The risk factors for miscarriage of viable intrauterine pregnancies in patients with heterotopic pregnancy after surgical intervention.

To summarize the clinical characteristics and explore the risk factors for miscarriage of a viable intrauterine pregnancy following surgical intervention in patients with heterotopic pregnancy (HP). A total of 106 women diagnosed with HP that underwent surgical intervention in the Women's Hospital School of Medicine Zhejiang University between January 2014 and December 2021 were included in this retrospective study. They were divided into a miscarriage group (n = 13) and an ongoing pregnancy group (n = 93) according to the outcomes of the HP within 2 weeks after surgery. Data regarding clinical characteristics, surgical conditions, postoperative recovery, and complications were collected and compared between the groups. Logistic multivariate analysis was performed to explore the risk factors for miscarriage in patients with HP within 2 weeks of surgical intervention. Among the 106 women with HP, 80 had tubal HP, 8 had cornual HP, and 18 had interstitial HP. Eighty-seven (82.1%) patients developed clinical symptoms that manifested primarily as abnormal vaginal bleeding and/or abdominal pain, whereas 19 (17.9%) patients had no clinical symptoms. The mean gestational age on the day of surgery was 7.2 weeks (inter-quartile range, 6.4-8.3). The miscarriage rate within 2 weeks of surgical intervention was 12.3% in patients with HP. Compared to the ongoing pregnancy group, the miscarriage group had a higher body mass index, earlier gestational age at treatment, and higher volume of hemoperitoneum (P < .05 for all). Logistic multivariate analysis indicated that the women with a hemoperitoneum volume > 200 mL had significantly higher risk of miscarriage after adjusting covariates [OR (odds ratio) = 5.285, 95% CI (confidence interval) (1.152-24.238), P < .05]. Hemoperitoneum volume was independently associated with miscarriage of viable intrauterine pregnancies in patients with HP within 2 weeks of surgical intervention.

Ultrafast Response in Nonenzymatic Electrochemical Glucose Sensing with Ni(II)-MOFs by Dimensional Manipulation.

Metal-organic frameworks (MOFs) are emerging as promising candidates for electrochemical glucose sensing owing to their ordered channels, tunable chemistry, and atom-precision metal sites. Herein, the efficient nonenzymatic electrochemical glucose sensing is achieved by taking advantage of Ni(II)-based metal-organic frameworks (Ni(II)-MOFs) and acquiring the ever-reported fastest response time. Three Ni(II)-MOFs ({[Ni6L2(H2O)26]4H2O}n (CTGU-33), {Ni(bib)1/2(H2L)1/2(H2O)3}n (CTGU-34), {Ni(phen)(H2L)1/2(H2O)2}n (CTGU-35)) have been synthesized for the first time, which use benzene-1,2,3,4,5,6-hexacarboxylic acid (H6L) as an organic ligand and introduce 1,4-bis(1-imidazoly)benzene (bib) or 1,10-phenanthroline (phen) as spatially auxiliary ligands. Bib and phen convert the coordination mode of CTGU-33, affording structural dimensions from 2D of CTGU-33 to 3D of CTGU-34 or 1D of CTGU-35. By tuning the dimension of the skeleton, CTGU-34 with 3D interconnected channels exhibits an ultrafast response of less than 0.4 s, which is superior to the existing nonenzymatic electrochemical sensors. Additionally, a low detection limit of 0.12 µM (S/N = 3) and a high sensitivity of 1705 µA mM-1 cm-2 are simultaneously achieved. CTGU-34 further showcases desirable anti-interference and cycling stability, which demonstrates a promising application prospect in the real-time detection of glucose.

An analysis of factors that influence patient preference of third-line therapy for overactive bladder.

