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BackgroundPrimary perivascular epithelioid cell tumors (PEComas) of the female reproductive tract have been primarily reported as case reports owing to their clinical rarity. Limited incidence rates and clinical case data hinder a comprehensive understanding of the risks and invasiveness of this disease. We discuss herein the diagnosis, treatment, and prognosis of this disease to enhance comprehension and therapeutic strategies.MethodsWe conducted a clinical analysis of patients with PEComa treated at the Gynecology Department of The West China Second University Hospital of Sichuan University between May 2018 and January 2024. Diagnosis and treatment were evaluated based on pertinent literature.ResultsOverall, eight patients (seven patients with tumors in the uterus and one patient with tumors in the pelvic cavity) were evaluated. One patient with PEComa of unknown malignant potential and two patients with malignant PEComa underwent hysterectomy and bilateral adnexectomy with or without adjuvant therapy and did not develop recurrence. Meanwhile, three patients who underwent lesion resection only exhibited radiological evidence of new lesions. Furthermore, postoperative imaging identified new pulmonary nodules in three patients.ConclusionAlthough the current criteria are generally effective in assessing the tumor invasiveness of PEComa, emphasizing the significance of complete lesion resection remains crucial. Inadequate treatment significantly increases the risks of recurrence and metastasis. Additionally, the prevalence of pulmonary metastases may have been underestimated. Refining risk stratification to prevent overtreatment of low-grade malignancies or overlooking highly aggressive tumors is an important area for further study.

Abstract Background Embryonal rhabdomyosarcoma (ERMS) of the uterine cervix is rare, but the population affected is mostly underage females. The scope of surgery has now evolved from extensive to limited, and organ-preserving surgery combined with chemotherapy is recommended to preserve the patient’s fertility. However, reports of birth outcomes are rare. Case A minor woman with cervical ERMS who underwent only an outpatient biopsy of the lesion had no residual lesion on subsequent multipoint cervical biopsy and refused radical surgery or cervical conization, after which the patient received a nonclassical regimen of chemotherapy. The patient stopped the chemotherapy on her own, but the patient conceived spontaneously 16 years later with a good pregnancy outcome and no recurrence. Conclusions This case suggests that preservation of reproductive function is often feasible in immature women with cervical ERMS, and the prognosis is usually good as long as the primary tumour can be surgically removed and the lesion is free of residual disease. We also look forward to reports of subsequent growth and pregnancy outcomes in other children with reproductive tract RMS. In cervical ERMS, accurate evaluation of the disease and development of an individualized treatment plan are crucial, and the protection of reproductive function and psychological well-being deserves special attention.

Rhabdomyosarcoma (RMS) is a highly aggressive pediatric neoplasm that originates from striated muscle or undifferentiated mesenchymal cells. Based on its histopathological characteristics, the World Health Organization categorizes RMS into four distinct subtypes: embryonal RMS, alveolar RMS, pleomorphic RMS, and sclerosing/spindle cell RMS. Embryonal RMS represents the predominant subtype and primarily manifests in the head and neck region, with the genitourinary system being the subsequent most frequent site of occurrence. Embryonal rhabdomyosarcoma of the cervix (cERMS) is more insidious in the reproductive tract, and there is still a lack of consensus on its treatment. Patient-derived organoids (PDOs) are being prioritized for use in guiding personalized medicine. The application of PDOs to test the sensitivity of chemotherapy drugs in patients with cERMS has rarely been reported. In this case report, we delineate the presentation and diagnosis of a 16-year-old adolescent with cERMS, emphasizing the utilization of PDOs in the management of this infrequent neoplasm. We intend to elucidate the diagnostic and therapeutic processes associated with cERMS by referencing previously reported literature on this infrequent tumor, aiming to offer a foundation for clinical practice.

