Successful intracytoplasmic sperm injection in a macrozoospermia case with novel compound heterozygous aurora kinase C (AURKC) mutations.

PURPOSE: To explore the application possibility of macrocephalic sperm from a patient with 100% macrocephalic sperm and AURKC gene variations. METHODS: We diagnosed a case of macrozoospermia with 100% macrocephalic sperm and 39.5% multi-tailed spermatozoa by morphological analysis. Whole-exome sequencing (WES) was used for the patient and his wife. Sanger sequencing technique was used to verify the AURKC mutations in the patient's parents and his offspring. Sperm's ploidy was tested by flow cytometry. The couple asked for intra-couple ART therapy. RESULTS: The patient presented novel compound heterozygous AURKC mutations (c.434C > T, c.497A > T) by WES. Sanger sequencing validation showed that variant of c.434C > T was observed in his father and c.497A > T was observed in his mother. Flow cytometry revealed that there existed a certain proportion of haploid sperm. Macrocephalic spermatozoa whose heads were smaller than the diameter of injection needle were selected for microinjection. A singleton pregnancy was achieved after embryo transfer. Prenatal diagnosis revealed that the fetus had normal chromosomal karyotype. Sanger sequencing technique showed that the fetus carried a c.434C > T mutation in one AURKC allele. A 3730 g healthy male fetus was delivered at term. CONCLUSION: Our study reported a successful live birth from a patient with definite AURKC gene variants and may provide insights for such patients to choose donor sperm or their own sperm.

Anchoring grassland sustainability with a nature-based small burrowing mammal control strategy.

Over the last 40 years, a burrowing mammal eradication policy has been prevalent on the Qinghai-Tibetan Plateau (QTP). This policy is based on similar burrowing mammal eradication programs in other areas and is justified on the assumptions that burrowing mammals compete with livestock for forage and contribute to grassland degradation. However, there is no clear theoretical or experimental evidence supporting these assumptions. This paper synthesizes the ecological functioning of small burrowing mammals in natural grasslands and discusses the irrationality and consequences of burrowing mammal eradication for sustainable livestock grazing and grassland degradation. Past burrowing mammal eradication efforts have failed because increased food availability for the remaining rodents and reduced predator populations led to rapid population rebounds. Herbivores differ in diet, and there is clear evidence that burrowing mammals, especially plateau zokors Myospalax baileyi, have a different diet than livestock. In QTP meadows, burrowing mammal eradication induces a shift towards plant communities with fewer species preferred by livestock and more species preferred by burrowing mammals. Thus, eradicating burrowing mammals has the opposite effect, a reduction in livestock preferred vegetation. We suggest that the policy of poisoning burrowing mammals needs to be reconsidered and revoked as soon as possible. We argue that incorporating density-dependent factors such as predation and food availability are essential for maintaining a low burrowing mammal density. For degraded grasslands, we suggest that the optimal sustainable approach is to decrease the intensity of livestock grazing. Lower grazing induces changes in vegetation structure and plant species composition that increases predation on burrowing mammals and decreases the abundance of plants preferred by burrowing mammals. Such a nature-based grassland management system maintains the density of burrowing mammals at a low stable density while minimizing human management and interventions.

The origins of potentially superior properties and multifunctionalities of carbon-nano zero-valent iron in the carbonization pyrolysis process.

Although carbon-nano zero-valent iron (C@nZVI) composites with unique properties have been used for environmental remediation, the origins of their superior properties and multifunctionalities of C@nZVI still need to be verified. Here, iron precursor nanoparticles (PML-Fe NPs) synthesized by Pinus massoniana Lamb and carbonized C@nZVI were systemically compared to reveal the origins of the structure and performance of C@nZVI composites. Characterizations showed that structure-modulated C@nZVI has favorable properties of good crystallinity, graphite carbon-rich structure but also defects when compared to PML-Fe NPs. The resultant carbon layer fundamentally improved its dispersion and anti-oxidation properties. Further experiments demonstrated that the evolution of material crystallinity, graphitization and defects affected the reaction pathway of hexavalent chromium (Cr(VI)), oxytetracycline hydrochloride (OTC), and 17ß-estradiol (ßE2). The multifunctionalities covered adsorption, reduction and catalytic oxidation. This study explains the origins of multifunctional C@nZVI by understanding the structure-property correlation in the carbonization process.