OBJECTIVE: Patients with overactive bladder (OAB) refractory to first- and second-line therapy may pursue third-line therapies, including intradetrusor onabotulinum toxin-A (BTX), peripheral tibial nerve stimulation (PTNS), and sacral neuromodulation (SNM). The factors that influence patient preference for each treatment modality have not yet been explored. This study sought to investigate the specific parameters that patients consider in choosing a third-line therapy for OAB. METHODS: Patients refractory to first- and second-line therapies for OAB were identified in our outpatient clinic and asked to watch an educational video providing information on the risks and benefits of each third-line treatment option. They were then given a questionnaire to rank their preference of therapy and select reasons for why they found each therapy favorable and unfavorable. Patients under age 18 years, non-English speakers, those with a developmental disability, and those with a diagnosis of neurogenic bladder were excluded. RESULTS: Of the 98 patients included in the study, 40 participants (40.8%) chose intradetrusor BTX injections, 34 (34.7%) chose PTNS, and 16 (16.3%) chose SNM as their first choice. Seven patients (7.1%) chose none of the offered therapies, and one patient (1.0%) chose all three therapies with equal preference. BTX was found most attractive for its long efficacy (47%); its least attractive feature was the potential need for self-catheterization due to urinary retention (54%). PTNS was found most attractive for being a nonsurgical option (32%) and having no reported significant complications (39%); its least attractive feature was need for frequent office visits (61%). SNM was found most attractive for its potential for long-term relief without frequent office visits (53%); its least attractive feature was need for an implanted device (33%). Patients opting for SNM had higher scores on Urinary Distress Inventory-6 and Incontinence Impact Questionnaire-7 questionnaires when compared to patients opting for BTX injections or PTNS (p < 0.05). 47.4% of patients eventually pursued a third-line therapy. Of those, there was a 67.6% concordance rate between the therapy patients ranked first and the therapy they eventually underwent. CONCLUSIONS: Patients with more severe OAB symptoms opt for more invasive and less time-consuming therapy with the potential for long-term relief, namely SNM. Despite thorough counseling, many patients do not progress to advanced OAB therapies. Understanding factors that influence patients' affinity toward a specific type of treatment can aid with individualized counseling on third-line OAB therapies.

A Randomized Controlled Trial Comparing Telemedicine Versus In-Person Office Visits for the Follow-Up of Overactive Bladder.

IMPORTANCE: Overactive bladder is a condition that may be ideally suited for the use of telemedicine because initial treatment options are behavioral modification and pharmacotherapy. OBJECTIVE: We sought to evaluate if there was an overall difference in patient follow-up rates between telemedicine and in-person visits. STUDY DESIGN: New patients presenting with overactive bladder from July 2020 to March 2021 were randomized into telemedicine and in-person visits groups. A prospective database was maintained to compare follow-up rates, satisfaction rates, and time commitment. RESULTS: Forty-eight patients were randomized, 23 to the telemedicine group and 25 to the in-person visits group. There was no significant difference in follow-up rates between the telemedicine and in-person follow-up groups at 30 days (39% vs 28%, P = 0.41), 60-days (65% vs 56% P = 0.51) or 90 days (78% vs 60%, P = 0.17). There was no significant difference in satisfaction rates between the 2 groups. There was a significant difference between the average telemedicine visit time and in-person visit time (12.1 ± 6.9 minutes vs 22.8 ± 17.1 minutes; P = 0.02). For in-person visits, the average travel time was 49 minutes (interquartile range, 10-90 minutes) and average miles traveled was 22.1 miles (interquartile range, 10-70 miles). CONCLUSIONS: There was no significant difference in follow-up or satisfaction rates between telemedicine and in-person visits. Telemedicine visits took half the length of time compared with in-person visits. On average, patients in the telemedicine group saved approximately 1 hour per follow-up visit. Telemedicine visits save both the health care provider and patient significant amounts of time without sacrificing patient satisfaction and follow-up rates.

Comparisons of Stroke Knowledge and Health Behaviors in Patients With Hypertensive Stroke at Different Recurrence Risk Strata: The Comprehensive Reminder System Based on the Health Belief Model Study.