Abstract Background Acute lung injury (ALI) is a common lung disorder that affects millions of people every year. The infiltration of inflammatory cells into the lungs and death of the alveolar epithelial cells are key factors to trigger a pathological cascade. Trophoblast stem cells (TSCs) are immune privileged, and demonstrate the capability of self-renewal and multipotency with differentiation into three germ layers. We hypothesized that intratracheal transplantation of TSCs may alleviate ALI. Methods ALI was induced by intratracheal delivery of bleomycin (BLM) in mice. After exposure to BLM, pre-labeled TSCs or fibroblasts (FBs) were intratracheally administered into the lungs. Analyses of the lungs were performed for inflammatory infiltrates, cell apoptosis, and engraftment of TSCs. Pro-inflammatory cytokines/chemokines of lung tissue and in bronchoalveolar lavage fluid (BALF) were also assessed. Results The lungs displayed a reduction in cellularity, with decreased CD45+ cells, and less thickening of the alveolar walls in ALI mice that received TSCs compared with ALI mice receiving PBS or FBs. TSCs decreased infiltration of neutrophils and macrophages, and the expression of interleukin (IL) 6, monocyte chemoattractant protein-1 (MCP-1) and keratinocyte-derived chemokine (KC) in the injured lungs. The levels of inflammatory cytokines in BALF, particularly IL-6, were decreased in ALI mice receiving TSCs, compared to ALI mice that received PBS or FBs. TSCs also significantly reduced BLM-induced apoptosis of alveolar epithelial cells in vitro and in vivo. Transplanted TSCs integrated into the alveolar walls and expressed aquaporin 5 and prosurfactant protein C, markers for alveolar epithelial type I and II cells, respectively. Conclusion Intratracheal transplantation of TSCs into the lungs of mice after acute exposure to BLM reduced pulmonary inflammation and cell death. Furthermore, TSCs engrafted into the alveolar walls to form alveolar epithelial type I and II cells. These data support the use of TSCs for the treatment of ALI.

Abstract Background In a number of disease processes, the body is unable to repair injured tissue, promoting the need to develop strategies for tissue repair and regeneration, including the use of cellular therapeutics. Trophoblast stem cells (TSCs) are considered putative stem cells as they differentiate into other subtypes of trophoblast cells. To identify cells for future therapeutic strategies, we investigated whether TSCs have properties of stem/progenitor cells including self-renewal and the capacity to differentiate into parenchymal cells of fetal organs, in vitro and in vivo. Methods TSCs were isolated using anti-CD117 micro-beads, from embryonic day 18.5 placentas. In vitro, CD117+ TSCs were cultured, at a limiting dilution in growth medium for the development of multicellular clones and in specialized medium for differentiation into lung epithelial cells, cardiomyocytes, and retinal photoreceptor cells. CD117+ TSCs were also injected in utero into lung, heart, and the sub-retinal space of embryonic day 13.5 fetuses, and the organs were harvested for histological assessment after a natural delivery. Results We first identified CD117+ cells within the labyrinth zone and chorionic basal plate of murine placentas in late pregnancy, embryonic day 18.5. CD117+ TSCs formed multicellular clones that remained positive for CD117 in vitro, consistent with self-renewal properties. The clonal cells demonstrated multipotency, capable of differentiating into lung epithelial cells (endoderm), cardiomyocytes (mesoderm), and retinal photoreceptor cells (ectoderm). Finally, injection of CD117+ TSCs in utero into lungs, hearts, and the sub-retinal spaces of fetuses resulted in their engraftment on day 1 after birth, and the CD117+ TSCs differentiated into lung alveolar epithelial cells, heart cardiomyocytes, and retina photoreceptor cells, corresponding with the organs in which they were injected. Conclusions Our findings demonstrate that CD117+ TSCs have the properties of stem cells including clonogenicity, self-renewal, and multipotency. In utero administration of CD117+ TSCs engraft and differentiate into resident cells of the lung, heart, and retina during mouse development.

