Photobiomodulation therapy at 632 nm wavelength ameliorates intrauterine adhesion via activation of cAMP/PKA/CREB pathway.

Intrauterine adhesion (IUA), a major cause of uterine infertility, is pathologically characterized by endometrial fibrosis. Current treatments for IUA have poor efficacy with high recurrence rate, and restoring uterine functions is difficult. We aimed to determine the therapeutic efficacy of photobiomodulation (PBM) therapy on IUA and elucidate its underlying mechanisms. A rat IUA model was established via mechanical injury, and PBM was applied intrauterinely. The uterine structure and function were evaluated using ultrasonography, histology, and fertility tests. PBM therapy induced a thicker, more intact, and less fibrotic endometrium. PBM also partly recovered endometrial receptivity and fertility in IUA rats. A cellular fibrosis model was then established with human endometrial stromal cells (ESCs) cultured in the presence of TGF-ß1. PBM alleviated TGF-ß1-induced fibrosis and triggered cAMP/PKA/CREB signaling in ESCs. Pretreatment with the inhibitors targeting this pathway weakened PBM's protective efficacy in the IUA rats and ESCs. Therefore, we conclude that PBM improved endometrial fibrosis and fertility via activating cAMP/PKA/CREB signaling in IUA uterus. This study sheds more lights on the efficacy of PBM as a potential treatment for IUA.

Synergistic effects of electroacupuncture and bone marrow mesenchymal stem cell transplantation on rat intrauterine adhesion： an observation. / 电针联合骨髓间å è´¨å¹²ç»†èƒžç§»æ¤æ²»ç–—å¤§é¼ å®«è ”ç²˜è¿žçš„ååŒæ•ˆåº”è§‚å¯Ÿ.

OBJECTIVES: To investigate the effects of electroacupuncture(EA) combined with bone marrow mesen-chymal stem cells(BMSCs) transplantation on the endometrium of rats with intrauterine adhesions(IUA), so as to explore the possible mechanisms underlying their combined therapeutic effects. METHODS: Forty adult female SD rats were randomly divided into control, model, cell, and combined groups. The IUA rat model was established using a dual injury method of mechanical scratching and lipopolysaccharide infection. After successful modeling, on days 1, 3, and 7, rats in the model group received tail vein injection of phosphate buffered solution, while rats in the cell group received tail vein injection of BMSCs suspension for BMSCs transplantation；and rats in the combined group received BMSCs transplantation combined with EA treatment (2 Hz/15 Hz, 1-2 mA), targeting the "Guanyuan"(CV4), bilateral "Zusanli"(ST36) and "Sanyinjiao"(SP6) for 20 min daily for 3 consecutive estrous cycles. After intervention, uterine tissue was collected from 5 rats in each group. Histological analysis was performed using hematoxylin and eosin staining to evaluate endometrial thickness and glandular number. Masson staining was used to assess endometrial fibrosis area. Immunohistochemistry was performed to detect the positive expressions of vascular endothelial growth factor(VEGF), proliferating cell nuclear antigen(PCNA), and estrogen receptor(ER). Western blot analysis was conducted to determine the protein expressions of homeobox A10(HoxA10) and leukemia inhibitory factor(LIF), both key regulators of endometrial receptivity. The remaining 5 rats in each group were co-housed with male rats, and the uterine function recovery was evaluated by assessing the number of embryo implantations. RESULTS: Compared with the control group, the model group showed thinning endometrium(P<0.001), decreased glandular number(P<0.001), increased endometrial fibrosis area(P<0.001), reduced positive expressions of VEGF, PCNA, ER, expressions of HoxA10 and LIF, and decreased embryo implantation number (P<0.001) on the injured side of the uterus. Compared with the model group, the combined group showed a reversal of the aforementioned indicators(P<0.001, P<0.01)；the cell group exhibited thicker endometrium(P<0.001) and reduced endometrial fibrosis area(P<0.001). Compared with the cell group, the combined group showed increased endometrial thickness(P<0.01), elevated glandular number(P<0.05), significantly decreased endometrial fibrosis area(P<0.05), enhanced positive expressions of VEGF, PCNA and ER, expressions of HoxA10 and LIF in the endometrium, and a significant increase in embryo implantation number (P<0.001, P<0.05, P<0.01) on the injured side of the uterus, indicating better results than the cell group. CONCLUSIONS: The combination of EA and BMSCs synergistically promotes the repair of damaged endometrium, improves endometrial morphology, reduces fibrosis levels, enhances vascular regeneration and matrix cell proliferation, improves endometrial receptivity, which ultimately facilitates embryo implantation.