BACKGROUND: Risk factor management via behavioral change contributes substantially to secondary stroke prevention. The health belief model identified self-perceived risk as a significant factor in behavior change. In previous studies, people have tended to incorrectly estimate their risk of stroke. Little is known about the differences in stroke knowledge and health behaviors in patients who have had a stroke with different risks of stroke recurrence in China. OBJECTIVE: The aims of this study were to determine the accuracy of self-perceived risk of stroke recurrence and to compare stroke knowledge and health behaviors in patients with hypertensive stroke at different recurrence risk strata. METHODS: Baseline data from 174 patients in the Comprehensive Reminder System based on the Health Belief Model (CRS-HBM) study were used. Self-perceived risk was assessed via the susceptibility subcategory of the Short-Form Health Belief Model Scale, and actual risk was stratified using the Essen Stroke Risk Score. RESULTS: Only 27.0% of the patients estimated their risks of stroke recurrence accurately. Patients who perceived themselves to be at higher risk had better knowledge of warning signs. Compared with patients who underestimated their risk of stroke recurrence, those who accurately estimated or overestimated their risk less likely to smoke. CONCLUSIONS: Most patients incorrectly estimated their risk of stroke recurrence. Communicating with patients about their future risk of recurrent stroke may help improve their stroke knowledge and health behaviors. Implementation of the Comprehensive Reminder System based on the Health Belief Model focusing on risk education aimed at prevention of stroke recurrence is warranted in China.

Gender Difference in the Association Between Stroke Knowledge and Health Behavior Before the Onset of Stroke Among Chinese Hypertensive Patients.

ABSTRACT: BACKGROUND: Previous research has shown that men and women have different levels of stroke knowledge and differing health behaviors, which are important factors affecting blood pressure, as hypertension is a key risk factor for stroke occurrence. There has been little research on the effects of sex on the association between these 2 variables before the onset of stroke among Chinese hypertensive patients. METHODS: A cross-sectional study and a convenience sampling method were used. 272 male and 118 female hypertensive stroke patients were recruited. Each patient completed the Stroke Knowledge Questionnaire and the Health Behavior Scale for stroke patients. RESULTS: Compared with female patients, male patients had greater stroke knowledge and worse prestroke health behavior. The Pearson correlation coefficient between stroke knowledge and prestroke health behavior was 0.149 and 0.223 in male and female participants, respectively, P < .05. The results of a multiple regression analysis showed that Chinese hypertensive stroke patients' prestroke health behavior was significantly influenced by sex and stroke knowledge. CONCLUSION: Chinese male and female hypertensive stroke patients had disparities in stroke knowledge and prestroke health behavior; moreover, the correlation between these 2 variables before experiencing a hypertensive stroke was different between men and women. Men with hypertension should be considered at a higher risk for an initial or recurrent stroke. Developing sex-specific intervention for primary or secondary stroke prevention in China is essential.

Intelligent Electromagnetic Sensing with Learnable Data Acquisition and Processing.

Electromagnetic (EM) sensing is a widespread contactless examination technique with applications in areas such as health care and the internet of things. Most conventional sensing systems lack intelligence, which not only results in expensive hardware and complicated computational algorithms but also poses important challenges for real-time in situ sensing. To address this shortcoming, we propose the concept of intelligent sensing by designing a programmable metasurface for data-driven learnable data acquisition and integrating it into a data-driven learnable data-processing pipeline. Thereby, a measurement strategy can be learned jointly with a matching data post-processing scheme, optimally tailored to the specific sensing hardware, task, and scene, allowing us to perform high-quality imaging and high-accuracy recognition with a remarkably reduced number of measurements. We report the first experimental demonstration of "learned sensing" applied to microwave imaging and gesture recognition. Our results pave the way for learned EM sensing with low latency and computational burden.

Involvement of noradrenergic and serotonergic systems in risk-based decisions between options of equivalent expected value in rats.

