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Objective: This report was designed to assess the functional role of miR-218/dachshund family transcription factor 1 (DACH1) in diabetic kidney disease (DKD) and investigate its possible molecular mechanism. Materials and Methods: From the GEO database, we downloaded different datasets for analyzing the expression of miR-218 and DACH1 in DKD. TargetScan was adopted to predict the binding sites between miR-218 and DACH1, which was further verified by dual-luciferase reporter assays. The renal proximal tubule cells (HK-2) treated with high glucose (HG) were used as an in vitro model. QRT-PCR and western blot were used to determine the expression of DACH1 and other relative factors. Cell counting kit-8 and flow cytometer were applied to detect cell viability and apoptosis. The levels of inflammatory cytokines were determined by an ELISA assay. Results: A prominent raise of miR-218 was observed in DKD through bioinformatics analysis, which was further confirmed in the HG-induced model. DACH1 is a target of miR-218. miR-218 reduced cell viability and induced apoptosis by negatively regulating DACH1. Moreover, upregulating miR-218 in HG models increased the concentrations of pro-inflammatory cytokines TNF-α and IL-1β, reduced the level of anti-inflammatory cytokine IL-10, and promoted the epithelial-mesenchymal transition (EMT) process, which is possibly achieved by targeting DACH1. While downregulating miR-218 showed the opposite results. Conclusion: These data demonstrated that, under an in vitro HG environment, miR-218 suppressed the HK-2 cells proliferation, promoted apoptosis, caused an inflammatory response, and facilitated the EMT process largely by targeting DACH1, providing an insight into the therapeutic intervention of DKD.

Background Electroconvulsive therapy (ECT) is the most rapid and effective treatment for patients with depression, ECT can achieve remarkable antidepressant effects in the initial 3–4 sessions, but significant side effects limit its use. However, recent low-charge electrotherapy (LCE) studies have demonstrated antidepressant or antipsychotic effects with significantly fewer side effects. The aim of this study is to propose a novel two-step charge set strategy for ECT treatment, referred to as Hybrid-ECT, to decrease side effects by using a low charge while preserving treatment efficacy. Methods/design A randomized, double-blinded, standard-controlled, parallel-group design will be carried out. We plan to enroll 112 inpatients diagnosed with depression (unipolar or bipolar) and randomly assign them to conventional ECT (control group) or to Hybrid-ECT (treatment group, 3 ECT sessions followed by LCE sessions (approximately 2.8 joules per session)). We will evaluate participants across a wide variety of domains including clinical symptoms, cognitive, psychological and functional metrics. We will also perform magnetic resonance imaging (MRI) and event-related potential (ERPs) assessments during treatment to explore brain function differences between ECT and LCE. Discussion This research proposes a simple but completely novel ECT strategy that aims to rapidly relieve depressive symptoms and minimize side effects. The mechanism of ECT and LCE will be further discussed. Trial registration Chinese Clinical Trial Registry, Number: ChiCTR1900022905 (Registration date: April 30, 2019).

Background: This study investigated the clinicopathological characteristics and factors influencing the recurrence of pelvic endodermal sinus tumor. Methods: Fifty-four cases were retrospectively analyzed from at the Zhejiang Cancer Hospital. Imaging and serological indicators were used to determine whether disease recurred, to evaluate progression-free survival, and to compare the influence of related factors on disease recurrence. SPSS 19.0 software was used for statistical analysis. Statistical significance was defined as p < 0.05. Results: The median age at initial treatment was 21 years (range, 11–52 years). Six patients had extragonadal endodermal sinus tumor, and four had histological features of endodermal sinus tumor combined with embryonal carcinoma. Thirty-nine patients underwent fertility-preserving surgery, 18 patients had a childbearing history, and eight patients had residual tumor after initial treatment. Twenty-six patients had a tumor diameter of more than 15 cm, and 30 patients had a serum α‑fetoprotein level greater than 10,000 ng/mL before initial management. The median follow-up time was 47.5 months (range, 14–212 months). During follow-up, 15 patients experience recurrence, with a recurrence rate of 27.8% and a 5-year PFS rate of 61.1%. In univariate analysis, the International Federation of Gynecology and Obstetrics stage (stage III-IV VS. I-II; HR= 10.054 pConclusions: Stage is a prognostic factor for recurrence of pelvic endodermal sinus tumor. The first surgery should remove the tumor as completely as possible, and initial treatment should require a sufficient dose and full course of platinum-based chemotherapy, which may reduce the recurrence rate. Patients with endodermal sinus tumor and embryonal carcinoma may have increased susceptibility of recurrence.

