Association between parity and female mortality: the mediative role of depressive symptoms.

STUDY QUESTION: Is parity associated with all-cause and cause-specific mortality among women in a nationally representative cohort of the US population, and does depression mediate this association? SUMMARY ANSWER: Nulliparous women have a higher risk of all-cause and cause-specific mortality, with depression partially mediating the relationship between parity and women's all-cause and cause-specific mortality. WHAT IS KNOWN ALREADY: Parity, a significant state in reproductive life, has enduring implications for women's health. There is also a complex relationship between depression, a prevalent mental and emotional disorder, and female fertility. Previous studies have elucidated the relationships between parity and depression, both of which are associated with mortality. However, findings from studies examining parity and women's mortality have been inconsistent. Moreover, few studies have investigated whether the effect of parity on mortality is mediated by depression. STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional study using data from seven cycles of the National Health and Nutrition Examination Survey (NHANES) spanning 2005-2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study cohort comprised adult women with available parity and survival follow-up data. Parity data were self-reported and sourced from the Reproductive Health Questionnaire. Depression scores were derived from the Patient Health Questionnaire 9, and cause-specific deaths were identified using the International Statistical Classification of Diseases, 10th Revision (ICD-10). Weighted multivariable Cox regression was applied to analyze the association between parity, depression, and mortality. Weighted linear regression was performed to examine the relationship between parity and depression. Mediation analyses were employed to determine whether and to what extent depression mediated the effect of parity on mortality. MAIN RESULTS AND THE ROLE OF CHANCE: Our study ultimately encompassed 16 962 American women. Following multivariable adjustment, compared to nulliparous women, those with one to three live births exhibited a 17% and 33% reduction in all-cause and cancer mortality, respectively (all-cause mortality: HR = 0.83, 95% CI = 0.69-0.99, P = 0.040; cancer mortality: HR = 0.67, 95% CI = 0.45-0.99, P = 0.045). Women with more than four live births demonstrated lower all-cause mortality and mortality from other (not cancer or cardiovascular disease) diseases (all-cause mortality: HR = 0.73, 95% CI = 0.58-0.93, P = 0.011; other diseases mortality: HR = 0.66, 95% CI = 0.47-0.91, P = 0.013). No correlation was detected between parity and the risk of cardiovascular disease mortality among women. Furthermore, depression was found to partially mediate the impact of parity on all-cause mortality and mortality from other diseases in women. LIMITATIONS, REASONS FOR CAUTION: Firstly, a single index of parity was used as an exposure factor, and other reproductive factors such as birth spacing, age at first birth, and mode of delivery were not taken into account. Secondly, despite accounting for important potentially confounders in our analysis, such as BMI, smoking status, and educational level, the influence of unmeasured confounders (e.g., social class, latent reproductive system diseases) on reproductive behavior or mortality cannot be dismissed. Thirdly, women's vulnerability to depression fluctuates across reproductive stages, and the effect of depression on female fertility varies over time. Due to data constraints, we were unable to obtain information on women's mental health status at different reproductive stages. Fourthly, due to the data accessibility limitations of NHANES, we were unable to specifically explore the relationship between parity and different specific types of cancer, a limitation that may obscure potential correlations. Additionally, despite our efforts to control for various confounding factors in subgroup analyses, the smaller sample sizes in some subgroups may limit the statistical power, affecting the ability to detect effects. Finally, studies exploring the association between parity and depression are cross-sectional designs, making it difficult to infer causality. These results should be interpreted with caution, and further research is warranted to corroborate our findings. WIDER IMPLICATIONS OF THE FINDINGS: Our study underscores the elevated risk of all-cause and cause-specific mortality in nulliparous women and reveals that depression partially mediates the negative correlation between parity and women's all-cause mortality and mortality from other diseases. These results should be interpreted with caution, and further investigation is needed to support our findings. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research and Development Program of China (2023YFC2705700), the Key Research & Developmental Program of Hubei Province (2022BCA042), and the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University (JCRCWL-2022-001). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Insights on the NF-κB system in polycystic ovary syndrome, attractive therapeutic targets.

