Therapeutic roles of platelet-rich plasma to restore female reproductive and endocrine dysfunction.

Millions of women worldwide are infertile due to gynecological disorders, including premature ovarian insufficiency, polycystic ovary syndrome, Asherman syndrome, endometrial atrophy, and fallopian tube obstruction. These conditions frequently lead to infertility and have a substantial impact on the quality of life of the affected couples, primarily because of their psychological implications and high financial costs. Recently, using platelets to stimulate cell proliferation and tissue differentiation has emerged as a promising approach in regenerative medicine. Platelet-rich plasma (PRP) shows considerable potential for promoting endometrial hypertrophy and follicle development, making it a promising therapeutic option for tissue repair or replacement. This review provides an overview of the recent advancements and underlying mechanisms of PRP therapy for various female reproductive diseases and presents new therapeutic options for addressing female infertility.

Efficacy and safety of oral ibrexafungerp in Chinese patients with vulvovaginal candidiasis: a phase III, randomized, double-blind study.

PURPOSE: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). METHODS: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. RESULTS: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. CONCLUSIONS: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CN REGISTRY NUMBER: CTR20220918.

Lactobacillus reuteri's multifaceted role in mitigating ionizing radiation-induced injury in Drosophila melanogaster.

The numerous beneficial probiotic properties of Lactobacillus reuteri (L. reuteri) include decreasing metabolic syndrome, preventing disorders linked to oxidative stress, improving gut flora imbalances, controlling immunological function, and extending life span. Exposure to ionizing radiation is closely associated with several disorders. We examined the protective and salvaging effects of L. reuteri on ionizing radiation-induced injury to the intestinal tract, reproductive system, and nervous system of Drosophila melanogaster. We also examined its effects on lifespan, antioxidant capacity, progeny development, and behavioral aspects to assess the interaction between L. reuteri and ionizing radiation-induced injury. The findings demonstrated that L. reuteri improved the median survival time following irradiation and greatly extended its lifespan. In addition, it raised SOD activity, reduced ROS levels in intestinal epithelial cells, and increased the quantity of intestinal stem cells. Furthermore, L. reuteri enhanced the adult male flies' capacity to move. It also successfully safeguarded the generations' growth and development. L. reuteri dramatically enhanced expression of the AMPKα gene and regulated expression of its pathway-related gene, mTOR, as well as the autophagy-related genes Atg1 and Atg5 in female Drosophila exposed to irradiation. Notably, no prior reports have been made on the possible effects of L. reuteri on injuries caused by irradiation. As a result, our research offers important new information regarding L. reuteri's possible role as a shield against ionizing radiation-induced injury.

NIR-II Ratiometric Fluorescence Probes Enable Precise Determination of the Metastatic Status of Sentinel Lymph Nodes.

Accurately determining the metastatic status of sentinel lymph nodes (SLNs) through noninvasive imaging with high imaging resolution and sensitivity is crucial for cancer therapy. Herein, we report a dual-tracer-based NIR-II ratiometric fluorescence nanoplatform combining targeted and nontargeted moieties to determine the metastatic status of SLNs through the recording of ratio signals. Ratiometric fluorescence imaging revealed approximately 2-fold increases in signals in tumor-draining SLNs compared to inflamed and normal SLNs. Additionally, inflamed SLNs were diagnosed by combining the ratio value with the enlarged size outputted by NIR-II fluorescence imaging. The metastatic status diagnostic results obtained through NIR-II ratiometric fluorescence signals were further confirmed by standard H&E staining, indicating that the ratiometric fluorescence strategy could achieve distant metastases detection. Furthermore, the superior imaging quality of ratiometric probes enables visualization of the detailed change in the lymphatic network accompanying tumor growth. Compared to clinically available and state-of-the-art NIR contrast agents, our dual-tracer-based NIR-II ratiometric fluorescence probes provide significantly improved performance, allowing for the quick assessment of lymphatic function and guiding the removal of tumor-infiltrating SLNs during cancer surgery.

Oteseconazole versus fluconazole for the treatment of severe vulvovaginal candidiasis: a multicenter, randomized, double-blinded, phase 3 trial.

