Genome-wide Analyses of Chromatin State in Human Mast Cells Reveal Molecular Drivers and Mediators of Allergic and Inflammatory Diseases.

Mast cells (MCs) are versatile immune cells capable of rapidly responding to a diverse range of extracellular cues. Here, we mapped the genomic and transcriptomic changes in human MCs upon diverse stimuli. Our analyses revealed broad H3K4me3 domains and enhancers associated with activation. Notably, the rise of intracellular calcium concentration upon immunoglobulin E (IgE)-mediated crosslinking of the high-affinity IgE receptor (FcεRI) resulted in genome-wide reorganization of the chromatin landscape and was associated with a specific chromatin signature, which we term Ca2+-dependent open chromatin (COC) domains. Examination of differentially expressed genes revealed potential effectors of MC function, and we provide evidence for fibrinogen-like protein 2 (FGL2) as an MC mediator with potential relevance in chronic spontaneous urticaria. Disease-associated single-nucleotide polymorphisms mapped onto cis-regulatory regions of human MCs suggest that MC function may impact a broad range of pathologies. The datasets presented here constitute a resource for the further study of MC function.

Self-powered stable high-performance UV-Vis-NIR broadband photodetector based on PVP-Cobalt@Carbon nanofibers/n-GaAs heterojunction.

The self-powered PVP-Co@C nanofibers/n-GaAs heterojunction photodetector (HJPD) was fabricated by electrospinning of the nanofibers onto GaAs. An excellent rectification ratio of 6.60 × 106was obtained fromI-Vmeasurements of the device in the dark. TheI-Vmeasurements of the fabricated device under 365 nm, 395 nm and 850 nm lights, as well asI-Vmeasurements in visible light depending on the light intensity, were performed. The HJPD demonstrated excellent photodetection performance in terms of a good responsivity of âˆ¼225 mA W-1(at -1.72 V) and at zero bias, an impressive detectivity of 6.28 × 1012Jones, and a high on/off ratio of 8.38 × 105, all at 365 nm wavelength. In addition, the maximum external quantum efficiency and NPDR values were 3495% (V = -1.72 V) and 2.60 × 1010W-1(V= 0.0 V), respectively, while the minimum NEP value was ∼10-14W.Hz-1/2for 365 nm atV= 0.V volts. The HJPD also exhibited good long-term stability in air after 30 d without any encapsulation.

Impact of continuity of care on older adults diagnosed with mental and behavioural disorders at risk of death due to intentional self-harm: a retrospective Korean cohort study.

OBJECTIVES: The aim of this study was to evaluate the impact of continuity of care on older adults diagnosed with mental and behavioural disorders who are at risk of death due to intentional self-harm. STUDY DESIGN: This was a retrospective cohort study. METHODS: Data from the Korean National Health Insurance Service-Elderly Cohort Database (2002-2013) were used. A total of 53,980 patients who had visited the outpatient clinic three or more times within the year following the initial diagnosis of mental and behavioural disorders were included. A generalised estimating equation model was generated to examine the impact of continuity of care (CoC) on the risk of death due to intentional self-harm among older adults with mental illnesses. RESULTS: The risk of death due to intentional self-harm was significantly higher in those with poor CoC for mental and behavioural disorders than in those with good CoC. The risk ratio, adjusting for all covariates, was larger for the Usual Provider of Care index (adjusted risk ratio [aRR]: 1.63, 95% confidence interval [CI]: 1.25-2.12) than for the CoC index (aRR: 1.50, 95% CI: 1.18-1.90), indicating a stronger association with the concentration of contact with the most frequently visited provider. CONCLUSIONS: Poor CoC among Korean older adults diagnosed with mental and behavioural disorders was identified as a significant risk factor for death due to intentional self-harm. The results of this study highlight the need for interventions that can prevent suicidal behaviour in older adults, such as institutionalising the usual providers of mental health care for older adults.

Health benefits of combined oral contraceptives - a narrative review.