TPI1 activates the PI3K/AKT/mTOR signaling pathway to induce breast cancer progression by stabilizing CDCA5.

BACKGROUND: Triosephosphate isomerase 1 (TPI1), as a key glycolytic enzyme, is upregulated in multiple cancers. However, expression profile and regulatory mechanism of TPI1 in breast cancer (BRCA) remain mysterious. METHODS: Western blotting and immunohistochemistry (IHC) assays were used to investigate the expression of TPI1 in BRCA specimens and cell lines. TPI1 correlation with the clinicopathological characteristics and prognosis of 362 BRCA patients was analyzed using a tissue microarray. Overexpression and knockdown function experiments in cells and mice models were performed to elucidate the function and mechanisms of TPI1-induced BRCA progression. Related molecular mechanisms were clarified using co-IP, IF, mass spectrometric analysis, and ubiquitination assay. RESULTS: We have found TPI1 is highly expressed in BRCA tissue and cell lines, acting as an independent indicator for prognosis in BRCA patients. TPI1 promotes BRCA cell glycolysis, proliferation and metastasis in vitro and in vivo. Mechanistically, TPI1 activates phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway to regulate epithelial-mesenchymal transformation (EMT) and aerobic glycolysis, which is positively mediated by cell division cycle associated 5 (CDCA5). Moreover, TPI1 interacts with sequestosome-1 (SQSTM1)/P62, and P62 decreases the protein expression of TPI1 by promoting its ubiquitination in MDA-MB-231 cells. CONCLUSIONS: TPI1 promotes BRCA progression by stabilizing CDCA5, which then activates the PI3K/AKT/mTOR pathway. P62 promotes ubiquitin-dependent proteasome degradation of TPI1. Collectively, TPI1 promotes tumor development and progression, which may serve as a therapeutic target for BRCA.

A novel solution for freezing individual spermatozoa using a right angular cryopiece embedded in a grooved petri dish.

Herein, we introduced a novel individual sperm freezing device named SpermCD, which consists of a right angular cryopiece (RA-Cryopiece, or "C") and a grooved petri dish ("D"). SpermCD allows embryologists to transfer sperm and perform ICSI on the same focal plane. Thirty-five patients underwent single sperm cryopreservation using SpermCD, including four patients with non-obstructive azoospermia (NOA), 14 patients with virtual azoospermia and 17 patients with cryptozoospermia. One hundred and twenty-five cryopreserved spermatozoa from nine patients were thawed on the day of the oocyte retrieval and 121 spermatozoa were found, with a sperm recovery rate of 97.1 ± 4.6%. Sixty-five MII oocytes from their spouse were injected with thawed sperm. Normal fertilization and high-quality embryo rates were 68.0% ± 33.2% and 24.4% ± 22.2%. Nineteen transplantable embryos were formed after fertilization with frozen sperm, eight of which were transplanted in five couples, resulting in four successful deliveries. SpermCD is a simple and practical individual sperm freezing device.

Bimetallic Fe/Ni nanoparticles derived from green synthesis for the removal of arsenic (V) in mine wastewater.

Since the incidences of arsenicosis have significantly increased worldwide in the last decade, remediation of arsenic (As) pollution is now imperative. In this study, calcined green synthesized Fe/Ni nanoparticles (C-Fe/Ni NPs) were evaluated for their efficacy for As (V) removal from aqueous solution. Under optimal experimental conditions As (V) removal efficiency reached 87.3%. Analysis of changes in the surface properties of C-Fe/Ni NPs before and after interaction with As (Ⅴ) using a range of advanced characterization techniques including IC-AFS, SEM-EDS, XPS and XRD revealed that the As removal mechanism involved only adsorption. Adsorption kinetics followed a pseudo-second order rate model (R2 > 0.986) and adsorption best fit the Langmuir isotherm model (R2 > 0.958). Thermodynamic studies indicated that adsorption was a spontaneous endothermic process. On the basis of these results, a removal mechanism of As (Ⅴ) by C-Fe/Ni NPs was proposed. Finally, the efficacy of the material for practical remediation of As from aqueous solution was assessed, including the influence of coexisting anions. While Cl-, NO3- and SO42- had little influence on As (V) removal, both H2PO4- and HCO3- significantly negatively affected removal.

