Lower serum AMH concentration is correlated with serum IgG1 decreased in the infertile woman: A real-world retrospective study.

OBJECTIVES: In this real-world approach, we examined the serum Anti-Mullerian Hormone (AMH) level and the relationship with serum IgG subclass in the infertile women. METHODS: A total of 574 female participants were recruited for this study. The serum AMH, IgG subclass(IgG1, IgG2, IgG3, IgG4) and immunoglobulin (Ig) G、IgM、IgA、IgE as well as complement C3, C4 were analyzed. The difference in serum AMH level was assessed according categorized as above or below the median of the ratio of serum IgG subclass(IgG1, IgG2, IgG3, IgG4) to total IgG (RIgG subclass/IgG). RESULTS: The serum AMH level of the low RIgG1/IgG group is significantly decreased than that high RIgG1/IgG group (p < 0.05). The Spearman correlation analysis showed that the serum AMH level was significantly negatively correlated with age and significantly positively correlated with serum IgG1 levels respectively (p < 0.05). GLMMs multivariate model showed that after adjusting the covariate and possible mixed factors including age, serum immunoglobulin, complement C3 and C4, the serum AMH level was significantly positively correlated with IgG1 level (p < 0.01). CONCLUSIONS: Decreased serum IgG1 may significantly affect the ovarian reserve function of women. Confirmation of this association and elucidation of its underlying mechanisms are needed to place these results in a clinical perspective.

Multimodal ultrasound evaluation of asymptomatic ulnar nerve dislocation at the cubital tunnel.

Background: Ultrasonography has received broad acceptance as an effective peripheral nervous imaging examination. Shear wave elastography (SWE) can quantitatively assess the stiffness of nerves; however, little research has been conducted on elastography for ulnar nerve dislocation. The purpose of this study was thus to investigate the characteristics of multimodal ultrasound, including high-resolution ultrasonography and SWE, for asymptomatic ulnar nerve dislocation at cubital tunnel. Methods: In this prospective cross-sectional study, 41 participants were recruited in Shandong Provincial Hospital Affiliated to Shandong First Medical University in July 2022. The inclusion criteria for participants were being in good health and being 18-60 years of age. Meanwhile, the exclusion criterion was a history of upper limb pain or fractures, peripheral neuropathy, or systemic or immunological diseases. Finally, 38 participants were enrolled. Two ultrasound doctors measured the maximum diameter, the maximum cross-sectional area (CSA), and the shear modulus of the ulnar nerve at the cubital tunnel independently. Another two ultrasound doctors determined whether dislocation was present during dynamic elbow flexion and extension and divided the elbows into a dislocation group and a control group. The descriptive statistics and independent sample t-test were used for data analysis, and intragroup correlation coefficient (ICC) was used to determine the consistency of evaluation between observers. Results: Ulnar nerve dislocation was observed in 15.8% (12/76) of the ulnar nerves. There was no significant difference in the maximum diameter between the dislocation group (0.194±0.022 cm) and the control group (0.181±0.023 cm) (t=1.888; P=0.063). The CSA and SWE of the ulnar nerve were 0.064±0.009 cm2 and 43.629±6.737 kPa in the dislocation group, respectively, and were 0.050±0.008 cm2 and 31.293±7.858 kPa in the control group, respectively. There were significant differences between the two groups in terms of CSA (P<0.001) and SWE (P<0.001). The ICCs of the maximum diameter, CSA, and SWE values between observers were 0.970, 0.900, and 0.915, respectively. Conclusions: Multimodal ultrasound consisting of high-resolution ultrasonography combined with elastography can comprehensively and quantitatively evaluate the morphological changes and mechanical properties of the dislocated ulnar nerve and monitor disease progress.

Diagnostic value of high-frequency ultrasound in omohyoid muscle syndrome.

