Rh(III)-Catalyzed Diastereo- and Enantioselective Regiodivergent (Hetero)Arylamidation of (Homo)Allylic Sulfides.

A rhodium-catalyzed 3-component conjunctive diastereo- and regioselective arylamidation of (homo)allylic sulfides, organon boronic acids, and dioxazolones is reported. These reactions deliver the 1,2-insertion and 2,1-insertion arylamidation products, respectively, for allylic sulfides and homoallylic sulfides. The enantioselective arylamidation of terminal and internal allylic sulfides is achieved, furnishing various 1,3-N,S compounds featuring one or two contiguous stereocenters in high yields and with high diastereo- and enantioselectivities. Mechanistic studies suggest a change in the turnover-limiting and selectivity-determining steps induced by the native and easily removable sulfide group.

Molecular regulation of DNA damage and repair in female infertility: a systematic review.

DNA damage is a key factor affecting gametogenesis and embryo development. The integrity and stability of DNA are fundamental to a woman's successful conception, embryonic development, pregnancy and the production of healthy offspring. Aging, reactive oxygen species, radiation therapy, and chemotherapy often induce oocyte DNA damage, diminished ovarian reserve, and infertility in women. With the increase of infertility population, there is an increasing need to study the relationship between infertility related diseases and DNA damage and repair. Researchers have tried various methods to reduce DNA damage in oocytes and enhance their DNA repair capabilities in an attempt to protect oocytes. In this review, we summarize recent advances in the DNA damage response mechanisms in infertility diseases such as PCOS, endometriosis, diminished ovarian reserve and hydrosalpinx, which has important implications for fertility preservation.

Factors affecting clinical pregnancy in controlled ovarian hyperstimulation with GnRH-a long protocol: a retrospective cross-sectional study.

This retrospective cross-sectional study was to investigate factors affecting clinical pregnancy in patients who received gonadotropin-releasing hormone agonist luteal phase long protocol (GnRH-a long protocol) and underwent fresh in-vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer cycle. One thousand five hundred and twenty-five patients who received GnRH-a long protocol and underwent fresh IVF/ICSI embryo transfer cycle were enrolled. The clinical pregnancy rate (63.1 vs. 22.4%, p < .05) and live birth rate (53.8 vs. 14.5%, p < .05) were significantly higher while the miscarriage rate (12.5 vs. 35.3%, p < .05) was significantly lower in the two embryo group than those in the one embryo group. The clinical pregnancy rate (48.5 vs. 64.1%, p < .05) and live birth rate (38.4 vs. 55.0%, p < .05) were significantly lower in patients older than 33.5 years than those in younger patients. The clinical pregnancy rate (52 and 60.6 vs. 79.7%, p < .05) and live birth rate (36 and 51.4 vs. 69.6%, p < .05) of the thin and mediate groups were significantly lower than those in the thick group, whereas the ectopic pregnancy rate (11.5 and 1.9 vs. 0%, p < .05) was significantly higher in the thin group than in the mediate and thick group. Multivariate logistic regression analysis showed that age (OR = 0.956, 95% CI [0.931, 0.982], p < .05), number of embryos transferred (OR = 2.491, 95% CI [1.670, 3.715], p < .05) and endometrial thickness on the transplantation day (OR = 1.124, 95% CI [1.067, 1.185], p < .05) were independent factors significantly associated with clinical pregnancy. In conclusion, endometrial thickness (>14.69 mm) on the day of transfer, two cleavage embryos transferred, and female age (≤33.5 years) are independent factors affecting clinical pregnancy outcomes in controlled ovarian hyperstimulation with GnRH-a long protocol for assisted conception. IMPACT STATEMENTWhat is already known on this subject? Fresh embryo transfer cycle with GnRH-a long protocol will result in a higher pregnancy rate in controlled ovarian hyperstimulation cycles.What do the results of this study add? Endometrial thickness on the day of transfer, number of embryos transferred, and female age were independent factors affecting clinical pregnancy outcomes.What are the implications of these findings for clinical practice and/or further research? When performing a fresh IVF/ICSI embryo transfer cycle with GnRH-a long protocol for ovulation induction, the independent affecting factors should be taken into consideration.

