KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer's disease.

BACKGROUND: Epidemiological studies have revealed a correlation between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2D). Insulin resistance in the brain is a common feature in patients with T2D and AD. KAT7 is a histone acetyltransferase that participates in the modulation of various genes. AIM: To determine the effects of KAT7 on insulin patients with AD. METHODS: APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes, respectively. An in vitro model of AD was established by Aß stimulation. Insulin resistance was induced by chronic stimulation with high insulin levels. The expression of microtubule-associated protein 2 (MAP2) was assessed using immunofluorescence. The protein levels of MAP2, Aß, dual-specificity tyrosine phosphorylation-regulated kinase-1A (DYRK1A), IRS-1, p-AKT, total AKT, p-GSK3ß, total GSK3ß, DYRK1A, and KAT7 were measured via western blotting. Accumulation of reactive oxygen species (ROS), malondialdehyde (MDA), and SOD activity was measured to determine cellular oxidative stress. Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation, respectively. Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR. A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A. RESULTS: KAT7 expression was suppressed in the AD mice. Overexpression of KAT7 decreased Aß accumulation and MAP2 expression in AD brains. KAT7 overexpression decreased ROS and MDA levels, elevated SOD activity in brain tissues and neurons, and simultaneously suppressed neuronal apoptosis. KAT7 upregulated levels of p-AKT and p-GSK3ß to alleviate insulin resistance, along with elevated expression of DYRK1A. KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A. HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion. CONCLUSION: We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation. Our findings suggest that KAT7 is a novel and promising therapeutic target for the resistance in AD.

Exosomes derived from induced cardiopulmonary progenitor cells alleviate acute lung injury in mice.

Cardiopulmonary progenitor cells (CPPs) constitute a minor subpopulation of cells that are commonly associated with heart and lung morphogenesis during embryonic development but completely subside after birth. This fact offers the possibility for the treatment of pulmonary heart disease (PHD), in which the lung and heart are both damaged. A reliable source of CPPs is urgently needed. In this study, we reprogrammed human cardiac fibroblasts (HCFs) into CPP-like cells (or induced CPPs, iCPPs) and evaluated the therapeutic potential of iCPP-derived exosomes for acute lung injury (ALI). iCPPs were created in passage 3 primary HCFs by overexpressing GLI1, WNT2, ISL1 and TBX5 (GWIT). Exosomes were isolated from the culture medium of passage 6-8 GWIT-iCPPs. A mouse ALI model was established by intratracheal instillation of LPS. Four hours after LPS instillation, ALI mice were treated with GWIT-iCPP-derived exosomes (5 × 109, 5 × 1010 particles/mL) via intratracheal instillation. We showed that GWIT-iCPPs could differentiate into cell lineages, such as cardiomyocyte-like cells, endothelial cells, smooth muscle cells and alveolar epithelial cells, in vitro. Transcription analysis revealed that GWIT-iCPPs have potential for heart and lung development. Intratracheal instillation of iCPP-derived exosomes dose-dependently alleviated LPS-induced ALI in mice by attenuating lung inflammation, promoting endothelial function and restoring capillary endothelial cells and the epithelial cells barrier. This study provides a potential new method for the prevention and treatment of cardiopulmonary injury, especially lung injury, and provides a new cell model for drug screening.

Tao-Hong-Si-Wu-Tang Improves the Depressive-like Behaviors in Mice Experiencing Perimenopausal Depression Through Modulating Activity of the Hypothalamic-Pituitary-Adrenal-Ovary Axis and Activating the BDNF-TrkB-CREB Signaling Pathway.