Human exposure to OPEs is pervasive and should be of great concern due to associations with adverse health effects, especially in susceptible populations. In this study, body burdens and exposure pathways of OPEs were investigated for 76 healthy elderly people in Jinan, China based on the measured OPE and metabolite concentrations in human bio-samples (whole blood and urine) and paired environmental matrices (air and dust), as well as food frequency questionnaire. Eight of 16 OPEs and 5 of 11 metabolites were detected in > 50% of whole blood and urine samples, respectively. Tri(1-chloro-2-propyl) phosphate (TCIPP), tris(2-chloroethyl) phosphate (TCEP), tri-phenyl phosphate (TPHP), and 2-ethylhexyl di-phenyl phosphate (EHDPP) were frequently detected and abundant in whole blood, while their corresponding metabolites were detected at low frequencies or levels in urine. The reduced metabolic and/or excretory capacity of elderly people may be an important reason, implying a higher health risk to them. Fourteen OPEs had over 50% detection frequencies in indoor air and dust, while 6 di-esters in indoor dust. Tris(2-ethylhexyl) phosphate (TEHP) in indoor dust and tri-n-butyl phosphate (TnBP) in indoor air were positively correlated with paired levels in blood but not with their metabolites (BEHP and DnBP) in urine. Combined with the direct intakes of BEHP and DBP from dust, blood is indicated as more suitable biomarker for TEHP and TnBP exposure. High consumption frequencies of several foods were associated with higher blood concentrations of three OPEs and urinary levels of four di-OPEs, indicating the importance of dietary exposure pathway. Estimated daily total intakes of OPEs via inhalation, dust ingestion, and dermal absorption ranged from 2.78 to 42.0 ng/kg bw/day, which were far less than the reference dosage values. Further studies were warranted to explore the potential health effects of OPE exposure in the elderly populations.

The ubiquity of organophosphate esters (OPEs) in various environmental matrices inevitably pose human exposure risks. Numerous studies have investigated human exposure pathways to OPEs, including air inhalation, dust ingestion, dermal contact, and dietary and drinking water intake, and have indicated that indoor dust and indoor air routes are frequently the two main human exposure pathways. This article reviews the literature on OPE contamination in indoor air and dust from various microenvironments and on OPE particle size distributions and bioavailability in dust conducted over the past 10 years. Ways in which sampling strategies are related to the uncertainty of exposure assessment results and comparability among different studies in terms of sampling tools, sampling sites, and sample types are addressed. Also, the associations of OPEs in indoor dust/air with human biological samples were summarized. Studies on two emerging matrices, hand wipes and silicone wristbands, are demonstrated to be more comprehensive and accurate in reflecting personal human exposure to OPEs in microenvironments and are summarized. Given the direct application of some diester OPEs (di-OPEs) in numerous products, research on their existence in indoor dust and food and on their effects on human urine are also discussed. Finally, related research trends and avenues for future research are prospected.

Ovarian cancer is a common cancer worldwide. Epithelial ovarian cancer (EOC) is the most common subtype of ovarian cancer. This study was designed to explore the function of miR-362-3p in EOC. QRT-PCR analysis was used to test miR-362-3p levels in EOC tissues and cell lines. Cell viability was tested via MTT assay. Transwell systems were applied to assay cell migration. The target gene of miR-362-3p was evaluated using dual luciferase reporter assays. The MyD88 protein in EOC cells was tested via western blot. Our data showed that miR-362-3p was expressed at low levels in EOC tissues and cells. miR-362-3p inhibited cell proliferation and migration, bound the 3′-untranslated region (UTR) of MyD88, and inhibited MyD88 expression. MyD88 was inversely correlated with miR-362-3p in EOC, and MyD88 overexpression partly reduced the anti-proliferative effect of miR-362-3p in EOC cells. In conclusion, our data showed that miR-362-3p has an anti-proliferative effect on EOC.