Novel tetrahydrobenzo[b]thiophen-2-yl)urea derivatives as novel α-glucosidase inhibitors: Synthesis, kinetics study, molecular docking, and in vivo anti-hyperglycemic evaluation.

α-Glucosidase inhibitors, which can inhibit the digestion of carbohydrates into glucose, are one of important groups of anti-type 2 diabetic drugs. In the present study, we report our effort on the discovery and optimization of α-glucosidase inhibitors with tetrahydrobenzo[b]thiophen-2-yl)urea core. Screening of an in-house library revealed a moderated α-glucosidase inhibitors, 5a, and then the following structural optimization was performed to obtain more efficient derivatives. Most of these derivatives showed increased inhibitory activity against α-glucosidase than the parental compound 5a (IC50 of 26.71 ± 1.80 µM) and the positive control acarbose (IC50 of 258.53 ± 1.27 µM). Among them, compounds 8r (IC50 = 0.59 ± 0.02 µM) and 8s (IC50 = 0.65 ± 0.03 µM) were the most potent inhibitors, and showed selectivity over α-amylase. The direct binding of both compounds with α-glucosidase was confirmed by fluorescence quenching experiments. Kinetics study revealed that these compounds were non-competitive inhibitors, which was consistent with the molecular docking results that compounds 8r and 8s showed high preference to bind to the allosteric site instead of the active site of α-glucosidase. In addition, compounds 8r and 8s were not toxic (IC50 > 100 µM) towards LO2 and HepG2 cells. Finally, the in vivo anti-hyperglycaemic activity assay results indicated that compounds 8r could significantly decrease the level of plasma glucose and improve glucose tolerance in SD rats treated with sucrose. The present study provided the tetrahydrobenzo[b]thiophen-2-yl)urea chemotype for developing novel α-glucosidase inhibitors against type 2 diabetes.

The development and application of a duplex reverse transcription loop-mediated isothermal amplification assay combined with a lateral flow dipstick method for Macrobrachium rosenbergii nodavirus and extra small virus isolated in China.

White tail disease (WTD), a major disease prevailing in the larval stage of Macrobrachium rosenbergii, caused by Macrobrachium rosenbergii nodavirus (MrNV) associated with extra small virus (XSV), led to the economic loss of shrimp industry in China. In order to establish a convenient, sensitive and selective molecular diagnostic method to detect MrNV and XSV for the Chinese shrimp (MrNV/XSV-chin), a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay combined with a lateral flow dipstick (LFD) method were developed. A set of four specific primers and a labeled probe were designed according to the six conserved gene sequence regions encoding for the MrNV capsid protein CP43 and the XSV capsid protein CP17. The detection of MrNV and XSV simultaneously by RT-LAMP was performed at 61 °C in a single reaction for 60 min followed by hybridization with an FITC-labeled probe for 5 min and visualized by LFD. The RT-LAMP-LFD assay had a sensitivity of approximately 100-fold higher than conventional PCR. In addition, the assay could detect MrNV/XSV-chin from limited amount of RNA extracts as low as 1.0 pg extracted from Macrobrachium rosenbergii. This assay was simple to use, required little instrumentation, and exhibited excellent specificity for the MrNV/XSV-chin compared with other shrimp viruses. In conclusion, a convenient, sensitive and selective practical molecular diagnostic method was developed with the potential for diagnosis and prevention of WTD.

From Metal-Organic Framework to Porous Carbon Polyhedron: Toward Highly Reversible Lithium Storage.

By application of a newly designed T-shaped ligand 5-(4-pyridin-4-yl-benzoylamino)isophthalic acid (H2PBAI) to assemble with Zn(II) ions under solvothermal conditions, a novel porous polyhedral metal-organic framework (Zn-PBAI) with pcu topology has been obtained. When treated as a precursor by annealing of Zn-PBAI at various temperatures, porous carbon polyhedra (PCP) were prepared and tested as an anode material for lithium-ion batteries. The results show that PCP carbonized at 1000 °C (PCP-1000) manifest the highest reversible specific capacity of about 1125 mAh g-1 at a current of 500 mA g-1 after 200 cycles, which is supposed to benefit from the large accessible specific area and high electric conductivity. Moreover, PCP-1000 electrode materials also exhibit superior cyclic stability and good rate capacity.