Background To probe the differences of gut microbiota among major depressive disorder (MDD), bipolar disorder with current major depressive episode (BPD) and health participants. Methods Thirty one MDD patients, thirty BPD patients, and thirty healthy controls (HCs) were recruited. All the faecal samples were analyzed by shotgun metagenomics sequencing. Except for routine analyses of alpha diversity, we specially designed a new indicator, the Gm coefficient, to evaluate the inequality of relative abundances of microbiota for each participant. Results The Gm coefficients are significant decreased in both MDD and BPD groups. The relative abundances of increased phyla Firmicutes and Actinobacteria and decreased Bacteroidetes were significantly in the MDD and BPD groups. At genus level, four of top five enriched genera (Bacteroides, Clostridium, Bifidobacterium, Oscillibacter and Streptococcus) were found increased significantly in the MDD and BPD groups compared with HCs. The genera Escherichia and Klebsiella showed significant changes in abundances only between the BPD and HC groups. At the species level, compared with BPD patients, MDD patients had a higher abundance of Prevotellaceae including Prevotella denticola F0289, Prevotella intermedia 17, Prevotella ruminicola, and Prevotella intermedia. Furthermore, the abundance of Fusobacteriaceae, Escherichia blattae DSM 4481 and Klebsiella oxytoca were significantly increased, whereas the Bifidobacterium longum subsp. infantis ATCC 15697 = JCM 1222 was significantly reduced in BPD group compared with MDD group. Conclusions Our study suggested that gut microbiota may be involved in the pathogenesis of both MDD and BPD patients, and the nuances of bacteria may have the potentiality of being the biomarkers of MDD and BPD.

Ovarian cancer is one of the most common cancers in women and is often diagnosed as advanced stage because of the subtle symptoms of early ovarian cancer. To identify the somatic alterations and new biomarkers for the diagnosis and targeted therapy of Chinese ovarian cancer patients, a total of 65 Chinese ovarian cancer patients were enrolled for detection of genomic alterations. The most commonly mutated genes in ovarian cancers were TP53 (86.15%, 56/65), NF1 (13.85%, 9/65), NOTCH3 (10.77%, 7/65), and TERT (10.77%, 7/65). Statistical analysis showed that TP53 and LRP1B mutations were associated with the age of patients, KRAS, TP53, and PTEN mutations were significantly associated with tumor differentiation, and MED12, LRP2, PIK3R2, CCNE1, and LRP1B mutations were significantly associated with high tumor mutational burden. The mutation frequencies of LRP2 and NTRK3 in metastatic ovarian cancers were higher than those in primary tumors, but the difference was not significant (P = 0.072, for both). Molecular characteristics of three patients responding to olapanib supported that BRCA mutation and HRD related mutations is the target of olaparib in platinum sensitive patients. In conclusion we identified the somatic alterations and suggested a group of potential biomarkers for Chinese ovarian cancer patients. Our study provided a basis for further exploration of diagnosis and molecular targeted therapy for Chinese ovarian cancer patients.

Aim: To investigate the expression of long intergenic noncoding RNA 00515 (LINC00515) in high-grade serous ovarian cancer (HGSOC) and its potential correlation with platinum resistance. Patients & methods: Expression of LINC00515 in HGSOC (n = 115) and normal (n = 19) tissues was detected via quantitative real-time PCR (qRT-PCR). We further explored the statistical significance of the relationship between LINC00515 expression and platinum resistance in HGSOC. Results: LINC00515 was gradually downregulated in the order of normal > platinum-sensitive > platinum-resistant tissue (p < 0.05). Results demonstrated that LINC00515 downregulation was correlated with platinum resistance and relapse-free survival (RFS) of HGSOC (p < 0.05). Conclusion: LINC00515 downregulation is correlated with HGSOC development, platinum resistance and RFS, supporting its utility as a potential biomarker to predict platinum resistance and prognosis of RFS.

This study was conducted to determine the prognostic value of serum α-fetoprotein (AFP) levels in patients with ovarian yolk sac tumor (OYST). We performed a systematic review and meta-analysis to assess the associations between serum AFP level and prognosis in OYST. A total of 12 quantitative studies met the inclusion criteria. Preoperative AFP was not found to be associated with overall survival (OS) [odds ratio (OR)=0.84, 95% confidence interval (CI): 0.43–1.62] in OYST. However, a high postoperative AFP level was associated with worse OS (OR=0.16, 95% CI: 0.05–0.48) and relapse-free survival (RFS) (OR=0.18, 95% CI: 0.08–0.43) compared to a low postoperative AFP level in patients with OYST. In addition, a postoperative AFP level of >1,000 ng/ml was associated with a decrease in OS (OR=0.16, 95% CI: 0.05–0.50) and RFS (OR=0.21, 95% CI: 0.08–0.57). In conclusion, the postoperative, but not the preoperative, AFP level was found to be a prognostic factor in patients with OYST. In particular, a postoperative AFP level of >1,000 ng/ml was an indicator of poor prognosis in patients with OYST.