Although organophosphate diester (di-OPE) metabolites in urine are usually used to assess human exposure to organophosphate esters (OPEs), whether they can reflect human exposure to all OPEs with great differences in chemical structures and properties is still currently unclear. In this study, we detected sixteen OPEs and ten di-OPEs in 52 paired whole blood, serum, and urine samples collected in Beijing, China to investigate the correlations between different compounds and matrices, thus providing proper biomarkers of human exposure to OPEs. The order of the median concentrations of ∑OPEs was whole blood (8.63 ng/mL) > serum (5.71 ng/mL) > urine (0.396 ng/mL), while those of ∑di-OPEs followed the order of urine (16.6 ng/mL) > whole blood (5.97 ng/mL) > serum (3.70 ng/mL). Ethylhexyl diphenyl phosphate (EHDPP) and cresyl diphenyl phosphate (CDPP) were the dominant OPEs in both whole blood and serum samples and were significantly correlated between these two matrices. The distribution of OPEs in human blood was evaluated according to serum-to-whole blood concentration ratios (S:WB ratios). The median S:WB ratios of triethyl phosphate (TEP), tri-n-butyl phosphate (TnBP), bisphenol-A bis(diphenyl phosphate) (BABP), EHDPP, and CDPP were lower than 1, indicating that these OPEs preferred to accumulated in blood cells rather than in serum/plasma. Bis(2-ethylhexyl) phosphate (BEHP) was the major di-OPEs and was detected in almost all whole blood, serum and urine samples. The median whole blood: urine (WB:UR) ratios of di-OPEs were significantly and positively correlated with their logKow values, indicating that di-OPEs with low hydrophobicity were prone to excretion via urine. Based on the relationships between OPEs and di-OPEs in these matrices, the parent OPEs in whole blood can be recommended for use as alternative biomarkers of aryl-OPEs exposure in future human biomonitoring studies, in addition to metabolites in urine.

Objectives: In this retrospective observational study, cases from our institution were included and the published literature reviewed to investigate the diagnosis and prognosis of cervical rhabdomyosarcoma, a rare group of tumours. Material and methods: The clinicopathological data of 12 patients with cervical rhabdomyosarcoma (RMS) treated at the West China Second University Hospital of Sichuan University from January 2006 to May 2023 were collected, and their clinicopathological characteristics, diagnoses, treatments, prognoses and pregnancy outcomes were retrospectively analysed. Results: (1) Clinical characteristics: The ages of the 12 RMS patients ranged from 15 to 50 years, with a median age of 17 years. Five of the patients were adults, and seven were adolescents. The initial symptoms were vaginal bleeding in 5 patients, vaginal tissue prolapse in 6 patients, and abdominal pain and urinary frequency in 1 patient. Two patients were considered to have "cervical polyps" and underwent polypectomy at the other hospitals, but the cervical mass recurred soon thereafter. (2) Pathological features: The maximum tumour diameter ranged from 3 to 25 cm. The twelve cases of cervical RMS consisted of embryonal rhabdomyosarcoma (ERMS) in 7 adolescents, ERMS in 3 adults, and pleomorphic rhabdomyosarcoma (PRMS) in 2 adults. Immunohistochemical results showed the expression of one or more characteristic markers of RMS. We reclassified tumour stage according to the Intergroup Rhabdomyosarcoma Study (IRS) clinical group and tumour node metastasis (TNM) classification. (3) Treatment: Eight patients underwent radical surgery (66.7%, 8/12), including all 5 of the included adults and 3 of the adolescents, 2 of whom were treated 10 years ago. Conservative surgical resection was performed on four patients (33.3%, 4/12), all of whom were adolescents. Postoperative chemotherapy was given to all patients except one, but one patient who underwent radical surgery discontinued chemotherapy on her own without receiving a full course. Two of the ERMS patients underwent preoperative chemotherapy, and the lesions were significantly reduced. (4) Prognosis: One of the 12 patients with cervical RMS was lost to follow-up. Of the remaining 11 patients, 10 (including seven adolescents and three adults) survived tumour free (90.9%, 10/11), and 1 adult patient with existing pulmonary multiple metastases (IRS stage IV, T2N0M1) at the initial diagnosis survived 9 months with progression-free disease (9.1%, 1/11). The median survival time was 91 months (5 to 213 months). Among 4 patients receiving fertility-sparing management, 1 conceived and delivered successfully (25%). Conclusions: The treatment of cervical RMS must take the patient's age and reproductive intent into account. The overall prognosis for cervical RMS in children and adolescents is good, and conservative surgical resection combined with chemotherapy is recommended to preserve fertility. The pregnancy outcome is also worth anticipating. For patients who have completed childbirth, radical surgery is preferred. Approaches to accurately assessing the patient's condition, grasping the indications and scope of surgery, and developing chemoradiotherapy regimens deserve further exploration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Organophosphate esters (OPEs) are common endocrine-disrupting chemicals, and OPE exposure may be associated with type 2 diabetes (T2D). However, greater knowledge regarding the biomolecular intermediators underlying the impact of OPEs on T2D in humans are needed to understand biological etiology. OBJECTIVES: We explored the associations between OPE exposure and glycometabolic markers among older Chinese adults 60–69 years of age to elucidate the underlying mechanisms using a multi-omics approach. METHODS: This was a longitudinal panel study comprising 76 healthy participants 60–69 years of age who lived in Jinan city of northern China. The study was conducted once every month for 5 months, from September 2018 to January 2019. We measured a total of 17 OPEs in the blood, 11 OPE metabolites in urine, and 4 glycometabolic markers (fasting plasma glucose, glycated serum protein, fasting insulin, and homeostatic model assessment for insulin resistance). The blood transcriptome and serum/urine metabolome were also evaluated. The associations between individual OPEs and glycometabolic markers were explored. An adverse outcome pathway (AOP) was established to determine the biomolecules mediating the associations. RESULTS: Exposure to five OPEs and OPE metabolites (trimethylolpropane phosphate, triphenyl phosphate, tri-iso-butyl phosphate, dibutyl phosphate, and diphenyl phosphate) was associated with increased levels of glycometabolic markers. The mixture effect analysis further indicated the adverse effect of OPE mixtures. Multi-omics analyses revealed that the endogenous changes in the transcriptional and metabolic levels were associated with OPE exposure. The putative AOPs model suggested that triggers of molecular initiation events (e.g., insulin receptor and glucose transporter type 4) with subsequent key events, including disruptions in signal transduction pathways (e.g., phosphatidylinositol 3-kinase/protein kinase B and insulin secretion signaling) and biological functions (glucose uptake and insulin secretion), may constitute the diabetogenic effects of OPEs. DISCUSSION: OPEs are associated with the elevated risk of T2D among older Chinese adults 60–69 years of age. Implementing OPE exposure reduction strategies may help reduce the T2D burden among these individuals, if the relationship is causal. [ABSTRACT FROM AUTHOR]

