Research progress of dydrogesterone in the treatment of endometriosis.

Endometriosis is a common gynecological disease among women of reproductive age. It is a chronic estrogen and progestin related inflammatory disease. At present, the main treatments for endometriosis are drug therapy and surgery. In drug therapy, progesterone is listed as the first-line recommendation in multinational guidelines. Dydrogesterone, as an oral reversal progesterone, can slow down the metabolism of progesterone, inhibit angiogenesis and extracellular matrix degradation to inhibit the proliferation of the ectopic endometrium, induce the atrophy of the ectopic endometrium through the pro-apoptotic pathway, and treat endometriosis through multiple mechanisms of regulating inflammatory factors to reduce inflammation. Clinically, dydrogesterone treatment of endometriosis can relieve patients' symptoms, promote fertility, be used in combination, and is safe. This article will review the mechanism and clinical application of dydrogesterone in the treatment of endometriosis.

Semi-supervised inference for nonparametric logistic regression.

We consider the problem of estimating the nonparametric function in nonparametric logistic regression under semi-supervised framework, where a relatively small size labeled data set collected by case-control sampling and a relatively large size of unlabeled data containing only observations of predictors are available. This problem arises in various applications when the outcome variable is expensive or difficult to be observed directly. A two-stage nonparametric semi-supervised estimator based on spline method is proposed to estimate the target regression function by maximizing the likelihood function of the labeled case-control data. The unlabeled data are used in the first stage for estimating the density function that involves in the likelihood function. The consistency and functional asymptotic normality of the semi-supervised two-stage estimator are established under mild conditions. The proposed method, by making use of the unlabeled data, produces more efficient estimation of the target function than the traditional supervised counterpart. The performance of the proposed method is evaluated through extensive simulation studies. An application is illustrated with an analysis of a skin segmentation data.

LncRNA HOTAIR regulates cell invasion and migration in endometriosis through miR-519b-3p/PRRG4 pathway.

Endometriosis is a common benign disease in gynecology and has malignant biological behaviors, such as hyperplasia, invasion, metastasis, and recurrence. However, the pathogenesis of endometriosis remains unclear. The present study aimed to investigate whether LncRNA HOTAIR regulates cell invasion and migration in endometriosis by regulating the miR-519b-3p/PRRG4 pathway. The qRT-PCR results showed that the average relative expression of LncRNA HOTAIR was much higher in ectopic endometrial tissues than in eutopic endometrial tissues. Scratch and transwell assays showed that the cell migration and invasion ability of LncRNA HOTAIR overexpression group was significantly higher than those in the control group. Conversely, the LncRNA HOTAIR knockdown group showed the opposite results. Bioinformatics analysis suggested that the downstream target genes of LncRNA HOTAIR were miR-519b-3p and Prrg4. Knockdown of LncRNA HOTAIR can reduce the up-regulation of Prrg4 by miR-519b-3p and then inhibit the invasion and migration ability of endometrial stromal cells. In Conclusion, LncRNA HOTAIR can regulate the ability of invasion and migration of endometrial stromal cells, and its mechanism is proved by regulating the miR-519b-3p/PRRG4 pathway.

Transcriptomic Complexity in Strawberry Fruit Development and Maturation Revealed by Nanopore Sequencing.

The use of alternative transcription start or termination sites (aTSS or aTTS) as well as alternative splicing (AS) produce diverse transcript isoforms, playing indispensable roles in the plant development and environmental adaptations. Despite the advances in the finding of the genome-wide alternatively spliced genes in strawberry, it remains unexplored how AS responds to the developmental cues and what relevance do these outcomes have to the gene function. In this study, we have systematically investigated the transcriptome complexity using long-read Oxford Nanopore Technologies along the four successive developmental stages. The full-length cDNA sequencing results unraveled thousands of previously unexplored transcript isoforms raised from aTSS, aTTS, and AS. The relative contributions of these three processes to the complexity of strawberry fruit transcripts were compared. The aTSS and aTTS were more abundant than the AS. Differentially expressed transcripts unraveled the key transitional role of the white fruit stage. Isoform switches of transcripts from 757 genes were observed. They were associated with protein-coding potential change and domain gain or loss as the main consequences. Those genes with switched isoforms take part in the key processes of maturation in the late stages. A case study using yeast two hybrid analysis supported the functional divergence of the two isoforms of the B-box protein 22. Our results provided a new comprehensive overview of the dynamic transcriptomic landscape during strawberry fruit development and maturation.