Mesoporous MnO/C-N Nanostructures Derived from a Metal-Organic Framework as High-Performance Anode for Lithium-Ion Battery.

By application of newly designed ligand 5-(3-(pyridin-3-yl)benzamido)isophthalic acid (H2PBI) to react with Mn(NO3)2 under solvothermal conditions, a 2-fold interpenetrated Mn-based metal-organic framework (Mn-PBI) with rutile-type topology has been obtained. When treated as a precursor by pyrolysis of Mn-PBI at 500 °C, mesoporous MnO/C-N nanostructures were prepared and treated as an lithium-ion battery anode. The MnO/C-N manifests good capacity of approximately 1085 mAh g-1 after 100 cycles together with superior cyclic stability and remarkable rate capacity, which is supposed to benefit from a large accessible specific area and unique nanostructures. The remarkable performances suggest promising application as an advanced anode material.

Assessment the carrier frequency of monogenic diseases in populations requiring assisted reproductive technology.

PURPOSE: The objective of this study is to assess the carrier frequency and pathogenic variation of monogenetic diseases in a population of 114 subjects in Han Chinese from Hebei province who are undergoing assisted reproductive technology through the utilization of Expanded Carrier Screening (ECS). METHODS: The study utilized a panel consisting of 155 severe monogenic recessive genetic diseases for ECS. Next-generation sequencing technology was employed to identify specific variants associated with ECS in a cohort of 114 subjects from 97 couples, comprising 97 females and 17 male spouses. RESULTS: A total of 114 individuals received ECS. The carrier rate of pathogenic genes in the enrolled population was 44.74% (51/114). Among the 97 females, the carrier rate of pathogenic genes was higher in those without assisted reproduction indicators than in those with assisted reproduction indicators (59.09% vs. 41.33%). However, the carrier rate of pathogenic genes in males without assisted reproductive technology was slightly lower than that with assisted reproductive technology (40% vs. 41.67%). Among both female and male participants, the carrier rate of pathogenic genes between individuals without indicators of assisted reproduction and those with such indicators was 55.55% vs. 41.38%. In 51 carriers, 72.55% (37/51) carried one genetic variant, 25.49% (13/51) carried two genetic variants, and 1.96% (1/51) carried three genetic variants. A total of 38 pathogenic genes were detected in this study, and GJB2 and MMACHC were most common. The carrier rates of the two genes were both 5.26% (6/114). A total of 55 variations were detected, and c.235delC was most frequently found. The carrier rate was 3.51% (4/114). The incidence of couples carrying the same pathogenic genes was 1.03% (1/97). CONCLUSIONS: The findings elucidate the carrier rate of pathogenic genes among 155 severe monogenic recessive genetic diseases and underscore the significance of ECS as a preventive measure against congenital anomalies. When both partners carry the same genetic mutation for a monogenic disease, preventive strategies can be taken in offspring through preimplantation genetic testing (PGT), prenatal genetic testing, or the utilization of donor gametes. ECS is instrumental in assessing reproductive risk, guiding fertility-related decisions, and reducing the prevalence of monogenic recessive genetic disorders in subsequent generations.

Expression profile analysis of LncRNAs and mRNAs in pre-receptive endometrium of women with polycystic ovary syndrome undergoing in vitro fertilization-embryo transfer.

