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Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. Inadequate understanding of the ovulation drivers hinders PCOS intervention. Herein, we report that follicle stimulating hormone (FSH) controls follicular fluid (FF) glutamine levels to determine ovulation. Murine ovulation starts from FF-exposing granulosa cell (GC) apoptosis. FF glutamine, which decreases in pre-ovulation porcine FF, elevates in PCOS patients FF. High-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal, metabolic, and morphologic PCOS traits. Mechanistically, follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine, which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apoptotic pathway. FSH and glutamine inhibit the rapture of cultured murine follicles. Glutamine removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or EsR1 -KO. These suggest that glutamine, FSH, and ASK1-JNK pathway are targetable to alleviate PCOS. [ABSTRACT FROM AUTHOR]

Objective. Gout is a chronic disease that causes inflammatory arthritis, which is closely related to urate accumulation induced by a disorder of uric acid metabolism and the consequent deposition of monosodium urate crystals. Dendrobium loddigesii Rolfe is an herbal medicine that has been used in some traditional Chinese medicine formulae in the treatment of gout. This study aimed to explore and verify the antigout activity of Dendrobium loddigesii extract (DLE) on alleviating the hyperuricaemia of mice and the acute gouty arthritis of rats. Methods. An animal model of hyperuricaemia was established using potassium oxonate (PO). We analysed the expression of uric acid transporter mRNA in the kidney in the hyperuricaemic mice after treatment with DLE. Simultaneously, a monosodium urate crystal-induced acute gouty arthritis rat model was used to evaluate the effects of DLE, according to the level of ankle swelling, as well as the protein levels of inflammatory receptors and cytokines, as assayed by WB and ELISA. Results. DLE alleviated hyperuricaemia in mice and inhibited acute gouty arthritis in rats (P < 0.05). Meanwhile, DLE regulated the levels of uric acid transporters mRNA transcripts, including mouse organic anion transporter 1 (mOAT1), organic anion transporter 3 (mOAT3), urate transporter 1 (mURAT1), and glucose transporter 9 (mGLUT9) in the kidney (P < 0.05), suggesting that DLE promoted uric acid metabolism. Furthermore, DLE significantly suppressed the protein levels of TLRs, MyD88, and NF-κB in the ankle joint's synovium (P < 0.05), and the serum levels of IL-1β, IL-6, and TNF-α were also reduced, which demonstrated the anti-inflammatory effects of DLE. Conclusion. DLE alleviates hyperuricaemia by regulating the transcription level of uric acid transporters in the kidney. It also inhibits acute gouty arthritis by inhibiting the pathway of TLRs/MyD88/NF-κB in the ankle joint's synovium. The findings of the present study imply that DLE alleviates gout by promoting uric acid metabolism and inhibiting inflammation related to the TLRs/MyD88/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Objectives: A radiographic study was designed to measure the relationship of the exiting nerve root and its surroundings to the corresponding intervertebral disc for percutaneous transforaminal endoscopic lumbar interbody fusion to better understand the regional anatomy and to improve clinical applications. Methods: A retrospective study from January 2017 to October 2017 was conducted at Tianjin Hospital. CT images were obtained from patients presenting low back pain (110 patients), and analysis was performed bilaterally from L2‐3 to L5S1. In the rotating coronal plane we analyzed: the nerve root–dural sac distance at the superior and inferior margins of the disc (Js, Ji); the nerve root–pedicle distance at the medial, middle, and lateral borders of the pedicle (Pa, Pb, Pc); the pedicle width (W); and the safe working zone, defined as a trapezoid bounded by the inferior pedicle and the exiting nerve root (S). In the transverse plane, the nerve root‐articular process and the shortest distance for the nerve root‐articular process joint surface were analyzed at the superior and inferior margins of the disc (Gs, Gi), respectively. The groups were analyzed using ANOVA, and paired t‐tests were used to compare the left and right sides. Results: From L2‐3 to L5S1, the distance of the nerve root to the dural sac was larger at the inferior margin of the disc. From L2‐3 to L5S1, each segment of the vertebral nerve root‐pedicle distance gradually decreased from medial to lateral. From L2‐3 to L5S1, the distance from the exiting nerve root to the middle and lateral margins of the pedicle gradually decreased, with L5S1 being the minimum. Some significant differences were observed between the left and right sides for L4‐5 and L5S1. The pedicle width of the vertebral body and the mean area for the safe working zone gradually increased from L2‐3 to L5S1. In the axial plane, the shortest distance between the nerve root and articular process joint surface at the inferior margin of the disc was greater than the distance for the nerve root to the articular process at the superior margin of the disc from L2‐3 to L5S1. There were no significant differences between the two sides. Conclusions: It is more difficult to implant a cage with a width of 10 mm above the L3‐4 level. By removing part of the superior articular process, the safe working area can be expanded, and damage to the nerve or other structures can be avoided when implanting a cage. [ABSTRACT FROM AUTHOR]

This paper creatively proposes a cluster boundary sampling method based on density clustering to solve the problem of resampling in IDS classification and verify its effectiveness experimentally. We use the clustering density threshold and the boundary density threshold to determine the cluster boundaries, in order to guide the process of resampling more scientifically and accurately. Then, we adopt the penalty factor to regulate the data imbalance effect on SVM classification algorithm. The achievements and scientific significance of this paper do not propose the best classifier or solution of imbalanced data set and just verify the validity and stability of proposed IDS resampling method. Experiments show that our method acquires obvious promotion effect in various imbalanced data sets. [ABSTRACT FROM AUTHOR]

The pathogenesis of glucocorticoid (GC)-induced osteonecrosis of the femoral head (GIONFH) is still disputed, and abnormal bone metabolism caused by GCs may be an important factor. In vitro , Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining were used to evaluate cellular proliferation, and western blotting was used to investigate osteogenesis. In vivo , we used micro-computed tomography (micro-CT), H&E staining, Masson staining, and immunohistochemistry (IHC) analysis to evaluate the impact of exosomes. In addition, the mechanism by which exosomes regulate osteogenesis through the miR-365a-5p/Hippo signaling pathway was investigated using RNA sequencing (RNA-seq), luciferase reporter assays, fluorescence in situ hybridization (FISH), and western blotting. The results of western blotting verified that the relevant genes in osteogenesis, including BMP2, Sp7, and Runx2, were upregulated. RNA-seq and qPCR of the exosome and Dex-treated exosome groups showed that miR-365a-5p was upregulated in the exosome group. Furthermore, we verified that miR-365a-5p promoted osteogenesis by targeting SAV1. Additional in vivo experiments revealed that exosomes prevented GIONFH in a rat model, as shown by micro-CT scanning and histological and IHC analysis. We concluded that exosomal miR-365a-5p was effective in promoting osteogenesis and preventing the development of GIONFH via activation of the Hippo signaling pathway in rats., Competing Interests: The authors declare no competing interests., (© 2020 The Author(s).)