Vulvovaginal candidiasis (VVC) is a common condition among women. Fluconazole remains the dominant treatment option for VVC. Oteseconazole is a highly selective inhibitor of fungal CYP51. This randomized, double-blinded, phase 3 trial was conducted to evaluate the efficacy and safety of oteseconazole compared with fluconazole in treating severe VVC. Female subjects presenting with vulvovaginal signs and symptoms score of ≥7 and positive Candida infection determined by potassium hydroxide test or Gram staining were randomly assigned to receive oteseconazole (600 mg on D1 and 450 mg on D2) or fluconazole (150 mg on D1 and D4) in a 1:1 ratio. The primary endpoint was the proportion of subjects achieving therapeutic cure [defined as achieving both clinical cure (absence of signs and symptoms of VVC) and mycological cure (negative culture of Candida species)] at D28. A total of 322 subjects were randomized and 321 subjects were treated. At D28, a statistically significantly higher proportion of subjects achieved therapeutic cure in the oteseconazole group than in the fluconazole group (66.88% vs 45.91%; P = 0.0002). Oteseconazole treatment resulted in an increased proportion of subjects achieving mycological cure (82.50% vs 59.12%; P < 0.0001) and clinical cure (71.25% vs 55.97%; P = 0.0046) compared with fluconazole. The incidence of treatment-emergent adverse events was similar between the two groups. No subjects discontinued study treatment or withdrew study due to adverse events. Oteseconazole showed statistically significant and clinically meaningful superiority over fluconazole for the treatment of severe VVC and was generally tolerated.

Causal relationship between female reproductive factors, sex hormones and uterine leiomyoma: a Mendelian randomization study.

RESEARCH QUESTION: Are the observed associations between female reproductive factors and sex hormones with the risk of uterine leiomyoma truly causal associations? DESIGN: The putative causal relationships between female reproductive factors and sex hormones with uterine leiomyoma were investigated using two-sample Mendelian randomization. Statistics on exposure-associated genetic variants were obtained from genome-wide association studies (GWAS). The uterine leiomyoma GWAS from the FinnGen and FibroGENE consortia were used as outcome data for discovery and replication analyses, respectively. Results were pooled by meta-analysis. Sensitivity analyses ensured robustness of the Mendelian randomization analysis. RESULTS: When FinnGen GWAS were used as outcome data, a causal relationship was found between age at menarche (OR 0.84, P < 0.0001), age at menopause (OR 1.08, P < 0.0001), number of live births (OR 0.25, P < 0.001) and total testosterone levels (OR 0.90, P < 0.001) with the risk of uterine leiomyoma. When FibroGENE GWAS were used as outcome data, Mendelian randomization results for age at menopause, the number of live births and total testosterone levels were replicated. In the meta-analysis, a later age at menopause (OR 1.08, P < 0.0001) was associated with an increased risk of uterine leiomyoma. A higher number of live births (OR 0.25, P < 0.0001) and higher total testosterone levels (OR 0.90, P < 0.0001) were associated with a decreased risk of uterine leiomyoma. CONCLUSIONS: A causal relationship between later age at menopause, lower number of live births and lower total testosterone levels with increased risk of uterine leiomyoma was found.

Genetically predicted serum testosterone and risk of gynecological disorders: a Mendelian randomization study.