Tao-Hong-Si-Wu-Tang (THSWT), a traditional Chinese herbal remedy, is commonly utilized for the treatment of female perimenopausal depression through regulating menstruation, but the mechanism remains unknown. In this study, ICR mice were randomly divided into six groups: low, medium, and high dose of THSWT (0.5, 1.5, and 4.5 g/kg), soy isoflavone (250 mg/kg), ovariectomy group, and control group. All mice, except the control group, had ovaries removed and were exposed to hypoxic stimulation for 28 days to establish a perimenopausal depression mice model. The mice, having unrestricted access to food and water, were administered THSWT treatment for a duration of 14 days. The Western blotting and Enzyme linked immunosorbent assay kits were used to determine protein and hormone levels, respectively. Experimental results showed that THSWT reduced the immobility time of mice from 150.8 s to 104.9 s in the tail suspension test, and it decreased the immobility time of mice from 165.7 s to 119.0 s in the forced swimming test, outperforming the results obtained with soy isoflavones. In addition, THSWT upregulated the protein expression of follicle-stimulating hormone receptor and downregulated the protein expression of corticotropin-releasing hormone-receptor 1 in the hippocampus. Compared with the oophorectomized group, treatment with THSWT decreased the levels of corticosterone and adrenocorticotropic hormone in serum by 173.7 and 23.4 ng/mL, respectively. These findings showed that THSWT could stimulate the perimenopausal nerve tissue and regulate the level of serum hormones in mice. THSWT exhibited promising potential as a viable alternative drug for hormone treatment of perimenopause in clinical use.

Cardiopulmonary progenitors facilitate cardiac repair via exosomal transfer of miR-27b-3p targeting the SIK1-CREB1 axis.

Ischemic heart disease, especially myocardial infarction (MI), is one of the leading causes of death worldwide, and desperately needs effective treatments, such as cell therapy. Cardiopulmonary progenitors (CPPs) are stem cells for both heart and lung, but their repairing role in damaged heart is still unknown. Here, we obtained CPPs from E9.5 mouse embryos, maintained their stemness while expanding, and identified their characteristics by scRNA-seq, flow cytometry, quantitative reverse transcription-polymerase chain reaction, and differentiation assays. Moreover, we employed mouse MI model to investigate whether CPPs could repair the injured heart. Our data identified that CPPs exhibit hybrid fibroblastic, endothelial, and mesenchymal state, and they could differentiate into cell lineages within the cardiopulmonary system. Moreover, intramyocardial injection of CPPs improves cardiac function through CPPs exosomes (CPPs-Exo) by promotion of cardiomyocytic proliferation and vascularization. To uncover the underlying mechanism, we used miRNA-seq, bulk RNA-seq, and bioinformatic approaches, and found the highly expressed miR-27b-3p in CPPs-Exo and its target gene Sik1, which can influence the transcriptional activity of CREB1. Therefore, we postulate that CPPs facilitate cardiac repair partially through the SIK1-CREB1 axis via exosomal miR-27b-3p. Our study offers a novel insight into the role of CPPs-Exo in heart repair and highlights the potential of CPPs-Exo as a promising therapeutic strategy for MI.

The construction and validation of ECM-related prognosis model in laryngeal squamous cell carcinoma.

Background: Laryngeal squamous cell carcinoma (LSCC) is a kind of common and aggressive tumor with high mortality. The application of molecular biomarkers is useful for the early diagnosis and treatment of LSCC. Methods: The expression and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Principal components analysis (PCA) was used to discriminate between LSCC and normal samples. The hub genes were screened out through univariate and multivariate cox analyses. The Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curve was used to validate the predictive performance. The single sample gene set enrichment analysis (ssGSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to determine the enrichment function. Protein-Protein Interaction (PPI) network was constructed in STRING. The immune analysis was performed by ESTIMATE, IPS and xCELL. The drug sensitivity was identified with GSCA database. Results: We identified that 47 extracellular matrix (ECM) genes were differentially expressed in LSCC compared with normal group. Univariate and multivariate cox analysis determined that leucine-rich glioma-inactivated 4 (LGI4), matrilin 4 (MATN4), microfibrillar-associated protein 2 (MFAP2) and fibrinogen like 2 (FGL2) were closely related to the disease free survival (DSS) of LSCC. ROC curve determined that the risk model has a good predictive performance. PPI network showed the top 100 genes with high correlation of hub genes. The ssGSEA, GO and KEGG enrichment analyses determined that immune response was significantly involved in the development of LSCC. Immune infiltration analysis showed that most immune cells and immune checkpoints were inhibited in high risk score group. Drug sensitivity analysis showed that MATN4, FGL2 and LGI4 were negatively related to various drugs, while MFAP2 was positively related to many drugs. Conclusion: We established a risk model constructed with four ECM-related genes, which could effectively predict the prognosis of LSCC.

Factors associated with disease relapse rate in the Neuromyelitis optica spectrum disorder.

BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is a group of demyelinating diseases of the nervous system with high relapse rate and high disability rate without treatment, and we aimed to explore the influencing factors related to the recurrence of NMOSD and provide basis for clinical treatment in this study. METHODS: Referring to the diagnostic criteria for NMOSD issued in 2015, 259 patients were enrolled. Clinical information, cerebrospinal fluid (CSF) and serum analysis results, brain and spinal cord magnetic resonance imaging (MRI) findings, treatment details, and prognosis were all recorded. RESULTS: 176 (68.00%) participants were found to be AQP4 Ab-positive in serum or CSF, and the relapse rate was 36.67% (95/259). These 259 individuals were separated into two groups: non-release (n = 164) and relapse (n = 95). In terms of EDSS scores at onset, EDSS score after treatment, lesion location, serum creatinine (Cr) and treatment strategy, there were statistical differences between the two groups. Multivariable logistic regression analyses revealed five predictors for recurrence of NMOSD patients within two years: EDSS scores at onset, transverse myelitis, brain/brainstem, Cr, and Rituximab/immunosuppressants. CONCLUSION: It is essential to explore the risk factors related to recurrence and prevent them to reduce the risk of disability and improve the prognosis, and the recurrence rate of NMOSD may be affected by several factors.

Anti-inflammatory effect and component analysis of Chaihu Qingwen granules.

ETHNOPHARMACOLOGICAL RELEVANCE: As prevalent acute respiratory condition in clinical practice, acute lung injury has a quick start and severe symptoms which can harm patients physically. Chaihu Qingwen granules (CHQW) is a classic formula for the treatment of respiratory diseases. Clinical observation shows that CHQW has good efficacy in treating colds, coughs, and fevers. AIM OF THE STUDY: The aim of this study was to investigate the anti-inflammatory effect of CHQW on lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in rats and to explore its potential mechanism, as well as to clarify its substance composition. MATERIALS AND METHODS: Male SD rats were randomly divided into the blank group, the model group, the ibuprofen group, the Lianhua Qingwen capsule group and the CHQW group (2, 4 and 8 g/kg, respectively). The LPS-induced acute lung injury (ALI) model in rats was established after pre-administration. The histopathological changes in the lung and the levels of inflammatory factors in bronchoalveolar lavage fluid (BALF) and serum of ALI rats were observed. The inflammation-related proteins toll-like receptor 4 (TLR4), inhibitory kappa B alpha (IκBα), phospho-IκBα (p-IκBα), nuclear-factor-kappa B (NF-κB), and NLR family pyrin domain containing 3(NLRP3) expression levels were measured by western blotting analysis and immunohistochemical analysis. The chemical composition of CHQW was identified by liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-Q-TOF-MS). RESULTS: CHQW significantly ameliorated lung tissue pathological injury in LPS-induced ALI rats and decreased the release of inflammatory cytokines (interleukin-1ß, interleukin-17 and tumor necrosis factor-α) in BALF and serum. In addition, CHQW decreased the expression of TLR4, p-IκBα and NF-κB proteins, increased the level of IκBα, regulated the TLR4/NF-κB signaling pathway, and inhibited the activation of NLRP3. The chemical components of CHQW were analyzed by LC-Q-TOF-MS, and a total of 48 components were identified by combining information from the literature, mainly flavonoids, organic acids, lignans, iridoids and phenylethanoid glycosides. CONCLUSION: The results of this study showed that the pretreatment of CHQW had a strong protective effect on LPS-induced ALI in rats, reducing lung tissue lesions and decreasing inflammatory cytokines released in BALF and serum. The protective mechanism of CHQW may be related to the inhibition of the TLR4/NF-κB signaling pathway and NLRP3 activation. The main active ingredients of CHQW are flavonoids, organic acids, lignans, iridoids and phenylethanoid glycosides.

Manipulating fluorescence by photo-switched spin-state conversions in an iron(ii)-based SCO-MOF.

