Mechanisms of Bushen Tiaoxue Granules against controlled ovarian hyperstimulation-induced abnormal morphology of endometrium based on network pharmacology.

Bushen Tiaoxue Granules (BTG) is an empirical Chinese herbal formula that has been used for the treatment of subfertility. The protective effect of BTG on controlled ovarian hyperstimulation (COH)-induced impaired endometrial receptivity has been reported in our previous study. This study aims to explore the mechanisms of BTG on ameliorating abnormal morphology of endometrium based on network pharmacology. Active compounds of BTG were identified via the traditional Chinese medicine systems pharmacology and UPLC-MS technology. The SwissTargetPrediction platform and HERB database were used to screen out the putative targets of BTG. Potential targets of endometrial dysfunction caused by COH were obtained from three GEO databases. Through the STRING database, the protein-protein interaction was carried out according to the cross-common targets of diseases and drugs. GO terms and KEGG pathways enrichment analyses were conducted via the Metascape database. AutoDock Vina was used for docking validation of the affinity between active compounds and potential targets. Finally, in vivo experiments were used to verify the potential mechanisms derived from network pharmacology study. A total of 141 effective ingredients were obtained from TCMSP and nine of which were verified in UPLC-MS. Six genes were selected through the intersection of 534 disease related genes and 165 drug potential targets. Enrichment analyses showed that BTG might reverse endometrial dysfunction by regulating adherens junction and arachidonic acid metabolism. Hematoxylin-eosin staining revealed that BTG ameliorated the loose and edematous status of endometrial epithelium caused by COH. The protein expression of FOXO1A, ß-Catenin and COX-2 was decreased in the COH group, and was up-regulated by BTG. BTG significantly alleviates the edema of endometrial epithelium caused by COH. The mechanisms may be related to adheren junctions and activation of arachidonic acid metabolism. The potential active compounds quercetin, taxifolin, kaempferol, eriodictyol, and isorhamnetin identified from the BTG exhibit marginal cytotoxicity. Both high and low concentrations of kaempferol, eriodictyol, and taxifolin are capable of effectively ameliorating impaired hESC cellular activity.

Application of mesenchymal stem cell therapy for premature ovarian insufficiency: Recent advances from mechanisms to therapeutics.

The incidence of premature ovarian insufficiency (POI) is increasing worldwide, particularly among younger women, posing a significant challenge to fertility. In addition to menopausal symptoms, POI leads to several complications that profoundly affect female reproductive function and overall health. Unfortunately, current clinical treatment strategies for this condition are limited and often yield unsatisfactory outcomes. These approaches typically involve hormone replacement therapy combined with psychological support. Recently, mesenchymal stem cell (MSC) therapies for POI have garnered considerable attention in global research. MSCs can restore ovarian reproductive and endocrine functions through diverse mechanisms, including controlling differentiation, promoting angiogenesis, regulating ovarian fibrosis, inhibiting apoptosis, enhancing autocrine and paracrine effects, suppressing inflammation, modulating the immune system, and genetic regulation. This editorial offers a succinct summary of the application of MSC therapy in the context of POI, providing evidence for groundbreaking medical approaches that have potential to enhance reproductive health and overall well-being for women.

Burden and attributable risk factors of ischemic stroke in China from 1990 to 2019: an analysis from the Global Burden of Disease Study 2019.

Background: The epidemiologic characteristics and attributable risk factors of ischemic stroke in China have changed over the past three decades. An up-to-date analysis on deaths, disability-adjusted life-years (DALYs), prevalence, incidence, and attributable risk factors of ischemic stroke for China is needed. This study aims to provide a comprehensive analysis of burden and attributable risk factors of ischemic stroke at national level in China by sex from 1990 to 2019. Methods: This is a secondary analysis of the Global Burden of Disease (GBD) study 2019. All data used in this study was derived from the 2019 GBD study. Deaths, DALYs, prevalence, incidence, and attributable risk factors of ischemic stroke in China by sex from 1990 to 2019 were analyzed. Results: From 1990 to 2019, the age-standardized deaths rate decreased by 3.3%, age-standardized DALYs rate decreased by 4%, age-standardized prevalence rate increased by 33.5%, and age-standardized incidence rate of ischemic stroke in China increased by 34.7%. In 2019, ambient particulate matter pollution became an important risk factor, whereas household air pollution from solid fuels was no longer a major risk factor for ischemic stroke in China. Burden of ischemic stroke was higher in China compared to other regions. Ambient particulate matter pollution among men, and diet high in sodium, smoking, household air pollution from solid fuels among women account for the increased deaths/DALYs due to ischemic stroke in China. Conclusion: Our study revealed that great changes have occurred in burden and attributable risk factors of ischemic stroke in China in the past three decades. Distinct sex-specific differences are observed in burden and attributable risk factors.

A modified mouse model of haemorrhagic transformation associated with tPA administration after thromboembolic stroke.