Risk perception is an important factor that may mediate risk-based decision-making processes regulated by noradrenergic (NA) and serotonergic (5-HT) systems. Most risk-based decision-making models involve complex factors, such as risk perception or reward value, such that the final decision is the result of the interactions among these factors. However, the contribution of risk perception per se in risk decisions has remained unclear. Therefore, in the present study, we made some modifications to the classical probabilistic discounting task (PDT) to focus on the impact of risk perception and noradrenergic/serotonergic systems on decision-making behavior. Meanwhile, we conducted an elevated plus-maze (EPM) test to detect the correlation between anxiety and choice behavior. In the current study, rats had to choose between a "certain" lever that delivered a certain number of pellets and a "risky" lever that delivered eight pellets in a probabilistic manner (descending: 50%, 25%, 12.5% or ascending 12.5%, 25%, 50% of the time). The long-term rewarding values of the two levers were always identical in each block within each session. According to their baseline performances in choosing the risky lever, rats were divided into the risk-prefer group and risk-averse group. The results showed that there was a significant correlation between open arm time in EPM and risky choice for both descending order and ascending order, indicating that highly anxious rats more often preferred the safe option under risk. Pharmacological stimulation of α2-adrenergic receptors via dexmedetomidine (0.01 mg/kg) decreased the preference of probabilistic rewards in the risk-prefer group, while blocking α2 receptors by atipamezole (0.3 mg/kg) also reduced risky choices. The NA reuptake inhibitor, atomoxetine, increased the preference for risky choices in the risk-prefer group, the effect of which was attained via multiple superimposed doses. Administration of the 5-HT2A receptor agonist, DOI (0.1 mg/kg), increased risk-taking behavior in the risk-prefer group. Taken together, these results suggest that NA may be more inclined to process negative information such as loss or uncertainty in the regulation of risk-related decision making, whereas 5-HT may function primarily to increase risk-taking behavior. Our findings may help to further elucidate how noradrenergic and serotonergic systems differentially affect individuals with different risk preferences in terms of regulating risk perception in risk-related decision making.

Serum androgen profiles in women with premature ovarian insufficiency: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to investigate serum androgen profiles (testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin) in women with premature ovarian failure and to establish if there is evidence of diminished androgen levels in these women. METHODS: Various Internet sources of PubMed, Cochrane library, and Medline were searched systematically until February, 2018. Out of a pool of 2,461 studies, after applying the inclusion/exclusion criterion, 14, 8, 10, and 9 studies were chosen for testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin, respectively, for this meta-analysis. The effect measure was the standardized mean difference with 95% confidence interval (95% CI) in a random-effects model. RESULTS: The testosterone concentrations in premature ovarian insufficiency were compared with fertile controls: stamdard mean difference (IV, random, 95% CI) -0.73 [-0.99, -0.46], P value < 0.05. The dehydroepiandrosterone sulfate concentrations in premature ovarian insufficiency compared to fertile controls: standard mean difference (IV, random, 95% CI) -0.65 [-0.92, -0.37], P value < 0.05. Androstenedione in premature ovarian insufficiency were compared with fertile controls: standard mean difference (IV, random, 95% CI) -1.09 [-1.71, -0.48], P value < 0.05. Sex hormone-binding globulin levels did not show statistical significance. The dehydroepiandrosterone sulfate levels were reduced in premature ovarian insufficiency cases, but still showed a higher level than in postmenopausal women. CONCLUSIONS: Women with premature ovarian insufficiency are at risk for decreased concentrations of testosterone, dehydroepiandrosterone sulfate, and androstenedione. Dehydroepiandrosterone sulfate levels were more reduced in postmenopausal controls when compared with premature ovarian insufficiency cases.

Cholinergic M4 receptors are involved in morphine-induced expression of behavioral sensitization by regulating dopamine function in the nucleus accumbens of rats.