PURPOSE: To investigate the diagnostic value of high-frequency ultrasound in omohyoid muscle syndrome. MATERIAL AND METHODS: A retrospective analysis of 11 patients diagnosed with omohyoid muscle syndrome was carried out, and the characteristics of high-frequency ultrasound images were summarized. RESULTS: Ultrasonography of the omohyoid muscle showed a narrow band of hypoechoic muscle bundle. The ultrasonographic manifestation of omohyoid muscle syndrome showed a thickening of the omohyoid muscle on the affected side. The omohyoid muscle on the affected side bulged forward during swallowing and lifted the overlying sternocleidomastoid muscle. The difference between the thickness of the omohyoid muscle intermediate tendon on the affected side and the healthy side at rest was statistically significant (t = 58.23, P < 0.001). The difference between the thickness of the affected omohyoid muscle intermediate tendon at rest and during swallowing was statistically significant (t = 14.57, P < 0.001). There was no statistically significant difference between the thickness of the omohyoid muscle intermediate tendon on the healthy side at rest and during swallowing (t = 0.56, P > 0.05). CONCLUSION: High-frequency ultrasound is the preferred imaging method in the diagnosis of omohyoid muscle syndrome.

GIMAP7 inhibits epithelial-mesenchymal transition and glycolysis in lung adenocarcinoma cells via regulating the Smo/AMPK signaling pathway.

BACKGROUND: GTPase immunity-associated protein 7 (GIMAP7) has been previously recognized as a prognostic marker in pan-cancer. Our objective was to explore the function of GIMAP7 in the progression of lung adenocarcinoma (LUAD). METHODS: GIMAP7 was overexpressed by transfection with GIMAP7 plasmid, and knocked down using siRNAs. The biological functions of GIMAP7 were examined by employing CCK-8, EdU, colony formation, flow cytometry, wound healing, and transwell assays. The effects of GIMAP7 on the extracellular acidification rate (ECAR), oxygen consumption rate (OCR), lactate production, and glucose uptake were evaluated. In addition, the related mRNA and protein expression was detected employing immunohistochemical, western blot, and qRT-PCR. A xenograft tumor model was established in nude mice to evaluate the effects of GIMAP7 on tumor growth. RESULTS: GIMAP7 was lowly expressed in LUAD tissues and cells. GIMAP7 inhibited the proliferation, mobility, EMT, glycolysis, but promoted apoptosis in LUAD cells. Moreover, we also confirmed that GIMAP7 suppressed Smo/AMPK signaling in LUAD cells. By adding the Smo agonist SAG and AMPK agonist GSK621, the results of rescue experiments further verified that GIMAP7 played a role in LUAD inhibition through inhibition of the Smo/AMPK signaling pathway. Furthermore, the role of GIMAP7 in inhibiting tumor growth was verified in vivo. CONCLUSIONS: These results demonstrate that GIMAP7 could inhibit cell proliferation, mobility and glycolysis, but accelerate apoptosis via repressing the Smo/AMPK signaling pathway in LUAD.

Downregulation of CRHBP is associated with trophoblast invasion inhibition in recurrent pregnancy loss.

In brief: Corticotropin-releasing hormone binding protein (CRHBP) is fundamental to the stress response and plays an important role in parturition during pregnancy. This study shows that abnormal CRHBP expression could be an early warning sign of recurrent pregnancy loss and that CRHBP knockdown could suppress HTR8/SVneo cell invasion by the PKC signaling pathway via interacting with CRH receptor 2. Abstract: Trophoblast invasion is critical for placentation and pregnancy success. Trophoblast dysfunction results in many pregnancy complications, including recurrent pregnancy loss (RPL). Corticotropin-releasing hormone binding protein (CRHBP) is fundamental to the stress response and plays an important role in parturition during pregnancy via binding with CRH. To further characterize its function in early pregnancy, we explored the expression of CRHBP in villi during early pregnancy. Compared with normal pregnant women, we demonstrated that the expression of CRHBP decreased in the trophoblasts and villi in RPL patients and that knockdown of CRHBP expression could suppress HTR8/SVneo cell invasion significantly. Our further exploration indicated that the capacity of CRHBP for regulating trophoblast invasion was associated with the PKC signaling pathway via interacting with CRH receptor 2. These findings might provide a new fundamental mechanism for successful pregnancy and a new diagnostic and therapeutic target for RPL.

