Acupoint application therapy alleviates pain by regulating immune function through inhibiting TLR4/MyD88/NF-κB p65 signaling in a primary dysmenorrhea rat model. / 穴位贴敷通过TLR4/MyD88/NF-κBé€šè·¯è°ƒèŠ‚åŽŸå‘æ€§ç—›ç»å¤§é¼ çš„å ç–«åŠŸèƒ½.

OBJECTIVES: To investigate the effects of graphene-based warm uterus acupoint paste on uterine Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-kappa B p65 (NF-κB p65) signaling pathway and Th1/Th2 immune balance in primary dysmenorrhea ( PD ) model rats, so as to reveal its immunological mechanisms of relieving dysmenorrhea. METHODS: Thirty SD female rats were randomly divided into 3 groups：normal group, model group and acupoint paste group, with 10 rats in each group. PD rat model was established by subcutaneous injection of estradiol benzoate for 10 consecutive days. At the same time of modeling, graphene-based warm uterus acupoint paste was applied to the acupoints of "Guanyuan" (CV4), bilateral "Zigong" (EX-CA1) and "Sanyinjiao" (SP6) of rats in the acupoint paste group. The application was continuously applied once daily for 10 d, 5 h each time. On the 11th day, oxytocin was injected intraperitoneally to observe the writhing latency, writhing times within 30 min and writhing score of rats in each group. The spleen and thymus indexes were calculated. The pathological changes of spleen and thymus tissue were observed after HE staining. The contents of serum immunoglobulin (Ig) A, IgG, tumor necrosis factor-α (TNF-α), interleukin (IL)-2, interferon-γ (IFN-γ), IL-4 and IL-10 were detected by ELISA . The protein and mRNA expression levels of TLR4, MyD88 and NF-κB p65 in rat uterine tissue were detected by Western blot and real-time quantitative PCR, respectively. RESULTS: Compared with the normal group, the writhing times and writhing scores within 30 min of rats in the model group were significantly increased(P<0.001), and the rats showed writhing reaction (P<0.01). The spleen index and thymus index were significantly decreased(P<0.01, P<0.05). The spleen and thymus had obvious pathological changes. The contents of IgA, IgG, TNF-α, IL-2 and IFN-γ in serum were significantly increased, while the contents of serum IL-4 and IL-10 were significantly decreased(P<0.001, P<0.01). The expression levels of TLR4, MyD88, NF-κB p65 protein and corresponding mRNA in uterine tissue were significantly increased(P<0.001). Following intervention, compared with the model group, the writhing latency time of rats in the acupoint paste group was prolonged, and the writhing times and writhing scores within 30 min were significantly decreased (P<0.001). The spleen index and thymus index were significantly increased(P<0.01, P<0.05). The pathological changes of spleen and thymus were improved. The contents of serum IgA, IgG, TNF-α, IL-2 and IFN-γ were significantly decreased, while the contents of IL-4 and IL-10 were significantly increased(P<0.001, P<0.05, P<0.01). The expression of TLR4, MyD88, NF-κB p65 protein and the corresponding mRNA levels in uterine tissue were decreased(P<0.001, P<0.01). CONCLUSIONS: Graphene-based warm uterus acupoint paste can regulate the immune balance of Th1/ Th2 by regulating TLR4/ MyD88/ NF-κB p65 signaling pathway, repair the pathological damage of immune tissue, improve immune function, and effectively relieve the pain symptoms of PD rats.

Labisia pumila as a Culprit of Primary Uterine Rupture Alongside Abruptio Placentae: A Case Report.

Purpose: Uterine rupture is a rare obstetrical and surgical emergency but is often associated with a catastrophic obstetric complication. Traditionally, unscarred uteri without risk factors are considered immune to rupture and information about its risk factors is only few due to its rarity. Complementary and alternative medicine is commonly used in pregnant woman in southeast Asian countries such as Indonesia, however information regarding its toxicity due to irrational use is few. This case report presents a G2P1A0 35-year-old woman with acute abdomen with spontaneous unscarred uterine rupture >15 cm after continuously consuming herbal water made of Kacip Fatimah leaves in boiling water. Case Description: A 35-year-old pregnant woman was referred to hospital due to abdominal discomfort 3 hours before admission due to suspicion of intrauterine fetal death. She drank the extracted herbal water to help her when the labor comes, which was made from boiled water with rumput Fatimah from her neighbor's house. Then, she was diagnosed with G2P1A0 parturient aterm latent phase; acute abdomen due to suspicion of placentae abruption dd/ ruptur uteri; and Intrauterine Fetal Death. Exploratory laparotomy was decided due to acute abdominal pain, and during the procedure the operator decided to do subtotal hysterectomy on the patient. The operator found her uterine was already ruptured, approximately 15-18 cm and the placentae was located outside of the uterus. Conclusion: This case suggest that rational usage of herbal medicine must be implemented to avoid unwanted complication.

Effects of long-acting injectable progesterone supplementation at early dioestrus on pregnancy maintenance in beef and dairy recipient cattle.