Doping control analysis of total arsenic in equine plasma.

Arsenic can be easily found in our surrounding environment. Because of its ubiquitous nature, horse urine and blood invariably contain low levels of arsenic. Nevertheless, inorganic arsenic, despite its general use as a tonic for horses, is an effective doping agent having a deleterious effect because of its ability to induce gastroenteritis. The misuse of arsenic in horseracing has been controlled by an international urinary threshold of total arsenic at 0.3 µg/mL. However, an equivalent threshold for total arsenic in plasma is yet to be established. In this study, an inductively coupled plasma-mass spectrometry method has been developed for quantifying total arsenic in equine plasma. Statistical analysis determined that the data from a population study of 1,552 post-race and out-of-competition plasma samples fits a Gaussian mixture model with two Gaussian components. A rounded-up provisional threshold for plasma total arsenic at 2.5 ng/mL was subsequently established. Results from administration trials with a sodium arsanilate-containing supplement showed that both urinary and plasma arsenic was significantly elevated after administration. The maximum urinary detection time was around 22 h based on the international threshold. However, the maximum plasma detection time would be longer than 73 h if the provisional threshold of 2.5 ng/mL was adopted. In view of the high discrepancy between the urine and plasma detection times, a revised plasma threshold of 15 ng/mL is proposed to afford a comparable detection time in both matrices. The risk of a normal sample exceeding the proposed plasma total arsenic threshold is practically zero.

First-line renin-angiotensin system inhibitors vs. other first-line antihypertensive drug classes in hypertensive patients with type 2 diabetes mellitus.

First-line renin-angiotensin system (RAS) inhibitors are recommended for diabetic patients because of their potential nephron-protective properties. For hypertensive patients with type 2 diabetes mellitus, little is known about first-line RAS inhibitors vs. other first-line antihypertensive agents in terms of cardiovascular outcomes. We performed a meta-analysis of randomized controlled trials (RCTs) to assess the comparative efficacy of first-line RAS inhibitors vs. other first-line antihypertensive drug classes in hypertensive patients with type 2 diabetes mellitus. We identified RCTs by searching the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE up to December 15, 2015. Eighteen RCTs involving 18,862 participants were included. First-line RAS inhibitors were not different from first-line diuretics for all the primary outcomes. First-line RAS inhibitors reduced major cardiovascular events (2 RCTs, relative risk [RR] 0.78, 95% confidence interval [CI] 0.66, 0.91) and heart failure (4 RCTs, RR 0.72, 95% CI 0.61, 0.83) compared to first-line calcium channel blockers. Compared to ß-blockers, RAS inhibitors reduced the risk of all-cause mortality (1 RCT, RR 0.63, 95% CI 0.47, 0.84), major cardiovascular events (1 RCT, RR 0.76, 95% CI 0.62, 0.93) and heart failure (1 RCT, RR 0.60, 95% CI 0.40, 0.92). Our meta-analysis indicates that, in patients with type 2 diabetes mellitus and hypertension, first-line RAS inhibitors reduced adverse cardiovascular events to the same degree as first-line diuretics but to a greater degree than first-line calcium channel blockers and first-line beta blockers.

Association study of polymorphisms in the cyclooxygenase-2 gene and Alzheimer's disease risk in Chinese.

To determine if polymorphisms (-765G/C, -1195G/A and 8473T/C) of the cyclooxygenase-2 (COX-2) gene can be associated with Alzheimer disease (AD). The frequency of the polymorphisms was determined in 244 cases and 226 controls. The results revealed that the distributions of COX-2 -765G/C and 8473T/C polymorphisms were statistically not significant between AD cases and controls. The genotype distributions and allele frequencies of COX-2 -1195G/A polymorphism in the cases were statistically significantly different from the controls (P < 0.05). The A/A distribution and A allele frequency were significantly lower in the AD group. COX-2 -1195AA carriers showed a one-third lower risk of developing AD as compared to those with -1195GG and GA genotypes (OR = 0.3, 95 % CI 0.194-0.465, P = 0.000). This study suggested that -1195G/A polymorphism of the COX-2 gene is associated with the risk of AD, and the A allele represents a protective factor in patients with AD.