Enhanced removal of oxytetracycline from wastewater using bimetallic Fe/Ni nanoparticles combined with ZIF-8 nanocomposites.

The integration of metal-organic frameworks with other functional materials has recently emerged as a promising approach for creating innovative materials for environmental remediation. Here, a nano-sized iron/nickel (Fe/Ni) functionalized zeolitic imidazolate framework-8 (ZIF-8-Fe/Ni) was fabricated for oxytetracycline (OTC) removal from wastewater. Cyclic voltammetry and amperometric I-t measurements indicated that OTC was degraded by ZIF-8-Fe/Ni. X-ray diffraction spectroscopy (XRD), transmission electron microscopy mapping (TEM-mapping) and X-ray photoelectron spectroscopy (XPS) indicated that Fe/Ni was evenly dispersed throughout ZIF-8 and partially oxidized after reaction with OTC. OTC adsorption isotherms and kinetics best fitted the Langmuir isotherm (R2 > 0.982) and pseudo-second-order model (R2 > 0.997), respectively. Reduction kinetics data followed the pseudo-first-order model (R2 > 0.905), where the apparent activation energy (Ea) was 22.9 kJ mol-1, demonstrating that OTC degradation was mainly via a chemical process. The practical removal efficiency of OTC from real wastewater by ZIF-8-Fe/Ni was 92.6%, where even after application of ZIF-8-Fe/Ni for 5 consecutive removal cycles, a high OTC removal of 74.9% was maintained. Thus ZIF-8-Fe/Ni exhibited both high removal efficiency and good recyclability.

A comparison of pregnancy outcome of emergency modified transvaginal cervicoisthmic cerclage performed in twin and singleton pregnancies.

PURPOSE: To compare the pregnancy outcome of emergency cerclage performed in twin and singleton pregnancies. METHODS: A retrospective trial was carried out in the Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital in Zhejiang, China, from January 2013 to December 2018. A total of 89 women with acute cervical incompetence underwent the emergency cerclage. Main outcome measures were gestational age at delivery and the fetal outcome. RESULTS: There were 31 twin and 58 singleton pregnancies that underwent emergency cerclage. In singleton pregnancies, gestational age at delivery (31.57 ± 6.11 vs 28.81 ± 4.34, p = 0.016), and prolongation of pregnancy (8.69 ± 6.13 vs 5.41 ± 3.72, p < 0.001) were greater, and the preterm delivery rate before 34 weeks was lower (53.4% vs 80.6%, p = 0.011) compared with twin pregnancies. Fetal weight was greater in singletons than in twins (2377.3 ± 862.1 vs 1630.3 ± 557.6, p < 0.001), but the fetal survival rate was similar. The proportion of twin gestations was significantly higher in the group with preterm delivery before 34 weeks (44.6% vs 18.2%, p = 0.011) and the proportion of previous term delivery was higher in the group with delivery at or after 34 weeks (30.3% vs 12.5%, p = 0.039). The group with preterm delivery before 34 weeks had a significantly larger size of visible membranes at cerclage than the group with delivery at or after 34 weeks (2.23 ± 0.86 vs 1.64 ± 0.80, p = 0.001). In binary logistic regression analysis, twin gestations and a larger size of visible membranes were associated with an increased risk of preterm delivery. CONCLUSION: The pregnancy outcome of emergency cerclage appears to have a better prognosis in singleton pregnancies than in twin pregnancies, and twin pregnancy is a risk factor for preterm delivery.

Removal of low Sb(V) concentrations from mining wastewater using zeolitic imidazolate framework-8.