BACKGROUND: To compare the expression levels of long non-coding RNA (lncRNA) and messenger RNA (mRNA) in pre-receptive endometrium between patients with Polycystic Ovary Syndrome (PCOS)and normal ovulation undergoing in vitro fertilization-embryo transfer (IVF-ET). METHODS: Endometrial tissues were collected with endometrial vacuum curette in pre-receptive phase (3 days after oocytes retrieval) from PCOS and control groups. LncRNAs and mRNAs of endometrium were identified via RNA sequencing and alignments. A subset of 9 differentially expressed lncRNAs and 11 mRNAs were validated by quantitative reverse transcription polymerase chain reaction(qRT-PCR)in 22 PCOS patients and 18 ovulation patients. The function of mRNAs with differential expression patterns were explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: We found out 687 up-regulated and 680 down-regulated mRNAs, as well as 345 up-regulated and 63 down-regulated lncRNAs in the PCOS patients in contrast to normal ovulation patients. qRT-PCR was used to detect the expression of 11 mRNAs, and validated that the expression of these 6 mRNAs CXCR4, RABL6, OPN3, SYBU, IDH1, NOP10 were significantly elevated among PCOS patients, and the expression of ZEB1 was significantly decreased. qRT-PCR was performed to detect the expression of 9 lncRNAs, and validated that the expression of these 7 lncRNAs IDH1-AS1, PCAT14, FTX, DANCR, PRKCQ-AS1, SNHG8, TPT1-AS1 were significantly enhanced among PCOS patients. Bioinformatics analysis showed that differentially expressed genes (DEGs) involved KEGG pathway were tyrosine metabolism, PI3K-Akt pathway, metabolic pathway, Jak-STAT pathway, pyruvate metabolism, protein processing in endoplasmic reticulum, oxidative phosphorylation and proteasome. The up-regulation of GO classification was involved in ATP metabolic process, oxidative phosphorylation, RNA catabolic process, and down-regulation of GO classification was response to corticosteroid, steroid hormone, and T cell activation. CONCLUSION: Our results determined the characteristics and expression profile of endometrial lncRNAs and mRNAs in PCOS patients in pre-receptive phase, which is the day 3 after oocytes retrival. The possible pathways and related genes of endometrial receptivity disorders were found, and those lncRNAs may be developed as a predictive biomarker of endometrium in pre-receptive phase.

RT-qPCR analysis of dexB and galE gene expression of Streptococcus alactolyticus in Astragalus membranaceus fermentation.

Streptococcus alactolyticus strain FGM, isolated from chicken cecum, was used to increase the extract yield of polysaccharides during Astragalus membranaceus fermentation. It was previously demonstrated that polysaccharides from fermented A. membranaceus by S. alactolyticus had some similar properties to those from A. membranaceus in terms of its ability to help heal hepatic fibrosis in rats and modulate immunopotentiation of broiler chicken. However, methods to increase the yield of the polysaccharides during fermentation of A. membranaceus are not well understood. In this paper, we investigated the involvement of uridine diphosphate (UDP)-glucose 4-epimerase (galE) and glucan-1,6-α-glucosidase (dexB) during A. membranaceus fermentation through real-time reverse transcription quantitative PCR. The galE and dexB genes of S. alactolyticus were cloned by homology-based cloning and the genome walking method for the first time, and the 3D structure of dexB was analyzed by Swiss-PdbViewer 4.0.1 software. The expression of both the galE and dexB genes in A. membranaceus fermentation was studied using the determined ideal reference gene ldh for transcript normalization. The results showed that these two genes were both highly induced and peaked after 12 h of fermentation. The expression level of galE was stepwise increased from 48 to 72 h, while dexB transcripts were markedly increased at 60 h and decreased by 72 h. These data suggested that dexB and galE of S. alactolyticus strain FGM were involved in the regulation of A. membranaceus fermentation and they might play some roles in the increase of polysaccharides.

[Evaluation for the clinical application of all embryos cryopreservation: a multi-centre study in northern area of China].

