Impact of mildly evaluated thyroid-stimulating hormone levels on in vitro fertilization or intracytoplasmic sperm injection outcomes in women with the first fresh embryo transfer: a large study from China.

PURPOSE: This study aimed to investigate the association between mild elevation of thyroid-stimulating hormone (TSH) levels and pregnancy outcomes of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments in women with the first fresh embryo transfer. METHODS: Large single-center retrospective cohort study of 15,728 patients from January 2018 to December 2022 were enrolled in the analyses. Clinical pregnancy rates, live birth rates, miscarriage rates, and ectopic pregnancy rates were compared between the TSH levels < 2.5 mIU/L group (N = 10,932) and TSH levels ≥ 2.5 mIU/L group (N = 4796). Subgroup analysis was performed for patients with TSH levels ≥ 2.5 mIU/L, dividing them into the thyroid peroxidase antibody (TPO)-negative group (N = 4524) and the TPO-positive group (N = 272). RESULTS: There were no significant differences in the aforementioned pregnancy outcomes between the TSH levels < 2.5 mIU/L group and TSH levels ≥ 2.5 mIU/L group. Similarly, no significant differences were observed in the pregnancy outcomes between the TPO-negative group and the TPO-positive group. CONCLUSION: Mildly elevated pre-conception TSH levels in thyroid-normal infertile patients did not have an impact on pregnancy outcomes of IVF/ICSI treatments.

Circ_0115118 regulates endometrial functions through the miR-138-1-3p/WDFY2 axis in patients with PCOS†.

To investigate the expression profiles of circular RNAs (circRNAs) in the endometria of women with polycystic ovary syndrome (PCOS) and to explore the role of aberrant circ_0115118 expression in endometrial dysfunction in patients with PCOS. CircRNA microarray hybridization and bioinformatic analyses were performed to determine the expression patterns of circRNAs in the endometria of patients with or without PCOS, the expression of target circRNA was evaluated by real-time polymerase chain reaction (PCR). Cell counting kit-8 and Transwell assays were used to detect cellular proliferative, invasive, and migratory capacities. The influence of the circRNA on decidualization was explored by real-time PCR. Animal models were established to investigate the regulatory effect of the circRNA on embryo implantation. Downstream microRNAs and genes were predicted using bioinformatic websites and verified by dual-luciferase reporter assays, real-time PCR, and western blotting. In the endometria of patients with PCOS, there were 113 differentially expressed circRNAs in the secretory phase and 1119 differentially expressed circRNAs in the proliferative phase. The expression of circ_0115118 was significantly higher in endometrial stromal cells during the proliferative phase in patients with PCOS, leading to inhibition of cellular mobilization and embryo implantation. In addition, circ_0115118 exerted effects by sponging miR-138-1-3p, subsequently increasing the expression of WD repeat and FYVE domain-containing protein 2 (WDFY2). Circ_0115118 expression is dysregulated in the endometria of patients with PCOS and adversely affects endometrial function. Our findings reveal that circ_0115118 may be a potential therapeutic target to improve pregnancy outcomes in women with PCOS.

Genetic contribution of synapse-associated protein 97 to cerebellar functional connectivity changes in first-episode schizophrenia.

Our previous study data suggested that the synapse-associated protein 97 (SAP97) rs3915512 polymorphism is significantly related to clinical performance in schizophrenia. The cerebellum exhibits abundant expression of SAP97, which is involved with negative symptoms, cognition and emotion in schizophrenia. As functional dysconnectivity with the cortical-subcortical-cerebellar circuitry has been widely shown in patients with schizophrenia, cortical-subcortical-cerebellar dysconnectivity can therefore be considered a possible intermediate phenotype that connects risk genes with schizophrenia. In this study, resting-state functional magnetic resonance imaging (fMRI) was applied to evaluate whether the SAP97 rs3915512 polymorphism changes cortical/subcortical-cerebellar resting-state functional connectivity (RSFC) in 104 Han Chinese subjects (52 first-episode schizophrenia (FES) patients and 52 matched healthy controls (HCs)). To examine RSFC between cortical/subcortical regions and the cerebellum, a ROI (region of interest)-wise functional connectivity analysis was conducted. The association between abnormal cortical/subcortical-cerebellar connectivity and clinical manifestation was further assessed in FES patients with different genotypes. The interactive effect of disease and genotype on RSFC was found between the frontal gyrus (rectus) and cerebellum. A positive correlation was suggested between RSFC in the cerebellum and the hostility scores in FES patients with the A allele, and no correlation was found in FES patients with the TT genotype. The current findings identified that SAP97 may be involved in the process of mental symptoms in FES patients via cerebellar connectivity depending on the rs3915512 polymorphism genotype.