Identification of m6A Modification Regulated by Dysregulated circRNAs in Decidua of Recurrent Pregnancy Loss.

N6-methyladenosine (m6A) modification is a prevalent modification of messenger ribonucleic acid (mRNA) in eukaryote cells and is closely associated with recurrent pregnancy loss (RPL). Circular RNAs (circRNAs) play critical roles in embryo implantation, trophoblast invasion and immune balance, which are important events during pregnancy. However, how m6A modification is regulated by circRNAs and the potential regulatory mechanism of circRNAs on RPL occurrence remain largely unclassified. We displayed the expression profiles of circRNAs and mRNAs in the decidua of normal pregnancies and RPL patients based on circRNA sequencing and the Gene Expression Omnibus database. A total of 936 differentially expressed circRNAs were identified, including 509 upregulated and 427 downregulated circRNAs. Differentially expressed circRNAs were enriched in immune, metabolism, signaling and other related pathways via the analysis of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The competitive endogenous RNA (ceRNA) network was predicted to supply the possible role of circRNAs in RPL occurrence, and we further analyzed the profiles of nine m6A regulators (seven readers, one writer and one eraser) managed by circRNAs in this network. We also showed the expression profiles of circRNAs in the serum, trying to seek a potential biomarker to help in the diagnosis of RPL. These data imply that circRNAs are involved in pathogenesis of RPL by changing immune activities, metabolism and m6A modification in the ceRNA network. Our study might provide assistance in exploring the pathogenesis and diagnosis of RPL.

The role of ultrasonography in diagnosing acute closed volar plate injury of proximal interphalangeal joint.

BACKGROUND: Acute closed volar plate injury of the proximal interphalangeal joint (PIP) is a common hand injury. In the past, there were few objective evaluation imaging methods for the degree of volar plate injury. The purpose of this study was to investigate the role of high frequency ultrasonography in diagnosing volar plate injury, and to explore whether ultrasound can provide a beneficial guidance to clinical decision-making and appropriate treatment adopting through accurate US classification of volar plate injury. METHODS: From May 2019 to may 2022, 41 patients diagnosed with volar plate injury were included in this study. All patients underwent ultrasonography and X-ray examinations. The sonographic features were analyzed. A new kind of classification of volar plate injury based on ultrasonography findings was described. RESULTS: Either an injury of volar plate or an avulsion fracture of middle phalangeal base was identified clearly on ultrasonography, according to which volar plate injury could be divided into three types: A, B and C. Type A, avulsion fracture of the middle phalangeal base without volar plate rupture; Type B, full thickness tear of the volar plate without avulsion fracture; Type C, partial thickness tear of the volar plate. The average thickness of the three types of injured volar plate measured by ultrasound was 0.33 ± 0.05 cm, and the average thickness of the volar plate at the same site of the corresponding finger on the contralateral side was 0.22 ± 0.03 cm. There was significant difference between the two group (t = 11.823, p = 1.2476 *10^(-14)). CONCLUSIONS: High frequency ultrasonography could be a reliable, accurate, convenient and non-radioactive diagnostic imaging technique in the evaluation of acute closed volar plate injury of PIP. And ultrasound could provide a beneficial guidance to clinical decision-making and appropriate treatment adopting through accurate US classification.

Energy metabolism and maternal-fetal tolerance working in decidualization.

