific Journal Database, and China Biomedical Literature Database. Clinical randomized controlled trials of 6 Chinese patent medicines combined with mifepristone for the treatment of uterine fibroids, including Guizhi Fuling Capsule, Gongliuxiao Capsule, Gongliuqing Capsule, Danbie Capsule, Gongliuning Capsule, and Xiaojiean Capsule were retrieved. The search period was from January 2010 to April 2021. Two researchers screened the literature through EndNote and used Excel to extract data. RevMan 5.3 was used to evaluate the quality of the literature. Treatment measures were analyzed in R language, and a forest map and probability ranking map of various interventions were drawn. The network evidence map and correction comparison funnel map of various interventions were drawn by STATA 14.0 software. RESULTS: This study provides the clinical efficacy and safety of network meta-analysis of 6 kinds of Chinese patent medicines combined with mifepristone in the treatment of uterine fibroids will be systematically evaluated or descriptively analyzed. CONCLUSION: This study's purpose is to provide a reference for the clinical treatment of uterine fibroids to choose more effective intervention therapies.

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.

Brain reactivity to emotional stimuli in women with premenstrual dysphoric disorder and related personality characteristics.

AIMS: Premenstrual dysphoric disorder (PMDD) is a psychiatric condition that is associated with the menstrual cycle. Elucidation of the neural regulation mechanisms of brain reactivity to emotional stimuli among women with PMDD may inform PMDD treatment. METHODS: Eighty-six women (42 PMDD, 44 healthy controls) were allocated into two groups (anger-induced group: 23 PMDD vs. 23 controls; depression-induced group: 19 PMDD vs. 21 controls). During the luteal phases of the menstrual cycle, all the women were subjected to functional magnetic resonance imaging (fMRI). fMRI resting-state scans were performed before and after the study participants had performed an emotional stimuli task. After the emotional stimuli task, emotional status of the participants were evaluated by Self-Rating Depression Scales (SDS) and Trait Anger Expression Inventory-II (STAXI-II). In addition, all the participants were requested to complete the Eysenck Personality Questionnaire (EPQ) and the Twenty-Item Toronto Alexithymia Scale (TAS-20). RESULTS: Compared to healthy controls, all women with PMDD exhibited significantly high scores in Tas-20 (p<0.001), higher neuroticism and psychoticism scores as well as significantly low extraversion and social desirability scores (p<0.05). Compared to the controls, f-MRI revealed that PMDD women had elevated ReHo in the middle frontal gyrus (BA10), temporal lobe (BA42), left cerebellum (BA37), as well as decreased activation in the precuneus (BA7), superior frontal gyrus (BA8), lobulus paracentralis (BA6), and right cerebellum (BA48) (p<0.05). Moreover, depression stimuli showed that women with PMDD had elevated ReHo levels in the middle frontal gyrus (BA11), the middle gyrus (BA47) and in the cingulate gyrus (BA23) vs. healthy controls (p<0.05). CONCLUSIONS: Women with more neuroticism and psychoticism, less extraversion and social desirability tend to report PMDD symptoms. Women with this condition experience difficulties in regulating emotions during the luteal phase of the menstrual cycle. Abnormal ReHo levels in the precuneus, superior frontal gyrus, lobulus paracentralis, and right cerebellum may contribute to anger dysregulation. Hypoactivation in the middle frontal gyrus, the middle gyrus and the cingulate gyrus may be generally associated with depression dysregulation in PMDD.

Trends in Research Related to Premenstrual Syndrome and Premenstrual Dysphoric Disorder From 1945 to 2018: A Bibliometric Analysis.

Background: The global incidence of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) is increasing, with increasing suicide reports. However, the bibliometric analysis of global research on PMS and PMDD is rare. We aimed to evaluate the global scientific output of research on PMS and PMDD and to explore their research hotspots and frontiers from 1945 to 2018 using a bibliometric analysis methodology. Methods: Articles with research on PMS and PMDD between 1945 and 2018 were retrieved from the Web of Science Core Collection (WoSCC). We used the bibliometric method, CiteSpace V and VOSviewer to analyze publication years, journals, countries, institutions, authors, research hotspots, and trends. We plotted the reference co-citation network, and we used keywords to analyze the research hotspots and trends. Results: We identified 2,833 publications on PMS and PMDD research from 1945 to 2018, and the annual publication number increased with time, with fluctuations. Psychoneuroendocrinology published the highest number of articles. The USA ranked the highest among the countries with the most publications, and the leading institute was UNIV PENN. Keyword and reference analysis indicated that the menstrual cycle, depression and ovarian hormones were the research hotspots, whereas prevalence, systematic review, anxiety and depression and young women were the research frontiers. Conclusions: We depicted overall research on PMS and PMDD by a bibliometric analysis methodology. Prevalence and impact in young women, systematic review evaluations of risk factors, and the association of anxiety and depression with menstrual cycle phases are the latest research frontiers that will pioneer the direction of research in the next few years.