Background: Testosterone plays a key role in women, but the associations of serum testosterone level with gynecological disorders risk are inconclusive in observational studies. Methods: We leveraged public genome-wide association studies to analyze the effects of four testosterone related exposure factors on nine gynecological diseases. Causal estimates were calculated by inverse variance-weighted (IVW), MR-Egger and weighted median methods. The heterogeneity test was performed on the obtained data through Cochrane's Q value, and the horizontal pleiotropy test was performed on the data through MR-Egger intercept and MR-PRESSO methods. "mRnd" online analysis tool was used to evaluate the statistical power of MR estimates. Results: The results showed that total testosterone and bioavailable testosterone were protective factors for ovarian cancer (odds ratio (OR) = 0.885, P = 0.012; OR = 0.871, P = 0.005) and endometriosis (OR = 0.805, P = 0.020; OR = 0.842, P = 0.028) but were risk factors for endometrial cancer (OR = 1.549, P < 0.001; OR = 1.499, P < 0.001) and polycystic ovary syndrome (PCOS) (OR = 1.606, P = 0.019; OR = 1.637, P = 0.017). dehydroepiandrosterone sulfate (DHEAS) is a protective factor against endometriosis (OR = 0.840, P = 0.016) and premature ovarian failure (POF) (OR = 0.461, P = 0.046) and a risk factor for endometrial cancer (OR= 1.788, P < 0.001) and PCOS (OR= 1.970, P = 0.014). sex hormone-binding globulin (SHBG) is a protective factor against endometrial cancer (OR = 0.823, P < 0.001) and PCOS (OR = 0.715, P = 0.031). Conclusion: Our analysis suggested causal associations between serum testosterone level and ovarian cancer, endometrial cancer, endometriosis, PCOS, POF.

Leukocyte telomere length is associated with increased risk of endometriosis: a bidirectional two-sample Mendelian randomization study.

Background: Endometriosis (EMs) is a common gynecological disorder. Observational studies on the relationship between leukocyte telomere length (LTL) and EMs have shown conflicting results. The purpose of this study was to evaluate the precise causal relationship between LTL and EMs using Mendelian randomization (MR) methodology. Methods: We employed MR to assess the causal relationship between LTL and EMs. Summary data from several large-scale genome-wide association studies (GWAS) were used for bidirectional two-sample MR analysis. Sensitivity analyses were conducted to ensure the robustness of our results. All analyses were also replicated in another completely independent EMs dataset. Results: Our MR analysis indicated that genetically predicted longer LTL increased the risk of EMs (IVW: discovery, OR=1.169, 95%CI: 1.059-1.290, p=0.002; validation, OR=1.302, 95%CI: 1.140-1.487, p=0.000), while EMs had no causal impact on LTL (IVW: discovery, OR=1.013, 95%CI: 1.000-1.027, p=0.056; IVW: validation, OR=1.005, 95%CI: 0.995-1.015, p=0.363). Causal estimates were supported by various calculation models (including MR-Egger, Weighted median, MR-PRESSO, and MR-RAPS). Heterogeneity and pleiotropy analyses also indicated robustness of the results. Conclusion: Our findings substantiate the idea that a genetically predicted longer LTL elevates the risk of EMs, with no influence of EMs on LTL risk. This research bolsters the causal link between LTL and EMs, overcoming the constraints of earlier observational studies. It implies that LTL may potentially function as a biomarker for EMs, opening up novel possibilities for EMs prevention and treatment.

Dye-Triplet-Sensitized Downshifting Nanoprobes with Ratiometric Dual-NIR-IIb Emission for Accurate In Vivo Detection.

Despite the emerging near-infrared-IIb (NIR-IIb, 1500-1700 nm) bioimaging significantly improving the in vivo penetration depth and resolution, quantitative detection with accuracy remains challenging due to its inhomogeneous fluorescence signal attenuation in biological tissue. Here, ratiometric dual-NIR-IIb in vivo detection with excitation wavelengths of 808 and 980 nm is presented using analyte-responsive dye-triplet-sensitized downshifting nanoprobes (DSNPs). NIR cyanine dye IR-808, a recognizer of biomarker hypochlorite (ClO-), is introduced to trigger a triplet energy transfer process from the dye to Er3+ ions of DSNPs under 808 nm excitation, facilitating the formation of an analyte-responsive 1525 nm NIR-IIb assay channel. Meanwhile, DSNPs also enable emitting intrinsic nonanalyte-dependent downshifting fluorescence at the same NIR-IIb window under 980 nm excitation, serving as a self-calibrated signal to alleviate the interference from the probe amount and depth. Due to the two detected emissions sharing identical light propagation and scattering, the ratiometric NIR-IIb signal is demonstrated to ignore the depth of penetration in biotissue. The arthritis lesions are distinguished from normal tissue using ratiometric probes, and the amount of ClO- can be accurately output by the established detection curves.