PURPOSE: This review presents an update of the non-contraceptive health benefits of the combined oral contraceptive pill. METHODS: We conducted a literature search for (review) articles that discussed the health benefits of combined oral contraceptives (COCs), in the period from 1980 to 2023. RESULTS: We identified 21 subjective and/or objective health benefits of COCs related to (i) the reproductive tract, (ii) non-gynaecological benign disorders and (iii) malignancies. Reproductive tract benefits are related to menstrual bleeding(including anaemia and toxic shock syndrome), dysmenorrhoea, migraine, premenstrual syndrome (PMS), ovarian cysts, Polycystic Ovary Syndrome (PCOS), androgen related symptoms, ectopic pregnancy, hypoestrogenism, endometriosis and adenomyosis, uterine fibroids and pelvic inflammatory disease (PID). Non-gynaecological benefits are related to benign breast disease, osteoporosis, rheumatoid arthritis, multiple sclerosis, asthma and porphyria. Health benefits of COCs related to cancer are lower risks of endometrial cancer, ovarian cancer and colorectal cancer. CONCLUSIONS: The use of combined oral contraceptives is accompanied with a range of health benefits, to be balanced against its side-effects and risks. Several health benefits of COCs are a reason for non-contraceptive COC prescription.

A "Win-Win" Strategy to Modify Co/C Foam with Carbon Microspheres for Enhanced Dielectric Loss and Microwave Absorption Characteristics.

3D carbon foams have demonstrated their superiority in the field of microwave absorption recently, but the preparation processes of traditional graphene foams are complicated, while some novel carbon foams usually suffer from inadequate dielectric property. Herein, a simple "win-win" strategy is demonstrated to synchronously realize the construction of 3D Co/C foam and its surface decoration with carbon microspheres. Therein, the host Co/C foams and guest carbon microspheres interact with each other, resulting in the improvement of the dispersity of carbon microspheres and Co nanoparticles. The bilaterally synergistic effect can effectively enhance the interfacial polarization and conductive loss of these obtained samples. Electromagnetic analysis reveals that the optimized sample with moderate carbon microsphere content (about 33.5 wt%) displays a widened maximum effective absorption bandwidth of 5.2 GHz and a consolidated reflection loss intensity of -67.6 dB. Besides, the microwave absorption enhancement mechanisms are investigated and discussed in detail. It is believed that this work provides valuable ideas for the development of 3D-foam-based microwave absorbing materials for practical applications.

Construction of 1D Heterogeneous Co/C@Ag Nws With Tunable Electromagnetic Wave Absorption And Shielding Performance.

In this study, silver nanowires (Ag NWs) are synthesized at first, and then the 1D heterogeneous Co/C@Ag NWs with a kebab- and popsicle-like microstructures are constructed by in situ growth ZIF-67 on Ag NWs combined with calcination. Results show that the EM wave prevention performance of composites depends on the loading of Co/C particles threaded on the Ag NWs. The popsicle-like structure with high Co/C loading gives Co/C@Ag NWs excellent EM wave absorption performance, which achieved a minimum reflection loss (RLmin ) of -44.5 dB with a low filling of 30 wt.% in paraffin; while the kebab-like structure with low Co/C loading shows good electromagnetic interference (EMI) shielding effectiveness (SET ) of 30.2 dB at the same filler ratio. The enhanced EM wave absorption performance is attributed to the synergy of multiple energy dissipation mechanisms including dielectric loss, magnetic loss, polarization loss, eddy-current loss, multiple reflection loss, as well as proper impedance matching; the good EMI shielding performance is mainly due to the conduction loss brought by the Ag NWs with ultrahigh conductivity. This work provides a reference for the design of electromagnetic wave prevention material with tuned absorption and shielding performance.

Minimized microbial contamination rate in conventional IVF cycles after modifications of cumulus-oocyte complex handling.

