RESUMEN
BACKGROUND: Obesity is a common feature in women with polycystic ovary syndrome (PCOS) and is associated with multiple adverse reproductive outcomes. However, the impact of overweight and obesity on reproductive outcomes of women with PCOS who underwent in vitro fertilization-embryo transfer (IVF-ET) is currently controversial and appropriate body mass index (BMI) levels differ across ethnic groups. METHODS: This was a retrospective study including 1066 women with PCOS receiving IVF treatment at our institution between January 2018 and June 2021, among whom 960 underwent their first fresh or frozen embryo transfer. Participants were categorized according to BMI cut-off values proposed by the World Health Organization for Asian populations: normal weight (BMI < 23 kg/m2), overweight (BMI: 23-24.9 kg/m2), and obesity (BMI ≥ 25 kg/m2). The effect of BMI on clinical and embryological outcomes was evaluated by descriptive statistics and logistic regression models with confounders adjusted. The dose-response relationship between BMI as a continuous variable and IVF outcomes is also explored. INTERVENTIONS: no RESULTS: Increasing BMI was associated with significantly lower numbers of total oocytes retrieved, metaphase II oocytes, two pronuclear (2PN) zygotes, and good-quality embryos among women with PCOS. Patients with PCOS with a BMI ≥ 23 kg/m2 had significantly lower live birth rates (41.9% vs. 49.1%; adjusted odds ratio [aOR], 0.75; 95% confidence interval [CI], 0.57-0.97) and implantation rates (35.8% vs. 43.9%; aOR, 0.76; 95% CI, 0.61-0.93) than those with normal BMI. Moreover, BMI showed a non-linear relationship (p for nonlinearity <0.001) with the number of 2PN zygotes with the curve becoming steeper as BMI surpassed 22.4 kg/m2. CONCLUSIONS: Patients with PCOS with a BMI ≥ 23 kg/m2 have lower live birth rates than those with a BMI < 23 kg/m2. Defining obesity and overweight with ethnicity-specific BMI cut-offs may help to improve IVF outcomes among PCOS patients.
Asunto(s)
Sobrepeso , Síndrome del Ovario Poliquístico , Embarazo , Humanos , Femenino , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Síndrome del Ovario Poliquístico/complicaciones , Índice de Masa Corporal , Fertilización In Vitro , Estudios Retrospectivos , Índice de Embarazo , Obesidad/complicaciones , Obesidad/epidemiología , China/epidemiologíaRESUMEN
Visible random fiber lasers have garnered significant attention due to their unique emission properties and potential applications in various fields. We first, to the best of our knowledge, demonstrated a compact all-fiber structure, red wavelength, and random fiber laser (RFL) based on a double-clad Pr-doped ZBLAN fiber. The simple half-open cavity consists of a high-reflectivity fiber pigtail mirror and the Pr-doped ZBLAN fiber. The Pr-doped ZBLAN fiber not only served as a gain medium but also offered random backward scattering. We investigated the effects of different lengths on output power and slope efficiency of the RFL. For 21 m Pr-doped fiber, the RFL emitted a maximum output power of 208.50 mW with a slope efficiency of 11.09%. For 15 m Pr-doped fiber, the maximum power decreased to 120.18 mW with the slope efficiency of 7.27%. We are also numerically simulating the output power versus the pump power at different fiber lengths based on power steady-state light propagation equations. This novel RFL has the potential for broad applications in fields such as display technology, spectroscopy, biomedical imaging, and optical sensing due to its unique properties and simple all-fiber structure.
