Carborane-Cluster-Wrapped Copper Cluster with Cyclodextrin-like Cavities for Chiral Recognition.

Chiral atomically precise metal clusters, known for their remarkable chiroptical properties, hold great potential for applications in chirality recognition. However, advancements in this field have been constrained by the limited exploration of host-guest chemistry, involving metal clusters. This study reports the synthesis of a chiral Cu16(C2B10H10S2)8 (denoted as Cu16@CB8, where C2B10H12S2H2 = 9,12-(HS)2-1,2-closo-carborane) cluster by an achiral carboranylthiolate ligand. The chiral R-/S-Cu16@CB8 cluster features chiral cavities reminiscent of cyclodextrins, which are surrounded by carborane clusters, yet they crystallize in a racemate. These cyclodextrin-like cavities demonstrated the specific recognition of amino acids, as indicated by the responsive output of circular dichroism and circularly polarized luminescence signals of Cu16 moieties of the Cu16@CB8 cluster. Notably, a quantitative chiroptical analysis of amino acids in a short time and a concomitant deracemization of Cu16@CB8 were achieved. Density functional tight-binding molecular dynamics simulation and noncovalent interaction analysis further unraveled the great importance of the cavities and binding sites for chiral recognition. Dipeptide, tripeptide, and polypeptide containing the corresponding amino acids (Cys, Arg, or His residues) display the same chiral recognition, showing the generality of this approach. The functional synergy of dual clusters, comprising carborane and metal clusters, is for the first time demonstrated in the Cu16@CB8 cluster, resulting in the valuable quantification of the enantiomeric excess (ee) value of amino acids. This work opens a new avenue for chirality sensors based on chiral metal clusters with unique chiroptical properties and inspires the development of carborane clusters in host-guest chemistry.

Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.

Irbesartan ameliorates diabetic kidney injury in db/db mice by restoring circadian rhythm and cell cycle.

Background and Objectives: Irbesartan has been widely used in the clinical treatment of diabetic kidney disease (DKD). However, the molecular mechanism of its delay of DKD disease progression has not been fully elucidated. The aim of the present study was to investigate the mechanism of irbesartan in the treatment of DKD. Materials and Methods: C57BL/KsJ db/db mice were randomly divided into the model group and irbesartan-treated group. After treatment with irbesartan for 12 weeks, the effects on blood glucose, body weight, 24-h urinary albumin, and renal injuries were evaluated. Microarray was used to determine the differentially expressed genes (DEGs) in the renal cortex of mice. |Log FC| <0.5 and false discovery rate (FDR) <0.25 were set as the screening criteria. Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), protein-protein interaction (PPI) network and modules, and microRNA (miRNA)-DEGs network analysis were applied to analyze the DEGs. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the results of microarray. Results: The present study demonstrated irbesartan could significantly improve the renal function in db/db mice through decreasing 24-h urinary albumin and alleviating the pathological injury of kidney. Irbesartan may affect the expression of numerous kidney genes involved in circadian rhythm, cell cycle, micoRNAs in cancer, and PI3K-AKT signaling pathway. In the miRNA-DEGs network, miR-1970, miR-703, miR-466f, miR-5135, and miR-132-3p were the potential targets for irbesartan treatment. The validation test confirmed that key genes regulating circadian rhythm (Arntl, Per3, and Dbp) and cell cycle (Prc1, Ccna2, and Ccnb2) were restored in db/db mice on treatment with Irbesartan. Conclusion: Generally, irbesartan can effectively treat DKD by regulating the circadian rhythm and cell cycle. The DEGs and pathways identified in the study will provide new insights into the potential mechanisms of irbesartan in the treatment of DKD.

Irbesartan ameliorates diabetic kidney injury in db/db mice by restoring circadian rhythm and cell cycle.