RESEARCH QUESTION: Could the microbial contamination rate of oocytes and embryos in conventional IVF cycles be further reduced by modifying the handling procedures of cumulus-oocyte complexes (COC)? DESIGN: Two modifications were applied to COC handling procedures. First, a mark was made on the outer wall of the 10-cm Petri dish to indicate the site from which the follicular fluid was poured out during the oocyte retrieval process (modified handling 1) since May 2018. Second, a modified way of pipetting during denuding (modified handling 2) has been adopted since June 2019. The microbial contamination rates before and after each modification were compared. The clinic outcomes of patients with a history or at a high risk of microbial contamination were reported after incorporating the two modifications of COC handling. RESULTS: After the first modification was implemented, the contamination rate was remarkably reduced from 0.37% (9/2436) to 0.18% (2/1089). After adding the second modification, no new contamination occurred in the subsequent 3178 conventional IVF cycles (P = 0.001). Moreover, no contamination was noted in patients with a history of microbial contamination or persistent candidal vaginitis during conventional IVF after modifications of COC handling. CONCLUSIONS: Modifying the handling procedures of COC can minimize the microbial contamination rate in conventional IVF cycles. Contamination risk directly derived from the urogenital tracts might be less likely than what we thought to be with current IVF techniques.

Mutagenic impurities in pharmaceuticals: A critical assessment of the cohort of concern with a focus on N-nitrosamines.

The TTC (Threshold of Toxicological Concern; set at 1.5 µg/day for pharmaceuticals) defines an acceptable patient intake for any unstudied chemical posing a negligible risk of carcinogenicity or other toxic effects. A group of high potency mutagenic carcinogens, defined solely by the presence of particular structural alerts, are referred to as the "cohort of concern" (CoC); aflatoxin-like-, N-nitroso-, and alkyl-azoxy compounds are considered to pose a significant carcinogenic risk at intakes below the TTC. Kroes et al. (2004) derived values for the TTC and CoC in the context of food components, employing a non-transparent dataset never placed in the public domain. Using a reconstructed all-carcinogen dataset from relevant publications, it is now clear that there are exceptions for all three CoC structural classes. N-Nitrosamines represent 62% of the N-nitroso class in the reconstructed dataset. Employing a contemporary dataset, 20% are negative in rodent carcinogenicity bioassays with less than 50% of all N-nitrosamines estimated to fall into the highest risk category. It is recommended that CoC nitrosamines are identified by compound-specific data rather than structural alerts. Thus, it should be possible to distinguish CoC from non-CoC N-nitrosamines in the context of mutagenic impurities described in ICH M7 (R1).

Selection of Rattus norvegicus cumulus-oocyte complex for vitrification by brilliant cresyl blue.

The influence of the method of evaluating developmentally competent oocytes on their viability after cryopreservation still needs to be better understood. The objective of this study was to determine the cleavage and embryo developmental rates after parthenogenetic activation of cumulus-oocyte complexes (COCs) selected by different concentrations of brilliant cresyl blue (BCB) and cryopreservation. In the first experiment, COCs were separated into groups and incubated for 1 h in medium containing BCB (13 µM, 16 µM, or 20 µM). The control group was not exposed to BCB staining. In the second experiment, COCs were divided into four groups: 13 µM BCB(+), 13 µM BCB(-), fresh control (selected by morphologic observation and immediately in vitro matured) and vitrified control (selected by morphologic evaluation, vitrified, and in vitro matured). In the first experiment, the 13 µM BCB group displayed greater development rates at the morula stage (65.45%, 36/55) when compared with the other groups. In the second experiment, cleavage (47.05%, 72/153) and morula development (33.55%, 51/153) of the control group of fresh COCs were increased compared with the other groups. However, when comparing morula rates between vitrified COC control and BCB(+) groups, the BCB(+) group had better results (19.23%, 5/26 and 64.7%, 11/17, respectively). Our best result in rat COC selection by BCB staining was obtained using a concentration of 13 µM. This selection could be a valuable tool to improve vitrification outcomes, as observed by the BCB(+) group that demonstrated better results compared with the vitrified COC control.

Luteinizing hormone secretion, ovulatory capacity, and oocyte quality in peripubertal Gir heifers.