Wind turbine system (WTS) is a representative distributed power generation (DG). Establishment of WTS model and control strategies is of important practical significance. One critical field is the research of inverter system. It should be operated in stand-alone (SA) or grid-connected (GC) mode. The purpose of this thesis is to establish simulation platform of WTS inverter control model in Matlab/Simulink environment, which includes two typical DG control strategies, PQ and V/f. The wind fluctuation makes inverter output power harder to follow wind turbine (WT) power. In GC mode, PQ strategy was adopted to balance inverter output power and WT generated power. In SA mode, V/f strategy was applied to keep emergency load voltage stable. The bidirectional smooth transitions between SA and GC mode were well accomplished. Simulation proves the model can survive grid failures or load shedding. The study can be used in research of DG operation control.

The mu-opioid receptor (MOR), a membrane-bound G protein-coupled receptor, is the main target for opioids in the nervous system. MOR1 has been found in several types of cancer cells and reported to be involved in tumor progression and metastasis. However, the expression and clinical significance of MOR1 in esophageal squamous cell carcinoma (ESCC) remain unclear. In our study, the expression of MOR1 was confirmed in ESCC cell lines (KYSE180, KYSE150, and EC109) by Western blot. MOR1 was also detected on tissue microarrays of ESCC samples in 239 cases using immunohistochemical staining. We found that MOR1 was mainly located in the cytoplasm and occasionally occurred in the membrane or nucleus of ESCC cells. Moreover, results indicated that MOR1 expression in the cytoplasm was associated with lymph node metastasis (R = 0.164, P = 0.008, Kendall's tau-b-test). No more associations were found between MOR1 expression status and other clinical parameters. However, no statistical significant differences were found between MOR1 expression in the cytoplasm, nucleus/membrane, and the overall survival of ESCC patients (P = 0.848; P = 0.167; P = 0.428, respectively, log-rank test). Our results suggest that the cytoplasmic MOR1 may be a high-risk factor for lymph node metastasis of ESCC patients. We also hypothesize that MOR1 agonists used in ESCC patients should be prudent, and opioid receptor antagonists may be novel therapeutic drugs for ESCC patients.

Background: The aim of this study was to evaluate patient characteristics and findings after mammary ductoscopy in an effort to reduce the pain experienced during the procedure. Patients and Methods: We evaluated outpatients in whom mammary ductoscopy was performed under local or intraductal anesthesia without preference, and their clinical characteristics and findings were recorded. Average and maximum pain scores were determined after the examination for statistical analysis. Results: The overall average pain score was 3.74 ± 1.353, and the maximum pain score was 6.40 ± 1.681. The type of anesthesia, total operation time, nipple retraction, and discharge status significantly correlated with the pain score. Intraductal anesthesia lowered the average pain score by 0.60, whereas a total procedure time greater than 12 min increased the average pain score by 0.956. The pain score decreased if patients had nipple retraction, and intraductal anesthesia proved suitable for patients with normal nipples. Conclusion: Intraductal anesthesia is suitable for most patients, and ductoscopy should not exceed 12 min to minimize the pain. Nipple retraction does not significantly increase pain, but local anesthesia should be used in patients with retracted nipples. Patient age, breastfeeding history, menstrual stage, and presence of intraductal tumors were not associated with the level of pain experienced.