OBJECTIVE: To investigate the clinical outcome of patients who underwent cryopreservation of all embryos. METHODS: A retrospective analysis was made in the clinical data of patients with cryopreservation of all embryos between April 2011 and September 2011 in four hospitals of North China. The patients were divided into five groups according to the reasons of cryopreservation of all embryos: ovarian hyperstimulation syndrome (OHSS) group, serum progesterone elevation group, endometrial group, hydrosalpinx group and others. The clinical pregnancy rate per transfer, implantation rate and cumulative clinical pregnancy rate were analyzed. RESULTS: The clinical pregnancy rate, implantation rate and cumulative clinical pregnancy rate of the OHSS group were 55.4%, 34.8% and 73.7%, respectively. The rates of the serum progesterone elevation group were 25.5%, 11.2% and 43.1%, respectively. The rates of the endometrial group were 54.8%, 34.4% and 61.5%, respectively. The rates of the hydrosalpinx group were 60%, 30% and 60%, respectively. The rates of the other factors group were 36.0%, 24.5% and 44.0%, respectively. CONCLUSION: The strategy of cryopreservation of all embryos could improve the clinical outcomes of patients with severe OHSS. It still needs a large multi-centre, randomized trial to evaluate its effectiveness and side effects, although it has the positive clinical application for other reasons of cryopreservation of all embryos.

The association of asthma duration with body mass index and Weight-Adjusted-Waist index in a nationwide study of the U.S. adults.

BACKGROUNDS: The association between obesity and asthma has been of interest, but whether the duration of asthma has an effect on obesity is still limitedly studied. AIM: The purpose of this study was to investigate the association between asthma duration and obesity-related indexes, where obesity-related indexes include Body mass index (BMI) and Weight-adjusted-waist index (WWI). METHODS: Data from National Health and Nutrition Examination Survey (NHANES) 2009-2018 were obtained to conduct this cross-sectional study. Duration of asthma was used as the independent variable and obesity-related indexes as the response variables. Multiple linear regression was used to assess the association between the independent variable and the response variables, and subsequently smoothed curve fitting and threshold effect analysis were performed to clarify whether there was a nonlinear correlation between the independent variable and the response variables. Finally, subgroup analysis was conducted to find sensitive populations. RESULTS: A total of 9170 participants were included in the analysis. Asthma duration was statistically different between the two groups when all participants were grouped by median WWI (Q1 < 11.65, Q2 ≥ 11.65) (P < 0.001), but not by median BMI (Q1 < 31.8, Q2 ≥ 31.8) (P = 0.130). There was a positive association between asthma duration and WWI [ß = 0.016, 95% CI (0.016, 0.017)], but a negative one with BMI [ß = - 0.098, 95% CI (- 0.112, - 0.085)], and the correlations between the independent and response variables became more pronounced with increasing asthma duration (P for trend < 0.01). In addition, there were nonlinear relationships between asthma duration with BMI and WWI (log likelihood ratio < 0.001), with the best valid inflection points for asthma duration being 2 years (with WWI as the response variable) and 3 years (with BMI as the response variable), respectively. In the subgroup analysis, the positive association between asthma duration and WWI was more pronounced in the participants who were male, aged less than 40 years, and had asthma onset before 12 years of age. In contrast, when BMI was used as the response variable, the negative association between it and asthma duration was more pronounced among participants of female, aged 60 years or older, and with asthma onset less than 12 years of age. CONCLUSIONS: In US adults, asthma duration might cause changes in obesity-related indexes. Longer asthma duration might cause weight loss, but might increase the risk of abdominal obesity.

Decreased AKAP4/PKA signaling pathway in high DFI sperm affects sperm capacitation.

The sperm DNA fragmentation index (DFI) is a metric used to assess DNA fragmentation within sperm. During in vitro fertilization-embryo transfer (IVF-ET), high sperm DFI can lead to a low fertilization rate, poor embryo development, early miscarriage, etc. A kinase anchoring protein (AKAP) is a scaffold protein that can bind protein kinase A (PKA) to subcellular sites of specific substrates and protects the biophosphorylation reaction. Sperm protein antigen 17 (SPA17) can also bind to AKAP. This study intends to explore the reason for the decreased fertilization rate observed in high sperm DFI (H-DFI) patients during IVF-ET. In addition, the study investigates the expression of AKAP, protein kinase A regulatory subunit (PKARII), and SPA17 between H-DFI and low sperm DFI (L-DFI) patients. SPA17 at the transcriptional level is abnormal, the translational level increases in H-DFI patients, and the expression of AKAP4/PKARII protein decreases. H2O2 has been used to simulate oxidative stress damage to spermatozoa during the formation of sperm DFI. It indicates that H2O2 increases the expression of sperm SPA17 protein and suppresses AKAP4/PKARII protein expression. These processes inhibit sperm capacitation and reduce acrosomal reactions. Embryo culture data and IVF outcomes have been documented. The H-DFI group has a lower fertilization rate. Therefore, the results indicate that the possible causes for the decreased fertilization rate in the H-DFI patients have included loss of sperm AKAP4/PKARII proteins, blocked sperm capacitation, and reduced occurrence of acrosome reaction.