One pivotal aspect of early pregnancy is decidualization. The decidualization process includes two components: the differentiation of endometrial stromal cells to decidual stromal cells (DSCs), as well as the recruitment and education of decidual immune cells (DICs). At the maternal-fetal interface, stromal cells undergo morphological and phenotypic changes and interact with trophoblasts and DICs to provide an appropriate decidual bed and tolerogenic immune environment to maintain the survival of the semi-allogeneic fetus without causing immunological rejection. Despite classic endocrine mechanism by 17 ß-estradiol and progesterone, metabolic regulations do take part in this process according to recent studies. And based on our previous research in maternal-fetal crosstalk, in this review, we elaborate mechanisms of decidualization, with a special focus on DSC profiles from aspects of metabolism and maternal-fetal tolerance to provide some new insights into endometrial decidualization in early pregnancy.

Comparative analysis of ultrasound diagnosis and pathological characteristics of external jugular venous aneurysm.

PURPOSE: This study aimed to investigate the diagnosis of the external jugular venous aneurysm on color Doppler ultrasound and its relationship with pathological characteristics. METHODS: A retrospective analysis of 17 patients with external jugular venous aneurysm admitted to the Provincial Hospital Affiliated with Shandong First Medical University from May, 2010, to June, 2020, was performed. The color Doppler ultrasound characteristics of 17 patients with external jugular vein aneurysms were analyzed and summarized, which were then compared with postoperative pathological outcomes. RESULTS: All 17 patients with external jugular venous aneurysms were presented with cystic structures adjacent to and communicated with the external jugular vein. Color Doppler flow imaging showed a bidirectional venous flow signal in the communication between the cystic structure and the external jugular vein. Among the 17 patients, ultrasound diagnosis showed true venous aneurysm due to degenerative changes in the venous wall in 8 cases, venous pseudoaneurysm in 4 cases, and external jugular venous aneurysm in 5 cases, and postoperative pathology indicated degenerative changes in the venous wall in all 17 patients. CONCLUSION: Bidirectional blood flow at the communication between the cystic lesion and the external jugular vein on color Doppler ultrasound should not be the criterion for the diagnosis of external jugular venous pseudoaneurysm, which requires pathological support.

A novel small-molecular CCR5 antagonist promotes neural repair after stroke.

Chemokine receptor 5 (CCR5) is one of the main co-receptors of HIV-1, and has been found to be a potential therapeutic target for stroke. Maraviroc is a classic CCR5 antagonist, which is undergoing clinical trials against stroke. As maraviroc shows poor blood-brain barrier (BBB) permeability, it is of interest to find novel CCR5 antagonists suitable for neurological medication. In this study we characterized the therapeutic potential of a novel CCR5 antagonist A14 in treating ischemic stroke mice. A14 was discovered in screening millions compounds in the Chemdiv library based on the molecular docking diagram of CCR5 and maraviroc. We found that A14 dose-dependently inhibited the CCR5 activity with an IC50 value of 4.29 µM. Pharmacodynamic studies showed that A14 treatment exerted protective effects against neuronal ischemic injury both in vitro and vivo. In a SH-SY5Y cell line overexpressing CCR5, A14 (0.1, 1 µM) significantly alleviated OGD/R-induced cell injury. We found that the expression of CCR5 and its ligand CKLF1 was significantly upregulated during both acute and recovery period in focal cortical stroke mice; oral administration of A14 (20 mg·kg-1·d-1, for 1 week) produced sustained protective effect against motor impairment. A14 treatment had earlier onset time, lower onset dosage and much better BBB permeability compared to maraviroc. MRI analysis also showed that A14 treatment significantly reduced the infarction volume after 1 week of treatment. We further revealed that A14 treatment blocked the protein-protein interaction between CCR5 and CKLF1, increasing the activity of CREB signaling pathway in neurons, thereby improving axonal sprouting and synaptic density after stroke. In addition, A14 treatment remarkably inhibited the reactive proliferation of glial cells after stroke and reduced the infiltration of peripheral immune cells. These results demonstrate that A14 is a promising novel CCR5 antagonist for promoting neuronal repair after ischemic stroke. A14 blocked the protein-protein interaction between CKLF1 and CCR5 after stroke by binding with CCR5 stably, improved the infarct area and promoted motor recovery through reversing the CREB/pCREB signaling which was inhibited by activated CCR5 Gαi pathway, and benefited to the dendritic spines and axons sprouting.