Electroacupuncture alleviates intrauterine adhesion through regulating autophagy in rats.

Autophagy is a well-conserved metabolic system that maintains homeostasis by relying on lysosomal breakdown. The endometrium of patients with intrauterine adhesion (IUA) and an animal model exhibits impaired autophagy. Autophagy is negatively correlated with inflammation. Activation of autophagy can inhibit the inflammatory response, while defects in autophagy will activate the inflammatory response. Here, we studied whether electroacupuncture (EA) inhibits inflammation and promotes endometrial injury repair by activating endometrial autophagy. The IUA animal model was established by mechanical injury plus lipopolysaccharide infection. EA stimulation was applied to the acupoints Guanyuan (CV4), bilateral Sanyinjiao (SP6), and Zusanli (ST36). The results indicated that EA could improve endometrial morphology, attenuate endometrial fibers, and enhance endometrial receptivity in the rat. EA could increase the autophagosomes of endometrial epithelial cells, increase the levels of LC3 and Beclin1, and decrease the level of p62. Additionally, EA may also suppress the nuclear factor kappa-B (NF-κB) signaling pathway and reduce the release of inflammatory factors. Additionally, the effect of EA was comparable to that of the autophagy agonist rapamycin, and the autophagy inhibitor 3-methyladenine reversed the therapeutic effect of EA. Therefore, we assume that EA may facilitate endometrial healing by activating autophagy and reducing NF-κB signal pathway-mediated inflammation.

Phyto-progestins for the treatment of abnormal uterine bleeding without organic cause in women at high risk for breast cancer and breast cancer survivors: a prospective, pilot study.

OBJECTIVES: Some plants, such as Dioscorea Villosa (DV), Vitex Agnus Castus (VAC) and Turnera diffusa (D) have some 'progesterone-like' properties. We have investigated their simultaneous administration in breast cancer (BC) survivors or carriers of specific genetic mutations that can increase the risk of developing BC suffering from abnormal uterine bleeding without organic cause. METHODS: Women with irregular cycles in terms of length (interval between ≤ 24 or ≥ 38 days) without a uterine organic disease (polyps, adenomyosis, fibroids, hyperplasia/malignancy) were included. A daily diary of bleeding, questionnaires about health-related quality of life (Short Form 36) and menstrual psychophysical well-being (PGWB-1) and the Greene Climacteric Scale (GCS) (in women older than 40 years old) questionnaire were used. The presence of some premenstrual syndrome (PMS) symptoms was also evaluated. RESULTS: In the analyzed group of women (n = 15), all experienced a regularization of the menstrual cycles, with a mean duration in the three months of use of 27.1 ± 3.2 days, with a significant reduction of menstrual pain (p = 0.02) and flow (p = 0.02) intensity. Women with PMS (7/15) reported an impovement in depression, headache and abdominal pain scores (p < 0.05). No specific deterioration of different questionnaires evaluated during treatment were observed. General satisfaction with the treatment was 6.8 ± 0.3/10 on a 10 point. CONCLUSIONS: A combination of DV, VAC and D could be a promising candidate to treat menstrual irregularities without an organic cause, with a significant reduction of menstrual pain and flow intensity and possible additional benefits in PMS symptoms treatment in women at genetic risk for BC and BC survivors.

Repairing and Regenerating Injured Endometrium Methods.

Good endometrium is the prerequisite and guarantee for reproduction and maternal and child health. Endometrial injury caused by operation or non-operation can lead to menstrual irregularities, amenorrhea, abortion, infertility, and other gynecological diseases to bother women. Intrauterine adhesions (IUA) and thin endometrium are common diseases caused by abnormal repair after endometrium damage. The incidence of IUA is not low after uterine operative surgery, and the recurrence is pretty high after uterine adhesiolysis. At present, there were many methods for endometrial repair in clinic or in the laboratory, but the efficacy was different from methods to methods. They are mainly including estrogen therapy, stem cell therapy, complementary medicine therapy, and some physical barrier therapy. In order to guide the effective repair and regeneration of endometrium in clinic, this paper reviews the merit and demerit of these methods for endometrium regeneration and repair that have been proved to be effective in experiments and clinical in recent years.