Induction of puberty in cattle breeds that attain puberty in later stages, such as Gir, allows the earlier beginning of reproductive life and it might increase oocyte quality. Here, the ovulatory capacity of prepuberal Gir heifers was studied and its relationship to follicular growth, luteinizing hormone (LH) secretion and oocyte quality was evaluated. Peripubertal Gir heifers were treated with a progesterone-based protocol and according to ovulatory response were separated into groups: not-ovulated (N-OV) and ovulated (OV). Serial blood samples were taken 24 h after estradiol treatment on day 12 to evaluate LH secretion. Cumulus-oocyte complexes (COCs) were collected using ovum pick-up and assessed for brilliant cresyl blue (BCB) staining rate, IVF-grade oocytes rate, and mean oocyte diameter, in comparison with cow oocytes. Gene expression of developmental competence markers (ZAR1, MATER, and IGF2R) was also analyzed. The largest follicle diameters were similar between N-OV and OV groups on the day of estradiol treatment (d12) and the next day and decreased (P = 0.04) in the N-OV group thereafter. LH pulse secretion was different between groups (N-OV = 3.61 ± 0.34 vs OV = 2.83 ± 0.21 ng/ ml; P = 0.04). COC assessment showed that the number of recovered oocytes, BCB+ rate, IVF-grade oocytes and oocyte size was similar (P > 0.05) among groups, resembling adult cow patterns. ZAR1, MATER and IGF2R gene expression in oocytes were also similar (P > 0.05) in N-OV and OV groups. In conclusion, our results demonstrate a lower LH secretion profile in peripubertal Gir heifers prone to ovulate after induction protocol, and that oocyte quality is not affected on a short-term basis by ovulation itself.

Extracellular Vesicles Isolation from Large Volume Samples Using a Polydimethylsiloxane-Free Microfluidic Device.

Extracellular vesicles (EV) have many attributes important for biomedicine; however, current EV isolation methods require long multi-step protocols that generally involve bulky equipment that cannot be easily translated to clinics. Our aim was to design a new cyclic olefin copolymer-off-stoichiometry thiol-ene (COC-OSTE) asymmetric flow field fractionation microfluidic device that could isolate EV from high-volume samples in a simple and efficient manner. We tested the device with large volumes of urine and conditioned cell media samples, and compared it with the two most commonly used EV isolation methods. Our device was able to separate particles by size and buoyancy, and the attained size distribution was significantly smaller than other methods. This would allow for targeting EV size fractions of interest in the future. However, the results were sample dependent, with some samples showing significant improvement over the current EV separation methods. We present a novel design for a COC-OSTE microfluidic device, based on bifurcating asymmetric flow field-flow fractionation (A4F) technology, which is able to isolate EV from large volume samples in a simple, continuous-flow manner. Its potential to be mass-manufactured increases the chances of implementing EV isolation in a clinical or industry-friendly setting, which requires high repeatability and throughput.

High Pseudocapacitance-Driven CoC2 O4 Electrodes Exhibiting Superior Electrochemical Kinetics and Reversible Capacities for Lithium-Ion and Lithium-Sulfur Batteries.

In this study, cuboid-like anhydrous CoC2 O4 particles (CoC2 O4 -HK) are synthesized through a potassium citrate-assisted hydrothermal method, which possess well-crystallized structure for fast Li+ transportation and efficient Li+ intercalation pseudocapacitive behaviors. When being used in lithium-ion batteries, the as-prepared CoC2 O4 -HK delivers a high reversible capacity (≈1360 mAh g-1 at 0.1 A g-1 ), good rate capability (≈650 mAh g-1 at 5 A g-1 ) and outstanding cycling stability (835 mAh g-1 after 1000 cycles at 1 A g-1 ). Characterizations illustrate that the Li+ -intercalation pseudocapacitance dominates the charge storage of CoC2 O4 -HK electrode, together with the reversible reaction of CoC2 O4 +2Li+ +2e- →Co+Li2 C2 O4 on discharging and charging. In addition, CoC2 O4 -HK particles are also used together with carbon-sulfur composite materials as the electrocatalysts for lithium-sulfur (Li-S) battery, which displays a gratifying sulfur electrochemistry with a high reversibility of 1021.5 mAh g-1 at 2 C and a low decay rate of 0.079% per cycle after 500 cycles. The density functional theory (DFT) calculations show that CoC2 O4 /C can regulate the adsorption-activation of reaction intermediates and therefore boost the catalytic conversion of polysulfides. Therefore, this work presents a new prospect of applying CoC2 O4 as the high-performance electrode materials for rechargeable Li-ion and Li-S batteries.