Manipulation of Mott-Schottky Ni/CeO2 Heterojunctions into N-Doped Carbon Nanofibers for High-Efficiency Electrochemical Water Splitting.

Designing affordable and efficient bifunctional electrocatalysts for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) has remained a long-lasting target for the progressing hydrogen economy. Utilization of metal/semiconductor interface effect has been lately established as a viable implementation to realize the favorable electrocatalytic performance due to the built-in electric field. Herein, a typical Mott-Schottky electrocatalyst by immobilizing Ni/CeO2 hetero-nanoparticles onto N-doped carbon nanofibers (abbreviated as Ni/CeO2 @N-CNFs hereafter) has been developed via a feasible electrospinning-carbonization tactic. Experimental findings and theoretic calculations substantiate that the elaborated constructed Ni/CeO2 heterojunction effectively triggers the self-driven charge transfer on heterointerfaces, leading to the promoted charge transfer rate, the optimized chemisorption energies for reaction intermediates and ultimately the expedited reaction kinetics. Therefore, the well-designed Ni/CeO2 @N-CNFs deliver superior HER and OER catalytic activities with overpotentials of 100 and 230 mV at 10 mA cm-2 , respectively, in alkaline solution. Furthermore, the Ni/CeO2 @N-CNFs-equipped electrolyzer also exhibits a low cell voltage of 1.56 V to attain 10 mA cm-2 and impressive long-term durability over 55 h. The innovative manipulation of electronic modulation via Mott-Schottky establishment may inspire the future development of economical electrocatalysts for diverse sustainable energy systems.

Association study of a genetic variant in the long intergenic noncoding RNA (linc01080) with schizophrenia in Han Chinese.

BACKGROUND: Schizophrenia is currently considered to be a polygene-related disease with unknown etiology. This research will verify whether the single nucleotide polymorphism (SNP) of the long intergenic noncoding RNA01080 (linc01080) contributes to the susceptibility and phenotypic heterogeneity of schizophrenia, with a view to providing data support for the prevention and individualized treatment of this disease. METHOD: The SNP rs7990916 in linc01080 were genotyped in 1139 schizophrenic and 1039 controls in a Southern Chinese Han population by the improved multiplex ligation detection reaction (imLDR) technique. Meanwhile, we assessed and analyzed the association between this SNP and schizophrenics' clinical symptoms, and the cognitive function. RESULT: There was no significant difference in genotype distribution, allele frequency distribution, gender stratification analysis between the two groups. However, the SNP of rs7990916 was significantly associated with the age of onset in patients with schizophrenia (P = 8.22E-07), patients with T allele had earlier onset age compared with CC genotype carriers. In terms of cognitive function, patients with T allele scored lower than CC genotype carriers in the Tower of London score and symbol coding score in the Brief assessment of Cognition (BACS), and the difference was statistically significant (P = 0.014, P = 0.022, respectively). CONCLUSION: Our data show for the first time that linc01080 polymorphism may affect the age of onset and neurocognitive function in patients with schizophrenia.

Mediator complex regulates alternative mRNA processing via the MED23 subunit.

Mediator complex is an integrative hub for transcriptional regulation. Here we show that Mediator regulates alternative mRNA processing via its MED23 subunit. Combining tandem affinity purification and mass spectrometry, we identified a number of mRNA processing factors that bind to a soluble recombinant Mediator subunit, MED23, but not to several other Mediator components. One of these factors, hnRNP L, specifically interacts with MED23 in vitro and in vivo. Consistently, Mediator partially colocalizes with hnRNP L and the splicing machinery in the cell. Functionally, MED23 regulates a subset of hnRNP L-targeted alternative splicing (AS) and alternative cleavage and polyadenylation (APA) events, as shown by minigene reporters and exon array analysis. ChIP-seq analysis revealed that MED23 can regulate hnRNP L occupancy at their coregulated genes. Taken together, these results demonstrate a crosstalk between Mediator and the splicing machinery, providing a molecular basis for coupling mRNA processing to transcription.

Mediator MED23 plays opposing roles in directing smooth muscle cell and adipocyte differentiation.