Diagnostic value of high-frequency ultrasound for Poland syndrome.

BACKGROUND: The imaging diagnosis of Poland syndrome is mostly computed tomography (CT) or magnetic resonance imaging (MRI), whereas high-frequency ultrasound for the diagnosis of Poland syndrome is relatively rare. PURPOSE: To investigate the diagnostic value of high-frequency ultrasound for Poland syndrome. MATERIAL AND METHODS: A retrospective analysis of 15 patients diagnosed with Poland syndrome was performed, and the characteristics of ultrasound images were summarized. RESULTS: High-frequency ultrasound clearly depict the anatomical structures of each layer of the chest wall in patients with Poland syndrome. Ultrasonography mainly showed partial or total absence of the pectoralis major muscle on the affected side, and some of which were combined with the absence of the pectoralis minor muscle. The difference was statistically significant in the thickness of the affected chest wall compared with the healthy side (P < 0.01). Out of 15 cases with Poland syndrome, 11 were associated with ipsilateral brachydactyly or syndactyly, and high-frequency ultrasonography showed that the bifurcation position of the common palmar digital artery on the affected finger was lower than that on the healthy side. CONCLUSION: High-frequency ultrasound is an effective imaging method for the diagnosis of Poland syndrome.

Decidual Stromal Cell Ferroptosis Associated with Abnormal Iron Metabolism Is Implicated in the Pathogenesis of Recurrent Pregnancy Loss.

Iron is necessary for various critical biological processes, but iron overload is also dangerous since labile iron is redox-active and toxic. We found that low serum iron and decidual local iron deposition existed simultaneously in recurrent pregnancy loss (RPL) patients. Mice fed with a low-iron diet (LID) also showed iron deposition in the decidua and adverse pregnancy outcomes. Decreased ferroportin (cellular iron exporter) expression that inhibited the iron export from decidual stromal cells (DSCs) might be the reason for local iron deposition in DSCs from low-serum-iron RPL patients and LID-fed mice. Iron supplementation reduced iron deposition in the decidua of spontaneous abortion models and improved pregnancy outcomes. Local iron overload caused ferroptosis of DSCs by downregulating glutathione (GSH) and glutathione peroxidase 4 levels. Both GSH and cystine (for the synthesis of GSH) supplementation reduced iron-induced lipid reactive oxygen species (ROS) and cell death in DSCs. Ferroptosis inhibitor, cysteine, and GSH supplementation all effectively attenuated DSC ferroptosis and reversed embryo loss in the spontaneous abortion model and LPS-induced abortion model, making ferroptosis mitigation a potential therapeutic target for RPL patients. Further study that improves our understanding of low-serum-iron-induced DSC ferroptosis is needed to inform further clinical evaluations of the safety and efficacy of iron supplementation in women during pregnancy.

Cu2O/Co3O4 nanoarrays for rapid quantitative analysis of hydrogen sulfide in blood.

2D heterostructure nanoarrays have emerged as a promising sensing material for rapid disease detection applications. In this study, a bio-H2S sensor based on Cu2O/Co3O4 nanoarrays was proposed, the controllable preparation of the nanoarrays being achieved by exploring the experimental parameters of the 2D electrodeposition in situ assembly process. The nanoarrays were designed as a multi-barrier system with strict periodicity and long-range order. Based on the interfacial conductance modulation and vulcanization reaction of Cu2O and Co3O4, the sensor exhibited superior sensitivity, selectivity, and stability to H2S in human blood. In addition, the sensor exhibited a reasonable response to 0.1 µmol L-1 Na2S solution, indicating that it had a low detection limit for practical applications. Moreover, first-principles calculations were performed to study changes in the heterointerface during the sensing process and the mechanism of rapid response of the sensor. This work demonstrated the reliability of Cu2O/Co3O4 nanoarrays applied in portable sensors for the rapid detection of bio-H2S.