The nuclear factor κappa B (NF-κB) signaling plays a well-known function in inflammation and regulates a wide variety of biological processes. Low-grade chronic inflammation is gradually considered to be closely related to the pathogenesis of Polycystic ovary syndrome (PCOS). In this review, we provide an overview on the involvement of NF-κB in the progression of PCOS particularly, such as hyperandrogenemia, insulin resistance, cardiovascular diseases, and endometrial dysfunction. From a clinical perspective, progressive recognition of NF-κB pathway provides opportunities for therapeutic interventions aimed at inhibiting pathway-specific mechanisms. With the accumulation of basic experimental and clinical data, NF-κB signaling pathway was recognized as a therapeutic target. Although there have been no specific small molecule NF-κB inhibitors in PCOS, a plethora of natural and synthetic compound have emerged for the pharmacologic intervention of the pathway. The traditional herbs developed for NF-κB pathway have become increasingly popular in recent years. Abundant evidence elucidated that NF-κB inhibitors can significantly improve the symptoms of PCOS. Herein, we summarized evidence relating to how NF-κB pathway is involved in the development and progression of PCOS. Furthermore, we present an in-depth overview of NF-κB inhibitors for therapy interventions of PCOS. Taken together, the NF-κB signaling may be a futuristic treatment strategy for PCOS.

Organ-on-a-chip: future of female reproductive pathophysiological models.

The female reproductive system comprises the internal and external genitalia, which communicate through intricate endocrine pathways. Besides secreting hormones that maintain the female secondary sexual characteristics, it also produces follicles and offspring. However, the in vitro systems have been very limited in recapitulating the specific anatomy and pathophysiology of women. Organ-on-a-chip technology, based on microfluidics, can better simulate the cellular microenvironment in vivo, opening a new field for the basic and clinical research of female reproductive system diseases. This technology can not only reconstruct the organ structure but also emulate the organ function as much as possible. The precisely controlled fluidic microenvironment provided by microfluidics vividly mimics the complex endocrine hormone crosstalk among various organs of the female reproductive system, making it a powerful preclinical tool and the future of pathophysiological models of the female reproductive system. Here, we review the research on the application of organ-on-a-chip platforms in the female reproductive systems, focusing on the latest progress in developing models that reproduce the physiological functions or disease features of female reproductive organs and tissues, and highlighting the challenges and future directions in this field.

Mechanisms of YAP1-mediated trophoblast ferroptosis in recurrent pregnancy loss.

PURPOSE: The purpose of our study is to investigate the function of YAP1 in the trophoblast ferroptosis and maternal-fetal interface communication of RPL. METHODS: We collected 25 villous tissues and detected the expression of YAP1. Cell counting kit-8 assay, scratch wound-healing assay, and Matrigel invasion assay were performed to observe the proliferation, migration, and invasion of HTR-8/SVneo and JAR cells. Subsequently, measured the levels of reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH), SLC7A11, SOD2, and GPX4. Ultimately, the use of ferroptosis activator (erastin) and inhibitor (Ferrostatin-1, fer-1) further confirmed the regulation by YAP1. In addition, established an in vitro-induced cell model to study the effect of YAP1 on the decidualization process. Finally, animal models were implemented for further confirmation. RESULTS: We found that YAP1 was downregulated in RPL patients. Overexpression of YAP1 could significantly enhance the proliferation, migration, and invasion of trophoblasts, and inhibit ferroptosis. Knocking down YAP1 exhibited the opposite effect. Rescue experiments have shown that YAP1 could upregulate the expression of SLC7A11 and GPX4, which are key molecules in the classic pathway of ferroptosis. In addition, the decidualization was impaired when hESCs were treated with conditioned medium of YAP1 knockdown trophoblasts. Moreover, we found that Yap1, Slc7a11, and Gpx4 were downregulated in the RPL mice, along with increased MDA and decreased GSH. CONCLUSION: Downregulation of YAP1 induces ferroptosis, thereby damaging the trophoblast invasion processes, which also disturbs the communication at the maternal-fetal interface. Our study identified YAP1 as a potential key molecule in the pathogenesis of RPL.