Three-Dimensional Histological Electrophoresis for High-Throughput Cancer Margin Detection in Multiple Types of Tumor Specimens.

Accurate identification of tumor margins during cancer surgeries relies on a rapid detection technique that can perform high-throughput detection of multiple suspected tumor lesions at the same time. Unfortunately, the conventional histopathological analysis of frozen tissue sections, which is considered the gold standard, often demonstrates considerable variability, especially in many regions without adequate access to trained pathologists. Therefore, there is a clinical need for a multitumor-suitable complementary tool that can accurately and high-throughput assess tumor margins in every direction within the surgically resected tissue. We herein describe a high-throughput three-dimensional (3D) histological electrophoresis device that uses tumor-specific proteins to identify and contour tumor margins intraoperatively. Testing on seven cell-line xenograft models and human cervical cancer models (representing five types of tissues) demonstrated the high-throughput detection utility of this approach. We anticipate that the 3D histological electrophoresis device will improve the accuracy and efficiency of diagnosing a wide range of cancers.

The promoting effect and mechanism of Nrf2 on cell metastasis in cervical cancer.

BACKGROUND: Cervical cancer (CC) has poor prognosis and high mortality rate for its metastasis during the disease progression. Epithelial-mesenchymal transition (EMT) and anoikis are initial and pivotal steps during the metastatic process. Although higher levels of Nrf2 are associated with aggressive tumor behaviors in cervical cancer, the detailed mechanism of Nrf2 in cervical cancer metastasis, especially EMT and anoikis, remains unclear. METHODS: Immunohistochemistry (IHC) was used to examine Nrf2 expression in CC. Wound healing assay and transwell analysis were used to evaluate the migration ability of CC cells. Western blot, qTR-PCR and immunofluorescent staining were used to verify the expression level of Nrf2, the EMT associated markers and anoikis associated proteins. Flow cytometry assays and cell counting were used to detect the apoptosis of cervical cancer cells. The lung and lymph node metastatic mouse model were established for studies in vivo. The interaction between Nrf2 and Snail1 was confirmed by rescue-of-function assay. RESULTS: When compared with cervical cancer patients without lymph node metastasis, Nrf2 was highly expressed in patients with lymph node metastasis. And Nrf2 was proved to enhance the migration ability of HeLa and SiHa cells. In addition, Nrf2 was positively correlated with EMT processes and negatively associated with anoikis in cervical cancer. In vivo, a xenograft assay also showed that Nrf2 facilitated both pulmonary and lymphatic distant metastasis of cervical cancer. Rescue-of-function assay further revealed the mechanism that Nrf2 impacted the metastasis of CC through Snail1. CONCLUSION: Our fundings established Nrf2 plays a crucial role in the metastasis of cervical cancer by enhancing EMT and resistance to anoikis by promoting the expression of Snail1, with potential value as a therapeutic candidate.

Immune evasion and therapeutic opportunities based on natural killer cells.

Natural killer (NK) cells can elicit an immune response against malignantly transformed cells without recognizing antigens, and they also exhibit cytotoxic effects and immune surveillance functions in tumor immunotherapy. Although several studies have shown the promising antitumor effects of NK cells in immunotherapy, their function is often limited in the tumor microenvironment because tumor cells can easily escape NK cell-induced death. Thus, for efficient tumor immunotherapy, the mechanism by which tumor cells escape NK cell-induced cytotoxicity must be fully understood. Various novel molecules and checkpoint receptors that mediate the disruption of NK cells in the tumor microenvironment have been discovered. In this review, we analyze and detail the major activating and inhibitory receptors on the surface of NK cells to delineate the mechanism by which tumor cells suppress NKG2D ligand expression and increase tumor receptor and inhibitory receptor expression [NKG2A, programmed cell death 1 (PD-1), and T-cell immunoglobulin and immunoreceptor tyrosine inhibitory motif (TIGIT)] on the NK cell surface, and thus inhibit NK cell activity. We also reviewed the current status of treatments based on these surface molecules. By comparing the therapeutic effects related to the treatment status and bypass mechanisms, we attempt to identify optimal single or combined treatments to suggest new treatment strategies for tumor immunotherapy.