Objective: To establish a new mouse model of haemorrhagic transformation associated with delayed tissue-type plasminogen activator (tPA) treatment to provide a novel tool to study therapeutic strategies for haemorrhagic transformation. Methods: Male C57BL/6 mice were subjected to carotid artery thrombosis stimulated with ferric chloride. The thrombus was then mechanically detached to induce migration toward the intracranial circulation. To induce haemorrhagic transformation, mice were intravenously injected with 10 mg/kg tPA 4.5 h after the onset of ischaemia and were sacrificed 24 h after tPA treatment. Results: In this new model, administration of tPA 4.5 h after stroke exacerbated the risk of intracerebral haemorrhage. Thrombolysis with tPA also exacerbated cerebral infarction, brain oedema, blood-brain barrier breakdown, and neurological deficits. However, cerebral blood flow was not significantly affected. Conclusion: The present model is reproducible, easy to perform, and mimics the clinical situation of haemorrhagic transformation after tPA treatment in humans. This modified model can be used as a new tool to test experimental drugs for haemorrhagic transformation associated with delayed tPA administration after an ischaemic stroke.

Efficacy of Chinese herbal medicine for tPA thrombolysis in experimental stroke: A systematic review and meta-analysis.

BACKGROUND: Tissue-type plasminogen activator (tPA) remains the sole FDA approved thrombolytic drug for ischemic stroke. But delayed thrombolytic therapy with tPA may increase the risk of hemorrhagic transformation. Many Chinese herbal medicines have been used as tPA helpers to enhance the capacity of tPA and minimize the risk of hemorrhagic transformation. The efficacy of Chinese herbal medicines on tPA thrombolysis is not systematically analyzed. METHODS: We searched the following three databases up to January 2022: Web of Science, PubMed, and Scopus. Studies that reported the efficacy and safety of Chinese herbal medicines on tPA thrombolysis in experimental stroke were included. The efficacy outcomes were neurological score and infarct volume, the safety outcomes were cerebral hemorrhage and blood brain barrier (BBB) damage. We used the checklist of CAMARADES to assess the quality of included studies. Standardized mean difference (SMD) with 95% confidence intervals were used to assess all the outcomes. Subgroup analyses were performed to explore the sources of heterogeneity. Trim and fill method and Egger's test were used to assess the potential publication bias. Sensitivity analyses were used to identify the stability of the results. RESULTS: A total of nine studies including 11 Chinese herbal medicines fulfilled the inclusion criteria and were subsequently analyzed. The pooled data demonstrated that Chinese herbal medicines improved neurological score (2.23 SMD, 1.42-3.04), infarct volume (1.08 SMD, 0.62-1.54), attenuated cerebral hemorrhage (1.87 SMD, 1.34-2.4), and BBB dysfunction (1.9 SMD, 1.35-2.45) following tPA thrombolysis in experimental stroke. Subgroup analysis indicated that the route of drug delivery, dosage of tPA, and stroke model used may be factors inducing heterogeneity and influencing the efficacy. CONCLUSION: Treatment with Chinese herbal medicines significantly improved neurological score and infarct volume, reduced cerebral hemorrhage and BBB damage after tPA thrombolysis. This study supports Chinese herbal medicine as an adjuvant therapy in reducing the side effects of tPA thrombolysis after acute ischemic stroke. The results should be interpreted with more caution since this article was based on animal studies.

[Effect and regulation mechanism of Chinese Bushen Huoxue prescriptions on endometrial receptivity].

Endometrial receptivity refers to the ability of endometrium to accept and accommodate endometrial implantation in the process of embryo implantation in implantation window period. It is an important factor affecting the rate of blastocyst implantation in assisted reproduction. It is worth mentioning that ovulation-promoting drugs in current assisted reproduction technology could reduce endometrial receptivity and inhibit blastocyst implantation, greatly affecting the success rate of assisted reproduction. By searching Chinese Scientific Citation Database, it was found that 121 studies from 2006 to 2017 showed that Chinese Bushen Huoxue prescriptions could significantly improve the development of pinopodes in the implantation window, promote the expression of endometrial receptors ER, PR, integrinß3, LIF, LPA3 and other molecules, and thus enhancing endometrial receptivity and improving embryo implantation. In the theory of traditional Chinese medicine, kidney deficiency is an important factor causing infertility. Chinese Bushen Huoxue prescriptions could nourish the kidney-essence, and promote blood circulation, playing an important role in treating infertility with combined application of western medicine and traditional Chinese medicine. These studies suggest that Chinese Bushen Huoxue prescriptions could improve endometrial receptivity, and their mechanisms are worth further investigation. This article has summarized the research progress of Chinese Bushen Huoxue prescriptions in the field of assisted reproduction, summarized the deficiency of current researches, and preliminarily discussed the potential application prospect of Chinese Bushen Huoxue prescriptions in the treatment of infertility.

A new prognostic scale for the early prediction of ischemic stroke recovery mainly based on traditional Chinese medicine symptoms and NIHSS score: a retrospective cohort study.