[Correlation of lipid metabolism-related single nucleotide polymorphisms with abnormal semen quality in men].

OBJECTIVE: To explore the potential impact of lipid metabolism-related single nucleotide polymorphisms (SNP) on semen quality in men. METHODS: We selected 284 semen samples from Xingtai Infertility Hospital and Hebei Human Sperm Bank collected between February and October 2023, 33 from oligozoospermia (OS), 97 from asthenozoospermia (AS) and 54 from oligoasthenozoospermia (OAS) patients and the other 100 from normal men. We performed computer-assisted semen analysis (CASA) of the samples, extracted blood DNA and, using the MassARRAY System, genotyped the target genes, determined the genotypes of 13 SNPs and compared their distribution, their correlation with BMI and semen quality in different groups. RESULTS: The mutant homozygous (TT) genotype of the FADS2 rs2727270 gene seemed to be a risk factor for AS (OR = 4.420, P= 0.047), while the APOA2 rs5082-A allele and MC4R rs17782313 heterozygous (TC) genotype important protective factors for OS (OR = 0.422 and 0.389; P= 0.045 and 0.043, respectively). A significantly higher sperm concentration was found associated with the MC4R rs17782313 heterozygous (TC) genotype than with the homozygous (CC) genotype. Stratification analysis showed that the protective effect of the TC genotype was decreased with increased BMI and remained with the interaction of the rs5082 and rs17782313 genotypes. CONCLUSION: FADS2 rs2727270, APOA2 rs5082 and MC4R rs17782313 were significantly correlated with the risk of abnormal semen parameters.

[Expressions of zinc homeostasis proteins, GPR39 and ANO1 mRNA in the sperm of asthenozoospermia patients and their clinical significance].

OBJECTIVE: To explore the expressions of zinc homeostasis-related proteins, G protein-coupled receptor 39 (GPR39) and ANO1 mRNA in the sperm of patients with asthenozoospermia (AS), and analyze their correlation with sperm motility. METHODS: We collected semen samples from 82 male subjects with PR+NP < 40%, PR < 32% and sperm concentration > 15×106/ml (the AS group, n = 40) or PR+NP ≥ 40%, PR ≥ 32% and sperm concentration > 15×106/ml (the normal control group, n = 42). We analyzed the routine semen parameters and measured the zinc content in the seminal plasma using the computer-assisted sperm analysis system, detected the expressions of zinc transporters (ZIP13, ZIP8 and ZNT10), metallothioneins (MT1G, MT1 and MTF), GPR39, and calcium-dependent chloride channel protein (ANO1) in the sperm by real-time quantitative PCR (RT qPCR), examined free zinc distribution in the sperm by laser confocal microscopy, and determined the expressions of GPR39 and MT1 proteins in the sperm by immunofluorescence staining, followed by Spearman rank correlation analysis of their correlation with semen parameters. RESULTS: There was no statistically significant difference in the zinc concentration in the seminal plasma between the AS and normal control groups (P>0.05). Compared with the controls, the AS patients showed a significantly reduced free zinc level (P<0.05), relative expressions of MT1G, MTF, ZIP13, GPR39 and ANO1 mRNA (P<0.05), and that of the GPR39 protein in the AS group (P<0.05). No statistically significant differences were observed in the relative expression levels of ZIP8, ZNT10 and MT1 mRNA between the two groups (P>0.05). The relative expression levels of GPR39, ANO1, MT1G and MTF mRNA were positively correlated with sperm motility and the percentage of progressively motile sperm (P<0.05). CONCLUSION: The expressions of zinc homeostasis proteins (MT1G, MTF and ZIP13), GPR39 and ANO1 mRNA are downregulated in the sperm of asthenozoospermia patients, and positively correlated with sperm motility.

The mechanism of Leonuri Herba in improving polycystic ovary syndrome was analyzed based on network pharmacology and molecular docking.