Research progress on the mechanism of cerebral blood flow regulation in hypoxia environment at plateau.

The plateau is a special environment with low air pressure and low oxygen content. The average altitude of Qinghai-Tibet is 3,500 m, and the atmospheric oxygen partial pressure in most areas is lower than 60% of that at sea level. In order to adapt to the plateau low-oxygen environment, the human body has developed corresponding physiological structure and functions adjust. In the present review, the regulation mechanism of cerebral blood flow (CBF) under high-altitude environments was elaborated in eight aspects: the arterial blood gas, endogenous substances in the nerve and blood, the cerebral neovascularization, the hematocrit, cerebral auto-regulation mechanism, cerebrovascular reactivity, pulmonary vasoconstriction, and sympathetic automatic regulation, aiming to further explore the characteristics of changes in brain tissue and cerebral blood flow in a hypoxic environment.

Progestin-Primed Ovarian Stimulation Protocol for Patients With Endometrioma.

Objective: To evaluate the pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) protocol for patients with endometrioma underwent in vitro fertilization/intra-cytoplasmic sperm injection embryo transfer (IVF/ICSI-ET). Design: Observational retrospective cohort study. Setting: University affiliated reproductive center. Study Participants: 605 infertile patients with endometrioma underwent IVF/ICSI-ET from January 2016 to March 2021 were included in this study. Methods: Multivariable logistic regression analyses were conducted to determine the independent effect of controlled ovarian stimulation (COS) protocols on reproductive outcomes of first embryo transfer (ET) cycles. The live birth was primary outcome, the implantation rate, biochemical pregnancy, clinical pregnancy and ongoing pregnancy were secondary outcomes. Results: Compared to PPOS protocol, the probability of implantation showed no significant difference with ultra-long gonadotrophin-releasing hormone agonist (GnRHa) protocol and gonadotrophin-releasing hormone antagonist (GnRHant) protocol (OR 1.7, 95% CI 0.9-3.1, OR 1.2, 95% CI 0.7-2.1, respectively). The PPOS protocol was correlated with a significantly lower biochemical pregnancy and clinical pregnancy than ultra-long GnRHa protocol in the multivariable logistic regression analysis (OR 2.3, 95% CI 1.1-4.9, OR 2.4, 95% CI 1.1-5.3, respectively). However, there was no significant difference in terms of biochemical pregnancy, clinical pregnancy and ongoing pregnancy between PPOS and GnRHant protocol (OR 1.4, 95% CI 0.7-2.7, OR 1.3, 95% CI 0.7-2.4, OR 1.1, 95% CI 0.6-2.3, respectively). In addition, compared to PPOS protocol, ultra-long GnRHa protocol and GnRHant protocol demonstrated no statistical difference in ongoing pregnancy (OR 2.0, 95% CI 0.9-4.5, OR 2.1, 95% CI 0.6-2.3, respectively). Notably, the ultra-long GnRHa protocol was associated with a significant higher probability of live birth than PPOS protocol both in crude analysis and multivariable logistic regression analysis (OR 2.6, 95% CI 1.3-5.1, OR 2.5, 95% CI 1.1-5.7, respectively). Nevertheless, no statistical difference was found in live birth between PPOS and GnRHant protocol either in crude analysis and multivariable logistic regression analysis (OR1.2, 95% CI 0.6-2.3, OR 1.2, 95% CI 0.6-2.5, respectively). Conclusions: Based on the reproductive outcomes of the first ET cycles in patients with endometrioma, PPOS protocol may associated with inferior reproductive outcomes in terms of biochemical pregnancy, clinical pregnancy and live birth than ultra-long GnRHa protocol. However, there was no significant difference in implantation rate, clinical pregnancy, ongoing pregnancy and live birth between PPOS and GnRHant protocol.