Study of the process of secondary failure of sulphonylurea by a Markov model.

PURPOSE: The study was to reflect and forecast the evolutive tendency and influence factors of secondary failure of sulphonylurea (SFS) changing with time by using a Markov (MKV) model in the elderly diabetic population in Shanghai. METHODS: A total of 549 patients with elderly diabetes mellitus (DM) were enrolled and grouped in the study. A door-to-door retrospective epidemiological survey was used to collect data. The MKV model was used to assess the process and influence factors of SFS and the MKV process decision support system was adopted to calculate state probability of the MKV process. RESULTS: The rate of SFS in the group of all cases, FPG < or = 10 mmol . L(-1) before treatment and FPG > 10 mmol . L(-1) before treatment, taking single type of sulphonylurea (SU) and taking two types of SU and over respectively was 9.11%, 3.55%, 11.03%, 8.54% and 11.21%. The years of changing into the state of secondary failure in half patients was 5 years, 11-12 years, 4 years, 5 years, 4 years, respectively in the following groups: all cases, FPG < or = 10 mmol . L(-1) before treatment and FPG > 10 mmol . L(-1) before treatment, taking single type of SU and taking two types of SU and over. CONCLUSIONS: A MKV model could predict the long-term evolutive process of SFS by a short-term observation; the speed of SFS was related to the degree of DM patients' condition, patients with higher glucose levels prior to treatment would develop SFS faster; but we cannot postpone the development of secondary failure by exchanging SU types.

Changes in brain interleukin-1beta following the coadministration of norfloxacin with biphenylacetic acid in rats.

We sought to determine the changes in brain interleukin-1beta (IL-1beta) following the coadministration of norfloxacin (25 mg/kg, i.p.) with biphenylacetic acid (100 mg/kg, p.o.) in rats. Norfloxacin provoked clonic convulsions in rats treated concomitantly with biphenylacetic acid, a major metabolite of the nonsteroidal anti-inflammatory drug fenbufen. Seizure activity was analyzed by EEG monitoring. Behavioral changes were also monitored. IL-1beta expressions in the prefrontal cortex and hippocampus at different time intervals were studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The epileptiform discharges appeared in all the rats, accompanied with limb twitching and clonic-tonic seizures after administration of norfloxacin coadministered with biphenylacetic acid. Norfloxacin plus biphenylacetic acid-induced convulsions rapidly and transiently enhanced IL-1beta mRNA in the prefrontal cortex and hippocampus. IL-1beta mRNA expression in the prefrontal cortex and hippocampus was detected as soon as 30 min after norfloxacin injection, and decayed to control levels by 6 h. ELISA analysis revealed significant increase of the IL-1beta protein in the prefrontal cortex and hippocampus at 2 h and 6 h. Administration of either norfloxacin or biphenylacetic acid alone did not elicit convulsions and increase in IL-1beta mRNA and protein expressions. The results suggest that the increased IL-1beta expressions in the prefrontal cortex and hippocampus induced by norfloxacin with biphenylacetic acid relate to seizure activities, and that these brain regions play pivotal roles in norfloxacin-induced convulsions.

Neuroprotective effects of stearic acid against toxicity of oxygen/glucose deprivation or glutamate on rat cortical or hippocampal slices.

AIM: To observe the effects of stearic acid, a long-chain saturated fatty acid consisting of 18 carbon atoms, on brain (cortical or hippocampal) slices insulted by oxygen-glucose deprivation (OGD), glutamate or sodium azide (NaN3) in vitro. METHODS: The activities of hippocampal slices were monitored by population spikes recorded in the CA1 region. In vitro injury models of brain slice were induced by 10 min of OGD, 1 mmol/L glutamate or 10 mmol/L NaN3. After 30 min of pre-incubation with stearic acid (3-30 micromol/L), brain slices (cortical or hippocampal) were subjected to OGD, glutamate or NaN3, and the tissue activities were evaluated by using the 2,3,5-triphenyltetrazolium chloride method. MK886 [5 mmol/L; a noncompetitive inhibitor of proliferator-activated receptor (PPAR-alpha)] or BADGE (bisphenol A diglycidyl ether; 100 micromol/L; an antagonist of PPAR-gamma) were tested for their effects on the neuroprotection afforded by stearic acid. RESULTS: Viability of brain slices was not changed significantly after direct incubation with stearic acid. OGD, glutamate and NaN3 injury significantly decreased the viability of brain slices. Stearic acid (3-30 micromol/L) dose-dependently protected brain slices from OGD and glutamate injury but not from NaN3 injury, and its neuroprotective effect was completely abolished by BADGE. CONCLUSION: Stearic acid can protect brain slices (cortical or hippocampal) against injury induced by OGD or glutamate. Its neuroprotective effect may be mainly mediated by the activation of PPAR-gamma.