Background: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder affecting women. Chinese herbs have been considered as an alternative treatment for PCOS, and Yi-mu-cao (Leonuri Herba) is one of the most commonly used herbs to treat PCOS, which can relieve symptoms of PCOS patients. But the mechanism of its treatment remains unclear. Method: The main active ingredients and potential targets of Leonuri Herba were obtained by TCMSP and Swiss Target Forecast, and the related targets of PCOS were obtained by searching DrugBank, GeneCard and DisGeNet databases. The Protein-Protein Interaction (PPI) network was constructed using STRING database. GO and KEGG were used to detect the enrichment pathways of key targets. Cytoscape software was used to construct the component-target-pathway network, analyze the PPI network core, and verify the reliability of target binding by molecular docking technology. Result: 8 components and 116 targets of Leonuri Herba on PCOS were screened. Common targets mainly involve the Lipid and atherosclerosis, Endocrine resistance, AGE-RAGE signaling in diabetic complications and other signaling pathways. It is suggested that it can form multi-target and multi-pathway regulatory network through quercetin, kaempferol and other active substances to regulate endocrine disorders and reduce inflammatory response, so as to systematically improve PCOS. Molecular docking experiments showed that the active constituents of Leonurus had good binding activity with potential targets of PCOS. Conclusion: In summary, this study elucidates the potential effect of Leonuri Herba on PCOS, which is helpful to provide reference for clinical practice. This is also conducive to the secondary development of motherwort and its monomer components, and precision medicine for PCOS.

Which transfer day results in the highest live birth rate for PCOS patients undergoing in vitro fertilization?

BACKGROUND: Polycystic ovary syndrome (PCOS) has unusual levels of hormones. The hormone receptors in the endometrium have a hostile effect and make the microenvironment unfavorable for embryo implantation. The use of gonadotropin stimulation during in vitro fertilization (IVF) may have an impact on embryo implantation and live birth rate. According to recent data, the clinical results of day 4 embryo transfer (D4 transfer) were on par with those of day 5 embryo transfer (D5 transfer) in IVF-ET. There are few studies comparing the outcomes of transplants with various etiologies and days. The purpose of this study was to determine which transfer day had the best result for PCOS patients undergoing IVF. METHODS: This retrospective cohort study was conducted in the Xingtai Infertility Specialist Hospital between January 2017 and November 2021. A total of 1,664 fresh ART cycles met inclusion criteria, including 242 PCOS transfers and 1422 tubal factor infertility transfers. CONCLUSIONS: PCOS individuals had the highest live birth rate on D4 transferred. It was not need to culture embryos to blastocysts to optimize embryo transfer for PCOS women. This could be a novel approach to transplantation for PCOS.

Synergistic Effect Improves the Response of Active Sites to Target Variations for Picomolar Detection of Silver Ions.

Heavy metal ions seriously threaten human health; even a trace of them can damage the renal, nervous, and immune systems irreversibly. Although established nanozyme-based colorimetric assays have been designed for the rapid detection of heavy metal ions, the general contained surface organic ligands of nanocatalysts and low absorptivity of metal ions on solid substrates might result in a weak effect on active sites and prevent the realization of their full detection potential. Here, we developed a nanozyme-based colorimetric sensor (CPM-Pt) made by pyrolysis of peat moss with preabsorbed traces of Pt ions to ultrasensitively detect Ag+. The calcination removes organic components and produces bare nanozymes that expose rich active sites. The strong protective effect from the porous carbon support enables the embedded Pt nanoparticles (Pt NPs) with a partially stable positive charge after pyrolysis (∼28% Pt2+ species). By the d8-d10 metal-metal interactions between Pt2+ (4f145d8) and Ag+ (4d10), the high proportion of Pt2+ species on the surface of Pt NPs can readily capture/absorb Ag+. Subsequently, Ag+ accepts electrons from the support to form Ag atoms, which rapidly cover the peroxidase-like active sites of bare Pt NPs, weakening the activation of H2O2 to realize the response of Ag+. The colorimetric detection limit of Ag+ reached an unprecedented 1.1 pM, and the corresponding naked-eye color recognition is ultrasensitive to extremely low levels (100 pM).

TNF-α/anti-TNF-α drugs and its effect on pregnancy outcomes.