Repeated administration of morphine profoundly influences the dopaminergic and cholinergic systems in the nucleus accumbens [including the shell of the nucleus accumbens (NAcS)]. Further, dopamine release is regulated by the cholinergic system, especially the M4 receptor. Drug priming is one of the main factors that induces relapse in drug addiction. The present study first investigated how activation of the M4 receptor in the NAcS affects the expression of morphine-induced behavioral sensitization, through the administration of an M4 agonist (LY2033298) and antagonist (tropicamide), as well as a combination of an acetylcholinesterase inhibitor and M4 antagonist (huperzine-A + tropicamide). Additionally, the influence of a dopamine receptor agonist, in conjunction with an M4 agonist (i.e., SKF38393 + LY2033298), was also examined. Behavioral sensitization was established by exposure to 5 mg/kg morphine once every three days for a total of three exposures. The expression of behavioral sensitization was challenged by 5 mg/kg morphine. Results showed that (1) microinjection of the M4 receptor agonist LY2033298 (0.2 µg/side), but not the antagonist tropicamide (5, 10, or 20 µM/side) into the NAcS blocked the expression of behavioral sensitization; (2) tropicamide (20 µM/side) reversed the inhibition effect of huperzine-A on this behavior; and (3) SKF38393 (1 µg/side) reversed the inhibitory effect of LY2033298 on the expression of morphine-induced behavioral sensitization. These results suggest that the cholinergic M4 receptor in the NAcS plays an important role in the morphine-induced expression of behavioral sensitization through the regulation of dopamine function in rats.

Effects of noradrenergic and serotonergic systems on risk-based decision-making and center arena activity in open field in rats.

Center arena activity in open field (OF) test is associated with risk-taking behaviors. Noradrenaline and serotonin (5-HT) are neurotransmitters involved in both center arena activity and risk-based decision-making. However, the effects of noradrenergic/serotonergic systems on risk-based decision-making in rats with different center arena activity levels have not been clearly characterized. In this study, we explored the effects of the noradrenergic and serotonergic systems on risk-based decision-making in long center-time (LCT group) and short center-time (SCT group) rats. The two groups were formed based on performance in OF test. Then we tested their risk-based decision-making using probability discounting task (PDT); rats had to choose between "small/certain" lever that always delivered one pellet and "large/risky" lever that delivered four pellets in a probabilistic manner (100%, 50%, 25%, 12.5%). The results showed the SCT group chose the large/risky lever less often in 12.5% block and were more sensitive to loss than the SCT group. α2-adrenergic receptor agonist dexmedetomidine (0.01 mg/kg) decreased the frequency of risky choice, while the noradrenaline reuptake inhibitor (NRI) reboxetine (10 mg/kg) had the opposite effect only in the SCT group. Serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine (5 mg/kg) decreased preference for the large/risky option only in the SCT group. In contrast, pharmacological manipulations of the serotonin system did not affect the frequency of risky choices. These results suggest that noradrenergic system may be involved in weighing gains and losses for probabilistic discounting. Our findings also provide a better understanding of the involvement of center arena activity in risk-taking.

The Efficacy of a Comprehensive Reminder System to Improve Health Behaviors and Blood Pressure Control in Hypertensive Ischemic Stroke Patients: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: The health behaviors of hypertensive stroke patients in China are not satisfactory. In this study, we tested the effect of a Health Belief Model Comprehensive Reminder System on health behaviors and blood pressure control in hypertensive ischemic stroke patients after occurrence and hospital discharge. METHODS: A randomized, parallel-group, assessor-blinded experimental design yielded participation of 174 hospitalized hypertensive ischemic stroke patients. The intervention consisted of face-to-face and telephone health belief education, a patient calendar handbook, and weekly automated short-message services. Data were collected at baseline and 3 months after discharge. RESULTS: Three months after discharge, the intervention group showed statistically, significantly better health behaviors for physical activity, nutrition, low-salt diet, and medication adherence. The intervention group also had statistically, significantly decreased systolic blood pressure and increased blood pressure control rate. Smoking and alcohol use behaviors were not affected. CONCLUSION: At 3 months, use of the Comprehensive Reminder System based on the Health Belief Model, yielded improvement in most health behaviors and blood pressure control in hypertensive ischemic stroke patients. Continued implementation of this intervention protocol is warranted to determine the long-term effect. Smoking and alcohol use behaviors need to be targeted with a different intervention.