Manipulating fluorescence by photo-switched spin-state conversions is an attractive prospect for applications in smart magneto-optical materials and devices. The challenge is how to modulate the energy transfer paths of the singlet excited state by light-induced spin-state conversions. In this work, a spin crossover (SCO) FeII-based fluorophore was embedded into a metal-organic framework (MOF) to tune the energy transfer paths. Compound 1 {Fe(TPA-diPy)[Ag(CN)2]2}·2EtOH (1) has an interpenetrated Hofmann-type structure, wherein the FeII ion is coordinated by a bidentate fluorophore ligand (TPA-diPy) and four cyanide nitrogen atoms and acts as the fluorescent-SCO unit. Magnetic susceptibility measurements revealed that 1 underwent an incomplete and gradual spin crossover with T1/2 = 161 K. Photomagnetic studies confirmed photo-induced spin state conversions between the low-spin (LS) and high-spin (HS) states, where the irradiation of 532 and 808 nm laser lights converted the LS and HS states to the HS and LS states, respectively. Variable-temperature fluorescence spectra study revealed an anomalous decrease in emission intensity upon the HS → LS transition, confirming the synergetic coupling between the fluorophore and SCO units. Alternating irradiation of 532 and 808 nm laser lights resulted in reversible fluorescence intensity changes, confirming spin state-controlled fluorescence in the SCO-MOF. Photo-monitored structural analyses and UV-vis spectroscopic studies demonstrated that the photo-induced spin state conversions changed energy transfer paths from the TPA fluorophore to the metal-centered charge transfer bands, ultimately leading to the switching of fluorescence intensities. This work represents a new prototype compound showing bidirectional photo-switched fluorescence by manipulating the spin states of iron(ii).

Premature timing of progesterone luteal phase support initiation did not negatively impact live birth rates in modified natural frozen thawed embryo transfer cycles.

Study question: In a modified natural cycle frozen-thawed embryo transfer (mNC-FET), does the premature timing of progesterone luteal phase support (LPS) initiation 24 h following human chorionic gonadotropin (hCG) trigger impact live birth? Summary answer: Premature LPS initiation did not negatively affect the live birth rate (LBR) in mNC-FET cycles compared with conventional LPS initiation 48 h after hCG triggering. What is known already: During natural cycle FET, human chorionic gonadotropin is routinely used to mimic endogenous luteinizing hormone (LH) surge to induce ovulation, which allows more flexibility in embryo transfer scheduling, thus relieving the burden of multiple visits by patients and laboratory workloads, which is also known as mNC-FET. Moreover, recent data demonstrates that ovulatory women undergoing natural cycle FETs have a lower risk of maternal and fetal complications due to the essential role of the corpus luteum in implantation, placentation and pregnancy maintenance. While several studies have confirmed the positive effects of LPS in mNC-FETs, the timing of progesterone LPS initiation is still unclear, as compared with fresh cycles where robust research has been conducted. To the best of our knowledge, no clinical studies comparing different beginning days in mNC-FET cycles have been published. Study design size duration: This retrospective cohort study involved 756 mNC-FET cycles performed at a university-affiliated reproductive center between January 2019 and August 2021. The primary outcome measured was the LBR. Participants/materials setting methods: Ovulatory women ≤42 years of age who were referred for their autologous mNC-FET cycles were included in the study. According to the timing of progesterone LPS initiation following the hCG trigger, patients were assigned into two categories: premature LPS group (progesterone initiation 24 h after hCG trigger, n = 182) versus conventional LPS group (progesterone initiation 48 h after hCG trigger, n = 574). Multivariate logistic regression analysis was used to control for confounding variables. Main results and the role of chance: There were no differences in background characteristics between the two study groups, except for the proportion of assisted hatching (53.8% in premature LPS group versus 42.3% in conventional LPS group, p = 0.007). In the premature LPS group, 56 of 182 patients (30.8%) had a live birth, compared to 179 of 574 patients (31.2%) in the conventional LPS group, with no significant difference observed between groups (adjusted odds ratio [aOR] 0.98, 95% confidence interval [CI] 0.67-1.43, p = 0.913). In addition, there was no significant difference between the two groups in other secondary outcomes. A sensitivity analysis for LBR according to the serum LH and progesterone levels on hCG trigger day also confirmed the aforementioned findings. Limitations reasons for caution: In this study, retrospective analysis was conducted in a single center and was therefore prone to bias. Additionally, we did not anticipate monitoring the patient's follicle rupture and ovulation after hCG triggering. Future prospective clinical trials remain necessary to confirm our results. Wider implications of the findings: While exogenous progesterone LPS was added 24 h after hCG triggering, embryo-endometrium synchrony would not be adversely affected so long as sufficient time was allowed for endometrial exposure to exogenous progesterone. Our data support promising clinical outcomes following this event. As a result of our findings, clinicians and patients will be able to make better informed decisions. Study funding/competing interests: No specific funding was available for this study. The authors have no personal conflicting interests to declare. Trial registration number: N/A.