Pregnancy is a complex biological process. The establishment and maintenance of foetal-maternal interface are pivotal events. Decidual immune cells and inflammatory cytokines play indispensable roles in the foetal-maternal interface. The disfunction of decidual immune cells leads to adverse pregnancy outcome. Tumour necrosis factor (TNF)-α, a common inflammatory cytokine, has critical roles in different stages of normal pregnancy process. However, the relationship between the disorder of TNF-α and adverse pregnancy outcomes, including preeclampsia (PE), intrauterine growth restriction (IUGR), spontaneous abortion (SA), preterm birth and so on, is still indefinite. In this review, we thoroughly reviewed the effect of TNF-α disorder on pathological conditions. Moreover, we summarized the reports about the adverse pregnancy outcomes (PE, IUGR, SA and preterm birth) of using anti-TNF-α drugs (infliximab, etanercept and adalimumab, certolizumab and golimumab) currently in the clinical studies. Overall, IUGR, SA and preterm birth are the most common adverse pregnancy outcomes of anti-TNF-α drugs. Our review may provide insight for the immunological treatment of pregnancy-related complication, and help practitioners make informed decisions based on the current evidences.

Electronic Metal-Support Interaction Directing the Design of Fe(III)-Based Catalysts for Efficient Advanced Oxidation Processes by Dual Reaction Paths.

Persistent organic pollutants (POPs) have a huge impact on human health due to their high toxicity and non-degradability. It is still of great difficulty to develop highly efficient catalysts toward the degradation of POPs. Herein, it is reported that regulating electronic structure of quasi-single atomic ferric iron (Fe(III)) in the VO2 support through the electronic metal-support interaction (EMSI) is a versatile strategy to enhance the catalytic activity. Activated Fe(III) can react with peroxydisulfate (PDS) to produce both radicals and high-valent iron (HVFe) simultaneously for the efficient and fast degradation of POPs. Density functional theory (DFT) calculations prove that the influence of EMSI promotes the electrons on Fe(III) 3d-bond center moving close to the Fermi level, facilitating the charge transfer from Fe(III) to the adsorbate. Through the control experiments, both the radical path by PDS and the HVFe path aroused by the EMSI are confirmed in the POP degradation process. Consequently, the Fe/VO2 catalyst exhibits record-breaking catalytic activity with the k-value as high as 56.7, 43.3 µmol s-1 g-1 for p-chlorophenol and 2,4-dichlorophenol degradation, respectively.

Irisin reduces the abnormal reproductive and metabolic phenotypes of PCOS by regulating the activity of brown adipose tissue in mice†.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disease in women, with clinical manifestations of anovulation and hyperandrogenaemia. The treatment of PCOS mainly focuses on improving clinical symptoms, such as insulin sensitivity or menstrual disorder, through drug treatment. However, due to the pathogenesis diversity of PCOS, there is still a lack of effective treatment in clinics. Metabolic disorder is the key factor in the occurrence of PCOS. Brown adipose tissue (BAT) is a special adipose tissue in the human body that can participate in metabolic balance by improving heat production. BAT has been demonstrated to be an important substance involved in the metabolic disorder of PCOS. Although increasing evidence indicates that BAT transplantation can improve the symptoms of PCOS, it is difficult to achieve BAT transplantation at present due to technical limitations. Stimulation of BAT activation by exogenous substances may be an effective alternative therapy for PCOS. In this study, we investigated the effects of Irisin on dehydroepiandrosterone (DHEA)-induced PCOS in mice and evaluated the effect of Irisin on serum hormone levels and changes in body temperature, body weight, and ovarian morphology. In our study, we found that Irisin can enhance the thermogenesis and insulin sensitivity of PCOS mice by activating the function of BAT. In addition, Irisin treatment can correct the menstrual cycle of PCOS mice, improve the serum steroid hormone disorder status, and reduce the formation of ovarian cystic follicles. In conclusion, our results showed that Irisin treatment significantly improved the metabolic disorder of PCOS and may provide a new and alternative therapy for the treatment of this pathology.