Identification of metabolic biomarkers for diagnosis of epithelial ovarian cancer using internal extraction electrospray ionization mass spectrometry (iEESI-MS).

BACKGROUND: Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies. The poor prognosis of EOC is mainly due to its asymptomatic early stage, lack of effective screening methods, and a late diagnosis in the advanced stages of the disease. OBJECTIVE: This study investigated metabolomic abnormalities in epithelial ovarian cancers. METHODS: Our study developed a novel strategy to rapidly identify the metabolic biomarkers in the plasma of the EOC patients using Internal Extraction Electrospray Ionization Mass Spectrometry (IEESI-MS) and Liquid Chromatography-mass Spectrometry (HPLC-MS), which could distinguish the differential metabolites in between plasma samples collected from 98 patients with epithelial ovarian cancer, including 78 cases with original (P), and 20 cases with self-configuration (ZP), as well as 60 healthy subjects, including 30 cases in the original sample (H), 30 cases in self-configuration (ZH), and 6 cases in a blind sample (B). RESULTS: Our study detected 880 metabolites based on criteria variable importance in projection (VIP) > 1, among which 26 metabolites were selected for further identification. They are mainly metabolism-related lipids, amino acids, nucleic acids, and others. The metabolic pathways associated with the differential metabolites were explored by the KEGG analysis, a comprehensive database that integrates genome, chemistry, and system function information. The abnormal metabolites of EOC patients identified by IEESI-MS and HPLC-MS included Lysophosphatidylcholine (16:0) [Lyso PC (16:0)], L-Phenylalanine, L-Leucine, Phenylpyruvic acid, L-Tryptophan, and L-Histidine. CONCLUSIONS: Identifying the abnormal metabolites of EOC patients through metabolomics analyses could provide a new strategy to identify valuable potential biomarkers for the screening and early diagnosis of EOC.

Decoding the transcriptome of muscular dystrophy due to Ptrf deficiency using single-nucleus RNA sequencing.

Lacking PTRF (polymerase I and transcript release factor), an essential caveolae component, causes a secondary deficiency of caveolins resulting in muscular dystrophy. The transcriptome responses of different types of muscle fibers and mononuclear cells in skeletal muscle to muscular dystrophy caused by Ptrf deletion have not been explored. Here, we created muscular dystrophy mice by Ptrf knockout and applied single-nucleus RNA sequencing (snRNA-seq) to unveil the transcriptional changes of the skeletal muscle at single-nucleus resolution. 11 613 muscle nuclei (WT, 5838; Ptrf KO, 5775) were classified into 12 clusters corresponding to 11 nuclear types. Trajectory analysis revealed the potential transition between type IIb_1 and IIb_2 myonuclei upon muscular dystrophy. Functional enrichment analysis indicated that apoptotic signaling and enzyme-linked receptor protein signaling pathway were significantly enriched in type IIb_1 and IIb_2 myonuclei of Ptrf KO, respectively. The muscle structure development and the PI3K-AKT signaling pathway were significantly enriched in type IIa and IIx myonuclei of Ptrf KO. Meanwhile, metabolic pathway analysis showed a decrease in overall metabolic pathway activity of myonuclei subtypes upon muscular dystrophy, with the most decrease in type IIb_1 myonuclei. Gene regulatory network analysis found that the activity of Mef2c, Mef2d, Myf5, and Pax3 regulons was enhanced in type II myonuclei of Ptrf KO, especially in type IIb_2 myonuclei. In addition, we investigated the transcriptome changes in adipocytes and found that muscular dystrophy enhanced the lipid metabolic capacity of adipocytes. Our findings provide a valuable resource for exploring the molecular mechanism of muscular dystrophy due to Ptrf deficiency.

Metabolic reprogramming and interventions in endometrial carcinoma.