We tested in the present study the hypothesis that supplementation with long-acting P4 (iP4) at different times of the initial dioestrus improves pregnancy rates in dairy and beef recipients submitted to fixed-time embryo transfer (FTET). Recipients from commercial farms had their oestrous cycle synchronized with an E2/P4-based protocol in three experiments (Exp. 1 to 3). In Exp. 1, dairy heifers (n = 76) and cows (n = 104) were randomly assigned to two experimental groups: the control group (n = 89) and the iP4D4 group (n = 91). For Exps. 2 and 3, suckled beef recipients were used. In Exp. 2, recipients were assigned to two experimental groups: Control group (n = 147) and iP4D7 group (n = 144); whereas in Exp. 3, recipients were randomly assigned to three experimental groups: Control group (n = 85), iP4-D4 group (n = 86) and iP4D7 group (n = 81). Recipients in the iP4D4 and iP4-D7 groups received an i.m. administration of 150 mg iP4, on D4 or D7 (D0 was the day of expected oestrus). On D7, all recipients were evaluated by transrectal ultrasonography and those that had a CL received a fresh or vitrified in vitro-produced embryo. In Exp. 2 and 3, the CL area was also determined by ultrasonography at the time of FTET. The pregnancy diagnosis was performed at 30 days in Exp. 1, 57 days in Exp. 2, and between 40 and 72 days of pregnancy in Exp. 3. In Exp. 1, the pregnancy rate did not differ (p > .1) between the Control group (38.2% [34/89]) and iP4D4 group (49.5% [45/91]); yet, a parity effect indicated a greater (p < .05) pregnancy rate in heifers (57.9% [44/76]) than cows (30.8% [32/104]). In Exp. 2, the pregnancy rate was greater (p < .05) in the iP4D7 group (45.0% [65/144]) than in the Control group (34.0% [50/147]). Also, a greater (p = .08) pregnancy rate was observed for recipients with a small CL (≤2.75 cm2 ) that were treated with iP4 on the day of FTET than the control recipients (46.4% [32/69] vs. 32.6% [28/86]). In Exp. 3, no significant effects (p > .1) of the treatment group or CL size were detected on pregnancy rates at days 30 and 60. In conclusion, the beneficial effects of iP4 supplementation at early dioestrus on pregnancy maintenance may vary according to the experimental conditions, but its use at the time of FTET can be used as an alternative to enhance the fertility of beef recipients in challenging conditions in commercial herds.

Comprehensive Analysis of Iron Deficiency Anemia and Its Related Disorders in Premenopausal Women Based on a Propensity Score Matching Case Control Study Using National Health Insurance Service Database in Korea.

BACKGROUND: Menorrhagia is a common cause of iron deficiency anemia (IDA) in premenopausal women. However, the effects of menorrhagia on IDA in premenopausal women have been underestimated compared to those on other IDA-related disorders (IRDs) such as gastrointestinal malignancies (GIMs). To better understand the relationship between menorrhagia and IDA in premenopausal women, we analyzed the National Health Insurance Service-National Health Information Database (NHIS-NHID). METHODS: From 2005 to 2008, data about women between the age of 20 and 59 years were extracted from the NHIS-NHID to create a propensity score-matched case (IDA) and control group. The annual incidence of IDA was calculated per age group. A 10-year follow up of the study population was determined to detect IRDs in case and control groups. We compared the risk of detection (ROD) of IRDs, including GIM and gynecological disorders associated with menorrhagia - leiomyoma of uterus (LM) and adenomyosis (AM), in the case and the control group. RESULTS: From 2005 to 2008, women diagnosed with IDA (n = 535,249) and healthy women as a control group (n = 1,070,498) were identified from the NHIS-NHID. The annual incidence of IDA was 767.4 (2005), 948.7 (2006), 981.6 (2007), and 897.7 (2008) per 100,000 women. The age distribution of IDA was similar each year; IDA was common in women aged 30-39 years (36-37%) and 40-49 years (30-32%), and its incidence was significantly decreased in women aged 50-59 years (< 10%). The ROD of IRDs were significantly higher in the IDA group than in the control group (LM: 20.8% vs. 6.9%, AM: 5.6% vs. 1.6%, and GIM: 2.6% vs. 0.7%). The corresponding hazard ratios were 3.89 (95% confidence interval [CI], 3.85-3.93) for LM, 4.99 (95% CI, 4.90-5.09) for AM, and 3.43 (95% CI, 3.32-3.55) for GIM. The ROD of the IRDs varied; the ROD of LM in the IDA group increased with age and decreased in the age group 50-59 years. AM was more frequently detected in women with IDA aged 30-39 years and less in women older than 40 years. The frequency of GIM increased with age. CONCLUSION: In this study, we found that the gynecologic disease is the main cause of IDA in premenopausal women. Gynecological evaluations should be performed more actively in the clinic to prevent and control IDA and IRDs.

Uterodilation effect of unripe fruit extract of Crataegus azarolus var. aronia L. on rat uterine smooth muscles.

