Serum Metabolites as Diagnostic Biomarkers in Patients with Endometriosis.

Endometriosis diagnosis is usually delayed. The gold standard for diagnosing endometriosis is laparoscopy, which is invasive and accompanied by several risks. Currently, there are no effective non-invasive biomarkers for diagnosing endometriosis. Here, we investigated whether metabolites whose levels are altered in patients with endometriosis hold potential as diagnostic biomarkers for the disease. This case-control study involved 32 patients with endometriosis and 29 patients with other benign gynecological disease. The diagnosis of all patients was confirmed through postoperative histopathological examination, and the patients were divided into two groups: an endometriosis group (EM) and a control group. Fasting blood was collected and used for non-targeted metabolomic-based detection. The data were processed through principal component analysis, orthogonal partial least squares discriminant analysis, and significance analysis of microarrays. A univariate receiver operating characteristic curve was used to evaluate the diagnostic value of the metabolites. The metabolite profiles of patients with endometriosis were markedly different compared with those of the controls. In addition, several metabolic pathways, including biosynthesis of unsaturated fatty acids, arginine biosynthesis, and glutathione metabolism, were altered. Ornithine and medorinone showed better potential as biomarkers for endometriosis diagnosis than CA125. We analyzed the altered metabolic profiles in patients with endometriosis and found ornithine and medorinone as potential non-invasive biomarkers for endometriosis diagnosis, whereas the combined ornithine-medorinone diagnosis is more valuable. These findings may help advance research on non-invasive diagnostic biomarkers for endometriosis. Further research with an improved study design and a larger cohort should be performed to confirm the diagnostic potential and clinical application of these biomarkers.

Dental and skeletal maturation of Chinese male children with unilateral cleft lip and palate.

The aim of this study was to determine whether the relationship between dental age (DA), cervical stage (CS) and chronological age (CA) in Chinese male children with unilateral cleft lip and palate (UCLP) is similar to that of children without clefts. Panoramic and cephalometric radiographs of 105 male UCLP patients, aged from 8 to 16 years, were collected and compared to 210 age-matched healthy control males. The Demirjian and cervical vertebral maturation (CVM) methods were used to visually examine the radiographs and Spearman's correlation analysis was used to identify differences between the two groups with regards to CS, DA and CA. There was a significant positive correlation between DA and CA in both groups and the mean CA-DA difference was significantly higher in children with UCLP when compared to controls (0.319 vs. 0.003, p < 0.05). A significant delay in tooth development was detected in UCLP children from 10 to 12 years-of-age. Both the UCLP and control groups showed high correlations between CS and DA. Calcification stage D appeared only before CS3; however, from CS5 to 6, all teeth have almost completed their maturation phase. Chinese male UCLP patients are likely to experience delayed tooth development compared to healthy controls, especially during the fast-growing period. Evaluating the stages of tooth mineralization could represent a rapid method to assess growth potential.

Role of ultrasonography in the evaluation of disease severity and treatment efficacy in adenomyosis.

BACKGROUND: Adenomyosis is a benign disorder characterized by the presence of ectopic endometrial glands and stroma within the myometrium. The main clinical manifestations of adenomyosis are dysmenorrhea, menorrhagia, and infertility, which affect patients' quality of life. Recently, with advancements in imaging techniques, magnetic resonance imaging, and ultrasonography have become the main diagnostic tools for adenomyosis. In addition to the diagnosis and differential diagnosis of adenomyosis, ultrasonography can also be used to evaluate the severity of adenomyosis. The emergence of new techniques, such as elastography and contrast-enhanced ultrasonography (CEUS), has significantly improved the accuracy of ultrasound-based diagnosis of adenomyosis. These two imaging tools can also be used for the differential diagnosis of adenomyosis and the evaluation of treatment efficacy after medication or ablation procedure. OBJECTIVE: we review the efficacy of ultrasonography as a diagnostic tool for adenomyosis. We also aim to introduce the potential of ultrasound imaging in the evaluation of the severity of this disease, as well as the application of elastography and contrast-enhanced ultrasonography (CEUS) in its diagnosis. RESULTS AND CONCLUSION: Our findings reveal the potential value of ultrasonography combined with elastography and/or CEUS as medication guidance and efficacy evaluation tools in the long-term management of adenomyosis.

Application of elastography to diagnose adenomyosis and evaluate the degree of dysmenorrhea: a prospective observational study.