In this paper, the electron mobility and sheet density of the two-dimensional electron gas (2DEG) in both air and argon environments at 600 °C were measured intermittently over a 5 h duration using unpassivated and Al2O3-passivated AlGaN/GaN (with 3 nm GaN cap) van der Pauw test structures. The unpassivated AlGaN/GaN heterostructures annealed in air showed the smallest decrease (~8%) in 2DEG electron mobility while Al2O3-passivated samples annealed in argon displayed the largest drop (~70%) based on the Hall measurements. Photoluminescence and atomic force microscopy showed that minimal strain relaxation and surface roughness changes have occurred in the unpassivated samples annealed in air, while those with Al2O3 passivation annealed in argon showed significant microstructural degradations. This suggests that cracks developed in the samples annealed in air were healed by oxidation reactions. To further confirm this, Auger electron spectroscopy was conducted on the unpassivated samples after the anneal in air and results showed that extra surface oxides have been generated, which could act as a dislocation pinning layer to suppress the strain relaxation in AlGaN. On the other hand, similar 2DEG sheet densities were observed in passivated and unpassivated AlGaN/GaN samples at the end of the 5-h anneal in air or argon due to the combined impact of strain relaxation and changes in the ionized electronic states. The results support the use of unpassivated GaN-capped AlGaN/GaN heterostructures as the material platform for high-temperature electronics and sensors used in oxidizing environmental conditions. [ABSTRACT FROM AUTHOR]