The Mediator complex functions as a control center, orchestrating diverse signaling, gene activities, and biological processes. However, how Mediator subunits determine distinct cell fates remains to be fully elucidated. Here, we show that Mediator MED23 controls the cell fate preference that directs differentiation into smooth muscle cells (SMCs) or adipocytes. Med23 deficiency facilitates SMC differentiation but represses adipocyte differentiation from the multipotent mesenchymal stem cells. Gene profiling revealed that the presence or absence of Med23 oppositely regulates two sets of genes: the RhoA/MAL targeted cytoskeleton/SMC genes and the Ras/ELK1 targeted growth/adipogenic genes. Mechanistically, MED23 favors ELK1-SRF binding to SMC gene promoters for repression, whereas the lack of MED23 favors MAL-SRF binding to SMC gene promoters for activation. Remarkably, the effect of MED23 on SMC differentiation can be recapitulated in zebrafish embryogenesis. Collectively, our data demonstrate the dual, opposing roles for MED23 in regulating the cytoskeleton/SMC and growth/adipogenic gene programs, suggesting its "Ying-Yang" function in directing adipogenesis versus SMC differentiation.

The Mediator subunit MED23 couples H2B mono-ubiquitination to transcriptional control and cell fate determination.

The Mediator complex orchestrates multiple transcription factors with the Pol II apparatus for precise transcriptional control. However, its interplay with the surrounding chromatin remains poorly understood. Here, we analyze differential histone modifications between WT and MED23(-/-) (KO) cells and identify H2B mono-ubiquitination at lysine 120 (H2Bub) as a MED23-dependent histone modification. Using tandem affinity purification and mass spectrometry, we find that MED23 associates with the RNF20/40 complex, the enzyme for H2Bub, and show that this association is critical for the recruitment of RNF20/40 to chromatin. In a cell-free system, Mediator directly and substantially increases H2Bub on recombinant chromatin through its cooperation with RNF20/40 and the PAF complex. Integrative genome-wide analyses show that MED23 depletion specifically reduces H2Bub on a subset of MED23-controlled genes. Importantly, MED23-coupled H2Bub levels are oppositely regulated during myogenesis and lung carcinogenesis. In sum, these results establish a mechanistic link between the Mediator complex and a critical chromatin modification in coordinating transcription with cell growth and differentiation.

The Mediator complex: a master coordinator of transcription and cell lineage development.

Mediator is a multiprotein complex that is required for gene transcription by RNA polymerase II. Multiple subunits of the complex show specificity in relaying information from signals and transcription factors to the RNA polymerase II machinery, thus enabling control of the expression of specific genes. Recent studies have also provided novel mechanistic insights into the roles of Mediator in epigenetic regulation, transcriptional elongation, termination, mRNA processing, noncoding RNA activation and super enhancer formation. Based on these specific roles in gene regulation, Mediator has emerged as a master coordinator of development and cell lineage determination. Here, we describe the most recent advances in understanding the mechanisms of Mediator function, with an emphasis on its role during development and disease.

Age-related changes in the mitochondria of human mural granulosa cells.

STUDY QUESTION: What changes in the mitochondria of human mural granulosa cells (mGCs) with maternal aging? SUMMARY ANSWER: The mitochondrial membrane potential (MMP) and the ability of oxidative phosphorylation (OXPHOS) of mGCs declines with reproductive aging, accompanied with more abnormal mitochondria. WHAT IS KNOWN ALREADY: Mitochondria play an important role in the dialogue between the mGCs and oocytes. However, the underlying mechanism of mitochondrial dysfunction in mGCs in aging is still poorly understood. STUDY DESIGN SIZE, DURATION: In total, 149 infertile women underwent IVF in the ART Centre of the Chinese PLA General Hospital, China from September 2016 to May 2017. Two age groups were investigated: the young group (<38 years old) and the old group (≥38 years old). PARTICIPANTS/MATERIALS, SETTING, METHODS: The mitochondrial ultrastructure of mGCs was observed by transmission electron microscopy, and real-time quantitative polymerase chain reaction was applied to quantify the mitochondrial DNA (mtDNA) copy number, 4977-bp deleted DNA and mRNA expression of mitochondrial ATP synthases ATP5A1 and ATP5I. MMP was detected by flow cytometry and fluorescence microscopy, respectively. Reactive oxygen species (ROS) was tested by flow cytometry. A luminometer was used to measure the ATP levels and western blot to analyse the OXPHOS complex. MAIN RESULTS AND THE ROLE OF CHANCE: In the young group, mitochondria were mostly round or oval, with a few intact parallel tubular-vesicular cristae and homogenous matrix density, while elongated mitochondria were mainly observed in the old group, which had numerous cristae and more high-density matrix particles. Abnormal mitochondria were more common in aging women (P = 0.012). mtDNA relative copy number was positively correlated with maternal age (r = 0.294, P = 0.009) and we found no one with 4977-bp deleted mitochondria. JC-1 (dye used as an indicator of MMP) ratio in the old group was significantly lower than the young group (3.01 ± 0.21 vs 3.85 ± 0.27, P = 0.033). Intracellular ROS levels between the groups did not differ significantly (P = 0.191). The intracellular ATP level in the young group was 1.75-fold higher than that of the advanced-age group (7.17 ± 1.16 vs 4.15 ± 0.60, P = 0.025). The protein expression of ATP5A1, as one of five proteins of OXPHOS, decreased with aging (P < 0.001). ATP5A1 mRNA expression was negatively correlated with aging (r = -0.341, P = 0.012). LIMITATIONS REASONS FOR CAUTION: The quantity of mGCs from some individual patient, especially an advanced-age individual, was small, which cannot meet the demands of all the detections. WIDER IMPLICATIONS OF THE FINDINGS: mGCs dysfunction with aging is mainly linked to impaired mitochondrial function, especially OXPHOS function. Improving the OXPHOS ability in mGCs should be the focus in resolving infertility among advanced age women and making mGCs the proper mitochondria donor cells in the autologous mitochondria transplantation to oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the grants of the National High Technology Research and Development Program of China, 863 Program No. SS2015AA020402, and the Key Projects of Military Medical Research, No. BWS11J058. There were no competing interests.