Background and Objectives: Irbesartan has been widely used in the clinical treatment of diabetic kidney disease (DKD). However, the molecular mechanism of its delay of DKD disease progression has not been fully elucidated. The aim of the present study was to investigate the mechanism of irbesartan in the treatment of DKD. Materials and Methods: C57BL/KsJ db/db mice were randomly divided into the model group and irbesartan-treated group. After treatment with irbesartan for 12 weeks, the effects on blood glucose, body weight, 24-h urinary albumin, and renal injuries were evaluated. Microarray was used to determine the differentially expressed genes (DEGs) in the renal cortex of mice. |Log FC| <0.5 and false discovery rate (FDR) <0.25 were set as the screening criteria. Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), protein-protein interaction (PPI) network and modules, and microRNA (miRNA)-DEGs network analysis were applied to analyze the DEGs. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the results of microarray. Results: The present study demonstrated irbesartan could significantly improve the renal function in db/db mice through decreasing 24-h urinary albumin and alleviating the pathological injury of kidney. Irbesartan may affect the expression of numerous kidney genes involved in circadian rhythm, cell cycle, micoRNAs in cancer, and PI3K-AKT signaling pathway. In the miRNA-DEGs network, miR-1970, miR-703, miR-466f, miR-5135, and miR-132-3p were the potential targets for irbesartan treatment. The validation test confirmed that key genes regulating circadian rhythm (Arntl, Per3, and Dbp) and cell cycle (Prc1, Ccna2, and Ccnb2) were restored in db/db mice on treatment with Irbesartan. Conclusion: Generally, irbesartan can effectively treat DKD by regulating the circadian rhythm and cell cycle. The DEGs and pathways identified in the study will provide new insights into the potential mechanisms of irbesartan in the treatment of DKD.

Follicular fluid-derived exosomal LncRNA LIPE-AS1 modulates steroid metabolism and survival of granulosa cells leading to oocyte maturation arrest in polycystic ovary syndrome.

OBJECTIVE: Women who are of reproductive age can suffer from polycystic ovary syndrome (PCOS), an endocrine disorder. Anovulatory infertility is mostly caused by aberrant follicular development, which is seen in PCOS patients. Due to the dysfunction of reproductive and endocrine function in PCOS patients, assisted reproduction treatment is one of the main means to obtain clinical pregnancy for PCOS patients. Long non-coding RNA (lncRNA) as a group of functional RNA molecules have been found to participate in the regulation of oocyte function, hormone metabolism, and proliferation and apoptosis of granulosa cells. In this study, we investigated the role of lncRNAs in follicular fluid-derived exosomes and the underlying mechanism of lncRNA LIPE-AS1. METHODS: We used RNA sequencing to analyze the lncRNA profiles of follicular fluid-derived exosomes in PCOS patients and controls. RT-qPCR was performed to detect the expression levels of these lncRNAs in control (n = 30) and PCOS (n = 30) FF exosome samples. Furthermore, we validated the performance of lncRNA LIPE-AS1 in oocyte maturation by in vitro maturation (IVM) experiments in mouse and steroid metabolism in granulosa cells. RESULTS: We found 501 lncRNAs were exclusively expressed in the control group and another 273 lncRNAs were found to be specifically expressed in the PCOS group. LncRNA LIPE-AS1, highly expressed in PCOS exosomes, was related to a poor oocyte maturation and embryo development in PCOS patients. Reduced number of MII oocytes were observed in the LIPE-AS1 group by in vitro maturation (IVM) experiments in mouse. LIPE-AS1 was also shown to modulate steroid metabolism and granulosa cell proliferation and apoptosis by LIPE-AS1/miR-4306/LHCGR axis. CONCLUSION: These findings suggested that the increased expression of LIPE-AS1, facilitated by follicular fluid exosomes, had a significant impact on both oocyte maturation and embryo development. We demonstrated the ceRNA mechanism involving LIPE-AS1, miR-4306, and LHCGR as a regulator of hormone production and metabolism. These findings indicate that LIPE-AS1 is essential in PCOS oocyte maturation and revealed a ceRNA network of LIPE-AS1 and provided new information on abnormal steroid metabolism and oocyte development in PCOS.

Extensive therapeutic effects, underlying molecular mechanisms and disease treatment prediction of Metformin: a systematic review.