RESUMEN
The mechanism involved in the pathogenesis of endometriosis is poorly understood. The purpose of this study is to identify key deubiquitinating enzymes (DUBs) for endometriosis diagnosis and elucidate the possible mechanism, offering novel insights for noninvasive early diagnosis and treatment. Four gene expression datasets were employed from the Gene Expression Omnibus to identify differentially expressed genes (DEGs) between endometriosis and normal controls. GO and KEGG pathways were performed for enrichment analysis. Calibration curves, ROC, DCA, and clinical impact curves verified the clinical usefulness of the nomogram model. In addition, the ssGSEA method was conducted to estimate 23 types of immune cells. A specific DUB gene signature was constructed with Lasso regression, univariate logistic regression, and SVM analysis. RT-qPCR validated the expression of biomarkers. A total of 85 endometriosis-related DUBs were identified in the eutopic endometrium. Among them, 20 DUBs were found to be correlated with the severity of endometriosis. A diagnostic risk model based on five DUB-related genes (USP21, USP48, ZRANB1, COPS5, and EIF3F) was developed using lasso-cox regression analysis. The nomogram model exhibited a strong predictive ability to diagnose endometriosis. KEGG analysis revealed that ubiquitin-mediated proteolysis was activated in patients suffering from severe symptoms. Analysis of immune cell infiltration revealed a positive correlation between USP21 and multiple immune cells in the eutopic endometrium. However, EIF3F showed an opposite relationship. Dysregulation of DUBs was related to the immune microenvironment in endometriosis. Results from RT-qPCR confirmed the expression of DEGs in clinical samples. In summary, the diagnostic model for endometriosis constructed using five differentially expressed DUB genes demonstrates strong diagnostic capability, suggesting that these genes could serve as potential candidate biomarkers and therapeutic targets.
RESUMEN
An obligately anaerobic, Gram-positive, rod-shaped bacterium (1.8-5.5 µm long, 0.6-0.9 µm wide), designated ZC22-4T, was isolated from a pickle-processing wastewater treatment plant in Zhejiang province, P.R. China. Strain ZC22-4T grows optimally at 37-40 °C and pH 7.0 in the presence of 1% (w/v) NaCl or 2.0% (w/v) sea salts. It contained C16:0 (25.9%), C14:0 (13.6%), and C16:1 cis 9 (10.6%) as the dominant cellular fatty acid (> 10%). Polar lipids include phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), one unidentified phospholipid (PL), two unidentified glycolipids (GL), three unidentified amino phosphoglycolipids (APGL1-3), one unidentified aminoglycolipid (AGL), and one unidentified lipid (L). The genomic DNA G + C content of ZC22-4T was 28.7%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain ZC22-4T belonged to the genus Clostridium and formed a clade with the most closely related Clostridium aestuarii HY-45-18T (96.3%), Clostridium ganghwense HY-42-06T (95.9%). The average nucleotide identity and DNA-DNA hybridization values among the genomes of strain ZC22-4T and C. aestuarii HY-45-18T and C. ganghwense HY-42-06T were 75.7% and 77.3%, 21.7% and 23.0%, respectively. Based on the phenotypic, phylogenetic, and genetic data, strain ZC22-4T represents a novel species in the Clostridium cluster I, for which the name Clostridium brassicae sp. nov. is proposed. The type strain is ZC22-4T (= MCCC 1K07510T = JCM 35370T).
Asunto(s)
Cloruro de Sodio , Aguas Residuales , Filogenia , Anaerobiosis , ARN Ribosómico 16S/genética , Composición de Base , Análisis de Secuencia de ADN , Clostridium , Ácidos Grasos/química , Fosfolípidos/química , Bacterias Anaerobias/genética , ADN , ADN Bacteriano/genética , Técnicas de Tipificación BacterianaRESUMEN
AIM: To introduce the novel use of lauromacrogol for cesarean scar pregnancy (CSP), and to compare the clinical efficacy and safety of curettage combined with ultrasound-guided sclerosant injection (USI) and curettage following uterine artery embolization (UAE) in the treatment of CSP. METHODS: CSP patients undergoing curettage combined with USI (n = 72) from December 2014 to May 2020 were compared to patient with curettage following UAE (n = 72).The basic clinical findings and clinical outcomes were reviewed between the two groups. RESULTS: For USI group, 69 patients underwent successful treatment (95.8% success rate), while the number of cured patients for the UAE group was 70 (97.2% success rate). Differences between USI group and UAE group in intraoperative blood loss (10.0 [10.0-20.0] vs. 10.0 [10.0-20.0] mL) and time for serum ß human chorionic gonadotropin (ß-hCG) to reduce to normal (28.0 [21.0-40.0] vs. 28.0 [21.0-35.0] days) were not statistically significant. The hospital stay for USI group was significantly shorter than that for UAE group (4.0 [4.0-6.0] vs. 6.0 [5.0-7.0] days, respectively). Statistically significant decreases were noted in hospitalization expenses and adverse events in USI group, compared to UAE group. There was no difference in live birth rate between the two groups with fertility intentions during the follow-up. CONCLUSION: For treatment of CSP, curettage combined with USI yielded clinical results comparable to those of curettage following UAE. Curettage combined with USI was associated with lower hospitalization expenses, shorter hospital stay and less complications, and it merited an effective and safe treatment for CSP.
