Association between endometriosis and metabolic syndrome: a cross-sectional study based on the National Health and Nutrition Examination Survey data.

BACKGROUND: Endometriosis has been reported to be associated with metabolism-related diseases, such as hypercholesterolemia and diabetes, while no studies have reported the association between endometriosis and metabolic syndrome. OBJECTIVE: This study aims to explore the association between endometriosis and metabolic syndrome. Also, the association between endometriosis and single metabolic syndrome indicator was explored. METHODS: This was a cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). A total of 2389 participants were finally included for analysis, with 2212 in the non-endometriosis group and 177 in the endometriosis group. Association between endometriosis and metabolic syndrome was explored using multivariate logistic regression analysis, with results shown as odds ratio (OR) with 95% confidence intervals (95%CI). Association between endometriosis and single metabolic syndrome indicator was explored using multivariate liner regression analysis. RESULTS: After adjusting age, race, education level, family poverty to income ratio (PIR), smoking, age at menarche, gravidity, menopause, female hormones use, and dyslipidemia drug use, endometriosis was associated with the higher odds of metabolic syndrome (OR = 1.55, 95%CI: 1.01-2.35). Further adjusting hysterectomy or oophorectomy, we found the similar association despite no statistical significance (OR = 1.47, 95%CI: 0.96-2.25). Moreover, we found endometriosis was associated with the high level of triglyceride (TG) (ß = 0.38, 95%CI: 0.06-0.70). CONCLUSIONS: Our study found the association between endometriosis and metabolic conditions, indicating that metabolic conditions of endometriosis women should be focused, and monitoring the blood lipid levels may be significant in decreasing the risk of metabolic syndrome.

Intrauterine administration of G-CSF for promoting endometrial growth after hysteroscopic adhesiolysis: a randomized controlled trial.

STUDY QUESTION: Does intrauterine infusion of granulocyte colony-stimulating factor (G-CSF) prevent adhesion reformation and promote endometrial growth after hysteroscopic adhesiolysis? SUMMARY ANSWER: Intrauterine perfusion of G-CSF can increase endometrial thickness but does not prevent the recurrence of intrauterine adhesions (IUAs) in patients with Asherman syndrome (AS) after surgery. WHAT IS KNOWN ALREADY: Intrauterine infusion of G-CSF has been used in attempts to treat patients with recurrent miscarriage and an idiopathic thin endometrium for either fresh or frozen-thawed embryo transfer cycles but without uniform efficacy. There have been no reports on the effect of G-CSF on the recurrence of IUAs, endometrial regrowth or pregnancy results in specific populations with AS. STUDY DESIGN, SIZE, DURATION: This two-center prospective double-blind randomized controlled trial ran between April 2016 and August 2021. In it, 245 patients with moderate to severe AS were randomized to G-CSF and control groups at a 1:1 ratio; 229 women were included in the adhesion recurrence analysis; and 164 patients were analyzed for pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: All eligible patients received the first hysteroscopic adhesion separation and balloon placement procedure. Patients who met our inclusion and exclusion criteria were randomized after surgery. These patients returned for balloon removal and underwent intrauterine perfusion with 300 µg (1.8 ml) G-CSF or 1.8 ml normal saline according to randomization at 7 days after surgery. A second-look hysteroscopy was carried out 1-2 months later. The primary outcome was the rate of formation of new adhesions at the second hysteroscopy. The secondary outcomes included endometrial thickness in the periovulatory period after surgery, as well as the clinical pregnancy and live birth rates. MAIN RESULTS AND THE ROLE OF CHANCE: Age, menstrual cycle characteristics, pregnancy history and IUA score before surgery were similar between groups. There were no statistically significant differences in the adhesion reformation rate or median adhesion score reduction. However, G-CSF perfusion significantly improved endometrial thickness (7.91 ± 2.12 mm vs 7.22 ± 2.04 mm; P = 0.019, 95% CI for difference: -1.26 to -0.12), as well as cumulative pregnancy and live birth rate over time (P = 0.017 and P = 0.042). Furthermore, multivariate logistic regression analysis showed that postoperative endometrial thickness was an independent prognostic factor for pregnancy and live birth rates. LIMITATIONS, REASONS FOR CAUTION: These results cannot be extended to older patients or those without AS, as our subjects had moderate or severe AS and were aged <40 years. The low number of patients included in the fertility analysis could lead to biased results. WIDER IMPLICATIONS OF THE FINDINGS: Intrauterine perfusion of G-CSF could be an effective adjuvant therapy for patients with AS to increase endometrial thickness. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Key Research and Development Program of China (2018YFC1004800), the National Natural Science Foundation of China (82001624 and 81871209), the Natural Science Foundation of Zhejiang Province (LQ20H040004) and the provincial and ministerial construction project of Zhejiang Province (2017 WKJ-ZJ-1721). The authors declare that they have no conflicts of interest regarding this work. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT02855632). TRIAL REGISTRATION DATE: 4 March 2016. DATE OF FIRST PATIENT'S ENROLMENT: 13 April 2016.