A forced swim-based rat model of premenstrual depression: effects of hormonal changes and drug intervention.

Premenstrual dysphoric disorder (PMDD), a form of premenstrual syndrome (PMS), is a severe health disturbance that affects a patient's emotions; it is caused by periodic psychological symptoms, and its pathogenesis remains unclear. As depression-like symptoms are found in a majority of clinical cases, a reliable animal model of premenstrual depression is indispensable to understand the pathogenesis. Herein, we describe a novel rat model of premenstrual depression, based on the forced swimming test, with a regular estrous cycle. The results showed that in the estrous cycle, the depression-like behavior of rats occurred in the non-receptive phase and disappeared in the receptive phase. Following ovariectomy, the depression-like symptoms disappeared and returned after a hormone priming regimen. Moreover, fluoxetine, an anti-depressant, could reverse the behavioral symptoms in these model rats with normal estrous cycle. Further, the model rats showed significant changes in the serum levels of estrogen and progesterone, hippocampal levels of allopregnanolone, 5-hydroxytryptamine, norepinephrine, and γ-aminobutyric acid (GABA), and in the expression of GABAA receptor 4α subunit, all of which were reversed to physiological levels by fluoxetine. Overall, we established a reliable and standardized rat model of premenstrual depression, which may facilitate the elucidation of PMS/PMDD pathogenesis and development of related therapies.

Traditional Chinese medicine on treating premenstrual syndrome and premenstrual dysphoric disorder: A protocol for systematic review and meta-analysis.

BACKGROUND: Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are common disorders that manifest themselves in the late luteal phase, and significantly interfere with an individual's daily activities. Clinical evidence suggests that traditional Chinese medicine (TCM) may ease PMS/PMDD symptoms. Here, we review a protocol for exploring the effectiveness and safety of TCM in PMS/PMDD management. METHODS: We will conduct a literature search for randomized controlled trials (RCT) for TCM use in PMS/PMDD on PubMed, web of science, EMBASE, the Cochrane central register of controlled trials (Cochrane Library), Chinese national knowledge infrastructure, Chinese VIP Information, Wanfang, as well as Chinese biomedical literature database. The search included all relevant reports for up to June 1, 2020. The search results were independently analyzed by 2 reviewers who extracted the data. RCT quality will be assessed using the risk-of-bias tool. The evidence will be inspected using the grading of recommendations assessment development and evaluation (GRADE). We will utilize Stata and Revman for systematic review and meta-analysis and analysis of direct and indirect evidence. RESULTS: Based on current evidence, this study will elucidate the rationale for the utilization of TCM in PMS/PMDD treatment. CONCLUSION: Conclusions from this study will inform about the effectiveness and safety of TCM in PMS/PMDD management. TRIAL REGISTRATION NUMBER: CRD42020192822. ETHICS AND DISSEMINATION: Since all data utilized in this systematic review and meta-analysis are published, ethical approval is not needed. Additionally, in the trial of the review process, all data will be evaluated anonymously.

Highly Recurrent Copy Number Variations in GABRB2 Associated With Schizophrenia and Premenstrual Dysphoric Disorder.

OBJECTIVE: Although single-nucleotide polymorphisms in GABRB2, the gene encoding for GABAA receptors ß2 subunit, have been associated with schizophrenia (SCZ), it is unknown whether there is any association of copy number variations (CNVs) in this gene with either SCZ or premenstrual dysphoric disorder (PMDD). METHODS: In this study, the occurrences of the recurrent CNVs esv2730987 in Intron 6 and nsv1177513 in Exon 11 of GABRB2 in Chinese and German SCZ, and Chinese PMDD patients were compared to controls of same ethnicity and gender by quantitative PCR (qPCR). RESULTS: The results demonstrated that copy-number-gains were enriched in both SCZ and PMDD patients with significant odds ratios (OR). For combined-gender SCZ patients versus controls, about two-fold increases were observed in both ethnic groups at both esv2730987 (OR = 2.15, p = 5.32E-4 in Chinese group; OR = 2.79, p = 8.84E-3 in German group) and nsv1177513 (OR = 3.29, p = 1.28E-11 in Chinese group; OR = 2.44, p = 6.17E-5 in German group). The most significant copy-number-gains were observed in Chinese females at nsv1177513 (OR = 3.41), and German females at esv2730987 (OR=3.96). Copy-number-gains were also enriched in Chinese PMDD patients versus controls at esv2730987 (OR = 10.53, p = 4.34E-26) and nsv1177513 (OR = 2.39, p = 3.19E-5). CONCLUSION: These findings established for the first time the association of highly recurrent CNVs with SCZ and PMDD, suggesting the presence of an overlapping genetic basis with shared biomarkers for these two common psychiatric disorders.