Asunto(s)
Soluciones Esclerosantes , Embolización de la Arteria Uterina , Cesárea/efectos adversos , Cicatriz/terapia , Femenino , Humanos , Metotrexato , Polidocanol , Embarazo , Estudios Retrospectivos , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
AIMS: To introduce and compare the modified laparoscopic Vecchietti and Davydov techniques for vaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Moreover, the long-term treatment of vaginal agenesis was followed-up. METHODS: This comparative retrospective cohort study enrolled a total of 53 women with MRKH syndrome. The patients underwent surgical creation of a neovagina including 32 patients who underwent the modified laparoscopic Vecchietti technique, and 21 patients who underwent the modified laparoscopic Davydov technique from January 2009 to February 2019. The perioperative parameters, complications, anatomical, and functional outcomes of the two groups were compared. Patients' sexual functions were evaluated over a long-term follow-up using the female sexual function index (FSFI) and the revised female sexual distress scale (FSDS-R). RESULTS: The medians (25th-75th) of the surgery duration for modified Vecchietti procedures was 50.0 (40.0-59.0) minutes, comparing to 135.0 (117.5-162.5) min for Davydov procedures (p < 0.001). The intraoperative blood loss was 20 (7.5-20.0) mL versus 50.0 (50.0-100.0) mL using the modified Vecchietti and Davydov approaches (p < 0.001), respectively. In the 39 follow-up cases, the lengths of the neovagina of the patients for Vecchietti group versus Davydov group were 7.9 ± 1.0 cm versus 8.6 ± 1.2 cm at 6 months after the vaginoplasty and 8.3 ± 0.7 cm versus 8.5 ± 0.9 cm after 2 years. There was no statistical difference in the FSFI and FSDS-R scores between the two groups. CONCLUSIONS: Both the modified Davydov and Vecchietti laparoscopic procedures successfully achieved optimal anatomic and functional outcomes in treatments of vaginal agenesis. The modified Vecchietti technique is relatively simpler than the modified Davydov technique.
Asunto(s)
Trastornos del Desarrollo Sexual 46, XX , Anomalías Congénitas , Laparoscopía , Procedimientos de Cirugía Plástica , Trastornos del Desarrollo Sexual 46, XX/cirugía , Anomalías Congénitas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Laparoscopía/métodos , Conductos Paramesonéfricos/anomalías , Conductos Paramesonéfricos/cirugía , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Vagina/anomalías , Vagina/cirugíaRESUMEN
STUDY OBJECTIVE: To evaluate in vitro fertilization (IVF) outcomes of proximal fallopian tube embolization by interventional radiology compared with laparoscopic salpingectomy before embryo transfer (ET) in patients with hydrosalpinx. DESIGN: A single-center, off-label, nonrandomized prospective study. SETTING: Academic university hospital. PATIENTS: One hundred fifty-five patients with hydrosalpinx were identified on ultrasound or hysterosalpingography desiring IVF between April 2016 and December 2017. INTERVENTIONS: Radiologically guided tubal occlusion with embolization microcoils (RTO-EM) and laparoscopic salpingectomy. MEASUREMENTS AND MAIN RESULTS: Of the 155 analyzed patients, 42 were treated with RTO-EM and 113 with laparoscopic salpingectomy. The subsequent IVF outcomes, including implantation, clinical pregnancy, miscarriage, ectopic pregnancy, and ongoing pregnancy (i.e., a fetal heartbeat on ultrasound beyond 10 weeks) were compared between the 2 groups. Implantation and clinical pregnancy per ET cycle in the RTO-EM group were similar to that of the salpingectomy group (26.7% vs 30.2% [p = .51] and 39.0% vs 45.3% [pâ¯=â¯.40], respectively), with a similar miscarriage rate. There was no statistically significant difference in ectopic pregnancies between the 2 groups. Moreover, no difference was detected in ongoing pregnancy per cycle between the 2 groups (33.9% vs 41.2%; pâ¯=â¯.32). The ongoing-pregnancy rate per patient following RTO-EM was 47.6% (20 of 42) compared with 61.9% (70 of 113) following salpingectomy (odds ratio, 0.56; 95% confidence interval, 0.27-1.14; pâ¯=â¯.11). CONCLUSION: Pregnancy in the RTO-EM group was comparable to the salpingectomy group in patients with hydrosalpinx before ET treatment. RTO-EMs may be an alternative to salpingectomy for patients with hydrosalpinx planning for IVF-ET.