Softening and Shape Morphing of Stiff Tough Hydrogels by Localized Unlocking of the Trivalent Ionically Cross-Linked Centers.

The mechanical properties (e.g., stiffness, stretchability) of prefabricated hydrogels are of pivotal importance for diverse applications in tissue engineering, soft robotics, and medicine. This study reports a feasible method to fabricate ultrasoft and highly stretchable structures from stiff and tough hydrogels of low stretchability and the application of these switchable hydrogels in programmable shape-morphing systems. Stiff and tough hydrogel structures are first fabricated by the mechanical strengthening of Ca2+ -alginate/polyacrylamide tough hydrogels by addition of Fe3+ ions, which introduces Fe3+ ionically cross-linked centers into the Ca2+ divalent cross-linked hydrogel, forming an additional and much less flexible trivalent ionically cross-linked network. The resulting stiff and tough hydrogels are exposed to an L-ascorbic acid (vitamin C, VC) solution to rapidly reduce Fe3+ to Fe2+ . As a result, flexible divalent ionically cross-linked networks are formed, leading to swift softening of the stiff and tough hydrogels. Moreover, localized stiffness variation of the tough hydrogels can be realized by precise patterning of the VC solution. To validate this concept, sequential steps of VC patterning are carried out for local tuning of the stiffness of the hydrogels. With this strategy, localized softening, unfolding, and sequential folding of the tough hydrogels into complex 3D structures is demonstrated.

[Effect of different laparoscopic procedures for hydrosalpinx on pregnancy outcome of embryo transfer].

OBJECTIVE: To explore the effects of different laparoscopic procedures before embryo transfer (ET) for hydrosalpinx on pregnancy outcomes. METHODS: Group A (n = 269) underwent laparoscopic bilateral salpingectomy before ET while group B (n = 178) had laparoscopic bilateral tubal salpingostomy for hydrosalpinx. And the pregnancy outcomes of ET were evaluated. RESULTS: The implantation, pregnancy, abortion, ectopic pregnancy and live birth rates were similar in 2 groups (P > 0.05). The interstitial pregnancy rate was 10.27% after bilateral salpingectomy. The clinical pregnancy rate increased while the interstitial pregnancy rate decreased when the intervals between salpingectomy and ET were prolonged. But there was no statistical significance (P > 0.05). CONCLUSION: Laparoscopic tubal salpingostomy is as effective as salpingectomy for hydrosalpinx before ET. The interstitial pregnancy rate increases after laparoscopic salpingectomy. The interval between salpingectomy and ET should be appropriately scheduled.

[Influencing factors of reproduction status of patients undergoing laparoscopic myomectomy].

OBJECTIVE: To explore the influencing factors of reproduction status in women undergoing laparoscopic myomectomy (LM). METHODS: A total of 278 LM patients were recruited.We retrospectively reviewed the reproduction status of 87 pregnant cases after LM. The correlations of their pregnancy outcomes and such clinical profiles as age, operative techniques, biological characteristics of fibroids (number, type, size and location) were analyzed.No uterine rupture occurred during the gestation period. RESULTS: None of them switched to open surgery due to laparoscopic difficulties. However, one patient had a laparoscopic suture for secondary bleeding of uterine incision. At 3 months post-operation, sonography showed no heterogeneous echo, effusion and hematoma in uterine incision.Incision through uterine cavity occurred intraoperatively in 8 cases, but no intrauterine adhesion was found on hysteroscopy 3 months later. And 87 women became pregnant and the postoperative fertilization time was from 2 months to 5 years. Age influenced the postoperative pregnancy rate.Other factors such as location, number and size of fibroid had no impact on fertility. CONCLUSION: For achieving a high conception rate and guaranteeing the safety of pregnant women, a clinician should select reasonable surgical approaches, perform accurate anatomical restoration, apply strict hemostasis and choose a right time of conception.