Comparison of pregnancy outcomes of letrozole-induced frozen-thawed embryo transfer cycles in PCOS women with two different abnormal ovulation patterns: A retrospective cohort study.

No studies have been conducted on the impact of different types of ovulatory dysfunction on the outcomes of frozen-thawed embryo transfers (FETs) in a letrozole-stimulated cycle in women with polycystic ovarian syndrome (PCOS). This study aimed to compare whether pregnancy outcomes of the letrozole-induced protocol in FET cycles differed between oligo-ovulatory and anovulatory women with PCOS. In a retrospective cohort study, women with PCOS who had undergone letrozole-induced FET at a university-affiliated fertility clinic from February 2014 to October 2020 were identified. The primary end point was live birth rate (LBR) per embryo transfer. Propensity score matching and multivariate logistic regression analyses were performed to control for the relevant confounders. A total of 652 women with PCOS undergoing letrozole-induced FET were included in the final analysis. Three hundred sixty-three of these women had oligo-ovulatory periods, while 289 had anovulatory periods. Propensity score matching analysis showed that LBR did not differ between groups (36.8% in oligo-ovulatory group vs 32.8% in anovulatory group, P = .431). Nevertheless, after controlling for potential confounding factors, LBR was significantly lower in anovulatory than oligo-ovulatory women (adjusted odds ratio 1.57, 95% confidence interval 1.08-2.29, P = .018). Furthermore, the pregnancy loss rate among the oligo-ovulatory group remained lower than those among the anovulatory group (adjusted odds ratio 0.23, 95% confidence interval 0.12-0.44, P < .001). Despite adjustment for confounding factors, those with oligo-ovulatory PCOS had a higher LBR and lower pregnancy loss rate compared with those with anovulatory PCOS. This may indicate that when oligo-ovulation is detected, PCOS patients should be intervened in time to conceive as soon as possible. Prospective studies must be conducted in the future to verify our findings.

Impact of progesterone-free luteal phase support following natural cycle frozen embryo transfer: Study protocol for a multicenter, non-inferiority, randomized controlled trial.

Introduction: Nowadays, frozen-thawed embryo transfer (FET) has become one of the standard treatments for infertility in the field of assisted reproductive technology (ART). Natural cycle FET (NC-FET) has many advantages, such as simplicity and economics, no effect on patients' menstrual cycles, estrogen and progesterone levels, as well as no interference in endometrial growth and transformation, which is aligned with the natural physiological state of embryo implantation. Nonetheless, there is a controversy regarding the need for luteal phase support (LPS) during NC-FET cycles. The purpose of this study is to assess whether LPS was not inferior to non-LPS in terms of OPR in NC-FET cycles. Methods and analysis: This study including 1,010 ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles with an elective freeze-all strategy followed by NC-FET will be performed at four university-affiliated reproductive centers. Participants will be randomly assigned in a 1:1 ratio to receive LPS treatment or not. This study is designed as an open-label, non-inferiority, randomized controlled trial (RCT), and the primary statistical strategies were intention-to-treat (ITT) and per-protocol (PP) analysis. Discussion: There may not have been any significant difference in the chance of a live birth after FET if no progesterone was supplemental during the luteal phase. However, due to the limited number of previous studies, which are mainly retrospective, evidence is still limited. Thus, by conducting this multicenter RCT, we intend to evaluate whether LPS is necessary in NC-FET. Ethics and dissemination: A Reproductive Ethics Committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine (SDUTCM) has approved this study. This study will handle the data as required by general data protection regulations. Participants will sign a written informed consent regarding participation in the study and storage of blood samples in a biobank for future research. This study will be monitored by study personnel trained in Good Clinical Practice who are not involved in the study. The results of this study will be disseminated through publication in international peer-reviewed scientific journals. Clinical trial registration: [https://www.chictr.org.cn/], identifier [ChiCTR2200057498].

Prevalence of smartphone addiction among Asian medical students: A meta-analysis of multinational observational studies.