Asunto(s)
Embolización Terapéutica , Transferencia de Embrión , Enfermedades de las Trompas Uterinas/cirugía , Fertilización In Vitro , Infertilidad Femenina/terapia , Uso Fuera de lo Indicado , Radiología Intervencionista , Adulto , Embolización Terapéutica/métodos , Enfermedades de las Trompas Uterinas/complicaciones , Trompas Uterinas/cirugía , Femenino , Fertilización In Vitro/métodos , Estudios de Seguimiento , Humanos , Infertilidad Femenina/etiología , Embarazo , Resultado del Embarazo , Índice de Embarazo , Radiología Intervencionista/estadística & datos numéricos , Salpingectomía/métodos , Adulto JovenRESUMEN
Bisphenol A (BPA) is a substance ubiquitously present in the environment, and its toxicity on reproductive function has been well characterised in animal models. However, it is still controversy about the effects of BPA exposure on human female reproduction. Therefore, in the present study, the associations of urinary BPA concentration with the outcomes of in vitro fertilisation (IVF) and embryo transfer from fresh and frozen cycles were analysed in the same cohort. 351 women who underwent IVF treatment from September 2013 to October 2016, at the Centre of Reproductive Medicine in the Women's Hospital School of Medicine at Zhejiang University were recruited. Single-spot urine samples were collected on the day of oocyte retrieval to detect BPA using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. A multivariable generalised linear mixed model was used to evaluate the association between the urinary BPA concentration and IVF outcomes. After adjustment for age, body mass index, baseline follicle-stimulating hormone level, baseline oestradiol level, and antral follicle count, a significant decrease in the number of retrieved oocytes and in the rates of clinical pregnancy and implantation was observed in the patients with a high urinary BPA concentration. We concluded that BPA exposure exert negative effects on oocyte retrieval and embryo implantation in women undergoing IVF.
Asunto(s)
Compuestos de Bencidrilo/orina , Implantación del Embrión/efectos de los fármacos , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/orina , Fertilización In Vitro , Infertilidad Femenina/orina , Recuperación del Oocito , Fenoles/orina , Adulto , Compuestos de Bencidrilo/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/toxicidad , Femenino , Humanos , Fenoles/toxicidad , EmbarazoRESUMEN
This study aimed to analyze the association between driver mutations and predictive markers for some anti-tumor agents in non-small cell lung cancer (NSCLC). A cohort of 785 Chinese patients with NSCLC who underwent resection from March 2016 to November 2017 in the First Affiliated Hospital of Guangzhou Medical University was investigated. The specimens were subjected to hybridization capture and sequence of 8 important NSCLC-related driver genes. In addition, the slides were tested for PD-L1, excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), thymidylate synthase (TS) and ß-tubulin III by immunohistochemical staining. A total of 498 (63.4%) patients had at least 1 driver gene alteration. Wild-type, EGFR rare mutation (mut), ALK fusion (fus), RAS mut, RET fus and MET mut had relatively higher proportions of lower ERCC1 expression. EGFR 19del, EGFR L858R, EGFR rare mut, ALK fus, HER2 mut, ROS1 fus and MET mut were more likely to have TS low expression. Wild-type, EGFR L858R, EGFR rare mut and BRAF mut were associated with lower ß-tubulin III expression. In addition, wild-type, RAS mut, ROS1 fus, BRAF and MET mut had higher proportion of PD-L1 high expression. As a pilot validation, 21 wild-type patients with advanced NSCLC showed better depth of response and response rate to taxanes compared with pemetrexed/gemcitabine (31.2%/60.0% vs 26.6%/45.5%). Our study may aid in selecting the optimal salvage regimen after targeted therapy failure, or the chemo-regimen where targeted therapy has not been a routine option. Further validation is warranted.