Wastewater generated during mining remains a significant source of antimony pollution, because techniques to quickly and efficiently remove antimony from wastewater do not exist. In this study, zeolitic imidazolate framework-8 (ZIF-8), a specific type of Metal Organic Frameworks (MOFs), was successfully used to remove trace levels (1 mg L-1) of Sb(V) with a high removal efficiency when the ZIF-8 dose was 0.5 g L-1. Scanning electron microscopy-X-ray energy dispersive spectrometry (SEM-EDS) indicated that Sb(V) was adsorbed onto the ZIF-8surface. The powder X-ray diffraction (XRD) pattern of ZIF-8 before and after adsorption of Sb(V) indicated that ZIF-8 was successfully synthesized, and remained structurally stable after Sb(V) was adsorbed. Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) both suggested complexation of zinc on ZIF-8 with Sb(V), where removal of Sb(V) by ZIF-8 followed the Langmuir adsorption isotherm with pseudo second-order kinetics. Thus, a possible removal mechanism was proposed which involved Sb(V) complexing with the zinc hydroxyl groups on ZIF-8 (Zn-OH-Sb). Practically, ZIF-8, could remove 78.6% of Sb(V) from a mining wastewater containing 20 µg L-1 Sb(V). Furthermore, ZIF-8 could be remain active after repeated uses and could still remove and 42.3% of Sb(V) from wastewater containing 1 mg L-1) Sb(V) even when the ZIF-8 was reused five time. This indicated that ZIF-8 had potential for practical removal of Sb(V) from mining wastewaters.

Quantitative Proteomic Profiling Reveals Novel Plasmodium falciparum Surface Antigens and Possible Vaccine Candidates.

Despite recent efforts toward control and elimination, malaria remains a major public health problem worldwide. Plasmodium falciparum resistance against artemisinin, used in front line combination drugs, is on the rise, and the only approved vaccine shows limited efficacy. Combinations of novel and tailored drug and vaccine interventions are required to maintain the momentum of the current malaria elimination program. Current evidence suggests that strain-transcendent protection against malaria infection can be achieved using whole organism vaccination or with a polyvalent vaccine covering multiple antigens or epitopes. These approaches have been successfully applied to the human-infective sporozoite stage. Both systemic and tissue-specific pathology during infection with the human malaria parasite P. falciparum is caused by asexual blood stages. Tissue tropism and vascular sequestration are the result of specific binding interactions between antigens on the parasite-infected red blood cell (pRBC) surface and endothelial receptors. The major surface antigen and parasite ligand binding to endothelial receptors, PfEMP1 is encoded by about 60 variants per genome and shows high sequence diversity across strains. Apart from PfEMP1 and three additional variant surface antigen families RIFIN, STEVOR, and SURFIN, systematic analysis of the infected red blood cell surface is lacking. Here we present the most comprehensive proteomic investigation of the parasitized red blood cell surface so far. Apart from the known variant surface antigens, we identified a set of putative single copy surface antigens with low sequence diversity, several of which are validated in a series of complementary experiments. Further functional and immunological investigation is underway to test these novel P. falciparum blood stage proteins as possible vaccine candidates.

A comparison of pregnancy outcome of modified transvaginal cervicoisthmic cerclage performed prior to and during pregnancy.

PURPOSE: To compare the pregnancy outcome of the modified transvaginal cerclage performed preconception and during pregnancy. METHODS: A retrospective trial was carried out in the Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital in Zhejiang, China. A total of 604 women with cervical incompetence underwent the cerclage, and the time of the operation was decided by the patients or depended on when the patient presented. Main outcome measures were the gestational age and the fetal outcome. RESULTS: After the cerclage, the mean gestational age at delivery and the term delivery rate were significantly higher in history-indicated conception cerclage compared to preconception cerclage (36.8 ± 3.7 vs 35.8 ± 4.7, p < 0.01; 76.1 vs 66.9%, p < 0.05). The mean gestational age at delivery and the term delivery rate were significantly higher in ultrasound-indicated compared to physical examination-indicated conception cerclage (35.0 ± 5.7 vs 31.0 ± 5.5, p < 0.01; 63.2 vs 23.3%, p < 0.001). The fetal survival rate had no difference in these two comparisons, respectively. CONCLUSIONS: The modified transvaginal cervicoisthmic cerclage is a promising and safe technique to improve obstetric outcomes in women with cervical incompetence in different cerclage indications, and history-indicated conception cerclage appears to have better pregnancy outcome.