Transcriptional profile of cumulus associated GJA1, PTX3, PRSS35, and SERPINE2 genes with oocytes and embryonic development in water buffalo.

BACKGROUND: In the present study, the potential of different groups of cumulus-oocyte complexes (COC's) for in vitro maturation (IVM) and embryonic development was assessed in two groups of COC's of water buffalo. Further, the expression pattern of cumulus-associated GJA1, PTX3, PRSS35, and SERPINE2 genes and their effects on embryonic development was analyzed. Slaughterhouse-derived buffalo COC's were graded into groups A and B. An equal number of 410 COC's were taken in both groups. IVM was carried out using Slaughterhouse-derived buffalo epididymis. A remarkable degree of cumulus expansion was noticed in group A (92.68%) as compared to group B (81.25%) oocytes. On in vitro fertilization (IVF) and embryo culture, group A produced a significantly higher rate of cleavage and blastocyst (92.682 ± 0.7179% and 42.682 ± 0.9683%) as compared to group B (85.365 ± 0.7608% and 31.707 ± 0.9688%). Also, the transcriptional analysis of cumulus-associated genes revealed significantly higher expression in group A as compared to group B. RESULTS: It was revealed that oocytes having good cumulus mass had a higher developmental potential. Based on differential gene expression of cumulus-associated genes, different quality of COC's, and the resultant embryos after IVF, it was concluded that these genes could be used as a marker for predicting the developmental competence of the oocytes. CONCLUSION: We concluded that morphologically good quality of COC's had a higher developmental competence, and also the differential expressions of cumulus-associated genes in cumulus cells and embryos. So, we can conclude that these genes could be used as marker genes for predicting the developmental competence of buffalo's oocytes.

Understanding the High-Performance Anode Material of CoC2 O4 ⋠2 H2 O Microrods Wrapped by Reduced Graphene Oxide for Lithium-Ion and Sodium-Ion Batteries.

Metal oxalate has become a most promising candidate as an anode material for lithium-ion and sodium-ion batteries. However, capacity decrease owing to the volume expansion of the active material during cycling is a problem. Herein, a rod-like CoC2 O4 ⋅2 H2 O/rGO hybrid is fabricated through a novel multistep solvo/hydrothermal strategy. The structural characteristics of the CoC2 O4 ⋅2 H2 O microrod wrapped using rGO sheets not only inhibit the volume variation of the hybrid electrode during cycling, but also accelerate the transfer of electrons and ions in the 3 D graphene network, thereby improving the electrochemical properties of CoC2 O4 ⋅2 H2 O. The CoC2 O4 ⋅2 H2 O/rGO electrode delivers a specific capacity of 1011.5 mA h g-1 at 0.2 A g-1 after 200 cycles for lithium storage, and a high capacity of 221.1 mA h g-1 at 0.2 A g-1 after 100 cycles for sodium storage. Moreover, the full cell CoC2 O4 ⋅2 H2 O/rGO//LiCoO2 consisting of the CoC2 O4 ⋅2 H2 O/rGO anode and LiCoO2 cathode maintains 138.1 mA h g-1 after 200 cycles at 0.2 A g-1 and has superior long-cycle stability. In addition, in situ Raman spectroscopy and in situ and ex situ X-ray diffraction techniques provide a unique opportunity to understand fully the reaction mechanism of CoC2 O4 ⋅2 H2 O/rGO. This work also gives a new perspective and solid research basis for the application of metal oxalate materials in high-performance lithium-ion and sodium-ion batteries.

SPAM1/HYAL5 double deficiency in male mice leads to severe male subfertility caused by a cumulus-oocyte complex penetration defect.