Asunto(s)
Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Mutación , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Pemetrexed/administración & dosificación , Pronóstico , Taxoides/uso terapéutico , GemcitabinaRESUMEN
AIMS: Early evaluation of pelvic floor muscle (PFM) in postpartum women is important for the treatment of stress urinary incontinence (SUI). Digital vaginal palpation and electromyography (EMG) evaluation based on Glazer protocol are widely used for the assessment of PFM. However, the correlation among digital palpation, EMG, and morbidity of postpartum SUI is still unclear. This study aims to investigate the relationship between postpartum SUI and PFM examinations. METHODS: This hospital-based cross-sectional study included 1,380 parturients during September 2016 to January 2018. We collected the clinical characteristics, PFM strength, and EMG variables of parturients 6-8 weeks after birth. Then the correlation among the results of EMG, digital palpation, and the occurrence of SUI was analyzed. RESULTS: There is no significant difference in digital palpation scores of PFM strength between SUI and non-SUI parturients. The EMG values were closely related to SUI: the multivariate logistic regression revealed that the most reliable evaluation indicators of postpartum SUI were pelvic floor contractile amplitude of endurance contraction (B = 0.021, p = 0.019) and pretest resting baseline (B = 0.056, p = 0.019). Correlation analysis demonstrated that the contraction variables of EMG had a significant correlation with the digital palpation PFM strength in postpartum women (r = 0.467-0.545, p < 0.001). CONCLUSION: The EMG proved to be reliable in assessing the PFM function in postpartum women. The decreased PFM activity, according to EMG, was correlated with postpartum SUI. Although digital palpation scores were positively correlated with EMG results, no correlation was observed with SUI incidence.
Asunto(s)
Electromiografía , Fuerza Muscular/fisiología , Palpación , Diafragma Pélvico/fisiopatología , Periodo Posparto , Incontinencia Urinaria de Esfuerzo/fisiopatología , Adulto , Estudios Transversales , Femenino , Humanos , Contracción Muscular , VaginaRESUMEN
AIM: To share the experience of local aspiration and instillation of methotrexate (MTX) to selective reduction of live interstitial pregnancy and to evaluate its clinical effect and the outcome of intrauterine pregnancy. METHODS: Twelve patients with heterotopic interstitial pregnancy were enrolled at Women's Hospital, Zhejiang University School of Medicine, from 2006 to 2017. All the pregnancies were derived from assisted reproductive technology (ART). The transvaginal aspiration to interstitial pregnancy sac and local instillation of MTX (range from 12.5 to 30 mg) were performed for the patients under ultrasound-guide. The prognosis and pregnancy outcomes were followed up. RESULTS: No severe side effects of medical treatment were observed in all patients. Three cases underwent subsequent laparotomy cornual resection, and no perioperative complications were found in these three patients. Twelve patients gave birth to 13 healthy infants without congenital anomalies. The average birth weight and gestational age was 2837 g (SD ± 605 g) and 36.8 weeks (SD ± 2.4 weeks). No growth anomalies and mental retardation were observed in live birth offspring. CONCLUSION: The transvaginal ultrasound-guided aspiration and injection of MTX might be a feasible alternative treatment for heterotopic interstitial pregnancy when vital signs of patients are stable.
Asunto(s)
Abortivos no Esteroideos/administración & dosificación , Metotrexato/administración & dosificación , Reducción de Embarazo Multifetal/métodos , Embarazo Heterotópico/terapia , Embarazo Intersticial/terapia , Técnicas Reproductivas Asistidas/efectos adversos , Adulto , Colposcopía/métodos , Estudios de Factibilidad , Femenino , Humanos , Embarazo , Resultado del Embarazo , Embarazo Heterotópico/etiología , Embarazo Intersticial/etiología , Resultado del Tratamiento , Ultrasonografía Intervencional/métodosRESUMEN
OBJECTIVE: To explore the correlation between methylation of insulin-like growth factor 1 (IGF-1) gene promoter and its placenta-specific expression and fetal macrosoma. METHODS: One hundred twenty nine healthy pregnant women were recruited between April 2011 and March 2012. Baseline data were collected with self-report questionnaires. Real-time quantitative PCR was used to determine the expression of IGF-1 mRNA in the placenta. Methylation level of the IGF 1 gene was determined with matrix-assisted laser desorption/ionization-time of flight mass spectrometry. RESULTS: The expression of IGF-1 in placenta and its methylation level showed no significant difference between macrosomic fetuses and controls. No linear correlation was found between IGF-1 mRNA expression and methylation level of IGF-1 promoter (r=0.128, P=0.295). IGF-1 promoter region in placenta showed a hypomethylation status. However, a positive correlation was found between IGF-1 expression and birth weight below 4260 g (r=0.264, P=0.022). The expression of IGF-1 mRNA was significantly higher in those with a birth weight below 4260 g, which suggested that placental IGF-1 expression may contribute to increased birth weight. In regard to fetal overgrowth, however, there seemed to be a negative correlation in which placental IGF-1 expression was downregulated to limit fetal overgrowth. CONCLUSION: No linear correlation was found between placental IGF-1 expression and methylation level of IGF-1 promoter with a hypomethylation status. The contribution of placental IGF-1 expression to birth weight is bidirectional. Increased expression seems to promote fetal growth, while decreased expressions may curb overgrowth, therefore control fetal growth in a relatively normal range.