Metformin (Met), a first-line management for type 2 diabetes mellitus, has been expansively employed and studied with results indicating its therapeutic potential extending beyond glycemic control. Beyond its established role, this therapeutic drug demonstrates a broad spectrum of action encompassing over 60 disorders, encompassing metabolic conditions, inflammatory disorders, carcinomas, cardiovascular diseases, and cerebrovascular pathologies. There is clear evidence of Met's action targeting specific nodes in the molecular pathways of these diseases and, intriguingly, interactions with the intestinal microbiota and epigenetic processes have been explored. Furthermore, novel Met derivatives with structural modifications tailored to diverse diseases have been synthesized and assessed. This manuscript proffers a comprehensive thematic review of the diseases amenable to Met treatment, elucidates their molecular mechanisms, and employs informatics technology to prospect future therapeutic applications of Met. These data and insights gleaned considerably contribute to enriching our understanding and appreciation of Met's far-reaching clinical potential and therapeutic applicability.

Role of ferroptosis in esophageal cancer and corresponding immunotherapy.

Esophageal cancer (EC) is one of the most common digestive system malignancies in the world. The combined modality treatment of EC is usually surgery and radiation therapy, however, its clinical efficacy for advanced patients is relatively limited. Ferroptosis, a new type of iron-dependent programmed cell death, is different from apoptosis, necrosis and autophagy. In recent years, many studies have further enlightened that ferroptosis plays an essential role in the occurrence, development and metastasis of tumors. Targeting ferroptosis stimulates a new direction for further exploration of oncologic treatment regimens. Furthermore, ferroptosis has a critical role in the immune microenvironment of tumors. This paper reviews the mechanism of ferroptosis and the ferroptosis research progress in the treatment of EC. We further elaborate the interaction between ferroptosis and immunotherapy, and the related mechanisms of ferroptosis participation in the immunotherapy of EC, so as to provide new directions and ideas for the treatment of EC.

Exosomal circ_0008285 in follicle fluid regulates the lipid metabolism through the miR-4644/ LDLR axis in polycystic ovary syndrome.

PURPOSE: Exosomal circRNA, as an essential mediator of the follicular microenvironment, has been implicated in the etiological and pathobiological studies of polycystic ovarian syndrome (PCOS). This study aimed to determine abnormal circular RNA (circRNA) expression profiles in follicle fluid (FF) exosomes in patients with PCOS and identify the role of circ_0008285/microRNA (miR)-4644/low-density lipoprotein receptor (LDLR) axis in PCOS. METHODS: Sixty-seven women undergoing IVF/ICSI, 31 PCOS patients and 36 non-PCOS patients were included in the cohort study. The circRNA expression profiles of FF exosomes in PCOS (n = 3) and control group (n = 3) were compared by RNA sequencing. In an additional cohort (PCOS:28 vs Control:33), the mRNA expression levels of four circRNAs from FF exosomes were further verified by qRT-PCR. Bioinformatic analysis and dual luciferase reporter gene assay verified the relationship between circ_0008285 and miR-4644 and between miR-4644 and LDLR. KGN cells were infected with sh-circ0008285 and transfected with miR-4644 mimic to verify their roles in lipid metabolism. RESULTS: Four circRNAs showed significantly different expressions. Circ_0044234 was overexpressed in PCOS patients, while circ_0006877, circ_0013167 and circ0008285 were decreased in PCOS. Among four differentially expressed circRNAs, circ0008285 was enriched in lipoprotein particle receptor activity and cholesterol metabolism pathway by GO and KEGG pathway analyses. Luciferase assay confirmed the competing endogenous RNA (ceRNA) network circ_0008285/miR-4644 /LDLR. The intercellular experiments on circ_0008285 and its reduction in KGN cells showed that the consumption of circ_0008285 in exosomes could increase the expression of miR-4644 in recipient cells and inhibit the expression of LDLR, as well as increase free fatty acid secretion. CONCLUSION: Circ_0008285 can combine with miR-4644 to promote the expression of LDLR and affect the cholesterol metabolism of ovarian granulosa cells in PCOS. Our findings revealed the ceRNA network of circ_0008285 and provided a new path to investigate lipid metabolism abnormalities in PCOS.

PDE4 inhibitor Roflumilast modulates inflammation and lipid accumulation in PCOS mice to improve ovarian function and reduce DHEA-induced granulosa cell apoptosis in vitro.