Combined therapy guided by multimodal imaging of fifteen retinal capillary hemangioblastomas in a monocular Von Hippel- Lindau syndrome case report.

BACKGROUND: To report the multimodal imaging and treatment of fifteen retinal capillary hemangioblastomas (RCHs) associated with Von Hippel-Lindau syndrome in a monocular patient during a long-term following-up, which supply high-resolution exquisite SS-OCTA images (VG200; SVision Imaging, Ltd., Luoyang, China) and management experience about multiple RCHs. CASE PRESENTATION: A 34-year-old monocular male patient complained decreased visual acuity (20/100) without pain and redness in the left eye five years ago. Von Hippel-Lindau syndrome were diagnosed with genetic testing. He, his son and daughter all carried a heterozygosity missense variant c.499C > T (p. Arg167Trp) in the Hg19 gene, a VHL gene located in Chr3:10,191,506. Fifteen RCHs were identified by the application of multimodal imaging, which including fundus photo, fundus autofluorescence (FAF), B-scan ultrasonography (US), fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA) and swept-source optical coherence tomography angiography (SS-OCTA). Transscleral cryotherapy and laser photocoagulation were performed to destroy the largest RCH with the size of 4 PD in diameter. Laser photocoagulation was conducted to seal the middle or tiny RCHs (< 1.5 PD) and their nourishing vessels. The retinal edema and exudative macular detachment were successfully relieved by intraocular injection of bevacizumab for 5 times. The RCHs in the left eye responded well to these treatments and best corrected visual acuity was 20/25 for three years. Three-month recall visits were recommended for him. CONCLUSION: For multiple retinal capillary hemangioblastomas in monocular patients, precise combined therapy guided by multimodal imaging has a profound impact on the management of new and recurrent RCHs.

INO80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion.

The INO80 complex, a SWI/SNF family chromatin remodeler, has regulatory effects on ESC self-renewal, somatic cell reprogramming and blastocyst development. However, the role of INO80 in regulating trophoblast cells and recurrent miscarriage (RM) remains elusive. To investigate the in vivo effects of Ino80 in embryo development, we disrupted Ino80 in C57 mice, which resulted in embryonic lethality. Silencing of Ino80 led to decreased survival capacity, migration and invasion of trophoblasts. Furthermore, RNA high-throughput sequencing (RNA-seq) revealed that Ino80 silencing closely resembled the gene expression changes in RM tissues. To investigate the mechanisms for these results, RNA-seq combined with high-throughput sequencing (ChIP-seq) was used in trophoblast cells, and it showed that Ino80 physically occupies promoter regions to affect the expression of invasion-associated genes. Last, Western blotting analyses and immunofluorescence staining revealed that the content of INO80 was reduced in RM patients compared to in healthy controls. This study indicates that INO80 has a specific regulatory effect on the viability, migration and invasion of trophoblast cells. Combined with its regulation of the expression of invasion-associated genes, it has been proposed that epigenetic regulation plays an important role in the occurrence of RM, potentially informing RM therapeutic strategies.

Hsa_circ_0000301 facilitates the progression of cervical cancer by targeting miR-1228-3p/IRF4 Axis.

BACKGROUND: With the broadened application of gene expression profiles analysis, the role of miRNA and circRNA are of increasing concern in recent years, especially during the pathogenesis of cancer. However, to date, the reported on this area in cervical cancer are limited. METHOD: In this study, Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis were utilized to screen out differentially expressed (DE) circular RNAs in cervical cancer, and then we predicted and screened the combined microRNAs (miRNA) and downstream mRNAs to construct circular (circ)RNA-miRNA-mRNA network. RESULT: As a result, a regulatory circular (circ)RNA-miRNA-mRNA with 1 circRNA node, 4 miRNA nodes, 135 mRNA nodes were constructed in an attempt to provide novel biomarkers for the pathogenesis of cervical cancer. In addition, enrichment analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on mRNAs in the network. After further screening of mRNAs by two online databases of GEPIA2 and RNAyhrid, precise target genes were obtained. Next, we screened out four target genes (CXCL16, IRF4, OAS3 and PTGER3) by constructing the protein-protein interaction (PPI) network, and mapped them to the initial network to reconstruct the circRNA-miRNA-mRNA network. Notably, the low expression of IRF4 was demonstrated to be associated with a significantly poorer overall survival in the GEPIA2 database, which was also verified by the immunofluorescence of the sections in Human Protein Atlas (HPA). The upstream miRNA corresponding to IRF4 is hsa-miR-1228-3p. CONCLUSION: From above concern, it can conclude that hsa_circ_0000301/hsa-miR-1228-3p/IRF4 may be involved in the occurrence and development of cervical cancer. However, the specific mechanism should be further studied and confirmed.

The treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

WHAT IS KNOWN AND OBJECTIVE: In recent years, the resistance of Mycoplasma pneumoniae to macrolide antibiotics has increased significantly. The health systems are facing significant challenges in carrying out the diagnosis and treatment of refractory Mycoplasma pneumoniae pneumonia in children. Levofloxacin is suitable for treating infectious diseases in various systems but limited in children due to arthropathy issues in weight-bearing joints. This study aimed to evaluate the efficacy and safety of levofloxacin in children with macrolide-resistant Mycoplasma pneumoniae pneumonia. METHODS: We retrospectively enrolled six confirmed cases of refractory Mycoplasma pneumoniae pneumonia who were admitted in the paediatric respiratory ward of Shandong provincial hospital Affiliated to Shandong first Medical University between 1st January 2020 and 29th February 2020. Levofloxacin was given to the patients through the intravenous or oral route as per the following dosages :<5 years, 8-10 mg/kg q12 h; >5 years, 8-10 mg/kg, qd for 10 days. The clinical data were collected and analysed. RESULTS AND DISCUSSION: The average age of the enrolled cases was six years and nine months (range, four years, and seven months to eleven years and seven months). All cases were found to be drug-resistant and were treated with azithromycin combined with antibacterial drugs. Levofloxacin was used in the patient's refractory to macrolide antibiotics. The temperature of five cases returned to normal 1-2 days after treatment with levofloxacin, and the imaging of the four cases showed expected improvements. The gastrointestinal symptoms, neurological manifestations, joint symptoms, blood parameters, liver and kidney functions, and exercise conditions of the children were closely monitored. The follow-up time of the patients ranged from one week to five months. No drug-related adverse reactions were observed in patients during treatment or during follow-up. WHAT IS NEW AND CONCLUSION: The clinical symptoms and imaging significantly improved after treatment with levofloxacin, and no drug-related adverse reactions were observed. Levofloxacin proved to be an effective and safe drug in the treatment of children with macrolide-resistant mycoplasma pneumonia. This study will provide a reference for evaluating the efficacy and safety of levofloxacin in the paediatric population.

Tailoring the Electronic Metal-Support Interactions in Supported Atomically Dispersed Gold Catalysts for Efficient Fenton-like Reaction.

The atomically dispersed metal is expected as one of the most promising Fenton-like catalysts for the degradation of recalcitrant organic pollutants (ROPs) by the strong "electronic metal-support interactions" (EMSIs). Here, we develop an atomically dispersed metal-atom alloy made by guest Au atoms substitute host V atoms in the two-dimensional VO2 (B) nanobelt support (Au/VO2 ) to activate Fenton-like oxidation for elimination of ROPs. The 2D nanobelt structure enlarges the exposure of atomically Au thus increasing the number of active sites to absorb more S2 O8 2- ions. And the EMSIs regulate the charge density in Au atoms to present positive charge Au+ , lowering the energy barrier of S2 O8 2- decomposition to produce SO4 .- . The Au/VO2 catalyst possesses excellent durable and reliable characteristics and exhibits record-breaking efficiency with TOF as high as 21.42 min-1 , 16.19 min-1 , and 80.89 min-1 for rhodamine, phenol, and bisphenol A degradation, respectively.

YY1-PVT1 affects trophoblast invasion and adhesion by regulating mTOR pathway-mediated autophagy.

