The Gengnianchun recipe attenuates insulin resistance-induced diminished ovarian reserve through inhibiting the senescence of granulosa cells.

Introduction: Insulin resistance (IR) is found in patients with polycystic ovary syndrome (PCOS), but the effects and mechanisms of IR on diminished ovarian reserve (DOR) remain unclear. This study set out to investigate the effects of IR on ovarian reserve; to explore the effects of high concentrations of insulin on the function of ovarian cells in vitro; and to validate the hypothesis that the Gengnianchun recipe (GNC) helps to attenuate DOR caused by IR through reducing the senescence of granulosa cells. Methods: Estrus cycle, follicle count, and sex hormone levels were detected to evaluate ovarian function in mice with IR caused by feeding a high-fat diet (HFD). In addition, KGN cells (human granulosa cell line) were treated with high concentrations of insulin. The staining for senescence-associatedß-galactosidase (SA-ß-gal), cell cycle, and expression levels of mRNA and gene proteins related to cell aging were detected in KGN cells treated with high concentrations of insulin. Mice treated with an HFD were fed metformin, GNC, or saline solution for 6 weeks by oral gavage. HOMA-IR, the area under the curve (AUC) of the oral glucose tolerance test (OGTT), levels of fasting blood glucose (FBG), and fasting serum insulin (FINS) were examined to confirm the IR status. Then estrus cycle, follicle count, and sex hormone levels were detected to evaluate ovarian function. Expression levels of mRNA and gene proteins related to cell aging were detected in the ovarian tissue of mice in each group. Results: The results demonstrated that IR reduced murine ovarian reserves, and high doses of insulin caused granulosa cells to senesce. There was a considerable improvement in HFD-induced IR status in the metformin (Met) and GNC treatment groups. In addition, the expression levels of aging-associated biomarkers were much lower in GNC mice than Met mice; and both the latter groups had considerably lower levels than the HFD group. Moreover, higher follicle counts in different stages and shorter diestrus in the Met or GNC groups compared to the HFD group indicated that ovarian aging could be largely reversed. Discussion: This work showed that: IR impaired ovarian reserve; high concentrations of insulin induced granulosa cell aging; and GNC attenuated ovarian function through inhibiting IR-induced cell aging.

Potential targeted therapy based on deep insight into the relationship between the pulmonary microbiota and immune regulation in lung fibrosis.

Pulmonary fibrosis is an irreversible disease, and its mechanism is unclear. The lung is a vital organ connecting the respiratory tract and the outside world. The changes in lung microbiota affect the progress of lung fibrosis. The latest research showed that lung microbiota differs in healthy people, including idiopathic pulmonary fibrosis (IPF) and acute exacerbation-idiopathic pulmonary fibrosis (AE-IPF). How to regulate the lung microbiota and whether the potential regulatory mechanism can become a necessary targeted treatment of IPF are unclear. Some studies showed that immune response and lung microbiota balance and maintain lung homeostasis. However, unbalanced lung homeostasis stimulates the immune response. The subsequent biological effects are closely related to lung fibrosis. Core fucosylation (CF), a significant protein functional modification, affects the lung microbiota. CF regulates immune protein modifications by regulating key inflammatory factors and signaling pathways generated after immune response. The treatment of immune regulation, such as antibiotic treatment, vitamin D supplementation, and exosome micro-RNAs, has achieved an initial effect in clearing the inflammatory storm induced by an immune response. Based on the above, the highlight of this review is clarifying the relationship between pulmonary microbiota and immune regulation and identifying the correlation between the two, the impact on pulmonary fibrosis, and potential therapeutic targets.

Advances in the cellular immunological pathogenesis and related treatment of primary ovarian insufficiency.

PURPOSE OF REVIEW: To describe the immunological mechanism in the pathogenesis of premature ovarian insufficiency (POI), summarize the alternations in humoral immunity and cellular immunity in patients with POI, and review some associated treatment methods based on these immunological changes. RECENT FINDINGS: Symptoms of patients with POI are similar to that of menopause, such as amenorrhea, anovulation, early depletion of the ovarian reserve, decreased estrogen, and elevated follicle-stimulating hormone (FSH) levels. Therefore, most previous research has focused on finding ovary-related antibodies. In recent years, advances in the field of immunology have increased our understanding of the pathogenic mechanism of POI, which includes changed levels of cytokines and immunological cells especially Tregs cells and Th17 cells. Based on these advances, many associatedtreatment methods including DHEA supplementation, Traditional Chinese Medicine, adoptive transfer of Treg cells and stem cell transplantation have become research hotspots. SUMMARY: This review focuses on the current literature regarding alterations in cellular immunity in patients with POI, as well as the role in the pathogenesis of POI, and summarizes treatment methods based on these immunological alternations, which have a great application potential in the clinical practice.

Therapeutic Effects of Modified Gengnianchun Formula on Stress-Induced Diminished Ovarian Reserve Based on Experimental Approaches and Network Pharmacology.