[Evodiamine induces extrinsic and intrinsic apoptosis of ovarian cancer cells via the mitogen-activated protein kinase/phosphatidylinositol-3-kinase/protein kinase B signaling pathways].

OBJECTIVE: To explore the effects of evodiamine on ovarian cancer cells and the mechanisms underlying such effects. METHODS: Human. ovarian cancer cells HO-8910PM were treated with evodiamine at 0, 1.25, 2.5, and 5 µM for 1-4 d. 3-(4,5-Dimethiylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the growth inhibition rate of evodiamine-treated HO-8910PM cells. The cell cycle was observed via propidium iodide (PI) staining. Apoptosis induction was assessed via Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) double staining assay. To verify the mechanism of apoptosis, caspase-dependent apoptotic pathway-related protein was detected by Western blot analysis. The expression levels of mitogen-activated protein kinase (MAPK) and/or phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway-related proteins were also investigated. RESULTS: Evodiamine significantly inhibited the proliferation of HO-8910PM cells in a dose- and time-dependent manner. Evodiamine induced G2/M arrest with an increase of cyclin B1 level, and promoted cell apoptosis with a decrease of B cell lymphoma/lewkmia-2 (Bcl-2) and an increase of Bcl-2-associated X protein (Bax) level. In addition, evodiamine treatment led to the activation of caspase-8, caspase-9, and caspase-3 and the cleavage of poly (ADP-ribose)-polymerase (PARP). Evodiamine targeted the MAPK and/or PI3K/Akt pathways by reducing the expression and activity of PI3K, Akt, and extracellular signal-regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK) and the activity of p38 MAPK. CONCLUSION: Evodiamine can inhibit the growth of ovarian cancer cells by G2/M arrest and intrinsic and extrinsic apoptosis. In addition, evodiamine-induced PI3K/Akt, ERK1/2 MAPK, and p38 MAPK signaling may be involved in cell death.

Comparison of progesterone measurement on day of, and day after, HCG administration in IVF-embryo transfer cycles.

The aim of this study was to identify whether progesterone measurement on the day after HCG administration has any additional clinical value, over that obtained from progesterone measurement on the day of HCG administration. This was a single-centre, non-interventional retrospective, observational, cohort of a consecutive series of 1457 ovarian stimulation cycles leading to fresh embryo transfer cycles between January 2011 and May 2013. Progesterone was found to rise and increase rapidly by about five-fold over a 24-h period. The result of logistic regression analysis suggests that progesterone measurement around the time of HCG administration is one of the three significant (P <0.001) variables affecting clinical pregnancy rate. The predictive value of progesterone measurement on the day of HCG administration could be improved by having a further measurement 24-h later. If the progesterone levels on both days were normal, the implantation rate was 36%, but if the progesterone level on both days were high, the implantation rate dropped to 22%. Progesterone measurement should be considered on the day of HCG administration and also the day after HCG administration to provide clinically useful information on whether or not embryos should be frozen and transfer deferred to a subsequent cycle.

[Effects of levonorgestrel intrauterine system on the expressions of estrogen receptor, progesterone receptor and insulin-like growth factor-1].

OBJECTIVE: To explore the effects of levonorgestrel intrauterine system on estrogen receptor (ER) and progesterone receptor (PR), insulin-like growth factor-1 (IGF-1) of endometrial polyps and surrounding endometrial tissue. METHODS: A total of 250 cases of hysteroscopic resection for endometrial polyps were divided into study group (n = 125) with placement of levonorgestrel intrauterine system after hysteroscopic electroresection and control group (n = 125) without placement. The intraoperative and postoperative expressions of ER, PR and IGF-1 in endometrial biopsy specimens were measured by immunohistochemistry. They were followed up for 2 years to analyze the recurrence of endometrial polyp. RESULTS: All patients had successful surgery. When intraoperative and postoperative specimens were compared with regards to the expressions of ER, PR and IGF-1, significant differences existed between two groups. During a 2-year follow-up, the recurrence of endometrial polyp was 10.89% in control group versus 0 in study group. CONCLUSION: Levonorgestrel intrauterine system may inhibit the recurrence and formation of endometrial polyp through lowering the expressions of ER, PR and IGF-1.