BACKGROUND: High prevalence of smartphone addiction among medical students may contribute to adverse physical and mental health outcomes. AIM: To estimate the prevalence of smartphone addiction, and explore the influencing factors and related mental health symptoms of smartphone addiction among Asian medical students. DESIGN: Systematic review and meta-analysis. METHODS: PubMed (MEDLINE), the Cochrane Central Register of Controlled Trials, and EMBASE were searched for relevant literature from the inception to September 10, 2021. Using Stata software 11.0, the meta-analysis of prevalence and the influencing factors of smartphone addiction were determined with 95% confidence intervals. RESULTS: Nineteen articles, published between 2014 and 2019, were included, producing medical student studies from seven different Asian countries. The included studies were conducted in India (n = 11) and Malaysia (n = 3), with China, Saudi Arabia, Turkey, Nepal, and Iran each contributing one study. Among a total of 5,497 medical students, the participants included 3,214 females, of whom 2,181 were medical students with smartphone addiction. The prevalence of smartphone addiction among Asian medical students was 41.93% (95% CI [36.24%, 47.72%]). The influencing factors of smartphone addiction among medical students included gender, duration of smartphone use, smartphone function, and marital status. Ten studies (52.63%) explored related mental health symptoms of smartphone addiction among Asian medical students. Smartphone addiction was positively correlated with poor sleep quality (r = .17-.31), stress (r = .30-.40), anxiety, depression, neuroticism, and general health among Asian medical students. CONCLUSION: Smartphone addiction is highly prevalent among Asian medical students. Smartphone addiction may adversely affect mental health, resulting in sleep disturbance, stress, anxiety, depression, and neuroticism. It is necessary to take appropriate precautionary actions and interventions to prevent smartphone overuse among medical students.

GnRH Agonist and hCG (Dual Trigger) Versus hCG Trigger for Final Oocyte Maturation in Expected Normal Responders With a High Immature Oocyte Rate: Study Protocol for a Randomized, Superiority, Parallel Group, Controlled Trial.

Introduction: The choice of trigger drug for the controlled ovarian hyperstimulation (COH) protocol correlates with the outcome of in vitro fertilization/intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET). The co-administration of gonadotropin releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG), i.e., dual trigger, for final oocyte maturation, has received much attention in recent years. This trial was designed to determine whether a dual trigger approach by lengthening the time between trigger and ovum pick-up (OPU) improves the quantity and quality of mature oocytes/top-quality embryos and pregnancy outcomes in expected normal responders with a high immature oocyte rate. Methods and Analysis: We propose a study at the Affiliated Hospital of Shandong University of Chinese Medicine. A total of 90 individuals undergoing COH use a fixed GnRH antagonist protocol. They will be assigned randomly into two groups according to the trigger method and timing: recombinant hCG (6500 IU) will be injected only 36 hours before OPU for final oocyte maturation (hCG-only trigger); co-administration of GnRH-a and hCG for final oocyte maturation, 40 and 34 hours prior to OPU, respectively (Dual trigger). The primary outcome is metaphase-II (MII) oocytes rate. Secondary outcomes are number of oocytes retrieved, fertilization rate, top-quality embryos rate, blastula formation rate, embryo implantation rate, clinical pregnancy rate, miscarriage rate, live birth rate, cumulative pregnancy/live birth rates, and ovarian hyperstimulation syndrome (OHSS) rate. Ethics and Dissemination: The reproductive ethics committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine certified this study (Identifier: SDUTCM/2021.7.26) as ethical. All individuals will sign written informed consent. All data and biological samples will be protected according to law. The results of this study will be disseminated in a peer-reviewed scientific journal. Clinical Trial Registration: [chictr.gov.cn], identifier [ChiCTR2100049292].

Short (seven days) versus standard (fourteen days) oestrogen administration in a programmed frozen embryo transfer cycle: a retrospective cohort study.