Crataegus azarolus var. aronia L. (C. aronia) is one of the most important medicinal plants used widely in folk medicine for the prevention of several diseases due to its content of several bioactive compounds like phenolic acid, aromatic amines, proanthocyanidins and flavonoids. This study investigated the uterodilation effect of methanol extract (ME) of C. aronia unripe fruit on the uterine smooth muscle in rats. The mechanism of action underlying the plant's extract was also screened. The unripe fruits were cleaned and extracted in methanol. The extract (1.9-4 mg/ml) was tested on rat uterine relaxation in calcium-free Kreb's solution and potassium chloride-induced uterine contraction. The plant extract was also studied in the presence of antagonists in separate experiments to determine the role of various ion channels and hyperpolarizing agents. The plant extract showed an uterodilation effect on the uterus, in which the ME produced a considerable relaxant effect. The results confirmed that the induced dilation was mediated mainly by the nitric oxide pathway and the activation of potassium channels with a limited role of the prostaglandin pathway and calcium channel activation. This in-vitro study provides the first scientific evidence of the claimed effect of C. aronia on uterine relaxation.

Field-of-view optimized and constrained undistorted single-shot study of intravoxel incoherent motion and diffusion-weighted imaging of the uterus during the menstrual cycle: a prospective study.

PURPOSE: This study aimed to compare the variability of the uterus during the menses phase (MP), follicular phase (FP), and luteal phase (LP) of the menstrual cycle using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). METHODS: This prospective study was conducted at the Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2022 and January 2023. Women of childbearing age (18-45 years) with appropriate progesterone levels were included in this study. Conventional magnetic resonance imaging and IVIM-DWI scans were performed during the MP, FP, and LP. The differences in IVIM-DWI-derived parameters between these phases were then compared, and the overlap was quantitatively described. RESULTS: The apparent diffusion coefficient (ADC) and pure molecular diffusion coefficient (D) values from the endometrium, uterine junctional zone (UJZ), and myometrium indicated statistical differences between the MP and FP and the MP and LP (ADC: endometrium, both P < 0.001; UJZ, P = 0.008 and P < 0.001, respectively; myometrium, P = 0.033 and P = 0.006, respectively; D: endometrium, both P < 0.001; UJZ, P = 0.008 and P = 0.006, respectively; myometrium, P = 0.041 and P = 0.045, respectively). The perfusion-related diffusion coefficient (D*) values from the myometrium indicated statistical differences between the FP and MP and the FP and LP (D*: myometrium, P = 0.049 and P = 0.009, respectively). The overlapping endometrium ratios between the MP and FP or LP were lower than 50% in the ADC and D values (ADC: overlapping of MP and FP: 33.33%, overlapping of MP and LP: 23.33%; D: overlapping of MP and FP: 40.00%, overlapping of MP and LP: 43.33%). CONCLUSION: The ADC and IVIM-derived parameters indicated differences in the uterus in diverse phases of the menstrual cycle, especially in the endometrium in relation to ADC and D values.

Feeding rumen-protected lysine prepartum alters placental metabolism at a transcriptional level.

Rumen-protected Lys (RPL) fed to Holstein cows prepartum resulted in a greater intake and improved health of their calves during the first 6 wk of life. However, whether increased supply of Lys in late gestation can influence placental tissue and, if so, which pathways are affected remain to be investigated. Therefore, we hypothesize that feeding RPL during late gestation could modulate placental metabolism, allowing for improved passage of nutrients to the fetus and thus influencing the offspring development. Therefore, we aimed to determine the effects of feeding RPL (AjiPro-L Generation 3, Ajinomoto Health and Nutrition North America) prepartum (0.54% DM of TMR) on mRNA gene expression profiles of placental samples of Holstein cows. Seventy multiparous Holstein cows were randomly assigned to 1 of 2 dietary treatments, consisting of TMR top-dressed with RPL (PRE-L) or without (control, CON), fed from 27 ± 5 d prepartum until calving. After natural delivery (6.87 ± 3.32 h), placentas were rinsed with physiological saline (0.9% sodium chloride solution) to clean any dirtiness from the environment and weighed. Then, 3 placentomes were collected, one from each placental region (cranial, central, and caudal), combined and flash-frozen in liquid nitrogen to evaluate the expression of transcripts and proteins related to protein metabolism and inflammation. Placental weights did not differ from cows in PRE-L (15.5 ± 4.03 kg) and cows in CON (14.5 ± 4.03 kg). Feeding RPL prepartum downregulated the expression of NOS3 (nitric oxide synthase 3), involved in vasodilation processes, and SOD1, which encodes the enzyme superoxide dismutase, involved in oxidative stress processes. Additionally, feeding RPL prepartum upregulated the expression of transcripts involved in energy metabolism (SLC2A3, glucose transporter 3; and PCK1, phosphoenolpyruvate carboxykinase 1), placental metabolism and cell proliferation (FGF2, fibroblast growth factor 2; FGF2R, fibroblast growth factor 2 receptor; and PGF, placental growth factor), Met metabolism (MAT2A, methionine adenosyltransferase 2-α), and tended to upregulate IGF2R (insulin-like growth factor 2 receptor). Placental FGF2 and LRP1 (low-density lipoprotein receptor-related protein 1) protein abundance were greater for cows that received RPL prepartum than cows in CON. In conclusion, feeding RPL to prepartum dairy cows altered uteroplacental expression of genes and proteins involved in cell proliferation, and in metabolism and transport of glucose. Such changes are illustrated by increased expression of SLC2A3 and PCK1 and increased protein abundance of FGF2 and LRP1 in uteroplacental tissue of cows consuming RPL.