Optimizing estradiol level for gonadotrophin-releasing hormone antagonist initiation among patients with simple tubal factor infertility.

Objective: The aim of this study is to investigate the optimal estradiol (E2) level on the day of gonadotropin-releasing hormone antagonist (GnRH-ant) initiation to maximize the clinical pregnancy rate (CPR) after fresh embryo transfer among patients with simple tubal factor infertility. Methods: A retrospective cohort study was conducted in the Reproductive Medicine Center, the Second Hospital of Hebei Medical University. A total of 1,493 IVF-ET cycles of patients diagnosed with single tubal factor infertility from August 2016 to August 2021 were included and equally allocated into five distinct groups according to the quintile serum E2 levels on the day of GnRH-ant initiation. The five groups had similar baseline data except for antral follicle count. Results: The serum E 2 level on GnRH-ant initiation day was determined as an independent predictor of clinical pregnancy after adjusting for confounding factors such as age, infertility duration, body mass index, cycle number, antral follicle count, and the number of transferred embryos. Through smooth curve fitting, we found that, with the increase of serum E2 levels on the day of GnRH-ant initiation, CPR showed a trend of slight increase and then slight decrease. The maximal CPR was achieved when the serum E2 level on GnRH-ant initiation day was 498 pg/ml. When E2 was less than 498 pg/ml, the odds ratio (OR) of clinical pregnancy was 1.05 (95% CI: 1.00, 1.11, P = 0.0583). When E2 was greater than 498 pg/ml, the OR of clinical pregnancy was 0.97 (95% CI: 0.95, 0.98, P = 0.0003). Furthermore, CPR remained high when E2 was 436.8-658.6 pg/ml but declined significantly by more than 40% when E2 was ≥ 894.4 pg/ml (P < 0.05). Conclusions: The serum E2 level should be considered as an adjuvant parameter for GnRH-ant initiation. The best E2 value was 498 pg/ml, and GnRH-ant administration could be recommended to initiate when serum E2 was 436.8-658.6 pg/ml. If GnRH-ant was initiated when serum E2 was above 894.4 pg/ml, then the CPR after fresh embryo transfer may decline dramatically, and thus, cancellation of fresh embryo transfer and earlier initiation of GnRH-ant in future cycles should be considered.

In vivo anthelmintic activity of chelidonine from Chelidonium majus L. against Dactylogyrus intermedius in Carassius auratus.

Dactylogyrus intermedius is one of the most common and serious cause of parasitic diseases of freshwater fish in aquaculture, and can cause morbidity and high mortality in most species of freshwater fish worldwide. To attempt controlling this parasite and explore novel potential antiparasitic agents, the present study was designed to ascertain the anthelmintic activity of Chelidonium majus L. whole plant and to isolate and characterize the active constituents against D. intermedius. The ethanol extract from C. majus whole plant showed significant anthelmintic activity against D. intermedius [EC(50) (median effective concentration) value = 71.5 mg L(-1)] and therefore subjected to further isolation and purification using various chromatographic techniques. A quaternary benzo[c]phenanthridine alkaloid exhibited significant activity against D. intermedius was obtained and identified as chelidonine. In vivo anthelmintic efficacy tests exhibited that chelidonine was 100% effective against D. intermedius at a concentration of 0.9 mg L(-1), with EC(50) value of 0.48 mg L(-1) after 48 h of exposure, which is more effective than the positive control, mebendazole (EC(50) value = 1.3 mg L(-1)). In addition, the 48-h median lethal concentration (LC(50)) for chelidonine against the host (Carassius auratus) was 4.54 mg L(-1). The resulting therapeutic index for chelidonine was 9.46. These results provided evidence that chelidonine might be potential sources of new antiparasitic drugs for the control of Dactylogyrus.

Letrozole for Female Infertility.