Organophosphorus flame retardants (OPFRs) have been increasingly used in various building and decoration materials to fulfill fire safety standards since the phasing out of polybrominated diphenyl ethers. We determined OPFR concentrations in the most commonly used building and decoration materials available in local markets and online in China. The OPFR concentrations varied significantly, from 14.78 ng/g (putty powder) to 9649000 ng/g (expanded polystyrene panel (EPS)). Relatively high concentrations of OPFRs were found in foam samples, followed by nonwoven and polyvinyl chloride (PVC) wallpaper, PVC pipes, sealing materials, boards, and paints. Low concentrations were found mostly in wall decoration powders, suggesting that no OPFRs had been added to these powders. Tris(1-chloro-2-propyl) phosphate and tris(1,3-dichloro-2-propyl) phosphate were the most detected halogenated OPFRs, while tri-n-butyl phosphate and tris(2-butoxyethyl) phosphate were the dominant nonhalogenated OPFRs, implying that they are commonly used in building and decoration materials. The estimated OPFR burden in interior decoration using nonwoven wallpaper was 330- and 2110-fold higher than that using latex paint and diatomite, respectively. The emission periods of OPFRs from nonwoven and PVC wallpaper may be greater than 13 years. We estimated that the total burden of OPFRs for decoration using wallpaper in newly decorated houses in China is ~63 t/y. Significantly higher concentrations of OPFRs in interior decoration materials, especially nonwoven wallpaper, pose potential health risks to the people using the buildings. [ABSTRACT FROM AUTHOR]

The high-temperature characteristics (at 600°C) of Ti/Al/Pt/Au multilayer contacts to gallium nitride (GaN) in air are reported. Microfabricated circular-transfer-line-method test structures were subject to 10 h of thermal storage at 600°C. Intermittent electrical characterization during thermal storage showed minimal variation in the contact resistance after 2 h and that the specific contact resistivity remained on the order of 10-5 Ω-cm². In addition, the thermally stored multilayer contacts to GaN showed ohmic I-V characteristics when electrically probed at 600 °C. The microstructural analysis with atomic force microscopy showed minimal changes in surface roughness after thermal storage. Observations of the thermochemical reactions after thermal storage using Auger electron spectroscopy chemical depth profiling showed diffusion of Pt and minimal additional Al oxidation. The results support the use of Ti/Al/Pt/Au multilayer metallization for GaN-based sensors and electronic devices that will operate within a high-temperature and oxidizing ambient. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is the most prevalent gynecological epithelial malignancy. DNA methylation is a promising cancer biomarker but limited use for detecting EC. We previously found that the level of cysteine dioxygenase 1 (CDO1) promoter methylation was elevated in EC patients through methylomics, but the role and mechanism of CDO1 in EC remained unclear. Here, the methylation level of CDO1 promoter was detected by bisulfite-sequencing PCR and methylation-specific PCR (bisulfite conversion-based PCR methods, which remain the most commonly used techniques for methylation detection). Cells were incubated with erastin (the ferroptosis activator). Cell vitality was measured using the cell counting kit-8 assay. FAM83H-AS1 cellular distribution was analyzed by the fluorescence in situ hybridization assay. Lipid reactive oxygen species level was examined by BODIPYC11 staining. The interactions between FAM83H-AS1, CDO1, and DNA methyltransferase1 (DNMT1) were analyzed by RNA-binding protein immunoprecipitation or chromatin immunoprecipitation assay. The xenograft mouse model was utilized to test CDO1 and FAM83H-AS1’s influence on tumor development in vivo. Results showed that CDO1 was hypermethylated and downregulated in EC. CDO1 knockdown reduced erastin-induced ferroptosis in EC cells. Mechanistically, DNMT1 is a DNA methyltransferase, which can transfer methyl groups to cytosine nucleotides in genomic DNA. Long noncoding RNA FAM83H-AS1 increased CDO1 promoter methylation level and inhibited its expression in EC cells by recruiting DNMT1. CDO1 knockdown or FAM83H-AS1 overexpression promoted EC tumor growth in vivo. Long noncoding RNA FAM83H-AS1 inhibited ferroptosis in EC by recruiting DNMT1 to increase CDO1 promoter methylation level and inhibit its expression. [ABSTRACT FROM AUTHOR]