Uric acid as a mediator in the correlation between white blood cells and preeclampsia severity: a retrospective cohort study.

This study aimed to analyze the independent risk factors for predicting preeclampsia severity and explore its underlying mechanism. Clinical data of patients with preeclampsia were collected from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Univariate and multivariate analyses were employed to assess the significant factors associated with preeclampsia severity. Additionally, we performed multivariate logistic regression analysis and mediation analysis to investigate the potential regulatory path. Based on inclusion and exclusion criteria, 731 participants were enrolled: severe preeclampsia (n = 381) and mild to moderate preeclampsia (n = 350). Age, white blood cells (WBC), platelet, creatinine, albumin, uric acid, aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and prothrombin time were significantly related to preeclampsia severity. Besides, hospital length of stay was significantly higher in the severe group. Notably, age and uric acid were independent predictors for preeclampsia severity. Further, WBC and creatinine were significantly associated with uric acid. Finally, the mediation analysis showed that uric acid was a mediator of the relationship between WBC and preeclampsia severity. In conclusion, WBC might affect preeclampsia severity and progression via the mediation of uric acid. This study might provide novel insight into preventing preeclampsia development.

Effects of brain-derived neurotrophic factor and adeno-associated viral vector on morphine-induced condition through target concentration changes in the ventral tegmental area and nucleus accumbens.

Morphine remains the standard analgesic for severe pain. However, the clinical use of morphine is limited by the innate tendency of opiates to become addictive. Brain-derived neurotrophic factor (BDNF) is a growth factor that is protective against many mental disorders. This study aimed to evaluate the protective function of BDNF on morphine addiction based on the behavioural sensitisation (BS) model and assess potential changes in downstream molecular tropomyosin-related kinase receptor B (TrkB) and cyclic adenosine monophosphate response element binding protein (CREB) expression caused by overexpression of BDNF. We divided 64 male C57BL/6 J mice into saline, morphine, morphine plus adeno-associated viral vector (AAV), and morphine plus BDNF groups. After administering the treatments, behavioural tests were conducted during the development and expression phases of BS, followed by a western blot analysis. All data were analysed by one- or two-way analysis of variance. The overexpression of BDNF in the ventral tegmental area (VTA) caused by BDNF-AAV injection decreased the total distance of locomotion in mice who underwent morphine-induced BS and increased the concentrations of BDNF, TrkB, and CREB in the VTA and nucleus accumbens (NAc). BDNF exerts protective effects against morphine-induced BS by altering target gene expression in the VTA and NAc.

Paternal early life stress exerts intergenerational effects on male C57Bl/6J offspring risk-taking behaviors and predator scent-induced c-Fos expression.

Paternal preconceptional health factors, such as exposures to stress, diet and exercise, have been found to significantly influence offspring phenotypes in a range of animal models. Preclinical studies have provided evidence that paternal stress is associated with increased stress responsivity and anxiety-related traits, particularly in male offspring. It was previously reported that a paternal history of maternal separation (MS) led to male offspring (PatMS) displaying reduced cautious behavior during exploration of a novel environment. The neural basis for that absence of behavioral moderation is unclear. Here, we investigated the adaptive behavioral responses of control and PatMS male offspring in the predator odor risk-assessment task (PORT). PatMS mice failed to moderate their behaviors in the presence of a predator odor 2,4,5-trimethylthiazoline (TMT). c-Fos mapping revealed reduced cellular activation in fear-regulating brain regions of PatMS mice, such as in the cingulate cortex, dentate gyrus of the hippocampus and the basolateral amygdala. Expression of the paternally imprinted gene Grb10 (previously identified as a key molecular regulator of risk-taking behavior) was unaltered in PatMS mice. However, other paternal imprinted genes such as Igf2 and PEG3 were differentially expressed in PatMS mice. Overall, our study provides the first evidence of an intergenerational influence of preconceptional paternal stress exposure on offspring brain zunction relevant to risk-taking behavior, which is also independent of Grb10 gene expression.

BDNF-AAV has protective effects on morphine-induced conditioned place preference through BDNF, TrkB, and CREB concentration changes in the VTA and NAc.