Asunto(s)
Metilación de ADN , Macrosomía Fetal/genética , Factor I del Crecimiento Similar a la Insulina/genética , Placenta/metabolismo , Regiones Promotoras Genéticas , Peso al Nacer , Femenino , Humanos , Recién Nacido , Embarazo , ARN Mensajero/análisisRESUMEN
Background: Previous epidemiological studies have reported associations between vitamin D and postpartum depression (PPD); however, the findings are inconsistent. This study employs bidirectional Mendelian Randomization (MR) to investigate the causal link between serum 25-hydroxyvitamin D [25(OH)D] levels and PPD. By utilizing genetic data from cohorts, this research aims to provide a more robust understanding of the potential relationship between vitamin D and PPD, addressing a critical gap in the current literature. Methods: A bidirectional MR analysis was conducted to investigate the genetic association between serum 25(OH)D and PPD using summary statistics extracted from GWAS datasets. The study included data from 15,668 patients with PPD and 376,755 healthy controls of European ancestry. The GWAS data for 25(OH)D were obtained from two studies within the UK Biobank, encompassing 496,946 and 79,366 participants. The primary analysis employed the inverse-variance weighted (IVW) method, while supplementary MR estimates were derived through the MR-Egger and weighted median (WME) methods. Furthermore, sensitivity analyses were implemented to ensure robustness and reliability, including Cochran's Q test, MR-PRESSO, MR-Egger intercept test, and the leave-one-out test. Results: The MR study revealed no substantial genetic correlation between serum 25(OH)D levels and PPD (OR = 1.065, 95%CI = 0.878-1.293, P = 0.522 for set A; OR = 0.978, 95 % CI = 0.669-1.430, P = 0.910 for set B). Additionally, in the reverse analysis, we did not observe a significant causal impact of PPD on serum 25(OH)D (OR = 1.001, 95%CI = 0.974-1.028, P = 0.951 for set A; OR = 1.011, 95%CI = 0.992-1.031, P = 0.261 for set B). The results obtained from MR-Egger and WME analyses concord with those derived from the IVW method. Conducting leave-one-out tests did not identify any single nucleotide polymorphism that might have influenced the MR results, confirming the robustness and reliability of the findings. Conclusions: The results suggest the absence of a causal link between vitamin D concentrations and PPD. Inconsistent observations in previous observational studies may be attributed to residual confounding.
RESUMEN
Magnaporthe oryzae is one of the most important fungal pathogens of rice. Chitin and avirulent strains can induce two layers of immunity response, pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI), in rice with cognate R genes. However, little is known about the assembly of the rice microbiome induced by PTI and ETI in rice. In this study, we investigate the impact of continuous treatment of the avirulent M. oryzae strain with AvrPi9 and chitin on the bacterial endophytic community of rice varieties harboring resistant gene Pi9 and their antagonistic activity against rice blast fungus. Analysis of the 16S rRNA showed a significant increase in the diversity and microbial co-occurrence network complexity and the number of beneficial taxa-Bacillus, Pseudomonas, Microbacterium, and Stenotrophomonas spp.-following the chitin and avirulent strain treatments. The antifungal assay with bacterial endophytes recovered from the leaves showed few bacteria with antagonistic potential in rice treated with avirulent strains, suggesting that the sequential treatment of the avirulent strain decreased the antagonistic bacteria against M. oryzae. Moreover, we identified Bacillus safensis Ch_66 and Bacillus altitudinis Nc_68 with overall antagonistic activities in vivo and in vitro. Our findings provide a novel insight into rice microbiome assembly in response to different innate immunity reactions.