[Effects of nano-lead exposure on learning and memory as well as iron homeostasis in brain of offspring rats].

OBJECTIVE: To investigate the effects of nano-lead exposure on learning and memory and iron homeostasis in the brain of the offspring rats on postnatal day 21 (PND21) and postnatal day 42 (PND42). METHODS: Twenty adult pregnant female Sprague-Dawley rats were randomly divided into control group and nano-lead group. Rats in the nano-lead group were orally administrated 10 mg/kg nano-lead, while rats in the control group were administrated an equal volume of normal saline until PND21. On PND21, the offspring rats were weaned and given the same treatment as the pregnant rats until 42 days after birth. The learning and memory ability of offspring rats on PND21 and PND42 was evaluated by Morris water maze test. The hippocampus and cortex s amples of offspring rats on PND21 and PND42 were collected to determine iron and lead levels in the hippocampus and cortex by inductively coupled plasma-mass spectrometry. The distributions of iron in the hippocampus and cortex were observed by Perl's iron staining. The expression levels of ferritin, ferroportin 1 (FPN1), hephaestin (HP), and ceruloplasmin (CP) were measured by enzyme-linked immunosorbent assay. RESULTS: After nano-lead exposure, the iron content in the cortex of offspring rats on PND21 and PND42 in the nano-lead group was significantly higher than those in the control group (32.63 ± 6.03 µg/g vs 27.04 ± 5.82 µg/g, P<0.05; 46.20 ±10.60 µg/g vs 36.61 ± 10.2µg/g, P<0.05). The iron content in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly higher than that in the control group (56.9 ± 4.37µg/g vs 37.71 ± 6.92µg/g, P<0.05). The Perl's staining showed massive iron deposition in the cortex and hippocampus in the nano-lead group. FPNl level in the cotfex of offspring rats on PND21 in the nano-lead group was significantly lower than that in the control group (3.64 ± 0.23 ng/g vs 4.99 ± 0.95 ng/g, P<0.05). FPN1 level in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly lower than that in the control group (2.28 ± 0.51 ng/g vs 3.69 ± 0.69 ng/g, P<0.05). The escape latencies of offspring rats on PND21 and PND42 in the nano-lead group were longer than those in the control group (15.54 ± 2.89 s vs 9.01 ± 4.66 s; 6.16 ± 1.42 s vs 4.26 ± 1.51 s). The numbers of platform crossings of offspring rats on PND21 and PND42 in the nano- lead group were significantly lower than those in the control group (7.77 ± 2.16 times vs 11.2 ± 1.61 times, P<0.05; 8.12 ± 1.51 times vs 13.0 ± 2.21 times, P<0.05). ONCLUSION: n Nano-lead exposure can result in iron homeostasis disorders in the hippocampus and cortex of offspring rats and affect their learning and memory ability.

miR-137: a new player in schizophrenia.