Arrest of mouse preterm labor until term delivery by combination therapy with atosiban and mundulone, a natural product with tocolytic efficacy.

There is a lack of FDA-approved tocolytics for the management of preterm labor (PL). In prior drug discovery efforts, we identified mundulone and mundulone acetate (MA) as inhibitors of in vitro intracellular Ca2+-regulated myometrial contractility. In this study, we probed the tocolytic potential of these compounds using human myometrial samples and a mouse model of preterm birth. In a phenotypic assay, mundulone displayed greater efficacy, while MA showed greater potency and uterine-selectivity in the inhibition of intracellular-Ca2+ mobilization. Cell viability assays revealed that MA was significantly less cytotoxic. Organ bath and vessel myography studies showed that only mundulone exerted inhibition of myometrial contractions and that neither compounds affected vasoreactivity of ductus arteriosus. A high-throughput combination screen identified that mundulone exhibits synergism with two clinical-tocolytics (atosiban and nifedipine), and MA displayed synergistic efficacy with nifedipine. Of these combinations, mundulone+atosiban demonstrated a significant improvement in the in vitro therapeutic index compared to mundulone alone. The ex vivo and in vivo synergism of mundulone+atosiban was substantiated, yielding greater tocolytic efficacy and potency on myometrial tissue and reduced preterm birth rates in a mouse model of PL compared to each single agent. Treatment with mundulone after mifepristone administration dose-dependently delayed the timing of delivery. Importantly, mundulone+atosiban permitted long-term management of PL, allowing 71% dams to deliver viable pups at term (>day 19, 4-5 days post-mifepristone exposure) without visible maternal and fetal consequences. Collectively, these studies provide a strong foundation for the development of mundulone as a single or combination tocolytic for management of PL.

Effect of Vitamin D3 on Chemerin and Adiponectin Levels in Uterus of Polycystic Ovary Syndrome Rats.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder with disrupted uterus structure and function. A positive effect of vitamin D3 (VD3) in female reproduction was observed. Chemerin (RARRES2) and adiponectin (ADIPOQ) are the main adipokines whose levels are altered in PCOS patients. Therefore, the aim of this study was to investigate the impact of VD3 supplementation on RARRES2 and ADIPOQ levels in the uterus of PCOS rats. METHODS: We analyzed the plasma levels and uterine transcript and protein expression of RARRES2 and ADIPOQ and their receptors (CCRL2, CMKLR1, GPR1, and ADIPOR1 and ADIPOR2, respectively) in rats with letrozole-induced PCOS. RESULTS: In control animals, VD3 did not change plasma levels of both adipokines, while in PCOS rats supplemented with VD3, they returned to control levels. The expression of RARRES2 and all investigated receptors increased in the uterus of VD3-treated rats; however, the levels of Rarres2 and Gpr1 genes remained unchanged. VD3 supplementation decreased RARRES2, CMKLR1, and GPR1 but increased CCRL2 level to the control value. In the uterus of VD3-treated rats, the transcript and protein levels of ADIPOQ and both receptors ADIPOR1 increased. At the same time, VD3 supplementation induced an increase in Adipoq, Adipor1, and Adipor2 gene expression and restored protein levels to control level values. CONCLUSIONS: our findings indicate a new mechanism of VD3 action in the uterine physiology of PCOS rats.

Modulatory properties of Thespesia garckeana (F. Hoffm.) Exell & Hillc. Aqueous fruit extract on female rats reproductive hormones and tissues histology and potential inhibitory activity of its constituents against SRD5α2.