Muscarinic receptors in the nucleus accumbens shell play different roles in context-induced or morphine-challenged expression of behavioral sensitization in rats.

Both drug-related cues and drug priming are the main factors that induce relapse of drug addiction. Previous research has reported that blockade of the muscarinic receptors could significantly depress addictive behavior, suggesting that the muscarinic receptors might be involved in drug use and relapse behavior. The nucleus accumbens (NAc), especially the shell of the NAc, where the muscarinic receptors are expressed, is critical for craving and relapse. This study investigated the effects of microinfusion of the muscarinic receptor antagonist scopolamine into the NAc shell on context- and morphine-induced expression of behavioral sensitization. Behavioral sensitization was established by exposure to 5mg/kg morphine once daily for five consecutive days. Expression of behavioral sensitization was induced by saline challenge or 5mg/kg morphine challenge. The results showed that: (a) the muscarinic receptor antagonist scopolamine (10.8µg/rat) microinjected into the NAc shell blocked expression of conditional sensitization; (b) acetylcholinesterase inhibitor huperzine-A (0.5 and 0.1µg/rat), but not scopolamine (10.8µg/rat), microinjected into the NAc shell blocked morphine-induced expression of sensitization; and (c) pre-infusion of scopolamine (10.8µg/rat) reversed the inhibitory effect of huperzine-A (0.5µg/rat) on morphine-induced sensitization. Our findings suggest that muscarinic receptors in the NAc shell play different roles in context-induced and morphine-challenged expression of behavioral sensitization.

Muscarinic acetylcholine receptor but not nicotinic acetylcholine receptor plays a role in morphine-induced behavioral sensitization in rats.

Background and Aim The cholinergic system can affect drug reward. The present study aimed to examine the roles of muscarinic acetylcholine receptor (mAChR) and nicotinic acetylcholine receptor (nAChR) in morphine-induced behavioral sensitization. METHODS: To analyze the roles of mAChR and nAChR in behavioral sensitization induced by morphine (5mg/kg), seven experiments were designed. Experiments 1 and 2 examined the effects of 3, 1, and 0.3 mg/kg scopolamine and 0.2, 0.1, and 0.05mg/kg scopolamine, respectively, on the locomotor activity when administered alone. Experiments 3 and 4 explored the effect of scopolamine on morphine-induced behavioral sensitization. Experiment 5 studied the effect of mecamylamine on morphine-induced behavioral sensitization. Experiments 6 and 7 investigated the effects of scopolamine+huperzine A and mecamylamine+huperzine A, respectively, on morphine-induced behavioral sensitization. RESULTS: The results revealed that 3mg/kg scopolamine, which significantly enhanced locomotor activity when administered alone, inhibited the acquisition of morphine-induced sensitization. However, mecamylamine (0.5, 1, 2mg/kg) did not have these effects. The co-administration of scopolamine (0.05 mg/kg)+huperzine A (0.4mg/kg) or mecamylamine (1mg/kg)+huperzine A (0.4mg/kg) did not affect the acquisition of morphine-induced behavioral sensitization. Scopolamine (0.05mg/kg) which did not affect the locomotor activity when administered alone, but not mecamylamine (1mg/kg), reversed the acute attenuation effect of huperzine A (0.4mg/kg) on morphine-induced locomotor activity at the acquisition stage and reversed the inhibition of huperzine A on the expression of morphine-induced sensitization. CONCLUSION: The mAChR might play a more important role in morphine-induced locomotor activity and the expression of morphine-induced behavioral sensitization. The mechanisms of mAChR and nAChR were relatively separate in morphine-induced sensitization.

Stroke prevention knowledge and prestroke health behaviors among hypertensive stroke patients in mainland China.