Schizophrenia is a complex genetic disease and characterized by affective, cognitive, neuromorphological, and molecular abnormalities that may have a neurodevelopmental origin. MicroRNAs (miRNAs) are critical to neurodevelopment and adult neuronal processes by modulating the activity of multiple genes within biological networks. MiR-137 as a brain-enriched microRNA, plays important roles in regulating embryonic neural stem cells (NSCs) fate determination, neuronal proliferation and differentiation, and synaptic maturation. Its dysregulation causes changes in the gene expression regulation network of the nervous system, thus inducing mental disorders. Recently, miR-137 has been confirmed as a gene related to schizophrenia susceptibility. In the following review, we summarize the expression pattern, epigenetic regulation and functions of miR-137. A more complete picture of the miR-137, which is dysregulated in psychiatric illness, may improve our understanding of the molecular mechanisms underlying schizophrenia.

Intermittent mild cold stimulation alleviates cold stress-induced pulmonary fibrosis by inhibiting the TGF-ß1/Smad signaling pathway in broilers.

To investigate the potential protective effect of intermittent cold stimulation on lung tissues of broilers exposed to acute cold stress (ACS). A total of 384 one-day-old broilers were assigned to 4 experimental groups with 6 replicates of 16 birds each: control (CON) and ACS groups were reared at normal feeding temperature from d 1 to 42; cold treatment groups (CS3+ACS and CS9+ACS) were reared, respectively, at 3°C or 9°C for 5 h on alternate days below the CON group from d 15 to 35. Animals in CS3+ACS, CS9+ACS, and ACS groups were exposed at 10°C for 24 h on d 43. Subsequently, lung tissues were collected to perform histopathological examination and measurement of relevant indexes. The results showed that lung tissues in CS9+ACS and ACS groups exhibited increased inflammatory cell infiltrates and collagen deposition compared to the CON group, while this pathological phenomenon was less pronounced in the CS3+ACS group. Compared to CON group, H2O2 and MDA contents were increased, and the activities of antioxidant enzymes (CAT, SOD, GPx, T-AOC) were reduced in CS9+ACS and ACS group (P < 0.05); mRNA and protein levels of inhibitor of NF-κB, Smad7, matrix metallopeptidase (MMP)-2, MMP9, and antioxidant-related genes were downregulated, whereas mRNA and protein levels of genes related to NF-κB/NLRP3 pathway-regulated inflammation and TGF-ß1/Smad pathway-regulated fibrosis were upregulated in cold-stressed broilers (P < 0.05). mRNA levels of heme oxygenase-1, NAD(P)H quinone oxidoreductase-1, and MMP9 were increased in CS3+ACS group (P < 0.05). Moreover, the expression of most antioxidant-related genes was increased, and that of inflammation- and fibrosis-related genes was reduced in CS3+ACS group (P < 0.05). Therefore, cold stress caused oxidative stress and inflammation, leading to pulmonary fibrosis in broilers, whereas intermittent mild cold stimulation at 3°C below normal rearing temperature alleviated fibrosis by inhibiting the TGF-ß1/Smad pathway modulated by the Nrf2/HO-1 and NF-κB/NLRP3 signaling pathway. This study suggests that intermittent mild cold stimulation can be a potential strategy to reduce ACS-induced lung damage in broilers.

Effect of participation of typical clinical pharmacists in patient medication in ICUs with different approaches: An investigation and case analysis.

Purpose: To investigate and study the impact on patient recovery of pharmacists' participation in the medication guidance and intervention of patients in intensive care units (ICUs). Patients and methods: We analyzed the drug use and typical cases of patients in the ICU of our hospital during clinical pharmacists' consultations or active monitoring from July 2019 to December 2020. This study included a total of 292 cases, which were distributed in the following eight areas: drug adjustment based on patients with hepatic and renal insufficiency,optimisation of treatment regimens based on drug interaction, identification and intervention based on adverse drug reactions, selection of blood purification methods based on drug intoxication, infusion access adjustment based on drug compatibility, drug adjustment based on genetic testing, antibiotic dose adjustment based on pharmacokinetics/pharmacodynamics (PK/PD) and others. The main observation indexes included consultation opinion efficiency rates and acceptance rates. The acceptance rate is calculated according to the acceptance of the clinical pharmacist's opinion by the competent doctor (fully accepted, partially accepted, not accepted). Calculate the efficiency rate according to the effect of the intervention measures. Definition of effectiveness: improvement of therapeutic effect of drugs; Avoid the occurrence of potential adverse drug reactions; Avoid the occurrence of potential drug compatibility reaction (for example, adjust the infusion sequence to avoid turbidity and sedimentation in the infusion pathway). Results: The results showed that clinical pharmacists participated in 292 cases of consultation or active monitoring of patients in the hospital's ICU based mainly on specific patient medications, drug interactions, adverse drug reactions, blood purification therapy, drug compatibility/venous infusion pathways, blood drug concentrations/drug-gene monitoring, drug PK/PD, etc. The doctor in charge acceptance rate of the consultation advice was 88.46% (completely accepted by 59.3%, partially accepted by 30.8%), and the effective rate of the consultation was 80.2%. Conclusion: Based on different purposes of intervention, the acceptance rate and efficiency rate were different. The efficiency rate with complete acceptance was significantly higher than that with partial acceptance or non-acceptance. The intervention opinions proposed by a comprehensive team in which pharmacists participate are of great help to patients and can reduce adverse reactions and medication risks. The higher the acceptance rate of their opinions, the higher the effective rate.