Serum Essential Trace Element Status in Women and the Risk of Endometrial Diseases: a Case-Control Study : Serum Essential Trace Element Status in Women and the Risk of Endometrial Diseases: a Case-Control Study.

Endometrial diseases, including uterine fibroids, polyps, intrauterine adhesion, endometritis, etc., are the major causes of infertility among women. However, the association between essential trace element status in women and the risk of endometrial disease is limited and unclear. This study aimed to investigate this association using a case-control study design; a total of 302 women patients with endometrial diseases and 302 healthy women were included. Compared to women in the control group, serum selenium (Se) (p = 0.024) and zinc (Zn) (p = 0.017) levels were significantly lower, while copper (Cu) (p = 0.004) and molybdenum (Mo) (p = 0.005) levels were significantly higher among women with endometrial diseases. In addition, compared to women in the first quartile of the copper/zinc (Cu/Zn) ratio value group, the adjusted ORs (95% CIs) of endometrial diseases were 1.50 (1.05, 2.14), 1.68 (1.18, 2.39), and 1.47 (1.02, 2.10), respectively, in the second, third, and fourth quartile of the Cu/Zn ratio value group (p trend = 0.047). In addition, the results from restricted cubic splines showed that the dose-response relationships of serum levels of these essential elements with the risk of endometrial diseases were nonlinear for Se, Cu, and Zn and relatively linear for Mo and Cu/Zn ratio. The present study showed serum levels of Zn and Se among women with endometrial diseases were significantly lower compared to that among healthy women, while serum levels of Cu and Mo were significantly higher, in addition, the serum Cu/Zn ratio value was also significantly and positively associated with the risk of endometrial diseases.

Efficacy of electrical stimulation combined with ultrasound acupuncture therapy on treatment in patients with intrauterine adhesions: Study protocol for a placebo-controlled, single-blind, single-center, randomized trial.

BACKGROUND: Recurrence of postoperative adhesions is one of the most important factors for poor reproductive outcomes after hysteroscopic surgery, particularly in cases diagnosed with severe intrauterine adhesions (IUAs), where the recurrence rate is significantly higher. This study aims to explore the effectiveness of the electrical muscle stimulation combined with ultrasound acupuncture therapy in preventing the recurrence of IUAs and improving reproductive outcomes after operative hysteroscopy. METHODS: This study is a single-center, randomized controlled trial. A total of 210 patients with IUAs will be randomly assigned into 2 groups according to the ratio of 1:1, as the treatment group and the control group. Participants will receive the electrical muscle stimulation combined with ultrasound acupuncture therapy and oral hormone supplementation or receive oral hormone supplementation only. The primary outcome was the clinical response rate. There were 3 menstrual cycles of treatment and 3 menstrual cycles of follow-up in this study. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the Reproductive Hospital of Guangxi Zhuang Autonomous Region (approval number: KY-LL-2022-06). This trial will be conducted in accordance with the principles of the Declaration of Helsinki as well as Good Clinical Practice. Study results will be disseminated at academic presentations and publications in peer-reviewed journals. TRIAL REGISTRATION: Registry name: Clinical value of electroultrasonic instrument in the treatment of IUAs and changes of related protein expression; Registry number: ChiCTR2200058901; registration date: April 19th, 2022; http://www.chictr.org.cn/showproj.aspx?proj=166155.

Efficacy of hyaluronic acid on the prevention of intrauterine adhesion and the improvement of fertility: A meta-analysis of randomized trials.

BACKGROUND: and purpose:Intrauterine adhesion (IUA) and re-adhesion were common problems in women of childbearing age. The aim of our research was to evaluate the efficacy of hyaluronic acid gel on preventing IUA and improving the fertility. METHODS: A systematic search for randomized controlled trial (RCT) articles that tested the effectiveness of using hyaluronic acid gel during intrauterine surgery in prevention of IUA and improvement of fertility was performed in PubMed, Medline, Embase, the Cochrane Library and clinicaltrials.gov until December 2020. Data were extracted independently and analyzed using RevMan statistical software version 5.3. RESULTS: Twelve articles (11 studies) were deemed eligible for inclusion. There was a significantly reduced proportion of IUA after using hyaluronic acid gel during intrauterine operation (OR 0.39, 95% CI 0.29 to 0.52). It has significantly reduced the incidence of moderate-to-severe IUA after using hyaluronic acid gel, but no effect on the mild IUA. In addition, our analysis showed that the hyaluronic acid gel group was associated with a significant increased incidence of pregnancy (OR 1.64, 95% CI 1.08 to 2.50). CONCLUSION: Our analysis confirmed that using hyaluronic acid gel during intrauterine operation seemed to be more helpful for patients with high risk of IUA. However, larger and well-designed studies would be desired in the future to confirm its efficacy and safety in protecting fertility.