Tim-3 Coordinates Macrophage-Trophoblast Crosstalk via Angiogenic Growth Factors to Promote Pregnancy Maintenance.

T-cell immunoglobulin mucin-3 (Tim-3) is an important checkpoint that induces maternal-fetal tolerance in pregnancy. Macrophages (Mφs) play essential roles in maintaining maternal-fetal tolerance, remodeling spiral arteries, and regulating trophoblast biological behaviors. In the present study, the formation of the labyrinth zone showed striking defects in pregnant mice treated with Tim-3 neutralizing antibodies. The adoptive transfer of Tim-3+Mφs, rather than Tim-3-Mφs, reversed the murine placental dysplasia resulting from Mφ depletion. With the higher production of angiogenic growth factors (AGFs, including PDGF-AA, TGF-α, and VEGF), Tim-3+dMφs were more beneficial in promoting the invasion and tube formation ability of trophoblasts. The blockade of AGFs in Tim-3+Mφs led to the narrowing of the labyrinthine layer of the placenta, compromising maternal-fetal tolerance, and increasing the risk of fetal loss. Meanwhile, the AGFs-treated Tim-3-Mφs could resolve the placental dysplasia and fetal loss resulting from Mφ depletion. These findings emphasized the vital roles of Tim-3 in coordinating Mφs-extravillous trophoblasts interaction via AGFs to promote pregnancy maintenance and in extending the role of checkpoint signaling in placental development. The results obtained in our study also firmly demonstrated that careful consideration of reproductive safety should be taken when selecting immune checkpoint and AGF blockade therapies in real-world clinical care.

Enrichment of antiplatelet peptides and removal of fishy odor from silver carp skin collagen hydrolysates by macroporous resins: pH value of loading sample affects the peptides separation.

Enrichment of antiplatelet peptides from silver carp skin collagen hydrolysates (CH) was studied using macroporous resins. Static adsorption showed that XAD-16 resin was the suitable resin due to its high adsorption capacity. The dynamic desorption of CH was studied on XAD-16 resin by ethanol gradient elution. Interestingly, pH value of loading sample had a great impact on the peptides separation. Results revealed that the yield and the antiplatelet activity of Ethl-20% fraction were highest at loading sample pH 6.0. The antiplatelet peptides were enriched in the 20% ethanol fraction with IC50 2.03 mg/mL compared to IC50 of CH, 4.7 mg/mL. Besides, the Ethl-20% fraction had a weakest fishy odor. Moreover, a series of peptides containing Hyp-Gly or Pro-Gly were identified from Ethl-20% fraction, which contributed to the antiplatelet activities. This study provided a simple and efficient method for large-scale separation enrichment of antiplatelet peptides as functional foods from CH.

The role of ultrasonography in diagnosis of neuralgic amyotrophy.

OBJECTIVE: To investigate the value of high frequency ultrasound in diagnosis of neuralgic amyotrophy. MATERIALS AND METHODS: From January 2010 to December 2020, the ultrasonographic images of 117 patients with neuralgic amyotrophy diagnosed by the Department of Neurology and hand & foot surgery of Shandong Provincial Hospital Affiliated to Shandong First Medical University were retrospectively analyzed. The ultrasonographic features were summarized. RESULTS: High frequency ultrasound could clearly show the degree of the affected nerves: No ultrasonic findings were found in 12 cases (10%). The affected nerves were thickening and hypoechogenicity with loss of normal fascicular definition in 28 cases (24%). The affected nerves showed hourglass-like changes, including constriction and torsion in 77 cases (66%). In addition, ultrasound can determine the extent of the lesion, and microvascular imaging can display small blood flow signal within the nerve. There was a significant statistical difference between the diameter of the thickened nerve fascicle and the diameter of the nerve fascicle at the corresponding site of the contralateral normal limb. CONCLUSIONS: High frequency ultrasound is a valuable imaging method for diagnosis of neuralgic amyotrophy.