Brain-derived neurotrophic factor (BDNF) is one of the neurotrophic factors that promotes the survival and protection of neurons in many disorders. The potential protective effect of BDNF and its mechanisms on morphine addiction are unclear. In this study, morphine-induced conditioned place preference (CPP) in mice was used to show the effect of BDNF on rewarding behavior. Western blot assays were used to determine the changes caused by BDNF, for example, changes in total BDNF, tropomyosin-related kinase receptor B (TrkB), and cAMP response element binding protein (CREB) in the ventral tegmental area (VTA) and nucleus accumbens (NAc). The results showed that the BDNF-adeno-associated viral vector (BDNF-AAV) injected in the VTA, attenuated morphine-induced CPP with synergistic changes in BDNF/TrkB/CREB concentrations in the VTA and NAc in the CPP acquisition and recurrence phases; however, the attenuation was lower in the extinction phase, with different changes in molecules downstream of the BDNF.

Later bedtime is associated with angina pectoris in middle-aged and older adults: results from the Sleep Heart Health Study.

OBJECTIVES: Sleep timing is related to several risk factors for angina pectoris (AP), such as obesity and diabetes. This study was designed to evaluate the relationship between sleep timing and AP, specifically whether later bedtime was associated with AP in middle-aged and older adults. METHODS: This community-based study was based on the Sleep Heart Health Study cohort and included 4710 participants (45.9% men, aged 63.3 ± 11.0 years). Lifestyle and epidemiological information were obtained from baseline records. Self-reported sleep measures provided information on bedtime and wake-up time of weekdays and weekends. Individuals were divided into three categories according to bedtime (≤22:00, 22:01-23:00, and >23:00). Odds ratios (OR) and 95% confidence intervals (CIs) of AP for bedtimes were estimated with multivariate logistic regression analysis. RESULTS: The prevalence of AP was 44.2% and the distribution of weekday bedtimes ≤22:00, 22:01-23:00, and >23:00 were 36.6%, 47.5% and 46.0%, respectively. After adjusting for potential confounders, weekday bedtimes >23:00 (OR 1.34; 95% CI 1.13-1.60; P = 0.001) and 22:01-23:00 (OR 1.54; 95% CI 1.29-1.82; P < 0.001) were significantly associated with an increased risk of AP compared with the reference group (≤22:00). In addition, weekend bedtimes >23:00 (OR 1.44; 95% CI 1.20-1.73; P < 0.001) and 22:01-23:00 (OR 1.70; 95% CI 1.40-2.05; P < 0.001) increased the risk of AP. CONCLUSIONS: Later bedtimes on both weekdays and weekends were significantly associated with an increased prevalence of AP. Early bedtimes may help people decrease the risk of AP.

Combination of noninvasive methods in diagnosis of infertile women with minimal or mild endometriosis, a retrospective study in China.

This study means to investigate a combination of noninvasive methods in diagnosis of minimal or mild endometriosis expecting to narrow down the range of laparoscopic exploration for female infertility.It is a retrospective case control study of totally 447 patients suspected unexplained infertility before surgery were eligible from May 2012 to February 2017. Of these, 299 patients were laparoscopy-proved minimal or mild endometriosis group, the remaining 148 patients served as control group (normal pelvis). Preoperative age, duration of infertility, type of infertility, body mass index, baseline follicle-stimulating hormone, anti-Müllerian hormone, serum CA125, clinical symptoms, findings on vagino-recto-abdominal examinations and pregnancy prognosis had been recorded. Every variable and their combinations were evaluated.Any single factor had limited diagnostic value. The cut-off value for CA125 was 19.25 IU/L. Parallel testing had a higher sensitivity at 81.3%. Serial tests of vagino-recto-abdominal examination combined with dysmenorrhea or positive CA125 got reasonable sensitivity (51.4% and 49%), remarkable high specificities (95.7% and100%) and Positive Predictive Value (96.4% and 100%). Multivariate logistic regression identified the following factors in decreasing order of importance: (1) vagino-recto-abdominal examinations, (2) CA125, (3) dysmenorrhea, their ORs being 16.148, 3.796, and 2.809, respectively. The spontaneous pregnancy rate (50.8%) in minimal or mild endometriosis was higher than control (35.6%, P = .043).A combination of noninvasive diagnostic methods had certain preoperative diagnostic value of minimal or mild endometriosis, which might benefit some patients from avoiding laparoscopic surgery.