Preparation of bupleurum nasal spray and evaluation on its safety and efficacy.

Radix Bupleuri is widely used in traditional medicine for the treatment of fever, pain, and inflammation associated with influenza or the common cold. The essential oil extracted from the herb is generally claimed to play the major role in the efficacious treatment of fever. The purpose of the present study was to formulate an intranasal delivery system for the essential oil in an aqueous solution used in the form of nasal spray. From 450 g Radix Bupleuri was extracted the essential oil in the amount of about 0.2 ml, which was slightly water-soluble and viscous with low-fluidity. In order to dissolve the essential oil evenly in the aqueous solution, tween-80 (TW-80, used in 10% (w/v) solution), propylene glycol (PG) and diethylene glycol monoethyl ether (TC) were selected as the favorable solubilizing agents, whose amount was respectively determined by L16(4(5)) orthogonal design. An aqueous solution with clarity and no ciliotoxicity was prepared when TW-80 8% (v/v), PG 14.4% (v/v) and TC 14.4% (v/v) were added. Employed to evaluate the acute toxicity, the rats grew well and were kept active and healthy within 14 d after an intranasal administration of this preparation at the dose of oil from 10 g Bupleuri/kg (50-fold higher than the clinical dose), indicating that there would be no serious toxicity at the normal dose. Intranasal administration of this preparation to 2 kg rabbits with fever induced by subcutaneous injection of turpentine decreased body temperature markedly (0.5, 0.8 and 1.0 degrees C respectively at the dose of oil from 1, 2 and 4 g Bupleuri/body). In addition, the administration significantly reduced fever in 200 g rats induced by intramuscular injection of colicine suspension (0.6 degrees C at the dose of oil from 0.8 g Bupleuri/body). The results suggest that the formulation of nasal spray for the essential oil from Radix Bupleuri can be potentially effective in the treatment of fever.

Assessment of quality of life and relevant factors in elderly diabetic patients in the Shanghai community.

PURPOSE: The study was to assess the quality of life (QOL) of the elderly diabetes mellitus (DM) in Shanghai community and to screen the possible risk factors. METHODS: A total of 951 patients with elderly DM and 1007 elderly subjects with normal glucose tolerance from the same community as control group were enrolled in the study. A door-to-door retrospectively epidemiological survey was used to collect data of QOL, demographic, and diabetic information. The SF-36 instrument (Chinese edition) was used to assess QOL. Multiple stepwise linear regression analysis was also used to identify possible risk factors of QOL in elder DM. RESULTS: In subjects with elderly DM, the general assessment of perceived health was worse, compared with the normal elderly people; the mean score of multi-item dimensions assessment had been decreased, the lowest and highest scores of which on SF-36, respectively, were general health and body pain (ranged from 42.08 to 77.00). Based on the multiple stepwise regression analysis, 23 risk factors entered 9 multiple regressive models (9 dependent variables of which stand for the scores of 8 dimensions and the total score on SF-36) with different amount ultimately. Within the 13 risk factors that affect QOL of the elderly diabetic patients, the negative correlated factors were gender, age, payment ability of medical treatment, tumor, level of fasting plasma glucose (FPG), medicines purchasing channels, diabetic microvascular complications, diabetic macrovascular complications, acute complications, while the positive correlated factors were occupation, income, exercises, knowledge of DM. The multiple correlation coefficient square (R2) represented the above 13 risk factors had a totally 30.5% impact on the entire QOL. CONCLUSIONS: QOL of elderly DM population had significantly been decreased; QOL of the elderly patients in Shanghai community had many risk factors, which on one hand stated the complexity of elderly DM, and on the other hand gave us many useful and practical methods to improve QOL of elderly DM.