Shaoyao-Gancao Decoction (SGD) has been widely used for the treatment of gynopathy. The present study aimed to evaluate the therapeutic effect and potential mechanism of SGD on hyperandrogenism in polycystic ovary syndrome (PCOS) rats. In the present work, SGD was orally administrated to the PCOS rats at the dose of 12.5, 25, and 50 g/kg/d for 14 consecutive days. UPLC–MS/MS was performed to identify the main chemical components of SGD. Body weight, ovarian weight, cystic dilating follicles, and serum levels of steroid hormones were tested to evaluate the therapeutic effect of SGD. In order to further clarify the underlying mechanism, we also measured mRNA and the protein levels of NF-κB, NF-κB p65, P-NF-κB p65, and IκB by RT-qPCR and Western blotting techniques. Our results showed that SGD treatment significantly alleviated hyperandrogenism in PCOS rats as evidenced by reduced serum levels of T and increased E2 and FSH levels. In addition, SGD effectively reduced the phosphorylation of NF-κB p65 and increased the expression of IκB. Results of the present study demonstrated that SGD could ameliorate hyperandrogenism in PCOS rats, and the potential mechanism may relate to the NF-κB pathway.

Background: Emerging evidence suggests that gut microbiota plays a vital role in the occurrence of multiple endocrine disorders including polycystic ovary syndrome (PCOS). Shaoyao-Gancao Decoction (SGD), a classical Chinese prescription, has been widely used in the treatment of PCOS for decades. In previous studies, we found that SGD treatment could effectively reduce ovarian inflammation in PCOS rats. However, whether the anti-inflammation effect of SGD involves the regulation of the gut microbiota remains elusive.Methods: Letrozole-induced PCOS rat models were established, and the therapeutic effects of SGD were evaluated. Specifically, body weight, serum hormone concentrations, estrus phase and ovary histopathology were assessed. Then the structure of gut microbiota was determined by 16s rRNA sequencing. Additionally, the serum levels of pro-inflammatory cytokines and LPS were measured by ELISA kits. The key gene and protein expressions of TLR4/NF-κB signaling pathway were detected by quantitative real-time PCR and western blot.Results: SGD could effectively reduce body weight, regulate estrous cycles and ameliorate hyperandrogenism in PCOS rats. In addition, SGD treatment decreased releases of pro-inflammatory cytokines, enhanced the expressions of tight junction (occludin and claudin1), and then prevented a translocation of LPS into bloodstream. SGD could significantly reduce the ratio of Firmicutes to Bacteroidetes, decrease the abundance of LPS-producing pathogens Proteobateria and enrich the abundance of Butyricicoccus, Coprococcus, Akkermansia Blautia and Bacteroides in PCOS rats. Furthermore, SGD blunted the key gene and protein expressions of TLR4/NF-κB signaling pathway both in vivo and in LPS-induced RAW264.7 cells.Conclusion: SGD administration could ameliorate the inflammatory response in PCOS rats by remodeling gut microbiome structure, protecting gut barrier, and suppressing TLR4/NF-κB signaling pathway.

Postinflammatory irritable bowel syndrome (PI-IBS) is a common functional gastrointestinal disorder, which is characterized by abdominal pain, low-grade inflammation, and visceral hypersensitivity. Shaoyao-Gancao decoction (SGD) has been used to improve the clinical symptoms of abdominal spasmodic pain accompanying acute gastroenteritis, but the underlying therapeutic mechanism has not been fully elucidated. In the present study, a rat model of PI-IBS was established via rectal administration of TNBS. Rats were scored daily for 28 days using disease activity index (DAI). Abdominal withdrawal reflex (AWR) was used to measure the pain threshold. After SGD (6.25, 12.5, and 25 g/kg/d) treatment for 14 days, rat colonic tissue was collected for histopathological grading, enterochromaffin (EC) cell count, and 5-HT content measurement. RT-qPCR and western blot analyses were employed to detect the gene and protein level of tryptophan hydroxylase (TPH), serotonin reuptake transporter (SERT), and transient receptor potential vanilloid 1 (TRPV1). To further validate the effect of SGD on TRPV1, another experiment was performed in cells. The results revealed that visceral hyperalgesia, reflected by increased DAI, AWR, pathological injury score, 5-HT content, and EC cell count in PI-IBS rats, was significantly ameliorated by SGD. In cells, SGD markedly inhibited the expression and function of TRPV1. Moreover, the expression levels of TPH were also repressed by SGD. The findings of the present study indicated that the therapeutic effect of SGD on visceral hyperalgesia may be closely associated with the regulatory role of TRPV1 and 5-HT signaling pathways.

The enterohepatic circulation of bile acids (BAs) critically depends on BA transporters and enzymes, which can be affected by inflammatory bowel disease. Diarrhea in colitis is believed to result in part from BA malabsorption. The work aimed to investigate whether diarrhea in colitis was associated with the expression of BA transporters, enzymes, and nuclear receptors. RT-qPCR and Western blot techniques were used to evaluate the gene and protein levels of Cyp7a1, Asbt, SHP, FXR, Ostβ in a 2,4,6-trinitrobenzenesulfonic-acid-induced rat model of colitis. The total BAs (TBAs) levels were assayed using ELISA kits, and the individual BAs were measured by LC–MS/MS. Results showed that the fecal excretions of TBAs were significantly increased by 1.6-fold in acute stage of colitis. In ileum, Asbt was significantly decreased; however, there was a compensatory increase in Cyp7a1 level in liver. Moreover, FXR has a decreased tendency and the downstream target gene SHP was downregulated. Contrary to acute stage, molecular changes were completely reversible during the remission phase. Our results indicated that the expression of Asbt and Cyp7a1 were altered in acute colitis, which performed vital roles in maintaining BA homeostasis. Early medical manipulation of BA transporters and enzymes may help prevent diarrhea.