The use of herbal treatments as alternatives to control uterine diseases in dairy cows.

Uterine diseases are a common gynecological issue that affects dairy cows during the postpartum period. The treatment of uterine diseases is mainly managed through antimicrobials; however, the problem of antibiotic residues, increased antimicrobial resistance of pathogens, and the abuse of antibiotics causes serious problems in the dairy chain around the world, which can affect the efficiency of conventional medicines. In these regards, alternative treatment strategies are needed to reduce the use of antibiotics in dairy production. This review primarily provides an overview that focuses on various alternative sources and methodologies, including plants extracts and essential oils, for the control of bovine uterine diseases, and it presents the advantages and limitations related to the use of these herbal therapies.

Supplementation with Spirulina platensis Prevents Uterine Diseases Related to Muscle Reactivity and Oxidative Stress in Rats Undergoing Strength Training.

Strength training increases systemic oxygen consumption, causing the excessive generation of reactive oxygen species, which in turn, provokes oxidative stress reactions and cellular processes that induce uterine contraction. The aim of this study was to evaluate the possible protective effect of Spirulina platensis (SP), an antioxidant blue algae, on the contractile and relaxation reactivity of rat uterus and the balance of oxidative stress/antioxidant defenses. Female Wistar rats were divided into sedentary (CG), trained (TG), and T + supplemented (TG50, TG100) groups. Reactivity was analyzed by AQCAD, oxidative stress was evaluated by the malondialdehyde (MDA) formation, and the antioxidant capacity was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Strength training increased contractile reactivity and decreased the pharmaco-mechanical component of relaxing reactivity in rat uterus. In addition, training decreased oxidation inhibition in the plasma and exercise increased oxidative stress in the uterine tissue; however, supplementation with algae prevented this effect and potentiated the increase in antioxidant capacity. Therefore, this study demonstrated that food supplementation prevents changes in reactivity and oxidative stress induced by strength training in a rat uterus, showing for the first time, that the uterus is a target for this exercise modality and antioxidant supplementation with S. platensis is an alternative means of preventing uterine dysfunction.

Fractions of Ageratum conyzoides L. (Compositae) induce mitochondrial-mediated apoptosis in rats: Possible option in monosodium glutamate-induced hepatic and uterine pathological disorder.

ETHNOPHARMACOLOGICAL RELEVANCE: Several pathological disorders have been attributed to either oxidative stress or defect in apoptotic signaling pathway. Some bioactive compounds elicit their antiproliferative properties by induction of apoptosis via mitochondrial permeability transition (mPT) pore opening. AIM OF STUDY: The present study therefore investigated the effects of various fractions of methanol extract of Ageratum conyzoides L. (MEAC) on mitochondrial-mediated apoptosis and the possible protective potential of the most potent against monosodium glutamate (MSG)-induced hepatic damage and uterine pathological disorder. The plant is folklorically used in the treatment of cancer and gynecological disorder. MATERIALS AND METHODS: The MEAC was partitioned in succession and concentrated at 40 °C to obtain chloroform(CFAC), ethylacetate(EFAC) and methanol(MFAC) fractions. Mitochondria were isolated by differential centrifugation. The opening of mPT pore, mATPase activity and hepatic DNA fragmentation were assessed spectrophotometrically. Caspases 9 and 3, SOD and GSH-Px activities and MDA level were determined using ELISA technique. Histological assessment of the liver and uterine sections and GC-MS analysis of the most potent fraction were carried out. RESULTS: The investigation showed that oral administration of the fractions caused induction of mPT pore opening, enhanced mATPase activity, upregulated the activities of caspases 9 and 3 and also, caused hepatic DNA fragmentation with CFAC being the most potent. The CFAC reversed severe MSG-induced hepatic damage and uterine hyperplasia. The MSG-induced oxidative stress was normalized by CFAC. The GC-MS analysis of CFAC revealed the presence of some pharmacologically relevant phytochemicals. CONCLUSION: These findings therefore suggest that fractions of Ageratum conyzoides induce mitochondrial-mediated apoptosis. Moreover, CFAC, which is the most potent has a promising antioxidant and antiproliferative potential against MSG-induced hepatic and uterine pathological disorder.