Paeonol at Certain Doses Alleviates Aggressive and Anxiety-Like Behaviours in Two Premenstrual Dysphoric Disorder Rat Models.

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS), a common mental health disturbance associated with several periodic psychological symptoms in women. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PMS/PMDD patients; however, side effects are inevitable, especially in long-term treatment. In previous studies, the natural compound paeonol in Moutan Cortex was found to play effective roles in central nervous system disorders with its anti-inflammatory, anti-oxidant, and neuroprotective effects. Consequently, we assume that paeonol might produce positive effects in the treatment of PMS/PMDD. In this study, the open-field test (OFT) and elevated plus maze (EPM) and light dark box (LDB) tests were performed in mice to determine the optimal dose of paeonol for treating anxiety. Then, paeonol was used to treat the progesterone withdrawal (PWD) and resident intruder paradigm (RIP) rat models of PMDD. Using these two reliable models, the OFT and EPM, LDB, and composite aggressive tests were performed to evaluate the effect of the drug on behavioural symptoms of PMDD. From the dosage screening results, the optimal anti-anxiety dose of paeonol was identified as 17.5 mg/kg/d for 7 days. With regard to the effect of paeonol on PMDD rat models, a significantly improvement was found in the behavioural symptoms, but the effective dose varied in different models. For the PWD model rats, treatment with 6.05 mg/kg paeonol could significantly improve anxiety and irritability, while that with 24.23 mg/kg paeonol resulted in anxiety-like effects in behavioural tests. In RIP model rats, treatment with 12.11 mg/kg paeonol demonstrated excellent effects in improving anxiety, particularly irritable emotional behaviour. In conclusion, our study indicates that paeonol is a potential therapeutic compound for PMS/PMDD; it is a drug option that helps establish dosage guidance for treatment of this condition.

A systematic review and meta-analysis of antibiotic resistance patterns, and the correlation between biofilm formation with virulence factors in uropathogenic E. coli isolated from urinary tract infections.

Urinary tract infection (UTI) is caused by the invasion of the pathogen in the urinary system that can manifest as symptomatic or asymptomatic bacteriuria. This study was conducted to investigate antibiotic resistance patterns, and the correlation between biofilm formations with virulence factors in uropathogenic E. coli isolates retrieved from UTI. We searched Scopus and Google Scholar, PubMed, Web of sciences for studies published in the English language between 1st 2005 to 31st December 2019. The Mesh terms and text words included "biofilms", OR "biofilm formation", AND "antibiotic resistance", OR "drug-resistance", OR "antimicrobial drug resistance", AND "urinary tract infections", OR "UTI", AND "biofilm related-genes", AND "virulence factors" AND "correlation", AND "Uropathogenic Escherichia coli", OR "Uropathogenic E. coli" AND "prevalence" AND "Iran". Data analyzed using Comprehensive Meta-Analysis (CMA) software. The random-effects model was used to calculate the pooled prevalence with 95% confidence interval (CI). The combined rates of biofilm formation in Uropathogenic E. coli (UPEC) isolates were achieved as 84.6% (95% CI: 72.7-91.9). Also, 24.8%, 26.1% and 44.6% of UPEC isolates were able to create strong, moderate and weak biofilm, respectively. The highest pooled antibiotic resistance was against Ampicillin followed by Tetracycline with resistance rates of 74.6% and 64.9%, respectively. Accordingly, some studies reported that biofilm production was significantly associated with antibiotic resistance and virulence genes (p < 0.05). This study showed a high tendency among UPEC isolates to form biofilm (more than 84%), also, most studies included in the present review reported a significant correlation between biofilm formation with antibiotic resistance and virulence factors.