This study was implemented to address the role of Roflumilast in polycystic ovary syndrome (PCOS) as well as to discuss its reaction mechanism in vivo and in vitro. In vivo, mice were administrated with 6 mg dehydroepiandrosterone (DHEA) per 100 g body weight and fed with 60% high fat diet to induce PCOS. The expression of phosphodiesterases 4 (PDE4) was assessed with RT-qPCR. The ovary pathology was observed by hematoxylin and eosin staining and follicles were counted. Enzyme-linked immunosorbent assay was adopted for the estimation of progesterone, testosterone and inflammatory factors and lipid accumulation was observed by Oil Red O staining. With the application of reverse transcription-quantitative PCR (RT-qPCR) and western blot, the messenger RNA (mRNA) and protein expressions of low-density lipoprotein receptor (LDLR) was resolved. In vitro, Cell counting kit-8 and flow cytometry analysis were applied for the assessment of cell proliferation and apoptosis. The proliferation- and apoptosis-related proteins were appraised with western blot. Additionally, the expressions of PDE-4 at both mRNA and protein levels were tested with RT-qPCR and western blot. Here, it was discovered that PDE4 was greatly elevated in PCOS mice and DHEA-induced ovarian granulosa cells (KGN). In PCOS mice, PDE4 was negative correlated with progesterone and had positive correlation with testosterone. Roflumilast could enhanced progesterone expression, increased the number of primary follicles, preantral follicles and antral follicles but reduced testosterone and decreased the number of cystic follicles in PCOS mice. It was also testified that Roflumilast could inhibit the release of inflammatory factors and lipid accumulation in PCOS mice. Besides, the proliferation of DHEA-induced KGN cells was enhanced while the apoptosis was declined by Roflumilast, accompanied by elevated contents of PCNA, Ki67 and antiapoptotic protein Bcl-2. Collectively, Roflumilast inhibited inflammation and lipid accumulation in PCOS mice to improve ovarian function and reduce DHEA-induced granulosa cell apoptosis.

Non-coding RNAs in hepatocellular carcinoma: Insights into regulatory mechanisms, clinical significance, and therapeutic potential.

Hepatocellular carcinoma (HCC) is a complex and heterogeneous malignancy with high incidence and poor prognosis. In addition, owing to the lack of diagnostic and prognostic markers, current multimodal treatment options fail to achieve satisfactory outcomes. Tumor immune microenvironment (TIME), angiogenesis, epithelial-mesenchymal transition (EMT), invasion, metastasis, metabolism, and drug resistance are important factors influencing tumor development and therapy. The intercellular communication of these important processes is mediated by a variety of bioactive molecules to regulate pathophysiological processes in recipient cells. Among these bioactive molecules, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), account for a large part of the human transcriptome, and their dysregulation affects the progression of HCC. The purpose of this review is to evaluate the potential regulatory mechanisms of ncRNAs in HCC, summarize novel biomarkers from somatic fluids (plasma/serum/urine), and explore the potential of some small-molecule modulators as drugs. Thus, through this review, we aim to contribute to a deeper understanding of the regulatory mechanisms, early diagnosis, prognosis, and precise treatment of HCC.

Clinical evaluation of contrast-enhanced CT combined with PET/CT in diagnosis of mediastinal lymph node metastasis of non-small-cell lung cancer.

Objectives: To investigate the clinical value of contrast-enhanced CT combined with PET/CT in the differential diagnosis of mediastinal lymph node metastasis (MLNM) of non-small-cell lung cancer (NSCLC). Methods: A total of 120 patients with NSCLC combined with mediastinal lymphadenopathy hospitalized in our hospital were selected. All the patients received radical resection of lung cancer and mediastinal lymphadenectomy. After pathological diagnosis, they were divided into MLNM group (malignant group, undergoing contrast-enhanced CT) and non-MLNM group (benign group, receiving contrast-enhanced CT combined with PET-CT). The results were judged by two senior radiologists independently. The results of different scanning methods and postoperative pathology were compared using the t test, χ2 test and Pearson correlation coefficient test. Results: Compared with the pathological results, contrast-enhanced CT diagnosed 31 cases, with a coincidence rate of 62%, and contrast-enhanced CT combined with PET-CT diagnosed 42 cases, with a coincidence rate of 84%, presenting a statistically significant difference (P = 0.02). Among the 120 patients with lung cancer, pathological examination confirmed MLNM in 50 patients and benign enlargement in 70 patients, contrast-enhanced CT alone detected metastasis in 40 patients and benign enlargement in 80 patients, and contrast-enhanced CT combined with PET-CT detected metastasis in 47 patients and benign enlargement in 73 patients. The sensitivity and accuracy of the latter were significantly higher than those of the former (sensitivity, P = 0.01; accuracy, P = 0.01). With the increase in the malignancy of lymph nodes, the degree of CT enhancement, the concentration of radioactive substances and SUV value increased, showing positive correlations. Conclusion: Contrast-enhanced CT combined with PET/CT in the diagnosis of MLNM of NSCLC presents higher coincidence rate, sensitivity and accuracy. With the increase in tumor malignancy, the enhancement degree and radioactive substance concentration increase. The two methods are synergistic and complementary in diagnosing MLNM.