Preventive effect of Rumex crispus L. on surgically induced intra-abdominal adhesion model in rats.

BACKGROUND: Rumex crispus L. (Polygonaceae), known as "Labada" in Turkey, was reported to be used for the treatment of gynecological diseases such as postpartum complications and infertility in folk medicine. Earlier studies on R. crispus have shown that leaf, fruit and root extracts have anti-inflammatory and antioxidant activities and are used for the treatment of tumors in the uterus. The hypothesis of this study is that R. crispus may generate potential anti-adhesive activity against complex factors such as inflammation, oxidation and fibrosis. OBJECTIVES: We aimed to investigate the potential anti-adhesive activity of aqueous methanol extracts of leaves, fruits and roots of R. crispus. METHODS: Abdominal adhesion model was performed in 72 female Wistar Albino rats. In the first step of the experiment, the rats were divided into six groups namely, Sham, Control, Reference and Experimental Groups (consisting of three sub-groups in which R. crispus leaf, fruit and root extracts were applied at 100 mg/kg dose). The test samples were administered once to the peritoneal cavity and the rats were sacrificied at the end of the 14th day. Root extract showed prominent activity, therefore this extract was subjected to fractionation to obtain 3 fractions (30-60-100% methanol fractions) by using vacuum-liquid chromatography. In the second stage, animals were divided into 6 groups as Sham, Control, Reference and Experimental Groups (R30, R60, R100 at 100 mg/kg dose). Adhesion scoring, tissue total antioxidant and oxidant levels, histopathological and immunohistochemical (TNF-α, IL-6 and IL-8) analyzes were performed. RESULTS AND CONCLUSION: Adhesion scores, inflammatory cytokines and inflammation cells decreased by the application of R. crispus root extract. The fractions also showed similar anti-inflammatory effects, but R60 was found to be more effective in prevention of intra-abdominal adhesions and uterine fibrosis. R60 fraction, possessing potential bioactivity, was investigated in terms of phenolic composition by HPLC.

Effect of Bushen Huoxue recipe on women with thin endometrial ovulation disorder and a rat model of thin endometrium resulted from kidney deficiency-related blood stasis.

To examine the therapeutic effect of Bushen Huoxue recipe (BHR) on women with thin endometrial ovulation disorder and on a rat model of kidney deficiency-related blood stasis. A total of 60 women with thin endometrial ovulation disorder was enrolled. The primary outcome of the study was the pregnancy rate three menstrual cycles after treatment. The study also examined the changes in the type and thickness of uterine artery, uterine artery pulsatility index (PI) and endometrial resistance index (RI). To establish kidney deficiency-related blood stasis in Sprague Dawley (SD) rats, an intragastric administration of hydroxyurea and a tail vein injection of Dextran were given, following with a flashing of the uterine cavity with 95% anhydrous ethanol. A combined regimen of BHR and estradiol valerate significantly increased the rate of pregnancy in women with thin endometrial ovulation disorder. The treatment was accompanied by a significant increase in endometrial thickness and decreases in uterine artery PI and endometrial RI. In rats, kidney deficiency-related blood stasis caused severe loss in endometrial architecture, thickness, and numbers of gland and blood vessel compared to the healthy SD rats. Treatment with BHR could ameliorate the endometrial damages associated with kidney deficiency-related blood stasis.

Effect of Gloriosa superba linn (EEGS) on mPT and monosodium glutamate-induced proliferative disorder using rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperplasia, Tumors and cancers are various forms of proliferative disorders affecting humans. Surgery is the main treatment approach while other options are also associated with adverse effects. There is therefore a need for the development of better alternative therapy that is cost effective and readily available with little or no adverse effect. Some bioactive agents in medicinal plants exhibit their anti-proliferative potential by induction of mitochondrial permeability transition pore (mPT) opening. Gloriosa superba, a medicinal plant, is folklorically used in the treatment of tumors and cancers. AIM OF THE STUDY: This study therefore aimed at investigating the effect of ethanol leaf extract of Gloriosa superba (EEGS) on mPT and monosodium glutamate-induced proliferative disorder in some specific tissues using rat model. MATERIALS AND METHODS: Isolated rat liver mitochondria were exposed to different concentrations (10, 30, 50, 70 and 90 µg/ml) of EEGS. The mPT pore opening, cytochrome c release, mitochondrial ATPase activity and lipid peroxidation were assessed spectrophotometrically. Caspases 9 and 3 activities were carried out using ELISA technique. Histological assessment of the liver, prostate and uterus of normal and monosodium glutamate (MSG)-treated rats were carried out. RESULTS: The results showed significant induction of mPT pore opening, release of cytochrome c, enhancement of mitochondrial ATPase activity, inhibition of lipid peroxidation and activation of caspases 9 and 3 activities by EEGS. The histological assessment revealed the presence of MSG-induced hepato-cellular damage, benign prostate hyperplasia and uterine hyperplasia which were ameliorated by EEGS co-administration. CONCLUSIONS: These findings suggest that EEGS contains putative agents that can induce apoptosis via induction of mPT pore opening and as well protect against MSG-induced hepato-cellular damage and proliferative disorder in prostate and uterus.