ETHNOPHARMACOLOGICAL RELEVANCE: Thespesia garckeana (F. Hoffm.) Exell & Hillc. is called Gorontula (Kola of Tula) in Nigeria, Morojwa in Bostwana, and Thespesia garckeana in South Africa and is widely distributed across Africa. Its parts reportedly possess multiple medicinal properties and are employed for treating various diseases. In Tula, Gombe State, Nigeria, the ripe fruit decoction is taken as remedy for female infertility as documented by Ochokwu and co in the Journal of Biology, Agriculture and Healthcare in 2015. AIM OF THE STUDY: This research examined the effects of aqueous fruit extract of T. garckeana (F. Hoffm.) Exell & Hillc. (AFETG) on selected reproductive tissues and hormones in female rats and also evaluated the inhibitory potentials of its phytoconstituents against human 5-alpha reductase 2 (SRD5α2) using in silico approach. METHODS: Twenty-five (25) sexually matured female rats were randomized into 5 groups (i.e. A - E). Oestrous in the rats was synchronized (subcutaneous oestradiol conjugate [10 µg/100 g BW]). Group A received distilled water (control). Group B received standard drug, clomiphene citrate (0.85 mg/kg BW), while groups C, D, and E received AFETG at 50, 100, and 200 mg/kg BW respectively. The animals were treated for five (5) days and sacrificed 24 h after. Their blood was collected and prepared for analysis of serum prolactin, oestradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) while ovaries, uteruses, and oviducts were studied for histological and histomorphometric changes. For the in silico study, the target protein, human steroid 5α-reductase 2 (SRD5α2) was prepared and its receptor grid was generated using Optimized Potential for Liquid Simulations-2005. The ligand 2D structures were prepared using LigPrep 2.4 software and docked using Glide. The binding energy of the ligands to the protein receptor was predicted using Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis. RESULTS: AFETG significantly increased serum levels of E2 but did not alter serum levels of prolactin, LH and FSH when compared with distilled water and clomiphene citrate. AFETG also significantly increased ovarian tertiary follicular diameter, oviductal epithelial height and serosa thickness as well as uterine endometrial epithelial height, endometrial thickness, and myometrial thickness when compared with control. Ovarian secondary follicular diameter and oviductal submucosa thickness and muscular thickness were significantly decreased by AFETG when compared with control. Two compounds in T. garckeana (F. Hoffm.) Exell & Hillc.; D-Melezitose (-12.55 kcal/mol XP GScore) and 1, 3, 4-trihydroxy-5-oxo cyclohexane-1-carboxylic acid (-9.136 kcal/mol XP GScore) exhibited higher binding affinities for SRD5α2 than the reference ligand, epristeride (-8.096 kcal/mol XP GScore). In conclusion, the ability of AFETG to increase serum E2 level, thickness of uterine endometrium and ovarian tertiary follicles size can be explored for the treatment of female infertility caused by thinning of the uterine endometrium and reduced follicular size. Two compounds in AFETG (i.e. D-Melezitose and 1, 3, 4-trihydroxy-5-oxo cyclohexane-1-carboxylic acid are potential inhibitors of SRD5α2, thus aiding the biosynthesis of E2. Available evidence therefore corroborate the traditional use of T. garckeana (F. Hoffm.) Exell & Hillc fruit as a female fertility enhancer in Northern Nigeria.

Hydroalcoholic extract of Glycyrrhiza glabra root combined with Linum usitatissimum oil as an alternative for hormone replacement therapy in ovariectomized rats.

Objective: Plant-derived estrogens (phytoestrogens) with structural similarity to primary female sex hormones could be suitable replacements for sex hormones. Therefore, the effects of the licorice root extract and Linum usitatissimum oil on biochemical and hormonal indices in the serum and uterine stereological changes in ovariectomized rats were evaluated. Design: In this study, 70 adult female rats were randomly divided into seven groups including 1) control group, 2) sham-operated group, 3) ovariectomized (OVX) group, 4) OVX rats that received 1 mg/kg estradiol for 8 weeks at the day of post-operation, 5) OVX rats which received 2.0 mg/kg body wt Linum usitatissimum oil for 8 weeks at the day of post-operation, 6) OVX rats which received 2.0 mg/kg body wt licorice extract for 8 weeks at the day of post-operation, and 7) OVX rats which received 2.0 mg/kg body wt Linum usitatissimum oil + 2.0 mg/kg body wt licorice extract for 8 weeks at the day of post-operation. After eight weeks, alkaline phosphatase activity, as well as calcium, estradiol, and progesterone concentrations were assessed and tissue samples of the uterus were serologically examined. Results: The results indicated that after 8 weeks of OVX the alkaline phosphatase activity (Mean = 637.7 IU/L) increased and the calcium (Mean = 7.09 mg/dl), estradiol (5.30 pmol/L), and progesterone (Mean = 3.53 nmol/L) reduced compared to other groups. Moreover, stereological changes in the uterus in ovariectomy groups were seen compared to the other groups. The treatment with Linum usitatissimum oil and licorice extract had a significant therapeutic effect on biochemical factors and stereological changes compared to the ovariectomized group. Conclusion: The results of this study showed that the combination of Linum usitatissimum oil with licorice extract showed the high potential of hormone replacement therapy in the reduction of OVX complications.

Stachydrine, a Bioactive Equilibrist for Synephrine, Identified from Four Citrus Chinese Herbs.

Four Chinese herbs from the Citrus genus, namely Aurantii Fructus Immaturus (Zhishi), Aurantii Fructus (Zhiqiao), Citri Reticulatae Pericarpium Viride (Qingpi) and Citri Reticulatae Pericarpium (Chenpi), are widely used for treating various cardiovascular and gastrointestinal diseases. Many ingredients have already been identified from these herbs, and their various bioactivities provide some interpretations for the pharmacological functions of these herbs. However, the complex functions of these herbs imply undisclosed cholinergic activity. To discover some ingredients with cholinergic activity and further clarify possible reasons for the complex pharmacological functions presented by these herbs, depending on the extended structure-activity relationships of cholinergic and anti-cholinergic agents, a simple method was established here for quickly discovering possible choline analogs using a specific TLC method, and then stachydrine and choline were first identified from these Citrus herb decoctions based on their NMR and HRMS data. After this, two TLC scanning (TLCS) methods were first established for the quantitative analyses of stachydrine and choline, and the contents of the two ingredients and synephrine in 39 samples were determined using the valid TLCS and HPLC methods, respectively. The results showed that the contents of stachydrine (3.04‱) were 2.4 times greater than those of synephrine (1.25‱) in Zhiqiao and about one-third to two-thirds of those of Zhishi, Qingpi and Chenpi. Simultaneously, the contents of stachydrine, choline and synephrine in these herbs present similar decreasing trends with the delay of harvest time; e.g., those of stachydrine decrease from 5.16‱ (Zhishi) to 3.04‱ (Zhike) and from 1.98‱ (Qingpi) to 1.68‱ (Chenpi). Differently, the contents of synephrine decrease the fastest, while those of stachydrine decrease the slowest. Based on these results, compared with the pharmacological activities and pharmacokinetics reported for stachydrine and synephrine, it is indicated that stachydrine can be considered as a bioactive equilibrist for synephrine, especially in the cardio-cerebrovascular protection from these citrus herbs. Additionally, the results confirmed that stachydrine plays an important role in the pharmacological functions of these citrus herbs, especially in dual-directionally regulating the uterus, and in various beneficial effects on the cardio-cerebrovascular system, kidneys and liver.