The glycosylphosphatidylinositol-anchored sperm hyaluronidases (Hyals), sperm adhesion molecule 1 (SPAM1) and HYAL5, have long been believed to assist in sperm penetration through the cumulus-oocyte complex (COC), but their role in mammalian fertilization remains unclear. Previously, we have shown that mouse sperm devoid of either Spam1 or Hyal5 are still capable of penetrating the COC and that the loss of either Spam1 or Hyal5 alone does not cause male infertility in mice. In the present study, we found that Spam1/Hyal5 double knockout (dKO) mice produced significantly fewer offspring compared with wild-type (WT) mice, and this was due to defective COC dispersal. A comparative analysis between WT and Spam1/Hyal5 dKO epididymal sperm revealed that the absence of these 2 sperm Hyals resulted in a marked accumulation of sperm on the outside of the COC. This impaired sperm activity is likely due to the deficiency in the sperm Hyals, even though other somatic Hyals are expressed normally in the dKO mice. The fertilization ability of the Spam1/Hyal5 dKO sperm was restored by adding purified human sperm Hyal to the in vitro fertilization medium. Our results suggest that Hyal deficiency in sperm may be a significant risk factor for male sterility.-Park, S., Kim, Y.-H., Jeong, P.-S., Park, C., Lee, J.-W., Kim, J.-S., Wee, G., Song, B.-S., Park, B.-J., Kim, S.-H., Sim, B.-W., Kim, S.-U., Triggs-Raine, B., Baba, T., Lee, S.-R., Kim, E. SPAM1/HYAL5 double deficiency in male mice leads to severe male subfertility caused by a cumulus-oocyte complex penetration defect.

Near-infrared dye-labeled antibody COC183B2 enables detection of tiny metastatic ovarian cancer and optimizes fluorescence-guided surgery.

OBJECTIVE: We aimed to evaluate the ability of the fluorescent monoclonal antibody probe COC183B2-Cy7 (Cy7-conjugated COC183B2 antibody) to detect tiny metastatic lesions of ovarian cancer and thus guide precise tumor resection. METHODS: The expression of the tumor-associated antigen OC183B2 in lymph nodes and SKOV3-Luc cells was detected using immunohistochemistry and immunofluorescence. A subcutaneous mouse tumor model and an intraperitoneal ovarian cancer metastasis model were constructed using SKOV3-Luc cells. Near-infrared fluorescence (NIRF) imaging was performed to determine the imaging parameters and evaluate the ability of COC183B2-Cy7 to detect tiny metastatic lesions. RESULTS: OC183B2 was expressed in metastatic lymph nodes and SKOV3-Luc cells. NIRF imaging of the subcutaneous mouse tumor model showed that the tumor background ratio was significantly higher in the COC183B2-Cy7 group than in the control group at different time points postinjection. Biodistribution study showed that COC183B2-Cy7 did not accumulate in other organs. COC183B2-Cy7 can detect tiny metastatic lesions of ovarian cancer. The smallest intraperitoneal metastatic tumor detected by COC183B2-Cy7 was approximately 1 mm. CONCLUSIONS: COC183B2-Cy7 probe has relatively high specificity and sensitivity. Our study suggests that COC183B2-Cy7 probe is a promising diagnostic tool for the complete and accurate resection of malignant lesions in fluorescence-guided surgery.

Simplifying contraception requirements for iPLEDGE: A decision analysis.

BACKGROUND: For persons of childbearing potential prescribed isotretinoin, the iPLEDGE program requires use of 2 simultaneous methods of contraception or commitment to abstinence. OBJECTIVE: To model the relative effectiveness of a variety of contraception strategies for patients taking isotretinoin, including those that are acceptable according to iPLEDGE. METHODS: We performed a decision analysis modeling the estimated rate of pregnancy with various contraception strategies during a typical 6-month course of isotretinoin. RESULTS: Tier 1 contraception options (eg, subdermal hormonal implant, intrauterine devices) each had effectiveness of >99.5% alone. When combined with a secondary form of contraception, tier 2 contraception options (eg, depot medroxyprogesterone injections, combined oral contraceptives) each had effectiveness >99%. LIMITATIONS: Sensitivity analyses were conducted to evaluate the impact of uncertain parameters on the results. CONCLUSION: There may be opportunities to simplify iPLEDGE by recognizing the high effectiveness of tier 1 contraception options and increasing use of secondary forms of contraception among those using tier 2 contraception options as their primary form of contraception. Future studies are needed to understand the most effective strategies in clinical practice to prevent unintended pregnancy for patients taking isotretinoin to improve outcomes and provide patient-centered care.