BACKGROUND: To determine whether there is a correlation between stiffness measured by strain elastography and the severity of dysmenorrhea and to determine the value of elastography in evaluating severe dysmenorrhea in patients with adenomyosis. METHODS: The correlation between tissue stiffness and dysmenorrhea was analyzed by performing elastography on premenopausal women diagnosed with adenomyosis. Expression levels of transforming growth factor-ß (TGF-ß), α-smooth muscle actin (α-SMA), and protein gene product 9.5 (PGP9.5) were detected by immunohistochemistry; the correlation of TGF-ß and α-SMA levels with the tissue stiffness and the degree of fibrosis was further analyzed. Also, the relationship of the PGP9.5 expression level with the tissue stiffness and degree of dysmenorrhea was determined. RESULTS: The degree of dysmenorrhea was significantly positively correlated with lesion stiffness in patients with adenomyosis but not with the uterine or lesion volume. The cutoff for the strain ratio was > 1.36 between the adenomyosis and control groups, with an area under the curve (AUC) of 0.987. For severe dysmenorrhea, the cutoff for the strain ratio was > 1.65 in patients with adenomyosis, with an AUC of 0.849. TGF-ß, α-SMA, and PGP9.5 expression levels were higher in adenomyotic lesions than in the endometrium of the adenomyosis and control groups. Both TGF-ß and α-SMA levels were positively correlated with the tissue stiffness and degree of fibrosis. Additionally, the expression level of PGP9.5 showed a positive correlation with the tissue stiffness and degree of dysmenorrhea. CONCLUSIONS: Elastography can be used to evaluate the degree of dysmenorrhea; the greater the tissue stiffness, the greater the degree of dysmenorrhea. In addition, elastography performed well in the diagnosis of adenomyosis and the evaluation of severe dysmenorrhea in patients with adenomyosis.

VOCs from fungi-infected apples attract and increase the oviposition of yellow peach moth Conogethes punctiferalis.

BACKGROUND: Plant volatile organic compounds (VOCs) modified by plant-associated microbes can attract or repel the oviposition of herbivores. Here, we explored the effects of three different fungi on apples' VOCs and the cascading impacts on the oviposition preference of yellow peach moth [YPM, Conogethes punctiferalis (Guenée)]. RESULTS: Among Penicillium crustosum-infected apples (PCA), Rhizopus oryzae-infected apples (ROA), Colletotrichum gloeosporioides-infected apples (CGA) and healthy apples (HA), mated YPM females preferred to oviposit eggs on ROA and CGA, and showed significant attractiveness to VOCs from PCA, ROA, and CGA under laboratory conditions. The VOCs analyses showed that there were significant differences between fungi-infected apples (ROA, CGA) and control treatments (mechanically damaged apples (MDA), HA) in terms of the relative contents of 13 VOCs. The relative contents of ethyl 2-methylbutyrate, ethyl caprylate, estragole, ethyl hexanoate in ROA and CGA were higher than those in MDA. The relative content of isopropyl 2-methylbutyrate in ROA was significantly higher than those in HA and CGA. The relative contents of 2-methylbutyl acetate, butyl 2-methylbutyrate, hexyl 2-methylbutyrate, amyl hexanoate, hexyl hexanoate, (E, E)-α-farnesene in ROA and CGA were lower than those in HA. The relative content of hexyl acetate in ROA and CGA was significantly higher than that in MDA, but lower than that in HA. Additionally, 10 fungi-induced VOCs were detected in ROA and/or CGA. When 20 VOCs from ROA and/or CGA were tested as individuals or mixed blends in Y-tube olfactometer assays, mated YPM females preferred amyl 2-methylbutyrate, isoamyl 2-methylbutyrate, isopropyl 2-methylbutyrate, hexyl propionate (common VOCs in ROA, CGA, and HA), and heptacosane (a fungi-induced VOC in ROA), but no significant preferences were observed between individual compounds and mixed blends, except for hexyl propionate. CONCLUSION: Different fungi infection increased the relative contents of common VOCs from healthy and fungi-infected apples, which ultimately resulted in the significant attractiveness for the oviposition of mated YPM females. This study clarified why fungi-infected apples were more attractive to YPMs than healthy apples and screened out the crucial VOCs for YPM oviposition. © 2023 Society of Chemical Industry.

Iron deposition in ovarian endometriosis evaluated by magnetic resonance imaging R2* correlates with ovarian function.