RESUMEN
BACKGROUND: Onradivir (ZSP1273) is a novel anti-influenza A virus inhibitor. Preclinical studies show that onradivir can inhibit influenza A H1N1 and H3N2 replication and increase the survival rate of infected animals. In this study, we aimed to evaluate the safety and efficacy of three onradivir dosing regimens versus placebo in outpatients with acute uncomplicated influenza A virus infection. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial at 20 clinical sites in China. Eligible participants were adults (18-65 years) with an influenza-like illness screened by rapid antigen testing at the first clinical visit, had the presence of a fever (axillary temperature ≥38·0°C), and had the presence of at least one moderate systemic and one respiratory symptom within 48 h of symptom onset. Patients were excluded if they were pregnant, allergic to onradivir, or had received any influenza antiviral medication within 7 days before enrolment. Participants were randomly assigned (1:1:1:1) into four groups by an interactive web response system: onradivir 200 mg twice per day group, onradivir 400 mg twice per day group, onradivir 600 mg once per day group, and a matching placebo group. A 5-day oral treatment course was initiated within 48 h after symptoms onset. The primary outcome was the time to alleviate influenza symptoms in the modified intention-to-treat population. Safety was a secondary outcome. We evaluated the patients' self-assessed severity of seven influenza symptoms on a 4-point ordinal scale, and the treatment-emergent adverse events in all patients. This trial is registered with ClinicalTrials.gov, number NCT04024137. FINDINGS: Between Dec 7, 2019, and May 18, 2020, a total of 205 patients were screened; of whom, 172 (84%) were randomly assigned to receive onradivir (n=43 in the 200 mg twice per day group; n=43 in the 400 mg twice per day group; and n=43 in the 600 mg once per day group), or placebo (n=42). Median age was 22 years (IQR 20-26). All three onradivir groups showed decreased median time to alleviate influenza symptoms (46·92 h [IQR 24·00-81·38] in the 200 mg twice per day group, 54·87 h [23·67-110·62] in the 400 mg twice per day group, and 40·05 h [17·70-65·82] in the 600 mg once per day) compared with the placebo group (62·87 h [36·40-113·25]). The median difference between the onradivir 600 mg once per day group and the placebo group was -22·82 h (p=0·0330). The most frequently reported treatment-emergent adverse event was diarrhoea (71 [42%] of 171), ranging from 33-65% of the patients in onradivir-treated groups compared with 10% in the placebo group; no serious adverse events were observed. INTERPRETATION: Onradivir showed a safety profile comparable to placebo, as well as higher efficacy than placebo in ameliorating influenza symptoms and lowering the viral load in adult patients with uncomplicated influenza infection, especially the onradivir 600 mg once per day regimen. FUNDING: National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, National Natural Science Foundation of China, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project, Emergency Key Program of Guangzhou Laboratory, Macao Science and Technology Development Fund, and Guangdong Raynovent Biotech.
Asunto(s)
Antivirales , Gripe Humana , Humanos , Gripe Humana/tratamiento farmacológico , Adulto , Masculino , Método Doble Ciego , Femenino , Persona de Mediana Edad , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Antivirales/efectos adversos , Adulto Joven , Adolescente , Anciano , Resultado del Tratamiento , China , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacosRESUMEN
Background: Ovarian cancer (OC) is the leading cause of gynecologic malignant tumors. The role of necroptosis-related lncRNAs (NRLs) in OC remains unclear. This study aims to explore the association between NRLs and prognosis in OC patients. Methods: The Cancer Genome Atlas (TCGA) and GTEx datasets were used to obtain OC's data. A NRLs signature associated with overall survival (OS) was constructed by Cox-LASSO regression analysis in training cohort for calculating risk score and then validated in testing cohort. Subsequently, the area under the curve (AUC) and Kaplan-Meier survival analysis were used to evaluate the predictive accuracy of the risk score. Finally, the immune infiltration and functional enrichment were compared between different risk groups. Results: A 8-NRLs signature including AC245128.3, AL355488.1, AC092794.1, AC068888.2, AL590652.1, AC008982.2, FOXP4-AS1, and Z94721.1 was identified to assess the OS of OC. Kaplan-Meier survival analysis, AUC value, and Cox regression analysis confirmed its predictive value and showed that the clinical outcomes were worse for high-risk patients. There were also differences in immunological functioning and immune pathways between the high-risk and low-risk groups. Conclusions: The signature based on eight NRLs has significant values in predicting prognostic prediction in OC, as well as providing a new sight for targeted therapies.