Forkhead Box i2 Transcription Factor Regulates Systemic Energy Metabolism Via Neuropeptide AgRP.

The neuropeptide AgRP is essential for maintaining systemic energy homeostasis. In the current study, we show that hypothalamic Foxi2, as a novel regulator of nutrient sensing, controls systemic energy metabolism by specifically stimulating AgRP expression. Foxi2 was highly expressed in the hypothalamus, and its expression was induced by fasting. Immunofluorescence assays demonstrated that Foxi2 was localized in AgRP neurons. We stereotactically injected adeno-associated virus to selectively overexpress Foxi2 in AgRP-IRES-Cre mice and found that Foxi2 overexpression in AgRP neurons specifically increased AgRP expression, thereby increasing food intake and reducing energy expenditure, subsequently leading to obesity and insulin resistance. Mechanistically, Foxi2 stimulated AgRP expression by directly binding to it and activating its transcription. Furthermore, Foxi2 overexpression activated AgRP neuron activity, as revealed by whole-cell patch-clamp experiments. Conversely, global Foxi2-mutant mice became leaner with age and were resistant to high-fat diet-induced obesity and metabolic disturbances. Collectively, our data suggest that Foxi2 plays an important role in controlling energy metabolism by regulating AgRP expression.

Diagnostic value and safety of medical thoracoscopy for pleural effusion of different causes.

BACKGROUND: Pleural effusions occur for various reasons, and their diagnosis remains challenging despite the availability of different diagnostic modalities. Medical thoracoscopy (MT) can be used for both diagnostic and therapeutic purposes, especially in patients with undiagnosed pleural effusion. AIM: To assess the diagnostic efficacy and safety of MT in patients with pleural effusion of different causes. METHODS: Between January 1, 2012 and April 30, 2021, patients with pleural effusion underwent MT in the Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University (Shaanxi, China). According to the discharge diagnosis, patients were divided into malignant pleural effusion (MPE), tuberculous pleural effusion (TBPE), and inflammatory pleural effusion (IPE) groups. General information, and tuberculosis- and effusion-related indices of the three groups were analyzed. The diagnostic yield, diagnostic accuracy, performance under thoracoscopy, and complications of patients were compared among the three groups. Then, the significant predictive factors for diagnosis between the MPE and TBPE groups were analyzed. RESULTS: Of the 106 patients enrolled in this 10-year study, 67 were male and 39 female, with mean age of 57.1 ± 14.184 years. Among the 74 thoracoscopy-confirmed patients, 41 (38.7%) had MPE, 21 had (19.8%) TBPE, and 32 (30.2%) were undiagnosed. Overall diagnostic yield of MT was 69.8% (MPE: 75.9%, TBPE: 48.8%, and IPE: 75.0%, with diagnostic accuracies of 100%, 87.5%, and 75.0%, respectively). Under thoracoscopy, single or multiple pleural nodules were observed in 81.1% and pleural adhesions in 34.0% with pleural effusions. The most common complication was chest pain (41.5%), followed by chest tightness (11.3%) and fever (10.4%). Multivariate logistic regression analyses showed effusion appearance [odds ratio (OR): 0.001, 95%CI: 0.000-0.204; P = 0.010] and carcinoembryonic antigen (OR: 0.243, 95%CI: 0.081-0.728; P = 0.011) as significant for differentiating MPE and TBPE, with area under the receiver operating characteristic curve of 0.977 (95%CI: 0.953-1.000; P < 0.001). CONCLUSION: MT is an effective, safe, and minimally invasive procedure with high diagnostic yield for pleural effusion of different causes.