[Effect of different laparoscopic procedures for hydrosalpinx on pregnancy outcome of embryo transfer].

OBJECTIVE: To explore the effects of different laparoscopic procedures before embryo transfer (ET) for hydrosalpinx on pregnancy outcomes. METHODS: Group A (n = 269) underwent laparoscopic bilateral salpingectomy before ET while group B (n = 178) had laparoscopic bilateral tubal salpingostomy for hydrosalpinx. And the pregnancy outcomes of ET were evaluated. RESULTS: The implantation, pregnancy, abortion, ectopic pregnancy and live birth rates were similar in 2 groups (P > 0.05). The interstitial pregnancy rate was 10.27% after bilateral salpingectomy. The clinical pregnancy rate increased while the interstitial pregnancy rate decreased when the intervals between salpingectomy and ET were prolonged. But there was no statistical significance (P > 0.05). CONCLUSION: Laparoscopic tubal salpingostomy is as effective as salpingectomy for hydrosalpinx before ET. The interstitial pregnancy rate increases after laparoscopic salpingectomy. The interval between salpingectomy and ET should be appropriately scheduled.

Reconstructing the electron and spin structures of nanoscale iron sulfide through a biosurfactant layer towards radical-nonradical co-dominant regime.

Radical-nonradical co-dominant pathways have become a hot topic in advanced oxidation, but achieving this on transition metal sulfides (TMS) remains challenging because their inherently higher electron and spin densities always induce radicals rather than nonradicals. Herein, a biosurfactant layer (BLR) was introduced to redistribute the electron and spin structure of nanoscale iron sulfide (FeS), which allowed both radical and nonradical to co-dominate the catalytic reaction. The resulting BLR-encased FeS hybrid (BLR@FeS) exhibited satisfactory removal efficiency (98.5 %) for hydrogen peroxide (H2O2) activation, outperforming both the constituent components [FeS (70.9 %) and BLR (86.2 %)]. Advanced characterizations showed that C, O, N-related sites (-CO and -NC) in BLR attracted electrons in FeS due to their strong electronegativity and electron-withdrawing capacity, which not only decreased electron density in FeS, but also resulted in a shift of the Fe/S sites from the high-spin to the medium-spin state. The reaction routes established by the BLR@FeS/H2O2 system maintained desirable stability against environmental interferences such as common inorganic anions, humic acid and changes in pH. Our study provides a state-of-the-art, molecule-level understanding of tunable co-dominant pathways and expands the targeted applications in the field of advanced oxidation.

Novel Splicing Variants in the ARR3 Gene Cause the Female-Limited Early-Onset High Myopia.

Purpose: Variants in the ARR3 gene have been linked to early-onset high myopia (eoHM) with a unique X-linked female-limited inheritance. However, the clinical validity of this gene-disease association has not been systematically evaluated. Methods: We identified two Chinese families with novel ARR3 splicing variants associated with eoHM. Minigene constructs were generated to assess the effects of the variants on splicing. We integrated previous evidence to curate the clinical validity of ARR3 and eoHM using the ClinGen framework. Results: The variants c.39+1G>A and c.100+4A>G were identified in the two families. Minigene analysis showed both variants resulted in abnormal splicing and introduction of premature termination codons. Based on genetic and experimental evidence, the ARR3-eoHM relationship was classified as "definitive." Conclusions: Our study identified two novel splicing variants of the ARR3 gene linked to eoHM and confirmed their functional validity via minigene assay. This research expanded the mutational spectrum of ARR3 and confirmed the minigene assay technique as an effective tool for understanding variant effects on splicing mechanisms.

A retrospective analysis of single-port laparoscopy in myoma management.