Effectiveness and safety assessment of drospirenone/ethinyl estradiol tablet in treatment of PCOS patients: a single center, prospective, observational study.

BACKGROUND: To investigate the effectiveness and safety of 3 mg drospirenone and 20 µg ethinyl estradiol tablet (3 mg DRSP/20 µg EE) in the treatment of polycystic ovary syndrome (PCOS). METHODS: This single center, prospective observational study was conducted in 140 patients with PCOS. They were prescribed 3 mg DRSP/20 µg EE in a 24/4/ regimen for 3 months. Patients were instructed to take oral DRSP/EE tablets (once daily) on the 2nd day of menstruation, for 28 consecutive days for 1 cycle. After 3 months of treatment, anthropometric assessments along with variations in sex hormones related index, glucolipid metabolic index, changes in bilateral ovarian volume, as well as adverse effect of the combination were evaluated. RESULTS: When compared to baseline, body mass index (BMI, 22.07 ± 4.09 vs. 21.35 ± 3.22, p < 0.001) and waist hip ratio (WHR, 0.86 ± 0.07 vs. 0.854 ± 0.06, p = 0.026) decreased significantly after treatment. Sex-hormones such as luteinizing hormone (LH) (10.88 vs. 5.81 U/L), testosterone (T) (1.85 vs. 1.51 nmol/L) and free androgen index (FAI) (5.37 vs. 1.50) decreased significantly after treatment (p < 0.001). Follicular stimulating hormone (FSH) increased significantly at 3 months as compared to before treatment (5.13 vs. 5.42 U/L, p = 0.009). Plasma insulin (11.03 vs. 11.10 pmol/L), fasting (4.97 vs. 4.93 mmol/L) and 2 h-blood glucose levels (7.18 vs. 7.04 mmol/L) did not change when compared to baseline. Plasma triglycerides (TG, 1.32 vs. 1.65 mmol/L) significantly increased 3 months after treatment when compared to before treatment (p < 0.001). However, high density lipoprotein-cholesterol (HDL-C) levels increased significantly after treatment (1.41 vs. 1.57 mmol/L, p < 0.001). It was seen that, when compared to baseline, bilateral ovarian volume (left and right) was significantly lower after treatment (p < 0.05). It was seen that 81 patients reported no adverse reactions. Of the common discomforts reported, breast swelling and pain, gastrointestinal disorder and dizziness and headache were most frequent. CONCLUSIONS: Treatment of PCOS patients with3 mg DRSP/20 µg EE has shown beneficial hormonal and lipid profile along with considerable safety profile. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900022001, March 2019, retrospectively registered.

Evaluation of a novel ovarian cancer-specific fluorescent antibody probe for targeted near-infrared fluorescence imaging.

BACKGROUND: To meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance. METHODS: The expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96 h postinjection, and the biodistribution assays were performed using NIRF imaging. RESULTS: In 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs. CONCLUSIONS: COC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.

Live birth following a single oocyte fertilized with ICSI and embryo transfer on day 2: a case report.

In this report, we present a case of a couple who obtained a live birth with a single oocyte fertilized by intracytoplasmic sperm injection. The oocyte was collected at 36 h post trigger and was found to be at metaphase II when sperm injection was performed. At 18 h post injection, the oocyte was found to be fertilized with two clear pronuclei. The embryo divided and generated a four-cell embryo on day 2, which was replaced to the uterine cavity. Pregnancy test gave a positive ß-human chorionic gonadotropin result, the scan performed at 7 weeks, revealed the presence of one amniotic sac with fetal heartbeat. Healthy live birth was obtained after 39 weeks of gestation.