Impact of vaccination against COVID-19 on the outcomes of in vitro fertilization-embryo transfer: a retrospective cohort study.

BACKGROUND: Vaccination against coronavirus disease 2019 (COVID-19) has become the primary approach in the fight against the spread of COVID-19. Studies have shown that vaccination against COVID-19 has adverse effects, particularly on human reproductive health, despite the fact that vaccination rates are still on the rise. However, few studies have reported whether vaccination affects the outcome of in vitro fertilization-embryo transfer (IVF-ET) or not. In this study, we compared the outcome of IVF-ET and the development of follicles and embryos between vaccinated and unvaccinated groups. METHODS: A single-center retrospective cohort study of 10,541 in vitro fertilization (IVF) cycles was conducted from June 2020 to August 2021. 835 IVF cycles with a history of vaccination against COVID-19 and 1670 IVF cycles that served as negative controls were selected and analyzed utilizing the Matchlt package of R software ( http://www.R-project.org/ ) and the nearest neighbor matching algorithm for propensity-matched analysis at a 1:2 ratio. RESULTS: The number of oocytes collected in the vaccinated group and the unvaccinated group were 8.00 (0, 40.00) and 9.00 (0, 77.00) ( P  = 0.073) and the good-quality embryo rates of the two groups were 0.56±0.32 and 0.56±0.31 averagely ( P  = 0.964). Clinical pregnancy rates for the vaccinated group and unvaccinated group were 42.4% (155/366) and 40.2% (328/816) ( P  = 0.486) and biochemical pregnancy rates were 7.1% (26/366) and 8.7% (71/816) ( P  = 0.355). Two other factors were analyzed in this study; vaccination among different genders and different types (inactivated vaccine or recombinant adenovirus vaccine) showed no statistically significant effect on the above outcomes. CONCLUSIONS: In our findings, vaccination against COVID-19 showed no statistically significant effect on the outcomes of IVF-ET and the development of follicles and embryos, nor did the gender of the vaccinated person or the formulation of vaccines show significant effects.

Clinical Features of Severe Ovarian Hyperstimulation Syndrome with Hydrothorax.

PROBLEM: Does the presence of hydrothorax suggest that severe ovarian hyperstimulation syndrome (OHSS) is associated with more severe conditions and worse pregnancy outcomes? METHOD OF STUDY: The clinical data for 868 hospital patients with severe OHSS following IVF-ET at Peking University Third Hospital between 1 January 2016 and 21 July 2021 were retrospectively analysed. The patients were divided into two groups, the ascites alone group (n = 417) and the ascites combined with hydrothorax group (n = 451), to investigate the clinical features and pregnancy outcomes of patients with severe ovarian hyperstimulation syndrome (OHSS) combined with hydrothorax plus ascites. RESULTS: The clinical data for 868 hospital patients with severe OHSS following IVF-ET were included. A total of 51.96% of patients with severe OHSS had hydrothorax plus ascites, mainly bilateral and moderate hydrothorax. Most cases with hydrothorax could be monitored and observed, and only 2.66% of the cases required thoracentesis and pleural drainage. Clinically, the time to visit due to worsening symptoms was longer; the hospital stay was shorter; and the OHSS-related laboratory tests, such as white blood cells (WBC), haematocrit (HCT), and ovarian diameter, were less severe in the ascites combined with hydrothorax group than in the ascites alone group. For live-birth outcomes of IVF-ET, the presence and the volume of hydrothorax were not independent risk factors, while the late onset of OHSS (odds ratio [OR]: 0.857 95% confidence interval [CI]: 0.795, 0.925) and a history of foetal reduction (OR: 13.796 95% CI: 1.808, 105.288) were independent protective factors for live birth. CONCLUSIONS: Patients with severe OHSS combined with hydrothorax plus ascites have less severe clinical manifestations and laboratory tests than those with ascites alone. The presence and the volume of hydrothorax are unrelated to live-birth outcomes following in vitro fertilization and embryo transfer (IVF-ET).