Insufficient trophoblast invasion is the key factor for the occurrence of recurrent spontaneous abortions (RSA). Our previous studies identified Yin Yang 1 (YY1) as a transcription factor involved in the regulation of trophoblast invasiveness at the maternal-fetal interface. Long noncoding RNAs (lncRNAs) can regulate gene expression and autophagy in many ways. The purpose of this study was to explore the relationship between YY1 and lncRNAs and the mechanism by which lncRNAs affect the biological behavior of trophoblasts. Bioinformatic analysis predicted that YY1 had three binding sites in the plasmacytoma variant translocation 1 (PVT1) promoter region. Chromatin immunoprecipitation experiments and electrophoretic mobility shift assays verified that YY1 can directly bind to the PVT1 promoter. Compared with its expression levels in human placental villi tissue samples from the normal pregnancy group, the PVT1 expression levels were significantly lower in tissues from the RSA group. PVT1 knockdown significantly reduced adhesion, invasion, autophagy, and mTOR expression in HTR-8/SVneo cells and greatly increased apoptosis in vitro. This study revealed a novel regulatory pathway in which YY1 can act directly on PVT1 promoter to regulate its transcription, which further affects trophoblast invasion and adhesion by regulating autophagy via the mTOR pathway, and these effects might be involved in RSA pathogenesis.

Prognostic value of infiltrating immune cells in clear cell renal cell carcinoma (ccRCC).

In this study, we attempted to evaluate the prognostic value of infiltrating immune/stromal cells in clear cell renal cell carcinoma (ccRCC), by using the immune scores and stromal scores based on the "Estimation of STromal and Immune cells in MAlignant Tumours using Expression data" algorithm to represent the levels of infiltrating immune cells and stromal cells. We found that the infiltrating immune cells were associated with poor prognosis of ccRCC. To assess the role of infiltrating immune cells in ccRCC cells, first, we performed differentially expressed genes analysis and functional analysis for validation. The results showed that the underlying mechanism by which infiltrating immune cells promoted cancer progression involved in regulating the nuclear division, angiogenesis, and immune response. Next, we investigated the relationship between infiltrating immune cells and mutations in ccRCC cells. We found that the infiltrating immune cells have certain effects on genetic mutations. In conclusion, infiltrating immune cells within the tumor microenvironment can be used to predict prognosis in ccRCC.

CTLA4 has a profound impact on the landscape of tumor-infiltrating lymphocytes with a high prognosis value in clear cell renal cell carcinoma (ccRCC).

Background: Cytotoxic T-lymphocyte associated protein 4 (CTLA4) inhibitors have been shown to significantly prolong the overall survival (OS) in a wide range of cancers. However, its application in clear cell renal cell carcinoma (ccRCC) is limited due to the therapy response, and the prognostic value of CTLA4 in ccRCC has not been investigated in detail. Methods: By using immunohistochemistry, Kaplan-Meier (K-M) analysis, uni- and multi-variate Cox analysis, we comprehensively and systematically studied the prognostic value of CTLA4 in ccRCC. Then, we applied Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and CIBERSORT, ESTIMATE algorithm, ssGSEA and somatic mutation analyses to reveal the impact of CTLA4 on the landscape of tumor-infiltrating lymphocytes (TILs) infiltration and genetic mutation. Besides, given current concerns caused by combined immunotherapy, we also investigated the relationship between CTLA4 and other immune checkpoints. Results: In vitro experiment and data mining showed that, CTLA4 was up-regulated in ccRCC tissues and closely related to the disease progression as well as a poor prognosis. Deeper researches demonstrated that CTLA4 regulates T cell activation and was significantly linked to TIL-abundant tumor microenvironment (TME), but was accompanied by an immunosuppressed phenotype. Mutation analysis showed that CTLA4 was associated with more frequent BRCA-associated protein 1 (BAP1) mutation. Moreover, we found that CTLA4 was markedly correlated with multiple immune checkpoints, which suggested that ccRCC patients with high expressed CTLA4 may benefit more from immune checkpoint blockades (ICBs) combined therapy. Conclusion: CTLA4 has a profound impact on the landscape of TILs and genetic mutation, and can be used as the biomarker with high prognosis value in ccRCC.