Mitochondrial dysfunction in cumulus cells is related to decreased reproductive capacity in advanced-age women.

OBJECTIVE: To reveal the relationship between mitochondrial function in cumulus cells (CCs) and the aging-related decline in ovarian function and reproductive capacity. DESIGN: Retrospective and transcriptome analysis of human tissue. SETTING: University hospital. PATIENT(S): A total of 186 infertile women with normal weight and no other diseases, including 86 young women (aged <38 years) with normal ovarian reserve and 100 advanced-age women (aged ≥38 years) with diminished ovarian reserve. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryo development data were analyzed. The mitochondrial ultrastructure of CCs was observed by transmission electron microscopy. Mitochondrial activity was detected by immunofluorescence. The per-CC mitochondrial deoxyribonucleic acid copy numbers and cellular adenosine triphosphate levels were quantified. Unbiased comprehensive genome-wide transcriptomics was performed. The functions of all annotated genes and biologic pathways were analyzed by the Kyoto Encyclopedia of Genes and Genomes. RESULT(S): Advanced-age women with diminished ovarian function had significantly fewer retrieved oocytes and lower embryo quality. The normal mitochondrial rate in CCs was significantly lower. In addition to mitochondrial morphology and structural changes, the fluorescence intensity of Fluo-3/AM was significantly higher, and that of MitoTracker was lower than that of young women with normal ovarian reserve, suggesting that age negatively affects the mitochondrial activity of CCs. The per-CC mitochondrial deoxyribonucleic acid copy number and adenosine triphosphate levels significantly decreased in the advanced-age group. The Kyoto Encyclopedia of Genes and Genomes analysis showed that differentially expressed genes were significantly enriched in the oxidative phosphorylation pathway. Additionally, most mitochondrially encoded genes related to oxidative phosphorylation were significantly down-regulated in the advanced-age group. CONCLUSION(S): We present current evidence that mitochondrial dysfunction in CCs may play a key role in the age-related decline in ovarian function and reproductive capacity.

Prostaglandin E2 receptor 3 promotes M1 macrophages polarization in unexplained recurrent pregnancy loss.

Unexplained recurrent pregnancy loss (uRPL) is associated with macrophage polarization, which can be modulated by prostaglandin E2 (PGE2). Our previous study demonstrated that PGE2 receptor 3 (EP3) signaling is induced in the first-trimester placentas of uRPL patients compared with its expression in healthy controls. However, whether EP3 plays a role in macrophage polarization at the maternal-fetal interface of uRPL women remains unknown. The positive expression of EP3 in decidual macrophages was confirmed by double immunofluorescence staining in the first-trimester placentas collected from uRPL patients and healthy controls. Antibodies CD68, iNOS, and CD163 were used as immunofluorescence marker for decidual macrophages, M1, and M2 macrophages. To clarify the effects of EP3 on macrophage polarization, THP-1 monocyte cells were applied as M0 macrophages after phorbol 12-myristate 13-acetate (PMA) treatment for in vitro study. The mRNA levels of representative M1 markers (interleukin-1ß and interleukin-6) and M2 markers (interleukin-10 and arginase-1) were quantified with qPCR in M0 macrophages being stimulated with sulprostone (an EP3 agonist) or L-798,106 (an EP3 antagonist). We found that EP3 expression was upregulated in the decidual macrophages of first-trimester placentas from uRPL patients compared with healthy controls. Furthermore, EP3 expression was increased in M1 macrophages compared with that in M2 macrophages in first-trimester placentas of uRPL patients. Sulprostone intensified the mRNA levels of IL-6 together with interferon-γ, whereas L-798,106 stimulated the mRNA expression of IL-10 and Arg-1 in a dose-dependent manner.