Appropriate cold stimulation changes energy distribution to improve stress resistance in broilers.

Appropriate cold stimulation can improve stress resistance in broilers and alleviate the adverse impacts of a cold environment. To investigate the effects of intermittent mild cold stimulation (IMCS) on energy distribution in the livers of broilers, 96 healthy 1-d-old Ross-308 male broilers were randomly divided into the control group (CC) and the cold stimulation group (H5). The CC group was raised at a normal thermal temperature, i.e., 35 °C until 3 d, after which the temperature was dropped gradually by 0.5 °C/d until 20 °C at 33 d. This temperature was maintained until 49 d. The H5 group was raised at the same temperature as the CC group until 14 d (35 to 29.5 °C) and at 3 °C below the temperature of the CC group starting at 0930 hours for 5 h every other day from 15 to 35 d (26 to 17°C). The temperature was returned to 20 °C at 36 d and maintained until 49 d. At 50 d, all broilers were subjected to acute cold stress (ACS) at 10 °C for 6 and 12 h. We found that IMCS had positive effects on production performance. Using transcriptome sequencing of the broiler livers, 327 differentially expressed genes (DEG) were identified, and highly enriched in fatty acid biosynthesis, fatty acid degradation, and the pyruvate metabolism pathway. When compared to the CC group, the mRNA levels of ACAA1, ACAT2, ACSL1, CPT1A, LDHB, and PCK1 in the H5 group were increased at 22 d (P < 0.05). The LDHB mRNA level was upregulated in the H5 group at 29 d compared to the CC group (P < 0.05). After 21 d of IMCS (at 36 d), the mRNA expression levels of ACAT2 and PCK1 were found to be significantly increased in the H5 group compared to the CC group (P < 0.05). Seven days after the IMCS had ended (at 43 d), the mRNA levels of ACAA1, ACAT2, and LDHB in the H5 group were higher than in the CC group (P < 0.05). The mRNA levels of heat shock protein (HSP) 70, HSP90, and HSP110 in the H5 group were higher than in the CC group after 6 h of ACS (P < 0.05). The protein levels of HSP70 and HSP90 in the H5 group were downregulated after 12 h of ACS, compared to the CC group (P < 0.05). These results indicated that IMCS at 3 °C lower than the normal temperature could improve energy metabolism and stress resistance in the livers of broilers, alleviate the damage of short-term ACS on broilers, help broilers adapt to the low temperature, and maintain stable of energy metabolism in the body.

Cold stimulation has a great impact on broilers. Excessive cold stimulation can lead to damage, while intermittent mild cold stimulation (IMCS) can make broilers adapt to the cold environment. Low temperature will make the body produce lots of heat to maintain metabolic stability. The liver controls the energy metabolism, and the avian livers are the main organ regulating lipid metabolism. In this study, the broilers of different ages were subjected to cold stimulation training and then acute cold stress (ACS). We found that IMCS had positive effects on production performance. Through transcriptome sequencing, we found that the differentially expressed genes were highly enriched in the energy metabolism pathway, and the expression levels of the most key genes and heat shock proteins were upregulated. The stress resistance was also enhanced, which could alleviate the damage of short-term ACS to the body. The broilers gradually adapted to the low-temperature environment and finally established cold adaptation. The findings of this work will be helpful to the development of animal husbandry in cold regions and improve animal welfare.

Influencing of serum inflammatory factors on IVF/ICSI outcomes among PCOS patients with different BMI.

Introduction: Overweight and obese are important factors leading to the occurrence of long-term complications in women with polycystic ovary syndrome (PCOS). There has been controversy over whether dissatisfaction with pregnancy outcomes in PCOS patients is influenced by chronic inflammatory status or obesity. This retrospective study analyzed the levels of inflammatory factors in PCOS patients with different body mass index (BMI) groups and effective predictors of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancy outcomes. Methods: There were 273 women with PCOS diagnosed who completed serum inflammatory factors test between January 2017 and June 2022 were selected. The data of 7,649 infertility PCOS patients who received their first IVF/ICSI treatment in the Reproductive Center of Peking University Third Hospital during the period of the study were collected. Finally, 92 PCOS patients were included in the high BMI group, while 97 patients were included in the normal BMI group. Baseline characteristics were collected and the pregnancy outcomes were compared among the two groups. Then, serum inflammatory factors' effect on IVF/ICSI pregnancy outcomes were analyzed with age, anti-Mullerian Hormone (AMH) and BMI adjusted. Results: PCOS patients in the high BMI group significantly had a lower number of oocytes retrieved and good quality embryos. The high BMI group PCOS patients had higher levels of IL-6 and lower cumulative clinical pregnancy and live birth rates. The level of GM-CSF was higher in the first cycle transfer and cumulative miscarriage group. High TNF-α was negatively correlated with the first transfer cycle and cumulative clinical pregnancy rates after age, AMH and high BMI adjusted. In addition, the cumulative live birth rate was negatively correlated with high IL-6, but the first cycle transfer and cumulative live birth rates were positively correlated with high IL-1ß. Discussion: For PCOS patients, in addition to BMI, attention should also be paid to inflammatory indicators. High levels of TNF-α and IL-6 were negatively correlated with pregnancy outcomes, but high IL-1ß was positively correlated with live birth rates among PCOS patients. The level of GM-CSF was higher in miscarriage PCOS patients.