Letrozole, an aromatase inhibitor that blocks estrogen synthesis by inhibiting the final step of the estrogen biosynthetic pathway, has been used in the applications of a wide range of infertility settings. It has been more than 20 years since the initial clinical trial of letrozole for ovulation induction. In light of the accumulating clinical and basic evidence, the efficacy and safety of letrozole have been identified. This mini review focuses on our current knowledge of the applications and mechanisms of letrozole for female infertility and various questions are put forward about how letrozole could be more effectively used.

Risk Factors for Different Types of Pregnancy Losses: Analysis of 15,210 Pregnancies After Embryo Transfer.

Objective: To evaluate the risk factors for different types of pregnancy losses after embryo transfer (ET). Design: Retrospective cohort study. Setting: Reproductive medicine center. Participants: A total of 15,210 pregnancies after fresh and frozen-thawed embryo transfer between January 2014 and June 2019. Main Outcome Measures: The primary outcome was pregnancy loss (PL) throughout the entire pregnancy. Secondary outcomes were non-visualized PL, early miscarriage, late miscarriage, and stillbirth. Methods: The effect of patients' baseline characteristics and IVF/ICSI cycle-specific factors on the risk of PL after fresh and frozen-thawed ET was determined by multivariate logistic regression analysis. Results: Compared to women under 35 years old, those between 35 and 40 had an increased risk of early miscarriage [odds ratio (OR) 1.49, 95% confidence interval (CI) 1.22-1.83], while those after 40 appeared to have an increased risk of both early miscarriage (OR 3.82, 95% CI 2.65-5.51) and late miscarriage (OR 2.79, 95% CI 1.64-4.77). Overweight patients were observed to have a higher risk of late miscarriage (OR 1.38, 95% CI 1.16-1.65), while obese patients showed a higher risk of both early miscarriage (OR 1.47, 95% CI 1.14-1.91) and late miscarriage (OR 1.80, 95% CI 1.33-2.44). Polycystic ovary syndrome (PCOS) was an independent risk factor for late miscarriage (OR 1.58, 95% CI 1.28-1.96), and the detrimental effect of PCOS was independent of obesity status. Women with uterine factors had a higher risk of early miscarriage (OR 1.77 (95% CI 1.32-2.38) than women without uterine factors. A negative correlation was observed between the thickness of the endometrium and PL (OR 0.95 95% CI 0.92-0.97). There was an increased risk of PL after frozen-thawed ET versus fresh ET (OR 1.12, 95% CI 1.01-1.24). Women who transferred ≥2 embryos showed lower risk of overall PL than women who transferred a single embryo, with adjusted ORs ranged from 0.57~0.94. However, women who transferred three embryos demonstrated a higher risk of late miscarriage than women who transferred a single embryo (OR 2.23, 95% CI 1.36-3.66). Conclusions: Patients with uterine factors demonstrated higher risk of early miscarriage and stillbirth. Being overweight, PCOS, and transferring three embryos was associated with late miscarriage. Being aged 40 and over, obese, and using frozen embryo transfer was associated with early and late miscarriage.

Study on clinical nursing pathway to promote the effective implementation of sepsis bundle in septic shock.

BACKGROUND: There is still a certain gap between the effective implementation and requirements of sepsis bundle. Our aim is to establish the clinical nursing pathway of the cluster treatment of septic shock in the Intensive Care Unit and promote effective implementation of the cluster treatment of septic shock. METHODS: By means of evidence-based method, quality control index requirements and on-site investigation, the implementation process of clinical nursing pathway of the cluster treatment within 6 h of diagnosis of septic shock was established. RESULTS: After the implementation of clinical nursing pathway, the completion rate of septic shock cluster treatment was 81.4% (66.4%) in 1 h, 89.4% (77.0%) in 3 h, 95.5% (82.3%) in 6 h (P < 0.05), which was significantly improved in the experimental group compared with the control group. CONCLUSIONS: The clinical nursing pathway of septic shock cluster treatment is guided by evidence-based nursing, which emphasizes standardization and standardization of septic shock cluster treatment nursing under the guidance of the guideline, and can promote the effective implementation of septic shock cluster treatment, significantly improve efficiency of septic shock treatment and the quality of medical care.