Maternal-fetal toxicity of Strychnos pseudoquina extract treatment during pregnancy.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants and herbs have been used by women throughout history for therapeutic purposes. Strychnos pseudoquina, a plant used in the treatment of various diseases, can also function as an abortive herb. There is no scientific confirmation of its effects during pregnancy, and the activity of this plant needs to be substantiated or refuted with experimental evidence. AIM OF THE STUDY: Evaluating the effect of the S. pseudoquina aqueous extract on maternal reproductive toxicity and fetal development. MATERIALS AND METHODS: The aqueous extract of S. pseudoquina bark was evaluated in Wistar rats. Pregnant rats were distributed into four experimental groups (n = 12 rats/group): Control = treated with water (vehicle); Treated 75, Treated 150, and Treated 300 = treated with S. pseudoquina at dose 75, 150 and 300 mg/kg, respectively. The rats were treated by an intragastric route (gavage) from day 0 to day 21 of pregnancy. At the end of pregnancy, maternal reproductive outcomes, organs, biochemical and hematological profiles, fetuses, and placentas were analyzed. Maternal toxicity was evaluated through body weight gain, water, and food intake. With knowledge of the harmful dosage of the plant, other rats were used on gestational day 4 for the evaluation of morphological analyses before embryo implantation. P < 0.05 was considered as statistically significant. RESULTS: The S. pseudoquina treatment showed elevated liver enzymatic activities. The Treated 300 group presented toxicity with reduced maternal body weight, water and food intake, and increased kidney relative weight compared to those of the Control group. At a high dosage, the plant presents an abortifacient activity, confirmed by embryo losses before and after implantation and degenerated blastocysts. In addition, the treatment contributed to an increased percentage of fetal visceral anomalies, decreased ossification sites, and intrauterine growth restriction (300 mg/kg dose). CONCLUSION: In general, our study showed that an aqueous extract of S. pseudoquina bark caused significant abortifacient activity that testified to its traditional use. Furthermore, the S. pseudoquina extract caused maternal toxicity that contributed to impaired embryofetal development. Therefore, the use of this plant should be completely avoided during pregnancy to prevent unintended abortion and risks to maternal-fetal health.

Production performance, egg quality, and uterine gene expression for layers as affected by N-Carbamylglutamate supplementation.

Introduction: Supplementation of exogenous additives is a strategy to improve laying performance of layers by regulating uterine function. N-Carbamylglutamate (NCG) as an activator for endogenous arginine synthesis has the potential to regulate the laying performance of layers, but its effects have not been fully understood. Methods: This study investigated the effects of dietary supplementation of NCG on production performance, egg quality, and uterine gene expression in layers. A total of 360 45-week-old layers with a genetic line of Jinghong No. 1 were used in this study. The experimental period was 14 weeks. All birds were divided into 4 treatments with 6 replicates per treatment and 15 birds per replicate. Dietary treatments were based on a basal diet and supplemented with 0, 0.08, 0.12, or 0.16% NCG to form C, N1, N2, and N3 groups. Results and discussion: We found that layers in group N1 had higher egg production rate than those in group C. Egg weight was significantly reduced, while eggshell thickness was significantly improved, by treatment. However, the albumen height and Haugh unit were the lowest in group N3. Based on the above results, groups C and N1 were selected for further transcriptomics analysis of uterine tissue by RNA-seq. More than 7.4 Gb clean reads and 19,882 tentative genes were obtained using the Gallus gallus genome as a reference. Transcriptomics analysis in uterus tissue revealed that 95 differentially expressed genes (DEGs) were upregulated and 127 DEGs were downregulated. Functional annotation and pathway enrichment analysis showed that DEGs in uterine tissue were mainly enriched in glutathione metabolism, cholesterol metabolism, and glycerolipid metabolism, etc. Vitamin A metabolism-related gene, RBP1, nutrient transport-related gene, ALB, protein synthesis-related gene, METTL21C, and calcium transport-related gene, RYR2, CACNB2, RAMP3, and STAC, were significantly regulated by 0.08% NCG supplementation. Therefore, we concluded that NCG supplementation at a dose of 0.08% improved production performance and egg quality of layers by regulating uterus function.

Construction and application of a prediction model for the delivery outcome of women with scarred uterus based on ultrasonic parameters.