AIM: To verify the effects of modified Gengnianchun formula (MGNC), a traditional Chinese medicine, on a stressed diminished ovarian reserve (DOR) animal model and predict the underlying mechanisms through network pharmacology strategies. METHODS: Sexually mature female C57BL/6 mice were allocated to five groups, abbreviated as the control (C) group, stress manipulated model (M) group, stress with normal saline gavage (N) group, stress with low-dose MGNC gavage (L) group, and stress with high-dose MGNC gavage (H) group. Body weight and the estrous cycle were monitored during the stress and gavage process. Serum stress hormones and reproductive hormones were evaluated by ELISA. Ovarian follicle counts were calculated, and ovarian follicle-stimulating hormone receptor (FSHR) and anti-Müllerian hormone (AMH) expression were assessed by Western blotting and immunohistochemistry. Network pharmacology strategies included active compound screening, drug and disease target analysis, gene ontology analysis, pathway analysis, and visualization of results. RESULTS: MGNC treatment significantly decreased serum corticosterone (CORT) and follicle-stimulating hormone (FSH) levels and increased testosterone (T) levels in the H group compared with the M and N groups. Primordial and preantral follicle counts and ovarian AMH and FSHR expression were significantly increased in the H group compared to those in the M and N groups. Through pharmacokinetic screening, we found 244 active compounds in MGNC. A total of 186 candidate intersection target genes of disease and MGNC were further screened to construct the interaction network. Gene ontology and KEGG pathway enrichment analysis ultimately unveiled a series of key targets that mainly mediated the effects of MGNC on DOR induced by chronic stress. The PI3K-Akt pathway may serve as the critical pathway underlying this therapeutic mechanism. CONCLUSION: MGNC is a promising formula to treat DOR induced by chronic stress, and the PI3K-Akt pathway may play an essential role in this effect.

A Simple Method to Differentiate Atrioventricular Node Reentrant Tachycardia from Orthodromic Reciprocating Tachycardia.

Discrimination between atrioventricular node reentry tachycardia (AVNRT) and orthodromic reciprocating tachycardia (ORT) during an electrophysiological study is sometimes challenging. This study aimed to investigate if the difference in the local VA (ventricle-atrium) interval during ventricular entrainment pacing and during tachycardia (DVA, defined as the shortest local VA interval of coronary sinus [CS] during entrainment minus the shortest local VA interval of CS during tachycardia) was different in patients with AVNRT and patients with ORT.Diagnoses of AVNRT or ORT through a concealed accessory pathway (AP) were made according to conventional electrophysiological criteria and ablation results. Entrainment by right ventricular (RV) pacing was performed in each patient before ablation and patients with successful entrainment were included in the study. The DVA was compared between patients with AVNRT and patients with ORT. The DVA in patients with AVNRT was significantly longer than that in patients with ORT (120 ± 20 versus 5.7 ± 9; P < 0.001). In each patient with AVNRT of slow-fast type, fast-slow type, and slow-slow type, the DVA was more than 48 ms. In each patient with ORT using a left free wall accessory pathway (AP), right free wall AP, and septal AP, the DVA was less than 20 ms.DVA was found to be a rapid, useful test in distinguishing patients with AVNRT from those with ORT.

A new method to evaluate linear block at the left atrial roof: is it reliable without pacing?

OBJECTIVE: The present study aimed to evaluate a new method for validation of complete linear block at the left atrial (LA) roof. BACKGROUND: Linear lesions at the LA roof have been reported to improve the success rate of catheter ablation of atrial fibrillation (AF). METHODS: Complete linear block at the LA roof was evaluated in 31 patients after complete isolation of pulmonary vein antrum (PVA) using a simple method. We hypothesized that complete linear block of the LA roof could be confirmed during sinus rhythm if (1) a continuous line of double potentials could be recorded at the LA roof, and (2) the activation sequence along the posterior wall changed to caudocranial. The results of this method were compared with standard pacing techniques. RESULTS: Thirty-nine lines were assessed using this method: 8 before and 31 after achievement of complete conduction block. After validation of complete linear block at the LA roof, double potentials with a mean interpotential interval of 60 +/- 13 ms were recorded in 25 patients and electroanatomical mapping of the left atrium showed the activation sequence of posterior wall changed to caudocranial in all 31 patients during sinus rhythm. The sensitivity, specificity, positive and negative predictive values of this method for validating complete linear block were 100%, 88.9%, 96.8%, and 100%, respectively. CONCLUSION: A corridor of double potentials along the roof line and a caudocranial activation sequence along the posterior wall during sinus rhythm can indicate conduction block at the LA roof after PVA isolation.

[Effect of Yufeining on induced sputum interleukin-8 in patients with chronic obstructive pulmonary disease at the stable phase].

OBJECTIVE: To evaluate the effect of Yufeining, a traditional Chinese medicine, on induced sputum interleukin-8 (IL-8) in patients with chronic obstructive pulmonary disease (COPD) at the stable phase. METHODS: Thirty-six patients with COPD were divided into trial group (18 cases) and control group (18 cases) randomly. The trial group was treated with Yufeining pills taken orally for half a year; the control group was not given any medicine. Routine lung function was recorded before and after treatment. Total cell count (TCC), differential cell counts (DCCs) and IL-8 in induced sputum were determined at the baseline and 6 months later. RESULTS: The indices of lung function improved significantly after 6 months' treatment in trial group (P < 0.05); TCC and absolute neutrophil count decreased significantly compared with baseline in the trial group (P < 0.05); Sputum IL-8 concentration dropped significantly after 6 months' treatment, from a mean of 5.216 +/- 2.914 microg/L to 4.222 +/- 2.140 microg/L (P < 0.05). There were insignificant changes in the parameters in the control group between baseline and 6 months later. CONCLUSION: Yufeining could improve lung function, decrease sputum TCC, absolute neutrophil count and IL-8 concentration, and relieve airway inflammation in patients with COPD in the stable phase.