Objective: This study assesses the effectiveness and safety of single-port laparoscopic myomectomy (SPLM) versus conventional laparoscopic myomectomy (CLM). Methods: We conducted a retrospective case-control study at a university tertiary hospital, involving 262 patients treated from July 2020 to December 2022. Participants were divided into two groups: 132 underwent SPLM and 130 underwent CLM. Results: The two groups were comparable in terms of age, body mass index, parity, delivery history, preoperative anemia, number of myomas, and size of the largest myoma. The SPLM group showed a significant reduction in operation time (average 93 min) and estimated blood loss (average 50 ml) compared to the CLM group (average 118.5 min and 100 ml, respectively). Subgroup analysis based on the size, location, and number of myomas further highlighted the advantages of SPLM, particularly for patients with large (diameter ≥8 cm) or multiple myomas (number ≥4). Patient satisfaction was also notably higher in the SPLM group. Conclusions: Single-port laparoscopic myomectomy offers a highly effective, safer, and patient-preferred option for the surgical management of fibroids, especially in cases of large or multiple myomas. These findings suggest that SPLM could become the preferred surgical approach for complex fibroid cases, promising less trauma and quicker recovery for patients.

The relationship of cardiovascular disease risk, clozapine antipsychotic use and cognitive function in a large Chinese schizophrenia cohort.

OBJECTIVE: This study explores the intricate relationship between clozapine use, cardiovascular disease (CVD) risk, and cognitive function in patients with schizophrenia (SCZ). METHODS: A cohort comprising 765 patients was stratified based on clozapine usage. Data on demographics, clinical characteristics, and glycolipid metabolism were collected. The Framingham Risk Score and vascular age were calculated using gender-specific Cox regression calculators. Cognitive function was assessed with the Repeatable Battery for Assessment of Neuropsychological Status. RESULTS: Among the patients, 34.6 % were clozapine users. Clozapine users exhibited lower systolic blood pressure, high-density lipoprotein cholesterol and total cholesterol (all ps < 0.05). Furthermore, clozapine users exhibited higher PANSS scores, along with lower scores in RBANS scores (all ps < 0.05). Correlation analysis revealed positive correlation between CVD risk in non-clozapine users and negative symptom scores (r = 0.074, p = 0.043), and negative correlation with positive symptom scores and RBANS scores (r = -0.121, p = 0.001; r = -0.091, p = 0.028). Multivariate stepwise regression analysis indicated that attention scores as predictive factors for increased CVD risk in clozapine users (B = -0.08, 95 %CI = -0.11 to -0.03, p = 0.003). CONCLUSIONS: Patients with SCZ using clozapine exhibit more severe clinical symptoms and cognitive impairments. Attention emerges as a predictor for increased CVD risk in clozapine users.

The involvement of RNA N6-methyladenosine and histone methylation modification in decidualization and endometriosis-associated infertility.

Defective decidualization of endometrial stromal cells (ESCs) in endometriosis (EM) patients leads to inadequate endometrial receptivity and EM-associated infertility. Hypoxia is an inevitable pathological process of EM and participates in deficient decidualization of the eutopic secretory endometrium. Enhancer of zeste homology 2 (EZH2) is a methyltransferase which catalyses H3K27Me3, leading to decreased expression levels of target genes. Although EZH2 expression is low under normal decidualization, it is abundantly increased in the eutopic secretory endometrium of EM and is induced by hypoxia. Chromatin immunoprecipitation-PCR results revealed that decidua marker IGFBP1 is a direct target of EZH2, partially explaining the increased levels of histone methylation modification in defected decidualization of EM. To mechanism controlling this, we examined the effects of hypoxia on EZH2 and decidualization. EZH2 mRNA showed decreased m6 A modification and increased expression levels under hypoxia and decidualization combined treatment. Increased EZH2 expression was due to the increased expression of m6 A demethylase ALKBH5 and decreased expression of the m6 A reader protein YTHDF2. YTHDF2 directly bind to the m6 A modification site of EZH2 to promote EZH2 mRNA degradation in ESCs. Moreover, selective Ezh2 depletion in mouse ESCs increased endometrial receptivity and improved mouse fertility by up-regulating decidua marker IGFBP1 expression. This is the first report showing that YTHDF2 can act as a m6 A reader to promote decidualization by decreasing the stability of EZH2 mRNA and further increasing the expression of IGFBP1 in ESCs. Taken together, our findings highlight the critical role of EZH2/H3K27Me3 in decidualization and reveal a novel epigenetic mechanism by which hypoxia can suppress EM decidualization by decreasing the m6 A modification of EZH2 mRNA.