The effects of iptakalim, a new ATP-sensitive potassium channel opener, were studied in spontaneously hypertensive rats (SHR). Treatment of 12-week-old male SHR (six animals in each group) with iptakalim by gastric lavage at doses of 1, 3, or 9 mg/kg/day for 12 weeks resulted in a lowering of blood pressure. Iptakalim provided significant renoprotection to SHR rats as measured by decreased proteinuria and improved renal function. Histological evidence demonstrated that iptakalim could reverse renal vascular remodeling (of afferent arterioles, arcuate arteries, or interlobular arteries), and improve pathological changes of glomerular, renal interstitial, and glomerular filtration membranes. These effects were accompanied by the decreased circulation and intrarenal concentrations of endothelin 1 and transforming growth factor beta1 (TGF-beta1), and down-regulated overexpression of genes for ET-1, endothelin-converting enzyme 1, TGF-beta1, and the subunits of ATP-sensitive potassium channels (K(ATP)), Kir1.1 and Kir6.1, in the kidney during hypertension. Abnormal expression of matrix components [collagen IV, fibronectin, matrix metalloproteinase 9 (MMP-9) and MMP tissue inhibitor 1 (TIMP-1)] was also significantly reversed by iptakalim. Our results demonstrate that chronic treatment with iptakalim not only reduces blood pressure but also preserves renal structure and function in SHR. In addition to reducing blood pressure, the renoprotective of iptakalim may be involved in inhibiting the circulation and intrarenal concentrations of endothelin 1 and TGF-beta1, regulating the expression of K(ATP) genes and correcting MMP-9/TIMP-1 imbalance in renal tissue, which may result in reducing the accumulation of extracellular matrix molecules.

The excessive contraction of small arteries under high blood pressure is the main contributor to the pathological change of hypertension. Current anti-hypertensive drugs, which lack a selective effect on small arteries in a hypertensive state, may cause many adverse effects. We have developed a novel opener of ATP-sensitive potassium channels, iptakalim, the vasorelaxing action of which is determined by the hypertensive status of small arteries. In conscious stroke-prone, spontaneously hypertensive rats and "two-kidneys, one-clip" renal hypertensive dogs, this compound produced long-lasting hypotensive effects, with no tolerance. Furthermore, it exerted a protective effect against hypertensive damage to target organs. Given its potency and fewer side effects, iptakalim hydrochloride is a promising drug for the treatment of hypertension.

Some potassium channel openers (KCOs) are potent vasodilators that mainly target the ATP-sensitive potassium channels in vascular smooth muscle cells. Their lack of tissue selectivity limits their clinical use in hypertension therapy. Iptakalim [2,3-dimethyl-n-(1-methylethyl)-2-butylamine], which belongs to a novel chemical type of KCO, possesses unique pharmacological characteristics. In vitro experiments have shown that iptakalim could limit its vasorelaxing actions to resistance vessels. In this study, we investigate the antihypertensive effects of iptakalim on two different experimental hypertensive models: stroke-prone, spontaneously hypertensive rats (SHRsps) and two-kidney with one-clip renal hypertensive dogs (2K1C RHD). In acute hypotensive tests, iptakalim showed stable, long-lasting antihypertensive effects in SHRsps and 2K1C RHDs. Mean-while, it had little effect on heart rate when compared with pinacidil, nifedipine, captopril, or bisoprolol. In experimental therapeutic tests, repeated doses in SHRsps for 30 days or in 2K1C RHDs for 14 days produced consistent antihypertensive effects without causing tolerance. In separate experiments, chronic administration of iptakalim resulted in reversing hypertensive vascular remodeling in spontaneously hypertensive rats and hypertensive cardiac remodeling in SHRsps. These results suggest that iptakalim is a promising antihypertensive drug.

Hypoxic pulmonary hypertension (HPH) is a serious and potentially devastating chronic disorder of the pulmonary circulation. Attempts to use drugs in the therapy of hypoxic pulmonary hypertension indicated the importance of prevention or reduction of vasoconstriction as well as of the reversal of remodeling within the cardiovascular system. Iptakalim (2,3-dimethyl-N-(1-methylethyl)-2-butylamine), a novel ATP-sensitive potassium channel opener, has the desired effects on hypoxic pulmonary arteries. Iptakalim decreases the elevated mean pressure in pulmonary arteries, and attenuates remodeling in the right ventricle, pulmonary arteries and airways. Moreover, iptakalim has selective antihypertensive effects: it significantly lowers arterial pressure in hypertensive animals, but has little if any effect in normotensive animals. In HPH iptakalim has selective effects on smaller arteries. Long-term iptakalim therapy decreases expression of sulfonylurea receptor 2 and of mRNA of inwardly rectifying potassium channel in smaller arteries of spontaneously hypertensive rats. Iptakalim inhibits the effects of endothelin-1, reduces the intracellular calcium concentration and inhibits the cell cycle in smooth muscle cells of pulmonary arteries. There is no evidence for the development of tolerance to the long-lasting antihypertensive action of iptakalim. At therapeutic doses iptakalim has no effects on the central nervous, respiratory, digestive, or endocrine systems. It has a broad therapeutic range, so that it can be safely used in the therapy of HPH.