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Objective: To investigate the correlation between monocyte to high-density lipoprotein ratio (MHR) and major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods: In this retrospective study, 120 ACS patients who received PCI in our hospital from September 2014 to August 2019 were selected and divided into MACE group and normal discharge (ND) group. Their clinical data were collected, and MHR values were compared. Logistic regression analysis was conducted to analyze the correlations between various factors and ACS. The correlation between MHR and Gensini score was subjected to Pearson’s analysis. Receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic value of MHR for MACE. Results: Hypertension degree, white cell count, Gensini score, MHR and the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), apolipoprotein A1 (ApoA1), ApoB, lipoprotein (a) [LP(a)] and uric acid (UA) in MACE group were significantly higher than those in ND group (P<0.05). HDLC, ApoA1, TC, MHR, LDLC and ApoB were independent risk factors for MACE of ACS patients after PCI (P<0.05). There was a positive correlation between MHR and Gensini score (r=0.832, P<0.05), and the optimal cutoff value of MHR for diagnosing MACE was 9.45. Conclusion: Serum MHR is positively correlated with Gensini score in ACS patients after PCI, which can be used as an independent predictor for MACE in hospital. doi: https://doi.org/10.12669/pjms.37.3.3469 How to cite this:Yu R, Hou R, Wang T, Li T, Han H, An J. Correlation between monocyte to high-density lipoprotein ratio and major adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention. Pak J Med Sci. 2021;37(3):---------. doi: https://doi.org/10.12669/pjms.37.3.3469 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

We develop a simple and efficient method to detect the concentration of the inulin-type fructan CPA from the roots of Codonopsis pilosula (Franch.) Nannf., then apply it to evaluate the pharmacokinetic behavior and distribution character in tissues and excretion in mice.

44The tumour stroma regulates nearly all stages of carcinogenesis. Stromal heterogeneity in 45 human triple-negative breast cancers (TNBCs) remains poorly understood, limiting the 46 development of stromal-targeted therapies. Single cell RNA-sequencing of five TNBCs 47 revealed two cancer-associated fibroblast (CAF) and two perivascular-like (PVL) 48 subpopulations. CAFs clustered into two states, the first with features of myofibroblasts and 49 the second characterised by high expression of growth factors and immunomodulatory 50 molecules. PVL cells clustered into two states consistent with a differentiated and immature 51 phenotype. We showed that these stromal states have distinct morphologies, spatial 52 relationships and functional properties in regulating the extracellular matrix. Using cell-53 signalling predictions, we provide evidence that stromal-immune crosstalk acts via a diverse 54 array of immunoregulatory molecules. Importantly, the investigation of gene signatures from 55 inflammatory-CAFs and differentiated-PVL cells in independent TNBC patient cohorts 56 revealed strong associations with cytotoxic T-cell dysfunction and exclusion, respectively. 57Such insights present promising candidates to further investigate for new therapeutic 58 strategies in the treatment of TNBCs. 59 60 61Heterotypic interactions between stromal, immune and malignant epithelial cells play 62 important roles in solid tumour progression and therapeutic response. Cancer-associated 63 fibroblasts (CAFs) play an integral part in the tumour microenvironment (TME), and can 64 influence many aspects of carcinogenesis including extracellular matrix (ECM) remodelling, 65 angiogenesis, cancer cell proliferation, invasion, inflammation, metabolic reprogramming 66 and metastasis [1]. Recent studies have described roles for CAFs in mediating immune 67 suppression and chemo-resistance, establishing CAFs as novel and attractive targets for 68 anti-cancer therapies in advanced breast cancer [2-6]. Despite their well-described roles in 69 cancer biology, CAFs remain enigmatic: limited studies suggest phenotypic heterogeneity, 70 plasticity and functional diversity, with both tumour-promoting and tumour-suppressive 71 properties [1]. The multi-faceted nature of CAFs suggests that they are comprised of diverse 72 subpopulations, and an improved understanding of stromal heterogeneity may explain how 73 CAFs contribute to the dynamic complexity and functional malleability of the tumour 74 ecosystem. 75 76CAFs of the tumour parenchyma are routinely studied using a handful of markers including 77 a-smooth muscle actin (a-SMA), fibroblast activation protein (FAP), CD90 (THY-1), platelet 78 derived growth factor receptor a and b (PDGFRa and PDGFRb), podoplanin (PDPN) and 79 fibroblast specific protein 1 (FSP-1, also named S100A4) [1, 7-9]. However, these markers 80 are not necessarily co-expressed, nor specific to the fibroblast lineage [4]. For instance, α-81 SMA not only identifies CAFs with a myofibroblast morphology but also serves as a genera...