Correlation between steroid levels in follicular fluid and hormone synthesis related substances in its exosomes and embryo quality in patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with various manifestations and complex etiology. Follicular fluid (FF) serves as the complex microenvironment for follicular development. However, the correlation between the concentration of steroid in FF and the pathogenesis of PCOS is still unclear. METHODS: Twenty steroid levels in FF from ten patients with PCOS and ten women with male-factor infertility undergoing in vitro fertilization were tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to explore their possibly correlation with PCOS. Meanwhile, the mRNA levels of core enzymes in steroid synthesis pathway from exosomes of FF were also detected by qPCR. RESULTS: The estriol (p < 0.01), estradiol (p < 0.05) and prenenolone (p < 0.01) levels in FF of PCOS group were significantly increased, compared to the normal group, and the progesterone levels (p < 0.05) were decreased in PCOS group. Increased mRNA levels of CYP11A, CYP19A and HSD17B2 of exosomes were accompanied by the hormonal changes in FF. Correlation analysis showed that mRNA levels of CYP11A and HSD17B2 were negatively correlated with percent of top-quality embryos and rate of embryos develop to blastocyst. CONCLUSION: Our results suggest that increased levels of estrogen and pregnenolone in follicular fluid may affect follicle development in PCOS patients, and the mechanism is partially related to HSD17B1, CYP19A1 and CYP11A1 expression change in FF exosomes.

[Electroacupuncture in the prevention and treatment of sore throat and nausea and vomiting after gastrointestinal surgery: a randomized controlled trial].

OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on postoperative sore throat (POST) and postoperative nausea and vomiting (PONV) after endotracheal intubation and general anesthesia. METHODS: According to the random number table, 60 patients of gastrointestinal surgery under general anesthesia with tracheal intubation were randomly divided into EA group (30 cases) and control group (30 cases). Patients in the EA group were given acupuncture at Shaoshang (LU11) 30 minutes before general anesthesia, and EA at Chize (LU5) and Hegu (LI4) continued until the operation was completed. The incidence and severity of POST and visual analogue scale (VAS) score at 12, 24, and 48 h after surgery, and the incidence and severity of PONV at 12, 24 h after surgery were analyzed, respectively. RESULTS: The incidence and severity of POST and PONV, and VAS score in the EA group were significantly lower than those in the control group 12 h and 24 h after surgery (P<0.05). Both groups had significant reductions in VAS score at 24 h and 48 h after surgery compared with that at 12 h (P<0.05). CONCLUSION: EA can significantly improve the prognosis of patients on sore throat and reduce the incidence of PONV.

The association between abnormal serum magnesium levels and prognosis of elderly patients with community-acquired pneumonia.

To investigate the association between abnormal serum magnesium levels and the prognosis of elderly patients with community-acquired pneumonia (CAP). Methods: A retrospective study was conducted on 1381 elderly patients with CAP in the First Hospital of Qinhuangdao between January 2015 and December 2018. Serum magnesium concentrations in the range of 0.75-1.25 mmol/L were defined as normal. Patients were assigned into normal, hypomagnesemia, and hypermagnesemia groups. The primary outcome was in-hospital mortality, indicating whether a patient died at the time of discharge from the hospital. The percentages of respiratory failure and mechanical ventilation were 18.6% and 10.6 % in the normal group, 29% and 16.5 % in the hypomagnesemia, and 42.9% and 35.7% in the hypermagnesemia groups. The occurrence of shock was 8.5% and 4.5% in the hypomagnesemia group and the normal group. The percentages of the length of stay at ICU were 14.9%, 18.8%, and 57.1% in the hypomagnesemia, normal, and hypermagnesemia groups. The in-hospital mortality rate was 5.3%, 9.1%, and 35.7% in the normal, hypomagnesemia, and hypermagnesemia groups, respectively. The results of univariate analysis showed that the in-hospital mortality in the hypomagnesemia group was 1.790 (95% confidence interval (CI): 1.009∼3.176, P=0.046) times higher than that in the normal group; in the hypermagnesemia group, it was 9.947 (95% CI: 3.238-30.556, P<0.001) times higher than that in the normal group. The results of multivariate logistic regression analysis showed that after adjusting for gender, age, diabetes, heart failure, cerebrovascular disease, cancer, estimated glomerular filtration rate (eGFR), glucose, and CURB-65 score, in the hypomagnesemia group, the in-hospital mortality was 1.746 (95% confidence interval (CI): 0.956∼3.186, P=0.070) times higher than that in the normal group, and 5.689 (95% CI: 1.583- 20.446, P=0.008) times higher in the hypermagnesemia group than that in the normal group. Abnormal serum magnesium levels are strongly associated with in-hospital mortality in elderly patients with CAP. The measurement of serum magnesium levels in elderly patients with CAP at admission may assist clinicians to determine the prognosis of such patients.