BACKGROUND: Ischemic stroke (IS) is a common disease, often resulting in death or disability. Previous studies on prognosis of stroke mainly focused on the baseline condition or modern expensive tests. However, the change of clinical symptoms during acute stage is considerably neglected. In our study, we aim to develop a new prognostic scale to predict the 90-day outcome of IS patients. METHODS: In this retrospective cohort study, a secondary data analysis was performed on 489 patients extracted from 1046 patients of 4 hospitals. A new prognostic scale was constructed to predict the recovery of IS mainly based on the National Institutes of Health Stroke Scale (NIHSS) score, traditional Chinese Medicine (TCM) symptoms & signs and the changes during the first 3 days of patients in the 3 TCM hospitals. Receiver Operating Characteristic (ROC) curve was used to determine the cutoff point for prediction. In the end, the scale was used to test the outcome of IS patients in Xuanwu hospital. RESULTS: The new prognostic scale was composed of 8 items including age degree (OR = 3.32; 95 % CI: 1.72-6.42), history of diabetes mellitus (DM) (OR = 2.20; 95 % CI: 1.19-4.08), NIHSS score (OR = 3.08; 95 % CI: 2.16-4.40), anxiety (OR = 3.17; 95 % CI: 1.90-5.29) and irritability (OR = 4.61; 95 % CI: 1.36-15.63) on the 1st day of illness onset, change in NIHSS score (OR = 2.49; 95 % CI: 1.31-4.73), and circumrotating (OR = 7.80; 95 % CI: 1.98-30.64) and tinnitus (OR = 13.25; 95 % CI: 1.55-113.34) during the first 3 days of stroke onset. The total score of the scale was 16.5 and the cutoff point was 9.5, which means patients would have poor outcome at 90 days of stroke onset if the score was higher than 9.5. The new scale was validated on the data of Xuanwu hospital, and the value of its sensitivity, specificity and overall accuracy were 69.6 %, 83.3 % and 75.0 % respectively. CONCLUSIONS: The 8-item scale, mainly based on TCM symptoms, NIHSS score and their changes during the first 3 days, can predict the 90-day outcome for IS patients while it still needs to be further validated and optimized clinically.

The use of repeated measures analysis of variance to study the effect of phlegm-heat syndrome on neurological deficits in patients with stroke.

OBJECTIVE: To explore the effect of phlegm-heat syndrome on the degree of neurological deficit and provide some data support for the correct recognition of the relationship between phlegm-heat syndrome and neurological deficits in stroke patients. METHODS: Clinical information were collected on 294 patients with acute ischemic stroke (AIS) whose syndrome and National Institute of Health stroke scale (NIHSS) score were checked at baseline (within the first 3-day admission) and at 7, 14, 28, and 90 days after admission to our clinical research centre. We explored the effect of phlegm-heat syndrome on the degree of neurological deficit following stroke by applying a repeated measures analysis of variance. RESULTS: Stroke patients with phlegm-heat syndrome had higher NIHSS score than patients without the syndrome (P <0.01), and there appeared to be a decrease in NIHSS score over time in all patients (P <0.01). CONCLUSIONS: Phlegm-heat syndrome in patients who have suffered stroke has an effect on the degree of neurological deficiency. Disappearance of phlegm-heat syndrome may improve the degree of neurological deficit observed in stroke patients.

[Study on the correlation between stroke of qi deficiency syndrome and the neurological impairment degree and its long-term prognosis].

OBJECTIVE: To explore the correlation between stroke of qi deficiency syndrome (QDS) and the neurological impairment degree, and to study its correlation between QDS and its long-term prognosis. METHODS: Recruited were 706 stroke patients with complete clinical information including diagnostic scale scoring of elements such as wind, fire, phlegm, blood stasis, qi deficiency, and yin deficiency, scoring of The National Institutes of Health Stroke Scale (NIHSS) within 72 h from attack, on the 7th, 14th, 28th, and 90th day after attack, and Barthel index (BI) scoring on the 90th day. They were assigned to the QDS group (330 cases) and the non-QDS group (376 cases). The NIHSS scores at different time points were compared between the two groups using analysis of variance of repeated measure data. The correlation between each syndrome element and the long-term prognosis of stroke was studied using Logistic regression analysis. RESULTS: Higher NIHSS score was found in patients of QDS than those of non-QDS at each time point (P < 0.01). Statistical difference existed in NIHSS score between the two groups at each time point (P < 0.01, P < 0.05). Besides, NIHSS score decreased gradually as time went by. The occurrence frequencies of blood stasis syndrome and phlegm syndrome were higher at each time point. On the 90th day after attack, 427 patients with BI > or = 95 (accounting for 60%) had favorable prognosis, while 279 with BI < 95 (accounting for 40%) had unfavorable prognosis. QDS at each time point was negatively correlated with the 90th-day BI, with the B value being -0.496, -0.714, -0.867, -0.567, and -0.764, respectively. CONCLUSIONS: Stroke patients of QDS had more severe neurological impairment than those of non-QDS. Stroke patients of acute-stage QDS was closely correlated with unfavorable prognosis on the 90th day after attack. Early actively invigorating healthy qi plays an important role in improving the long-term prognosis of stroke patients.