Cancer cells are usually featured by metabolic adaptations that facilitate their growth, invasion, and metastasis. Thus, reprogramming of intracellular energy metabolism is currently one of the hotspots in the field of cancer research. Whereas aerobic glycolysis (known as the Warburg effect) has long been considered a dominant form of energy metabolism in cancer cells, emerging evidence indicates that other metabolic forms, especially oxidative phosphorylation (OXPHOS), may play a critical role at least in some types of cancer. Of note, women with metabolic syndromes (MetS), including obesity, hyperglycemia, dyslipidemia, and hypertension, have an increased risk of developing endometrial carcinoma (EC), suggesting a close link between metabolism and EC. Interestingly, the metabolic preferences vary among EC cell types, particularly cancer stem cells and chemotherapy-resistant cells. Currently, it is commonly accepted that glycolysis is the main energy provider in EC cells, while OXPHOS is reduced or impaired. Moreover, agents specifically targeting the glycolysis and/or OXPHOS pathways can inhibit tumor cell growth and promote chemosensitization. For example, metformin and weight control not only reduce the incidence of EC but also improve the prognosis of EC patients. In this review, we comprehensively overview the current in-depth understanding of the relationship between metabolism and EC and provide up-to-date insights into the development of novel therapies targeting energy metabolism for auxiliary treatment in combination with chemotherapy for EC, especially those resistant to conventional chemotherapy.

UBE2E2 enhances Snail-mediated epithelial-mesenchymal transition and Nrf2-mediated antioxidant activity in ovarian cancer.

Dissemination of ovarian cancer (OvCa) cells can lead to inoperable metastatic lesions in the bowel and omentum, which have a poor prognosis despite surgical and chemotherapeutical options. A better understanding of the mechanisms underlying metastasis is urgently needed. In this study, bioinformatics analyses revealed that UBE2E2, a less-studied ubiquitin (Ub)-conjugating enzyme (E2), was upregulated in OvCa and was associated with poor prognosis. Subsequently, we performed western blot analysis and IHC staining with 88 OvCa and 26 normal ovarian tissue samples, which further confirmed that UBE2E2 protein is highly expressed in OvCa tissue but weakly expressed in normal tissue. Furthermore, the silencing of UBE2E2 blocked OvCa cell migration, epithelial-mesenchymal transition (EMT) and metastasis in vitro, whereas UBE2E2 overexpression exerted the opposite effects. Mechanistically, UBE2E2 promoted p62 accumulation and increased the activity of the Nrf2-antioxidant response element (ARE) system, which ultimately activated the Snail signaling pathway by inhibiting the ubiquitin-mediated degradation of Snail. Additionally, co-IP and immunofluorescence demonstrated that a direct interaction exists between UBE2E2 and Nrf2, and the N-terminal of UBE2E2 (residues 1-52) is required and sufficient for its interaction with Nrf2 protein. Mutations in the active site cysteine (Cys139) impaired both the function and cellular distribution of UBE2E2. More importantly, the deletion of UBE2E2 reduced tumorigenicity and metastasis in xenograft OvCa mouse models. Taken together, our findings reveal the role of the UBE2E2-Nrf2-p62-Snail signaling axis in OvCa and thus provides novel therapeutic targets for the prevention of OvCa metastasis.

Sperm quality impairment in males of couples with pregnancy loss is correlated with sexual dysfunction: a cross-sectional study.

BACKGROUND: Erectile dysfunction is a common problem in males of couples experiencing pregnancy loss. Erectile dysfunction in males with couple infertile has been extensively investigated and found to be closely linked with semen quality impairment and psychological distress, but it is less clear if this relation exists in males of couples experiencing pregnancy loss. METHOD: A cross-sectional analysis of 437 men who attended our outpatient clinic between June 2021 and October 2021 for couple pregnancy loss. All subjects underwent a complete physical examination, palpation, inspection of the male genitalia, and semen analysis. Validated assessment tools for erectile dysfunction (the International Index of Sexual Function5 -IIEF-5) and anxiety (the seven-item Generalized Anxiety Disorder Scale- GAD-7) were used. RESULTS: Among 437 men of couples with pregnancy loss, we found several relevant sperm parameters confirmed a significant correlation between IIEF-5 scores and sperm parameters, including: sperm progressive motility (r = 0.1627, p = 0.001), sperm normal morphology (r = 0.1373, p = 0.004) and sperm DNA fragmentation (r =-0.1248, p = 0.009). Males with an IIEF-5 scores range between 5-11 presented the worst results in terms of sperm progressive motility (p = 0.002), normal morphology (p = 0.001), and SDF levels (p = 0.003). GAD-7 score, as well as anxiety level, was significantly higher in those males with an IIEF-5 score between 5 and 11 (p = 0.000). CONCLUSION: Although current evidence does not demonstrate the importance of spermatozoa in the etiology of pregnancy loss, significant correlations have been observed between impaired sperm quality and low IIEF-5 scores. Also, anxiety is more likely to occur in males with sexual dysfunction.