OBJECTIVE: To explore the application value of the prediction model for delivery outcome of women with scarred uterus based on ultrasonic parameters. METHODS: In this retrospective study, a total of 100 pregnant women with scarred uterus who delivered in Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine were selected as the research subjects. Adverse pregnancy outcomes included premature delivery, low birth weight, neonatal asphyxia, postpartum hemorrhage, and uterine rupture. In line with delivery outcome, the pregnant women were segmented into good outcome group (n = 78) and poor outcome group (n = 22). We collected and compared the clinical data and the ultrasonic parameters of pregnant women of the two groups. Multivariate logistic regression analysis was conducted to explore the risk factors affecting the delivery outcome of women with scarred uterus and to establish a prediction model. RESULTS: Multivariate logistic regression analysis showed that low hemoglobin (Hb) before delivery, high grade of uterine scar, low muscle thickness of lower uterine segment, and low blood flow index were the risk factors for poor delivery outcome of women with scarred uterus. According to the risk factors, the prediction model was obtained: Prob = 1/[1 + e^ (-5.110-2.568 * Pre-delivery Hb - 1.697 * uterine scar grade -2.895 * lower uterine muscle thickness + 19.584 * blood flow index)]. The sensitivity, specificity and area under the curve were 90.0, 91.0 and 0.959, respectively. After validation, the sensitivity and specificity were 85.71 and 87.04, respectively. CONCLUSION: Low Hb before delivery, low grade of uterine scar, low musculature thickness of lower uterine segment, and low blood flow index were the risk factors for poor delivery outcome of women with scarred uterus. The establishment of prediction model based on risk factors could effectively evaluate the risk of poor delivery outcome of women with scarred uterus.

Accentuated Hippo pathway and elevated miR-132 and miR-195a lead to changes of uteri and ovaries in offspring mice following prenatal exposure to vinclozolin.

Vinclozolin (VCZ) has been identified as a broad-spectrum fungicide and an environmental endocrine disruptor. Also, the Hippo signaling pathway controls organ size by regulating cell proliferation and apoptosis, and moreover, overexpression of microRNA-132 (miR-132) and microRNA-195 (miR-195) inhibits cell proliferation and promotes apoptosis. So, in this study, the experimental mice were orally given 400 mg/kg/day VCZ (suspended in corn oil) at gestational day 12-18, while those of the control group were fed with corn oil of equal volume. Then unilateral ovaries and mid-uteri were isolated from 10 randomly-selected mice at the postnatal 1st week (7 days), 3rd week (20-21 days), and 7th week (48-49 days) respectively to observe gene levels, while 6 of the contralateral ovaries and uteri were subsequently examined for proteins respectively. Besides, 16 from both groups were determined with serum estradiol (E2) at week 7, of which 6 were randomized for histological observation. Here we found the levels of E2 reduced in VCZ-group at week 7, with fewer follicles and injured endometrium. Meanwhile, in VCZ mice of all ages, increased miR-132 and miR-195a, decreased G protein-coupled estrogen receptor (GPER), elevated phosphorylated large tumor suppressor (pLATS) and phosphorylated yes-associated protein (pYAP), and decreased yes-associated protein (YAP) were observed in their ovaries and uteri. These findings suggested ovarian and uterine dysplasia in the offspring induced by gestational VCZ-exposure were mainly attributed to higher miR-132 and miR-195a and accentuated Hippo-pathway.

Osteoprotective effects of kefir fortified with omega-3 and vitamin C in ovariectomized rats.

Nutritional interventions can be valuable for the prevention of postmenopausal osteoporosis. This study aimed to investigate the effects of kefir fortified with omega-3 and vitamin C on the bone and uterus parameters of ovariectomized rats. Seventy-seven female Sprague-Dawley rats were ovariectomized or sham-operated. The ovariectomized rats were assigned to six groups and received 1 ml/day of distilled water (OVX group), milk, kefir, kefir fortified with omega-3 fatty acids (kefir+ω3), kefir fortified with vitamin C (kefir+vit-C) or kefir fortified with omega-3 and vitamin C (kefir+ω3+vit-C) for 12 weeks. The sham group also received 1ml/day of distilled water. Subsequently, bone mineral content (BMC) and bone mineral density (BMD) of various bones were assessed. Femurs and uteri were harvested for bone ash analysis and histopathological examinations, respectively. Sera were analyzed for carboxy-terminal cross-linked telopeptide of type 1 collagen, procollagen type 1 amino-terminal propeptide, calcium, phosphorous, tumor necrosis factor-α (TNF-α) and total antioxidant capacity levels. Ovariectomy resulted in significant reduction in bone density (P<0.05). Kefir+ω3+vit-C significantly improved BMC of lumbar spine (0.699±0.027 g compared with 0.580±0.018 in the OVX group), and kefir, kefir+vit-C and kefir+ω3+vit-C significantly increased BMD of tibia (0.118±0.003 g/cm2, 0.119±0.001 and 0.120±0.004 compared with 0.102±0.005 in the OVX group). Moreover, ovariectomy markedly elevated TNF-α level, which was significantly reversed by kefir+ω3+vit-C. Significant atrophy of the uterus was observed following ovariectomy, although the uterus parameters did not change by any of the interventions. In conclusion, kefir fortified with omega-3 fatty acids and vitamin C may have protective effects against bone loss through suppressing inflammation.