Sleep Deprivation Aggravates Cognitive Impairment by the Alteration of Hippocampal Neuronal Activity and the Density of Dendritic Spine in Isoflurane-Exposed Mice.

Isoflurane contributes to cognitive deficits when used as a general anesthetic, and so does sleep deprivation (SD). Patients usually suffer from insomnia before an operation due to anxiety, fear, and other factors. It remains unclear whether preoperative SD exacerbates cognitive impairment induced by isoflurane. In this study, we observed the effects of pretreated 24-h SD in adult isoflurane-exposed mice on the cognitive behaviors, the Ca2+ signals of dorsal hippocampal CA1 (dCA1) neurons in vivo with fiber photometry, and the density of dendritic spines in hippocampal neurons. Our results showed that in cognitive behavior tasks, short-term memory damages were more severe with SD followed by isoflurane exposure than that with SD or isoflurane exposure separately, and interestingly, severe long-term memory deficits were induced only by SD followed by isoflurane exposure. Only the treatment of SD followed by isoflurane exposure could reversibly decrease the amplitude of Ca2+ signals when mice were freely moving and increase the duration of Ca2+ signals during the long-term memory behavior test. The density of dendritic spines with both SD and isoflurane exposure was lower than that with SD alone. This study suggests that SD should be avoided preoperatively in patients undergoing elective surgery under isoflurane anesthesia.

[Expression and Significance of IL-9 and IL-6 in Patients with BCR-ABL- MPN].

OBJECTIVE: To investigate the expression of IL-9 and IL-6 in patients with BCR-ABL- bone marrow proli- ferative tumor (MPN), and to explore its role in the occurrence and development of MPN. METHODS: A total of 71 newly diagnosis MPN patients treated in Tianjin Medical University General Hospital from 2018 to 2019 were selected, including 32 patients with polycythemia vera (PV) and 22 patients with primary thrombocytosis (ET), and 17 patients with primary myelofibrosis (PMF). Then 58 patients who retestine after treatment were selected as therapy group，and 20 healthy volunteers were recruited as control group. ELISA was used to detect the expression level of IL-6 and IL-9 in bone marrow supernatant, and the relative expression level of IL-6 and IL-9 mRNA in BMMNC was detected by real-time PCR. The proportion of Th9 cells in peripheral blood were detected by flow cytometry (FCM). The expression level of IL-6 mRNA and IL-9 mRNA of BMMNC and clinical indicators were analyzed, and the correlation between JAK2 gene mutation load and IL-9 level was further analyzed. RESULT: The level of IL-6 in bone marrow supernatant and the expression of IL-6 mRNA in BMMNC were higher in the newly diagnosed group as compared with those in the treated group and the control group (P<0.001). The expression level of IL-9 in bone marrow supernatant and the expression of IL-9 mRNA in BMMNC were lower in the newly diagnosed group as compared with those in the treated group and the control group (P<0.05). The proportion of Th9 cells in peripheral blood was lower in the newly diagnosed group as compared with that in the treated group and the control group (P<0.001). The level of IL-6 in bone marrow supernatant and the expression of IL-6 mRNA in BMMNC in JAK2+ group were higher than those in JAK2- group (P<0.05). The expression level of IL-9 in bone marrow supernatant and the expression of IL-9 mRNA in BMMNC were lower in JAK2+ group as compared with those in JAK2- group (P<0.05). The expression of IL-6 and IL-9 in the patient group showed correlation with the number of lymphocytes (IL-6: r=-0.49, P<0.01; IL-9: r=0.53, P<0.001), and also related with Hb in PV patients (IL-6: r= 0.87, P<0.001; IL-9: r=-0.54, P<0.01), and platelets in ET patients (IL-6: r=0.64, P<0.05; IL-9: r=-0.46, P<0.05). CONCLUSION: The increased expression of IL-6 in MPN and hyperfunction may promote the progression of BCR-ABL- MPN disease. The expression of IL-9 in MPN decreases, and it negatively correlates with the mutation load of JAK2 gene, which may be related with the decrease of tumor environmental antitumor immune effect.