Iron-Containing Protein-Mimic Supramolecular Iron Delivery Systems for Ferroptosis Tumor Therapy.

Ferroptosis provides an innovative theoretical basis and method for tumor therapy but is limited by the low efficiency of conventional iron delivery systems. Herein, an efficient supramolecular iron delivery system (SIDS) is demonstrated upon the hydrolysis of FeCl3, condensation of amino acids, and self-assembly of iron-containing components. The as-assembled SIDS possesses a shuttle-like core/shell structure with ß-FeOOH as the core and Fe3+/polyamino acid coordinated networks as shells. The iron content of SIDS is up to 42 wt %, which is greatly higher than that of ferritin. The iron-containing protein-mimic structure and shuttle-like morphology of SIDS facilitate tumor accumulation and cell internalization. Once exposed to the tumor microenvironment with overexpressed glutathione (GSH), the SIDS will disassemble, accompanied by the depletion of GSH and the release of Fe2+, leading to dual amplified ferroptosis. Primary studies indicate that SIDS exhibits outstanding antitumor efficacy on bladder cancer.

Poly-ADP-ribose polymerase (PARP) inhibitors and ovarian function.

Poly-ADP-ribose polymerase (PARP) plays an important role in DNA damage detection and repair. PARP inhibitors (PARPi) are a novel class of targeted agents used widely in the treatment of female cancer patients with BRCA mutations, including younger patients. However, the impact of PARPi on ovarian function remains a considerable problem in clinical practice. In this review article, we summarize the current understanding of PARPi's effects on the function of ovary and discuss their potential underlying mechanisms, highlighting the significance of further investigation on the criterion for ovarian failure and its preventive approaches during PARPi treatment.

Effectiveness and feasibility of self-sampling for human papillomavirus testing for internet-based cervical cancer screening.

Objectives: Worldwide, around 18.2% of cervical cancer occurred in China, mainly because of lower screening coverage and screening quality in regional disparities. To assess self-sampling for human papillomavirus (HPV) testing, combined with the internet, as a primary cervical cancer screening (CCS) method in low-resource settings, and to establish an internet-based self-sampling CCS-management model. Methods: The women who participated registered on a CCS website. We recruited 20,136 women, aged 30-59 years, from 13 provinces in China, to perform vaginal self-sampling for HPV testing as a primary CCS, based on the internet. A questionnaire was subsequently used to investigate the acceptability of self-sampling. Results: Of the 20,103 women with qualified samples, 35.80% lived in remote areas, 37.69% had never undergone CCS, 59.96% were under-screened, and the overall prevalence of a high-risk of HPV was 13.86%. Of 8,136 respondents, 95.97% of women felt that self-sampling was easy to perform, 84.61% had no discomfort when using a self-sampling brush, 62.37% women were more likely to choose self-sampling for CCS in future, and 92.53% were willing to introduce the concept to others around them. The reliability and ease of self-sampling were independent factors influencing selection of self-sampling (p < 0.05). Conclusions: The Internet-facilitated self-sampling for HPV testing and management model for cervical cancer prevention is feasible and effective. It can be used as a supplement to the conventional screening, particularly in outlying areas with few medical resources, to improve the coverage of CCS. Clinical trial registration: https://www.chictr.org.cn, identifier: ChiCTR2000032331.