Effects of sparrow-pecking moxibustion on the temperature and blood flow perfusion of moxibustion point area and uterus and serum AVP,PGF2α,and TXB2 in rats with dysmenorrhea / 针灸推拿医学（英文版）

Objective:To observe the effects of sparrow-pecking moxibustion at Shenque(CV8)and Guanyuan(CV4)on the writhing reaction and score,the temperature and blood flow perfusion of moxibustion point area and uterus,the serum levels of arginine vasopressin(AVP),prostaglandin(PG)F2α,and thromboxane(TX)B2 in rats with primary dysmenorrhea(PD)due to cold-dampness stagnation,and to explore the possible mechanism of sparrow-pecking moxibustion in treating PD.Methods:Thirty-two healthy non-pregnant female Wistar rats were randomly divided into a normal group,a model group,an ibuprofen group,and a sparrow-pecking moxibustion group,with 8 rats in each group.Except for the normal group,the other three groups were subjected to modeling with cold water bath combined with estradiol benzoate and oxytocin injection.Rats in the sparrow-pecking moxibustion group were treated with sparrow-pecking moxibustion at Shenque(CV8)and Guanyuan(CV4)on the 8th day of modeling,30 min/time,once a day for 3 d;those in the ibuprofen group were treated with 0.8 mL ibuprofen solution(a specification of 125 mg in 10 mL)on the 8th day of modeling,once a day for 3 d;those in the normal group and the model group were given 0.8 mL normal saline,once a day for 3 d.On the 11th day,rats in each group were intraperitoneally injected with oxytocin(2 U/rat),and the writhing incubation period and writhing score in 20 min were observed;the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus in vivo were detected;the serum levels of AVP,PGF2α,and TXB2 were determined.Results:The writhing incubation period was significantly longer(P<0.01)and the writhing score was significantly lower(P<0.01)in the sparrow-pecking moxibustion group and the ibuprofen group than in the model group;compared with the ibuprofen group,the writhing incubation period was prolonged(P<0.01)and the writhing score was decreased(P<0.01)in the sparrow-pecking moxibustion group;compared with the normal group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly decreased,while the serum PGF2α,AVP,and TXB2 levels were significantly increased(P<0.01)in the model group;compared with the model group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly increased,and the serum levels of PGF2α,AVP,and TXB2 were significantly decreased in the ibuprofen group and the sparrow-pecking moxibustion group(P<0.05 or P<0.01);compared with the ibuprofen group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly increased(P<0.05),the serum AVP and TXB2 levels were significantly decreased(P<0.05),while the serum PGF2α level had no statistical difference in the sparrow-pecking moxibustion group(P>0.05).Conclusion:Sparrow-pecking moxibustion had a remarkable analgesic effect on the rats with PD due to cold-dampness stagnation,and the mechanism may be related to the increased temperature and blood perfusion of the moxibustion point area and uterus,as well as the decreased serum PGF2α,AVP,and TXB2 levels.

INTERDEPENDENCE OF SKIN AND UTERUS IN PERSIAN MEDICINE

Persian Medicine, which flourished in the Islamic Golden Age (9th to 12th century AD), considers the human body a unified whole whose organs are in constant interaction and equilibrium with each other. The skin is one of these interdependent organs that play an important role in protecting internal organs, and as an excretion route, it can expel substances that are not consumed by the body. Alternatively, the uterus, a vital organ in pregnancy, excretes excess body material during menstruation to maintain a woman's health. This narrative study discussed the importance of aligning the structure and function of these two organs based on the main textbooks of Persian Medicine, especially those written during this historical period. Likewise, electronic databases were used for investigating related articles. The skin and uterus are two excretory organs. When the secretion of excess material through menstruation is physiologically or pathologically impaired, the body transfers these substances to the skin as the organ associated with the uterus. Thus, the clinical manifestations of some skin diseases can be a sign of imbalance in the function of the uterus and its related organs. Consequently, the structural and functional similarities of both organs can provide a new guide in the approach to their participatory diseases in the integration of Persian and conventional medicine.

HYSTERICAL APNEA IN THE WORK OF GALEN (CA 129 - 199 AD): GENDER EQUITY IN THE HISTORY OF PSYCHOSOMATIC MEDICINE.

OBJECTIVE: The aim: To presents clinical, epidemiological and pathophysiological aspects of the disease described by Galenos of Pergamon during the 2nd century AD and discusses its implications on contemporary discourse on gender equity and gender - based discrimination. PATIENTS AND METHODS: Materials and methods: The authors searched original medical texts written in Greek language and attributed to Galenos for records related to hysterical apnea. CONCLUSION: Conclusions: Galen attempted to interpret hysterical apnea by combining clinical and epidemiological observations with anatomical and functional lesions. His approach denounced the anatomically unsound notion of the wandering womb and availed the knowledge of his period in a rational manner. Investigating gender - related aspects of contemporary psychosomatic conditions related to fertility and pregnancy can help address gender - based discrimination in modern societies.