RESEARCH QUESTION: Does iron overload in patients with endometriosis affect ovarian function? Can a method be developed to visually reflect this? DESIGN: Magnetic resonance imaging (MRI) R2* was used to evaluate the correlation between iron deposition of ovarian and anti-Müllerian hormone (AMH) in patients with endometriosis. All patients underwent T2* MRI scanning. Serum AMH levels were measured preoperatively. The area of focal iron deposition, iron content of the cystic fluid and AMH levels between the endometriosis and control groups were compared using non-parametric tests. The effects of iron overload on AMH secretion in mouse ovarian granulosa cells were investigated by adding different concentrations of ferric citrate to the medium. RESULTS: A significant difference was found between endometriosis and control groups in area of iron deposition (P < 0.0001), cystic fluid iron content (P < 0.0001), R2* of lesions (P < 0.0001) and R2* of the cystic fluid (P < 0.0001). Negative correlations were found between serum AMH levels and R2* of cystic lesions in patients with endometriosis aged 18-35 years (rs = -0.6484, P < 0.0001), and between serum AMH levels and R2* of cystic fluid (rs = -0.5074, P = 0.0050). Transcription level (P < 0.0005) and secretion level (P < 0.005) of AMH significantly decreased with the increase in iron exposure. CONCLUSION: Iron deposits can impair ovarian function, which is reflected in MRI R2*. Serum AMH levels and R2* of cystic lesions or fluid in patients aged 18-35 years had a negative correlation with endometriosis. R2* can be used to reflect the changes of ovarian function caused by iron deposition.

Establishment and application of the "electronic follow-up platform for endometriosis" during the COVID-19 pandemic.

The management of endometriosis has been complicated by the COVID-19 pandemic. We aimed to introduce the establishment and application of a new follow-up method during the COVID-19 pandemic-the electronic follow-up (e-follow-up) platform for endometriosis-and to test the applicability of the platform-based follow-up management model and patient satisfaction. We used the platform for information entry and post-operative follow-up of 152 patients with endometriosis from January 2021 to August 2022, and compared patients' Zung's Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Visual Analogue Score (VAS) (range: 0 - 10, indicating: no pain-extreme pain) scores preoperatively and after 6-month of follow-up, together with recording patients' follow-up satisfaction and number of recurrence of lesions. Eventually, the SDS, SAS, and VAS scores were significantly lower than those at pre-surgery (p < .001), and the follow-up satisfaction rate reached 100%, with 91.41% expressing great satisfaction. The cumulative number of recurrences was 2 out of 138. Follow-up using this platform reduce the risk of COVID-19 transmission, enabled more efficient access to healthcare resources for patients with endometriosis, improved the efficiency of follow-up management, met the mental health needs of the patients.

Clinical efficacy and safety of trimonthly administration of goserelin acetate 10.8 mg in premenopausal Chinese females with symptomatic adenomyosis: a prospective cohort study.

OBJECTIVE: This prospective cohort study aimed to compare the clinical efficacy and safety of goserelin 10.8 mg administered trimonthly with goserelin 3.6 mg administered monthly in premenopausal females with symptomatic adenomyosis. METHODS: We recruited 139 premenopausal females with adenomyosis who complained of dysmenorrhea and/or menorrhagia. The first group (n = 70) received a single subcutaneous injection of goserelin 10.8 mg, and the second group (n = 69) received monthly subcutaneous goserelin 3.6 mg administered for 3 months. Follow-up was performed at the outpatient department after 12 weeks. RESULTS: Ultimately, 130 patients completed the study, including 68 and 62 patients in the goserelin 10.8 mg (n = 70) and 3.6 mg (n = 69) groups, respectively. We observed a significant decrease in the dysmenorrhea (NRS) score, uterine volume, and cancer antigen 125 (CA125) levels, and a significant increase in hemoglobin (HGB) levels in both treatment groups. There was no significant difference between the two groups. The sum of the adverse event scores was slightly higher in the goserelin 3.6 mg than in the 10.8 mg group. CONCLUSIONS: The clinical efficacy of trimonthly administration of goserelin 10.8 mg was equivalent to monthly 3.6 mg dosing and was non-inferior regarding safety and tolerability. Hence, it can be a more cost-effective and convenient alternative treatment option in premenopausal females with symptomatic adenomyosis. TRIAL REGISTRATION: ChiCTR2200059548.