Tough protein organohydrogels.

Tough protein organohydrogels were fabricated by applying a solvent displacement-induced toughening (SDIT) strategy. With SDIT, traditionally weak and brittle protein hydrogels were altered to protein organohydrogels with remarkably high performance in anti-freezing, non-drying, topological healing, thermal plasticizing, mechanical toughness and stretchability. The SDIT opens a reliable and straightforward path to develop novel biomimetic materials and artificial devices from abandunt protein-based sources.

Mechanochemical Regulated Origami with Tough Hydrogels by Ion Transfer Printing.

Stimuli-responsive hydrogels that undergo programmable shape deformation are of great importance for a wide variety of applications spanning from soft robotics and biomedical devices to tissue engineering and drug delivery. To guide shape morphing, anisotropic elements need to be encoded into the hydrogels during fabrication, which are extremely difficult to alter afterward. This study reports a simple and reliable mechanochemical regulation strategy to postengineer the hydrogels by encoding structures of high stiffness locally into prestretched tough hydrogels through ion transfer printing with a paper-cut. During printing, trivalent ions (Fe3+) were patterned and diffused into the prestretched tough gels, which dramatically increased the local stiffness by forming the second trivalent ionically cross-linked network. By removing the applied stretching force, the stiff anisotropy-encoded prestretched tough hydrogels underwent programmable shape morphing into complex three-dimensional origami structures due to the stiffness mismatch.

Social isolation induces schizophrenia-like behavior potentially associated with HINT1, NMDA receptor 1, and dopamine receptor 2.

Both genetic factors and early life adversity play major roles in the etiology of schizophrenia. Our previous studies indicated that social isolation (SI) during early postnatal development leads to several lasting abnormal behavioral and pathophysiological features resembling the core symptoms of some human neuropsychiatric disorders in mice. The glutamate and dopamine hypotheses are tightly linked to the development of schizophrenia. The cross-talk between glutamate N-methyl-D-aspartate acid receptors and dopamine receptors is associated with histidine triad nucleotide binding protein 1 (HINT1), which is correlated with diverse psychiatric disorders. We examined the effects of SI on schizophrenia-like behavior and used enzyme-linked immunosorbent assays to investigate the expression levels of HINT1, the NR1 subunit of N-methyl-D-aspartate acid receptor, and dopamine type 2 receptor (D2R) in C57 mice. We found that SI leads to a series of schizophrenia-related deficits, such as social withdrawal, anxiety disorder, cognitive impairments, and sensorimotor gating disturbances. These abnormal phenotypes paralleled changes of HINT1, NR1, and D2R. SI may be considered a robust model of the effects of early life stress on the schizophrenia-related behaviors in mice. Potential interactions among HINT1, NR1, and D2R may underlie the behavioral deficits induced by SI.

Different sperm sources and parameters can influence intracytoplasmic sperm injection outcomes before embryo implantation.

To evaluate the effects of sperm with different parameters and sources on the outcomes of intracytoplasmic sperm injection (ICSI), 1972 ICSI cycles were analyzed retrospectively. Groups 1 to 5 were composed of cycles using ejaculated sperm and were grouped according to sperm quantity, quality, and morphology into normal (288 cycles), or mild (329 cycles), moderate (522 cycles), severe (332 cycles), and extremely severe (171 cycles) oligozoospermia and/or asthenozoospermia and/or teratozoospermia (OAT) groups. Group 6 was composed of 250 cycles using testicular or epididymal sperm, and Group 7 consisted of 80 cycles using frozen-thawed sperm. We found that fertilization rates were gradually reduced from Groups 1 to 6, and reached statistical difference in Groups 5 and 6 (P<0.05). The high-quality embryo rate was higher in Group 1 than in Groups 2, 3, 5, 6, and 7 (P<0.05). No statistical differences were observed in the rates of embryo cleavage, clinical pregnancy, miscarriage, live-birth, premature birth, low birth weight, weeks of premature birth, average birth weight, or sex ratio for all seven groups (P>0.05). A total of nine cases of malformation were observed, with a malformation rate of 1.25% (9/719). In conclusion, different sperm sources and parameters can affect ICSI outcomes before embryo implantation. A full assessment of offspring malformation will require further study using a larger sample size.