Altered hierarchical organization between empathy and gambling networks in disordered gamblers.

Background: Despite the demonstrated association between empathy and gambling at the behavioral level, limited neuroimaging research on empathy and gambling disorder (GD) has been conducted. Whether and how the brain network of empathy and that of gambling interact in disordered gamblers has not been investigated. This study aimed to address this research gap by examining the hierarchical organizational patterns, in which the differences of causal interactions of these networks between disordered gamblers and healthy controls were revealed. Methods: Resting-state functional magnetic resonance imaging (fMRI) data of 32 disordered gamblers and 56 healthy controls were included in the formal analysis. Dynamic causal modeling was used to examine the effective connectivity within and between empathy and gambling networks among all participants. Results: All participants showed significant effective connectivity within and between empathy and gambling networks. However, compared with healthy controls, disordered gamblers displayed more excitatory effective connectivity within the gambling network, the tendency to display more excitatory effective connectivity from the empathy network to the gambling network, and reduced inhibitory effective connectivity from the gambling network to the empathy network. Conclusion: The exploratory study was the first to examine the effective connectivity within and between empathy and gambling networks among disordered gamblers and healthy controls. These results provided insights into the causal relationship between empathy and gambling from the neuroscientific perspective and further confirmed that disordered gamblers show altered effective connectivity within and between these two brain networks, which may be considered to be a potential neural index for GD identification. In addition, the altered interactions between empathy and gambling networks may also indicate the potential targets for the neuro-stimulation intervention approach (e.g., transcranial magnetic stimulation).

Correlations between omega-3 fatty acids and inflammatory/glial abnormalities: the involvement of the membrane and neurotransmitter dysfunction in schizophrenia.

Introduction: Macrophages or T-lymphocytes triggered inflammation and, consequently, activated glial cells may contribute to neuroinflammation and neurotransmitter dysfunction in schizophrenia (SZ), while omega(n)-3 polyunsaturated fatty acids (PUFAs) can attenuate some SZ symptoms through anti-inflammatory effects. However, the correlations between macrophage/T-lymphocyte-produced cytokines and glia phenotypes, between inflammatory status and PUFAs composition, between cytokines and neurotransmitter function, and between n-3 PUFAs and neurotransmitter abnormality in SZ are unclear. Methods: Changes in T-helper (h) patterns, peripheral macrophage/glial markers, PUFAs profile, membrane fluidity, and neurotransmitter functions were evaluated in SZ patients (n = 50) and healthy controls (n = 30) using ELISA, gas chromatography, fluorescence anisotropy techniques, and HPLC, respectively. Results: Compared to the control, blood lymphocyte proliferation, the concentration of macrophage/microglia phenotype M1 markers, including cytokines IL-1ß, TNF-α (Th1) and IL-6 (Th2), and astrocyte phenotype A1 marker S100ß was significantly increased, while IL-17 and n-3 PUFAs contents, n-3/n-6 ratio, and membrane fluidity (FLU) were significantly decreased in SZ. Moreover, increased DA and HVA, decreased 5-HT and NE, and their metabolites appeared in SZ. Moreover, negative correlations between IL-6 and A2 marker Brain-Derived Neurotrophic Factor (BDNF) or n-3 PUFAs EPA and between IL-1ß and FLU or 5HIAA, while positive correlations between EPA and 5-HIAA and between FLU and DHA were found in SZ. Discussion: These findings showed (1) no clear Th pattern, but pro-inflammatory-dominant immunity occurred; (2) the pro-inflammatory pattern may result in the activated microglia M1 and astrocyte A1 phenotype; and (3) increased pro-inflammatory cytokines were related to decreased n-3 PUFA and decreased membrane fluidity and dysfunctional neurotransmitter systems in SZ.