The Critical Roles of Circular RNAs in Basic Research and Clinical Application of Female Reproductive-Related Diseases.

Circular RNAs (circRNAs), produced by precursor mRNAs, are a type of covalently closed circular molecule without 5' caps and 3' polyadenylated tails. Recently, advances in high-throughput sequencing, transcriptomics and bioinformatics, have revealed that circRNAs with specific traits in tissue or cells play emerging roles in both physiological and panthological contexts instead of as simple by-products of transcription. However, bringing circRNAs to the forefront of clinical practice is still a long way off. In this review, we highlight the progress in the formation and function of circRNAs, and how circRNAs work in female reproductive-related diseases, such as recurrent spontaneous abortion, preeclampsia, and endometriosis. We also discussed the clinical potential of circRNAs as biomarkers, and therapeutic agents in female reproductive diseases as well as research controversies, technical issues, and biological knowledge gaps that need to be addressed. This review may instruct future basic research and clinical applications on circRNAs, especially in female reproduction.

Gut microbiota and metabolites in estrus cycle and their changes in a menopausal transition rat model with typical neuroendocrine aging.

Background: Neuroendocrine alterations in the mid-life hypothalamus coupled with reproductive decline herald the initiation of menopausal transition. The certain feature and contribution of gut microflora and metabolites to neuroendocrine changes in the menopausal transition remain largely unknown. Methods: Fecal samples of rats experiencing different reproductive stages were collected and processed for 16S rRNA and liquid chromatography-mass spectrometry sequencing. The differences of gut microbiota and metabolites between young and middle-aged rats during proestrus and diestrus were analyzed, and their relationships to neuroendocrine aging were then examined. Results: At the genus level, Anaeroyorax, Rikenella, Tyzzerella_3, and Atopostipes were abundant at proestrus, while Romboutsia, Turicibacter, Clostridium_sensu_stricto_1, Ruminococcaceae_NK4A214_group, CHKCI002, Ruminococcaceae_UCG-010, Staphylococcus, Family_XII_AD3011_group, Ruminococcaceae UCG-011, and Christensenellaceae_R_7_group were enriched in the diestrus of middle-aged rats. DNF00809, Phocea, and Lachnospiraceae_UCG-006 were found abundant during proestrus instead, while Bacteroides, Lactobacillus, Erysipelatoclostridium, Anaeroplasma, Anaerofustis, Parasutterella, and Enterococcus were enriched at the diestrus of young female individuals. Discriminatory metabolites were identified involving 90 metabolic pathways among the animal sets, which were enriched for steroid hormone biosynthesis, arachidonic metabolism, primary bile acid synthesis, and ovarian steroidogenesis. A total of 21 metabolites lacking in hormone-associated changes in middle-aged female individuals presented positive or negative correlations with the circulating luteinizing hormone, bile acid, fibroblast growth factor 19, and gut hormones. Moreover, close correlations were detected between the intestinal bacteria and their metabolites. Conclusion: This study documents specific gut microbial composition changes and concomitant shifting trends of metabolites during menopausal transition, which may initiate the gut-brain dysfunction in neuroendocrine aging.

Telehealth System Based on the Ontology Design of a Diabetes Management Pathway Model in China: Development and Usability Study.