The impact of granulocyte colony-stimulating factor (G-CSF) on thin endometrium of an animal model with rats.

MATERIALS AND METHODS: After forming of the thin endometrium by uterine injection of 0.2 ml 96% ethyl alcohol to the rats, five days of subcutaneous injections of 40 µg/kg G-CSF or saline were given. Endometrial thickness, immunohistochemically expression of vascular endothelial growth factor receptor-2 (VEGF-R2), proliferative cell nuclear antigen (PCNA) and fibronectin apoptosis with TUNEL method were compared in specimens among four groups of post-model rats. RESULTS: Endometrial thickness was significantly improved in thin but not in normal endometrium group with GCSF when compared to saline injection. Stromal and glandular epithelial expression of PCNA and pericapillary VEGF-R2 was significantly increased, and apoptosis was significantly decreased with G-CSF. Although fibronectin was also increased with G-CSF in the thin endometrium, the difference was non-significant. In further, G-CSF decreased apoptotic cells and increased expression of PCNA when compared to saline injection in normal endometrium. CONCLUSIONS: G-CSF improves endometrial thickness, proliferation, angiogenesis and DNA fragmentation in thin endometrium.

Relief of pain due to uterine cramping/involution after birth.

BACKGROUND: Women may experience differing types of pain and discomfort following birth, including cramping pain (often called after-birth pain) associated with uterine involution, where the uterus contracts to reduce blood loss and return the uterus to its non-pregnant size. This is an update of a review first published in 2011. OBJECTIVES: To assess the effectiveness and safety of pharmacological and non-pharmacological pain relief/analgesia for the relief of after-birth pains following vaginal birth. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (31 October 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials comparing two different types of analgesia or analgesia versus placebo or analgesia versus no treatment, for the relief of after-birth pains following vaginal birth. Types of analgesia included pharmacological and non-pharmacological. Quasi-randomised trials were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, conducted 'Risk of bias' assessment, extracted data and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: In this update, we include 28 studies (involving 2749 women). The evidence identified in this review comes from middle- to high-income countries. Generally the trials were at low risk of selection bias, performance bias and attrition bias, but some trials were at high risk of bias due to selective reporting and lack of blinding. Our GRADE certainty of evidence assessments ranged from moderate to very low certainty, with downgrading decisions based on study limitations, imprecision, and (for one comparison) indirectness. Most studies reported our primary outcome of adequate pain relief as reported by the women. No studies reported data relating to neonatal adverse events, duration of hospital stay, or breastfeeding rates. Almost half of the included studies (11/28) excluded breastfeeding women from participating, making the evidence less generalisable to a broader group of women. Non-steroidal anti-inflammatory drugs (NSAIDs) compared to placebo NSAIDs are probably better than placebo for adequate pain relief as reported by the women (risk ratio (RR) 1.66, 95% confidence interval (CI) 1.45 to 1.91; 11 studies, 946 women; moderate-certainty evidence). NSAIDs may reduce the need for additional pain relief compared to placebo (RR 0.15, 95% CI 0.07 to 0.33; 4 studies, 375 women; low-certainty evidence). There may be a similar risk of maternal adverse events (RR 1.05, 95% CI 0.78 to 1.41; 9 studies, 598 women; low-certainty evidence). NSAIDs compared to opioids NSAIDs are probably better than opioids for adequate pain relief as reported by the women (RR 1.33, 95% CI 1.13 to 1.57; 5 studies, 560 women; moderate-certainty evidence) and may reduce the risk of maternal adverse events (RR 0.62, 95% CI 0.43 to 0.89; 3 studies, 255 women; low-certainty