BACKGROUND AND OBJECTIVES: Individuals with hypertension are at risk of stroke, and patients with stroke histories are at risk of experiencing another stroke. At this time, however, only a few studies have reported on stroke prevention knowledge and health behaviors among hypertensive patients who have had an initial stroke. The purpose of this study was to determine stroke prevention knowledge and health behaviors and to analyze the association between these 2 variables among hypertensive stroke patients who have had an initial stroke. SUBJECTS AND METHODS: With the use of a descriptive correlational design, a sample of 112 hypertensive stroke patients was recruited from the departments of neurology of 3 hospitals in Guangzhou, China. Each patient completed 2 reliable, validated questionnaires, the Stroke Prevention Knowledge Questionnaire and the Health Promoting Lifestyle Profile II. Data were collected during patients' hospital admission for stroke, within 2 days of stroke onset, and before they received stroke education. Pearson correlation coefficient was used to examine the correlations between the study variables. Multiple stepwise regression analysis was used to predict both the level of knowledge relating to stroke prevention and health behaviors. RESULTS AND CONCLUSIONS: The participants showed a relatively low level of stroke prevention knowledge and a moderate level of engagement in healthy behaviors. Pearson correlation coefficient between these 2 variables was 0.423 (P < .001). The results of multiple regression analysis showed that stroke prevention knowledge was positively influenced by education level; health behaviors were positively influenced by both gender and stroke prevention knowledge. Findings suggest that male hypertensive patients and those with a lower education level need targeted stroke education. Because knowledge was unrelated to behavior with respect to smoking, alcohol use, and low-salt diet, behavioral interventions should be explored to address these important risk factors among patients at risk for stroke.

Combined therapy with methylprednisolone and ulinastatin in experimental autoimmune encephalomyelitis.

BACKGROUND: Our previous study had demonstrated that ulinastatin (UTI) had a neuroprotective effect in experimental autoimmune encephalomyelitis (EAE). Methylprednisolone has been recommended to be a standard drug in multiple sclerosis (MS) therapies. The present study was to investigate the protective effects of UTI combined methylprednisolone in EAE. METHODS: Mice were divided into a UTI treatment group, a methylprednisolone treatment group, a combined treatment group with UTI and methylprednisolone, a normal saline treatment group, and a normal control group. EAE mice were induced in groups receiving different combined treatments, or respective monotherapies. Demyelination was evaluated by Solochrome cyanin staining. 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)/ myelin basic protein (MBP)/ the precursor form of nerve growth factor (proNGF)/p75/ inducible nitric oxide synthase (iNOS) proteins in cerebral cortex of EAE were detected by Western blotting. RESULTS: The combined treatment group had a lower clinical score (0.61 ± 0.06) and demyelinating score (1.33 ± 0.33) than the groups with normal saline (clinical score: 1.39 ± 0.08, P < 0.001; demyelinating score: 2.75 ± 0.49, P < 0.05) or monotheraphies. Compared with the saline treated EAE group, UTI combined methylprednisolone significantly increased expressions of CNP (1.14 ± 0.06 vs. 0.65 ± 0.04, P < 0.001), MBP (1.28 ± 0.14 vs. 0.44 ± 0.17, P < 0.001), and decreased expressions of proNGF (1.08 ± 0.10 vs. 2.32 ± 0.12, P < 0.001), p75 (1.13 ± 0.13 vs. 2.33 ± 0.17, P < 0.001), and iNOS (1.05 ± 0.31 vs. 2.17 ± 0.13, P < 0.001) proteins in EAE. Furthermore, UTI combined methylprednisolone could significantly upregulate MBP (1.28 ± 0.14 vs. 1.01 ± 0.15, P < 0.05) expression and downregulate iNOS (1.05 ± 0.31 vs. 1.35 ± 0.14, P < 0.05) expression compared to methylprednisolone treatment EAE group. And proNGF expression was significantly lower in combined treatment (1.08 ± 0.10) than that in UTI (1.51 ± 0.24, P < 0.05) or methylprednisolone (1.31 ± 0.04, P < 0.05) treatment group. CONCLUSION: Combination treatment of UTI with methylprednisolone was shown to protect EAE, suggesting that combination therapy is a potential novel treatment in MS.

Ovarian stimulation with GnRH agonist, but not GnRH antagonist, partially restores the expression of endometrial integrin beta3 and leukaemia-inhibitory factor and improves uterine receptivity in mice.