RESEARCH QUESTION: What influence does seven days of oestrogen administration versus fourteen days have on the reproductive outcomes of frozen-thawed embryo transfer (FET) in programmed endometrial preparation cycles? DESIGN: In a retrospective study, conducted at a university-affiliated tertiary hospital, a total of 2628 infertile patients (4142 FET cycles) were divided into one of two groups between January 2014 and December 2020: group A (n = 1406, seven days of oestrogen before progesterone (P4) supplementation) and group B (n = 2716, fourteen days of oestrogen before P4 supplementation). The primary outcome was cumulative live birth rate (CLBR). Secondary outcomes were other pregnancy-related outcomes, maternal and neonatal complications. RESULTS: No significant difference in CLBR was observed when comparing seven versus fourteen days of oestrogen administration before starting P4 supplementation (47.6% vs. 48.8%, P = 0.537). Furthermore, multivariable logistic regression analysis revealed that oestrogen administration in programmed FET cycles (7 days vs. 14 days) was not significantly associated with CLBR (OR 1.04, 95% CI 0.89-1.23). The risks of maternal and neonatal complications were comparable between the two groups. CONCLUSIONS: Variation in the duration of oestradiol supplementation before P4 initiation does not impact FET reproductive outcomes. For infertile women who desire to conceive as soon as feasible, short (seven days) oestrogen administration in a programmed FET cycle may be a suitable alternative.

The role of CEMIP in tumors: An update based on cellular and molecular insights.

CEMIP was initially identified as an inner-ear specific protein in which three-point mutations cause folding changes in protein structure associated with non-syndromic hearing loss. CEMIP was also involved in other cellular activities, such as hyaluronan depolymerization independent of CD44 and other hyaluronidases. Growing evidence has demonstrated that CEMIP is involved in the progression of various tumors. However, whether the oncogenic effects of CEMIP relies on its enzymatic activity remain elusive. CEMIP is significantly related to metastasis and poor prognosis in patients with various tumors, suggesting that CEMIP is a potential, highly specific diagnostic tumor marker. Most preclinical experiments have shown that the overexpression of CEMIP in tumors mainly affects the adhesion, metastasis, and invasion of tumor cells and EMT. Other studies have also demonstrated that CEMIP can promote a variety of tumor processes by affecting tumor proliferation, dedifferentiation, and the tumor microenvironment. In terms of molecular mechanisms, existing research has shown that CEMIP mainly affects the WNT and EGFR signaling pathways. In addition, a variety of miRNAs have been shown to inhibit CEMIP in tumors. This paper elaborates on the clinical characteristics and regulatory dysfunction of CEMIP in different cancers. CEMIP provides a new potential target for therapy of multiple tumors, which is worthy of further study.

Effect of CX3CL1/CX3CR1 gene polymorphisms on the clinical efficacy of carboplatin therapy in Han patients with ovarian cancer.

Gene polymorphisms have a close relationship with the clinical effects of carboplatin for ovarian cancer. Here, we investigated the relationship between CX3CL1 and CX3CR1 genotypes and the clinical efficacy of carboplatin in ovarian cancer, thereby clarifying the unidentified genetic factors that influence the efficacy of carboplatin in ovarian cancer. Based on the above purposes, we used Sequenom Mass ARRAY technology to detect CX3CL1 and CX3CR1 gene polymorphisms in 127 patients with carboplatin-treated ovarian cancer. We performed various statistical analyses to evaluate the effects of CX3CL1 and CX3CR1 genetic variants, demographic data, and clinical characteristics on the effect of carboplatin therapy. The results show that the CX3CL1 genotypes rs223815 (G>C) and rs682082 (G>A) will significantly affect the clinical efficacy of carboplatin for ovarian cancer (p < 0.05), while the other six genotypes and all CX3CR1 genotypes have no significant effect (p > 0.05). In addition, only one population factor, age, had a significant effect on the clinical efficacy of carboplatin-treated ovarian cancer (p < 0.05). Based on the above research results, we concluded that the clinical efficacy of carboplatin in ovarian cancer patients was significantly correlated with age and CX3CL1 polymorphism factors; however, more in-depth effects and mechanisms need to be explored by large-scale, multicenter studies.

Anxiety and depression among pregnant women undergoing IVF-ET and WeChat group peer support during the COVID-19 pandemic: Study protocol for a randomized controlled trial.

INTRODUCTION: The psychological well-being of pregnant women following assisted reproductive has increasingly gained attention in recent years. Anxiety and depression may be associated to pregnancy outcomes. This study aims to determine whether peer support and the WeChat group platform will reduce anxiety and depression among in vitro fertilization and embryo transfer (IVF-ET) women. METHODS AND ANALYSIS: In the present randomized controlled study, 296 patients with confirmed clinical pregnancy following IVF-ET will be randomly assigned to receive standard intervention support or WeChat peer support on a 1:1 basis. The levels of anxiety and depression are the primary endpoints. Assessments will be performed at baseline measurements, first trimester, second trimester, and third trimester, and data will be collected. ETHICS AND DISSEMINATION: This study has been approved as ethical by the affiliated hospital of Shandong University of Traditional Chinese Medicine's Reproductive Ethics Committee. Each patient will sign a written statement of informed permission. All information and biological samples will be legally protected. A peer-reviewed academic journal will publish the findings of this investigation. DISCUSSION: Given the inconvenience of visits due to the current pandemic of COVID-19, this study addresses the patient's visit needs by combining WeChat, the most widely used social software in China, with peer support, while helping improve maternal anxiety, depression, and pregnancy outcomes following IVF-ET.