evidence). NSAIDs may be better than opioids for the need for additional pain relief, but the wide CIs include the possibility that the two classes of drugs are similarly effective or that opioids are better (RR 0.37, 95% CI 0.12 to 1.12; 2 studies, 232 women; low-certainty evidence). Opioids compared to placebo Opioids may be better than placebo for adequate pain relief as reported by the women (RR 1.26, 95% CI 0.99 to 1.61; 5 studies, 299 women; low-certainty evidence). Opioids may reduce the need for additional pain relief compared to placebo (RR 0.48, 95% CI 0.28 to 0.82; 3 studies, 273 women; low-certainty evidence). Opioids may increase the risk of maternal adverse events compared with placebo, although the certainty of evidence is low (RR 1.59, 95% CI 0.99 to 2.55; 3 studies, 188 women; low-certainty evidence). Paracetamol compared to placebo Very low-certainty evidence means we are uncertain if paracetamol is better than placebo for adequate pain relief as reported by the women, the need for additional pain relief, or risk of maternal adverse events (2 studies, 123 women). Paracetamol compared to NSAIDs Very low-certainty evidence means we are uncertain if there are any differences between paracetamol and NSAIDs for adequate pain relief as reported by the women, or the risk of maternal adverse events. No data were reported about the need for additional pain relief comparing paracetamol and NSAIDs (2 studies, 112 women). NSAIDs compared to herbal analgesia We are uncertain if there are any differences between NSAIDs and herbal analgesia for adequate pain relief as reported by the women, the need for additional pain relief, or risk of maternal adverse events, because the certainty of evidence is very low (4 studies, 394 women). Transcutaneous nerve stimulation (TENS) compared to no TENS Very low-certainty evidence means we are uncertain if TENS is better than no TENS for adequate pain relief as reported by the women. No other data were reported comparing TENS with no TENS (1 study, 32 women). AUTHORS' CONCLUSIONS: NSAIDs may be better than placebo and are probably better than opioids at relieving pain from uterine cramping/involution following vaginal birth. NSAIDs and paracetamol may be as effective as each other, whereas opioids may be more effective than placebo. Due to low-certainty evidence, we are uncertain about the effectiveness of other forms of pain relief. Future trials should recruit adequate numbers of women and ensure greater generalisability by including breastfeeding women. In addition, further research is required, including a survey of postpartum women to describe appropriately their experience of uterine cramping and involution. We identified nine ongoing studies, which may help to increase the level of certainty of the evidence around pain relief due to uterine cramping in future updates of this review.

Bear bile use at the intersection of maternal health in Cambodia.

BACKGROUND: The consumption of bear gallbladders and bear bile in Southeast Asia is a persistent threat to bear populations. As part of a larger effort to understand the characteristics of bear part consumption in Cambodia, we uncovered a consumer base of women seeking treatment for post-partum and uterine ailments. METHODS: To better understand this aspect of consumption, we interviewed 122 women in seven different provinces in Cambodia, probing into the motivations and influences for using bear bile, as well as what types of ailments Cambodian women use it for. RESULTS: We found that it is generally used by young or expecting mothers, and for such issues as post-partum "fatigue" (toas in Khmer), which could encompass post-partum depression. A desire to be supported by kin networks seems to facilitate the continued use of bear gallbladder and bile for these purposes. CONCLUSIONS: We suggest that efforts to reduce consumption should focus on encouraging older kin to change their means of support to Western/biomedical and by extension non-wildlife alternatives.

Effect of Perioperative Transfusion on Postoperative Morbidity Following Minimally Invasive Hysterectomy for Benign Indications.