Brain Morphological and Functional Changes in Adenomyosis with Pain: A Resting State Functional Magnetic Resonance Imaging Study.

The absence of clinically objective methods to evaluate adenomyosis-associated pain and the poor understanding of its pathophysiology lead to treatment limitations. We conducted a resting-state functional magnetic resonance imaging study with 49 patients with pain-related adenomyosis and 30 pain-free controls to investigate brain morphological alterations and regional dysfunctions in patients with pain-related adenomyosis. These patients had significantly higher scores for anxiety and depression than the control group (p < 0.05). They also had a lower gray matter volume (GMV) in the bilateral insula, left angular gyrus, precuneus, left inferior temporal gyrus, and left postcentral gyrus (p < 0.05, AlphaSim corrected). Similarly, decreased voxel-mirrored homotopic connectivity was observed in the bilateral insula, posterior cingulate cortex, middle frontal gyrus, and postcentral gyrus in the adenomyosis patient group (p < 0.05, AlphaSim corrected). Regional homogeneity showed significant differences mainly in the bilateral cerebellum, left inferior frontal gyrus, medial prefrontal cortex, and posterior cingulate gyrus. Correlation analysis showed that the degree of depression in patients with adenomyosis was negatively correlated with the GMV of the left angular gyrus. The results show that these patients exhibited changes in multiple brain regions associated with pain as well as emotion perception and processing.

The effect of melatonin on the mouse ameloblast-lineage cell line ALCs.

Melatonin plays a critical role in promoting the proliferation of osteoblasts and the growth and development of dental papilla cells. However, the effect and mechanism of melatonin on the growth and development of ALCs still need to be explored. CCK8 assay was used for the evaluation of cell numbers. qRT-PCR was used to identify the differentially expressed genes in ALCs after melatonin treatment. The number and morphology of ALCs were investigated by confocal microscopy. Alkaline phosphatase assay and Alizarin red S staining were used for measuring mineralization. Then, we focused on observing the crucial factors of the signaling pathway by RNA-seq and qRT-PCR. Melatonin limited the cell number of ALCs in a dose-dependent manner and promoted the production of actin fibers. A high concentration of melatonin significantly promoted the mRNA levels of enamel matrix proteins and the formation of mineralized nodules. RNA-seq data showed that Wnt signaling pathway may be involved in the differentiation of ALCs under the influence of melatonin. This study suggests that melatonin plays a regulatory role in the cell number, differentiation, and mineralization of the ALCs, and then shows the relationship between the Wnt signaling pathway with the ALCs under melatonin.

Melatonin-Medicated Neural JNK3 Up-Regulation Promotes Ameloblastic Mineralization.

Introduction: Melatonin, an endogenous neurohormone, modulates the biological circadian rhythms of vertebrates. It functions have been reported in previous stomatological studies as anti-inflammation, antioxidant, osseointegration of dental implants and stimulation to dental pulp stem cells differentiation, but its role in ameloblastic differentiation and mineralization has been rarely studied. Objective: To reveal the effects of melatonin on the mineralization of ameloblast lineage cells (ALCs), and to identify the change in gene expression and the potential mechanism based on ribonucleic acid sequencing (RNA-seq) analysis. Method: ALCs were induced in melatonin-conditioned medium. After 7-days culture, Western blot, real-time PCR, alkaline phosphatase (ALP) activity test, RNA-seq were accordingly used to detect the change in molecular level. After 1-month odontogenic induction in melatonin medium, Alizarin Red-S (ARS) staining showed the changes of mineral nodules. Differentially expressed genes (DEGs), enrichment of functions and signaling pathways analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) database were performed. The JNK3 antagonist (JNK3 inhibitor IX, SR3576) and ß-arrestin1 (Arrb1) overexpression were applied to confirm the fluctuation of melatonin-medicated JNK3 and Arrb1 expression. Results: In this study, we found out melatonin contributed to the ameloblastic mineralization, from which we can observed the elevated expression of enamel matrix protein, and increased ALP activity and mineralized nodules formation. RNA-seq analysis showed the up-regulation of neural JNK3 and down-regulation of Arrb1 in ALCs. Meanwhile, phosphorylated JNK3 deficiency (phosphorylated JNK3 inhibitor---SR3576 added to culture medium) led to mineralization delay, and Arrb1 overexpression proved Arrb1 takes bridge between melatonin receptors (MTNR) and JNK3 in MAPK signaling pathway.