BACKGROUND: Diabetes needs to be under control through management and intervention. Management of diabetes through mobile health is a practical approach; however, most diabetes mobile health management systems do not meet expectations, which may be because of the lack of standardized management processes in the systems and the lack of intervention implementation recommendations in the management knowledge base. OBJECTIVE: In this study, we aimed to construct a diabetes management care pathway suitable for the actual situation in China to express the diabetes management care pathway using ontology and develop a diabetes closed-loop system based on the construction results of the diabetes management pathway and apply it practically. METHODS: This study proposes a diabetes management care pathway model in which the management process of diabetes is divided into 9 management tasks, and the Diabetes Care Pathway Ontology (DCPO) is constructed to represent the knowledge contained in this pathway model. A telehealth system, which can support the comprehensive management of patients with diabetes while providing active intervention by physicians, was designed and developed based on the DCPO. A retrospective study was performed based on the data records extracted from the system to analyze the usability and treatment effects of the DCPO. RESULTS: The diabetes management pathway ontology constructed in this study contains 119 newly added classes, 28 object properties, 58 data properties, 81 individuals, 426 axioms, and 192 Semantic Web Rule Language rules. The developed mobile medical system was applied to 272 patients with diabetes. Within 3 months, the average fasting blood glucose of the patients decreased by 1.34 mmol/L (P=.003), and the average 2-hour postprandial blood glucose decreased by 2.63 mmol/L (P=.003); the average systolic and diastolic blood pressures decreased by 11.84 mmHg (P=.02) and 8.8 mmHg (P=.02), respectively. In patients who received physician interventions owing to abnormal attention or low-compliance warnings, the average fasting blood glucose decreased by 2.45 mmol/L (P=.003), and the average 2-hour postprandial blood glucose decreased by 2.89 mmol/L (P=.003) in all patients with diabetes; the average systolic and diastolic blood pressure decreased by 20.06 mmHg (P=.02) and 17.37 mmHg (P=.02), respectively, in patients with both hypertension and diabetes during the 3-month management period. CONCLUSIONS: This study helps guide the timing and content of interactive interventions between physicians and patients and regulates physicians' medical service behavior. Different management plans are formulated for physicians and patients according to different characteristics to comprehensively manage various cardiovascular risk factors. The application of the DCPO in the diabetes management system can provide effective and adequate management support for patients with diabetes and those with both diabetes and hypertension.

Circadian gene Rev-erbα influenced by sleep conduces to pregnancy by promoting endometrial decidualization via IL-6-PR-C/EBPß axis.

BACKGROUND: Sleep disturbance can cause adverse pregnancy outcomes by changing circadian gene expression. The potential mechanisms remain unclear. Decidualization is critical for the establishment and maintenance of normal pregnancy, which can be regulated by circadian genes. Whether Rev-erbα, a critical circadian gene, affects early pregnancy outcome by regulating decidualization needs to be explored. METHODS: QPCR, western blot and artificial decidualization mouse model were used to confirm the effect of sleep disturbance on Rev-erbα expression and decidualization. The regulatory mechanism of Rev-erbα on decidualization was assessed using QPCR, western blot, RNA-Seq, and Chip-PCR. Finally, sleep disturbance mouse model was used to investigate the effect of therapeutic methods targeting Rev-erbα and interleukin 6 (IL-6) on improving adverse pregnancy outcomes induced by sleep disturbance. RESULTS: Dysregulation of circadian rhythm due to sleep disturbance displayed abnormal expression profile of circadian genes in uterine including decreased level of Rev-erbα, accompanied by defective decidualization. Rev-erbα could regulate decidualization by directly repressing IL-6, which reduced the expression of CCAAT/enhancer-binding protein ß (C/EBPß) and its target insulin-like growth factor binding protein 1 (IGFBP1), the marker of decidualization, by inhibiting progesterone receptors (PR) expression. Moreover, deficient decidualization, higher abortion rate and lower implantation number were exhibited in the mouse models with sleep disturbance compared with those in normal mouse. Pharmacological activation of Rev-erbα or neutralization of IL-6 alleviated the adverse effect of sleep disturbance on pregnancy outcomes. CONCLUSIONS: Taken together, Rev-erbα regulated decidualization via IL-6-PR-C/EBPß axis and might be a connector between sleep and pregnancy outcome. Therapies targeting Rev-erbα and IL-6 might help improving adverse pregnancy outcomes induced by sleep disturbance.