Asymmetric Coordination Toward a Photoinduced Single-Chain Magnet Showing High Coercivity Values.

The production of photo-switchable molecular nanomagnets with substantial coercivity, which is indispensable for information storage and process applications, is challenging. Introducing photo-responsive spin-crossover units provides a feasible means of controlling the magnetic anisotropy, interactions, and overall nanomagnet properties. Herein, we report a cyanide-bridged chain 1⋅12H2 O ({[(Pz Tp)FeIII (CN)3 ]2 FeII (Pmat)2 }n ⋅12 H2 O) generated by linking the FeII -based spin-crossover unit with the [(Pz Tp)Fe(CN)3 ]- (Pz Tp: tetrakis(pyrazolyl)borate) building block in the presence of asymmetric ditopic ligand Pmat ((4-pyridine-4-yl)methyleneamino-1,2,4-triazole). Structural characterization revealed that the introduction of this asymmetric ligand led to a distorted coordination environment of FeII ions, which were equatorially coordinated by four cyanide N atoms, and apically coordinated by one pyridine N atom and one triazole N atom. Upon 808-nm light irradiation, 1⋅12H2 O underwent photoinduced spin-crossover and exhibited single-chain magnet behavior with a coercive field of up to 1.3 T. This represents a 3d-based photoinduced single-chain magnet exhibiting pronounced hysteresis.

[Platelet HPA Typing of Platelet Donors in Zhangjiakou Area].

OBJECTIVE: To analyze the polymorphism of the HPA1-5,15 system of the donors in Zhangjiakou area. METHODS: DNA was extracted from the blood samples of the donors, PCR- SSP method was used to divide HPA1-6, 15 genotype. The gene frequency and genotype frequency were calculated, compared with the difference and regiahal specificity of the populations in our country and foregiens was compared other populations. RESULTS: The gene expression in the HPA-1, HPA-2 and HPA-4 systems were all homozygous aa, and the donors who expressed homozygous bb was not exessed. Among them, one heterozygous ab expression was found in both HPA-1 and HPA-4 systems (1%), and 14 cases of heterozygous ab expression were found in HPA-2 system (14%). The gene expression in the HPA-5 system was mainly homozygous aa (98%), and a very few expressed homozygous bb (2%) was found. The degree of heterozygosity of gene expression in the HPA-3 and HPA-15 systems was relatively high. The proprotion of the expression of aa, ab and bb in the HPA-3 system was respectively 46%, 40% and 14%, the proprotion of the expression of aa, ab and bb in the HPA-15 system was respectively 21%, 64% and 15%. CONCLUSION: The gene frequency of platelet-specific antigen HPA1-5,15 system in zhangjiakou region shows local characteristics. The heterozygosity degree of gene expression in the HPA-3 and HPA-15 systems are both high, suggesting that they are more likely to result in alloimmunization and ineffective platelet transfusion, which should be pays attention to.

Voltage-dependent anion channels mediated apoptosis in refractory epilepsy.

The purpose of this study was to investigate the role of voltage-dependent anion channel (VDAC) in mitochondria-mediated apoptosis of neurons in refractory epilepsy. Western blot analyses were carried out to detect the changes in cytochrome C, caspase 9, Bax, and Bcl-2. TUNEL assays were also carried out to investigate cell apoptosis under the upregulation and downregulation of VDAC1 with or without Bax or Bcl-2. VDAC1 induced Bax, Bcl-2, and caspase 9, increasing the release of cytochrome C. VDAC1 played an essential role in the apoptotic cell death of refractory epilepsy. It is concluded that VDAC1 plays an important role in refractory epilepsy and could be a possible therapeutic target of anti-epileptic drugs. The current study provides a new understanding of the possible mechanisms of refractory epilepsy.