BACKGROUND: The impact of different ovarian stimulation (OS) protocols on endometrial receptivity remains controversial. In this study, the effects of different OS on the expression of endometrial integrin beta3 subunit and leukaemia-inhibitory factor (LIF) during the implantation window and the implantation rate in mice were investigated. METHODS: Three OS protocols were used, involving either pregnant mare's serum gonadotrophin (PMSG) alone, PMSG plus GnRH agonist or PMSG plus GnRH antagonist. Uterus samples were collected at 48 h after OS or ovulation and were detected with immunohistochemistry, Western blot and RT-PCR analyses. Normal embryos at gestation day 4 were transferred into the uteri of mice in the control and OS groups. RESULTS: All OS groups showed a significant decrease in the expression of both the endometrial integrin beta3 subunit and LIF during the implantation window and the implantation rate. Among the three OS groups, GnRH agonist-treated mice showed a higher endometrial integrin beta3 subunit and LIF expression and a higher implantation rate. No significant difference was found in the measured indices between the GnRH antagonist and PMSG groups. CONCLUSIONS: OS may inhibit the expression of endometrial integrin beta3 subunit and LIF and impair endometrial receptivity in mice. OS with GnRH agonist, but not GnRH antagonist, may partially restore the endometrial physiological secretion and improve uterine receptivity.

[The expression of integrin beta3 in mice's endometrium during the implantation window based on different ovarian stimulation protocols].

OBJECTIVE: To compare the uterine receptivity with different ovarian stimulation protocols, the endometrial expression of Integrin beta3 in mice's during the implantation window underwent different ovarian stimulation were studied. METHODS: Forty mice were randomly allocated into 4 groups of 10 mice. (1) GnRHant group, gonadotropin-releasing hormone antagonist (GnRHant) was given first for desensitizing the pituitary, then the pregnant mare's serum gonadotrophin (PMSG) was added for ovarian stimulation. (2) gonadotropin-releasing hormone agonist (GnRHa) group, GnRHa was given first for desensitizing the pituitary, then PMSG was added for ovarian stimulation. (3) PMSG group, injected with PMSG only; and (4) control group, given with saline of the same volume. Human chorionic gonadotropin (HCG) was injected to the mice of the GnRHant, GnRHa, and PMSG groups. Forty-eight hours after the mice of the control group the mice were killed. Their uteri were taken. RT-polymerase chain reaction (RT-PCR) was used to detect the expression of integrin beta3 mRNA. Immunohistochemistry (SP method) was used to locate and semiquantitatively measure the integrin beta3 in the endometrium during implantation window. RESULTS: (1) Immunohistochemistry: showed that the staining intensity of integrin beta3 was 3.74 +/- 0.15 in GnRHa group, 3.22 +/- 0.19 in the GnRHant group, and 3.24 +/- 0.18 in the PMSG group, all significantly lower than that in the control group (3.90 +/- 0.11, P = 0.023, 0.001, and 0.001). with a significant difference between the GnRHa group and the PMSG group (P = 0.001) and without a significant difference between the. GnRHant group and PMSG groups (P = 0.768). (2) RT-PCR showed that the relative quantity of integrin beta3 mRNA expression was 1.14 +/- 0.16 in the GnRHa group, 0.76 +/- 0.33 in the GnRHant group, and 0.73 +/- 0.26 in the PMSG group, all significantly lower than that in the control group (1.4 +/- 0.3, P = 0.045, 0.001, and 0.001). with a significant difference between the GnRHant and PMSG groups (P = 0.001) and without a significant difference between the GnRHant and PMSG groups (P = 0.857). CONCLUSION: All of the ovarian stimulation protocols do harm to the mice's uterine receptivity. Ovarian stimulation combining GnRHa protocol in mice is better than PMSG alone protocol, because it can improve the uterine receptivity. Ovarian stimulation combining GnRHant protocol in mice decrease the uterine receptivity as well as the PMSG alone protocol.