STUDY OBJECTIVE: To examine the impact of perioperative allogeneic blood transfusion (ABT) on postoperative infectious wound occurrences, sepsis-related events. and venous thromboembolism. DESIGN: Retrospective cohort study. SETTING: Hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). PATIENTS: Patients who underwent a minimally invasive hysterectomy for benign indications between 2012 and 2016 were selected from the ACS-NSQIP. Patients with concurrent open hysterectomy, prolapse, or malignancy were excluded. Those with preoperative, intraoperative or postoperative red blood cell transfusion were considered positive for perioperative ABT. INTERVENTION: Minimally invasive hysterectomy for benign indications. MEASUREMENTS AND MAIN RESULTS: Univariate analyses were performed to determine associations of preoperative and intraoperative patient variables and postoperative outcomes with perioperative ABT. Multivariate analysis was completed to test the independent associations of perioperative ABT with outcomes while adjusting for possible confounders. Of the 90,231 patients who met our inclusion criteria, 1447 had a perioperative transfusion (1.6%). Perioperative ABT was associated with multiple preoperative variables. After multivariate analysis, perioperative ABT remained significantly associated with infectious wound events (adjusted odds ratio [aOR], 1.96; 95% confidence interval [CI], 1.9-2.58; p < .001), thromboembolic events (aOR, 2.75; 95% CI, 1.5-5.05; p = .001), and sepsis events (aOR, 6.49; 95% CI, 4.29-9.79, p < .001). CONCLUSION: ABT is a commonly used to treat perioperative anemia in patients undergoing gynecologic surgery. The results of this study, however, show that perioperative ABT increases a patient's risk of postoperative complications following minimally invasive hysterectomy. Gynecologic surgeons should consider the use of alternative treatments for perioperative anemia, including intravenous iron supplementation, erythropoiesis-stimulating agents, normovolemic hemodilution, and preoperative hormonal suppression, to help reduce the morbidity associated with perioperative ABT.

Dietary supplementation of barley and/or dates attenuate hypercholesterolemic-induced endometrial dysfunction in Wistar albino rats via alleviation of apoptotic pathways and enhancing oxidative capacity.

Our study was conducted to characterize the efficacy of barley and/or date palm fruits (10%) in alleviation of hypercholesterolemic endometrial insults in obese rat model. Sixty-four Wistar albino rats were randomized into eight groups (n = 8); control, hypercholesterolemic- and hypercholesterolemic-treated groups. Animals were subjected to treatment for 4 months. After sacrifice, serum and uterine tissues were collected and processed for biochemical, histological, immunohistochemical, and electron microscopic investigations. In hypercholesterolemic rats, the endometrium displayed hyperplasia with necrotic patches in the surface epithelium and its glandular lining cells. Also, there was a remarkable increase in the endometrial thickness and significant decrease in corresponding glandular numbers. Prompted by these findings, immunohistochemical localization revealed that expression of proliferating cell nuclear antigen was downregulated, while cleaved caspase-3 was upregulated in the endometrial cells in hypercholesterolemic group. Accordingly, there was remarkable depletion of antioxidant enzymatic activities associated with increased lipid peroxidation and apoptotic markers. Contradictory, supplementation of barley and/or dates to hypercholesterolemic groups showed intriguing amelioration for the histological architecture of the endometrium and balancing its oxidative redox. In conclusion, the administration of barley and/or dates confers enhanced synergistic effects in attenuation of hypercholesterolemic induced-endometrial dysfunction. This is clear evidence that endometrial amelioration was directly linked to the implication of highly potential antioxidant capacity of barley and/or dates phytochemicals, ß-glucan, polyphenols, and other trace elements, which can be utilized to establish a phyto-therapeutic strategy for activating endometrial cell regeneration. PRACTICAL APPLICATIONS: Barley and dates confer both hypoglycemic and hypocholesterolemic potentials. Therefore, their ingredients would be implicated in the amelioration of uterine functions in obese women. These favorable potentials were directly linked to the restraining of endometrial inflammation and retrieving the oxidative capacity. Furthermore, our findings demonstrated that barley and dates substantially diminished the expression of TNF-α, mitigated DNA damage and prevented leukocytic infiltration in the endometrial tissue; based on their high content of dietary phytochemicals, ß-glucan, polyphenols, and other trace elements.

Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening.

Endometrial disorders represent a major gynaecological burden. Current research models fail to recapitulate the nature and heterogeneity of these diseases, thereby hampering scientific and clinical progress. Here we developed long-term expandable organoids from a broad spectrum of endometrial pathologies. Organoids from endometriosis show disease-associated traits and cancer-linked mutations. Endometrial cancer-derived organoids accurately capture cancer subtypes, replicate the mutational landscape of the tumours and display patient-specific drug responses. Organoids were also established from precancerous pathologies encompassing endometrial hyperplasia and Lynch syndrome, and inherited gene mutations were maintained. Endometrial disease organoids reproduced the original lesion when transplanted in vivo. In summary, we developed multiple organoid models that capture endometrial disease diversity and will provide powerful research models and drug screening and discovery tools.