Successful pregnancy in a female with embryonal rhabdomyosarcoma of the cervix who received biopsy and chemotherapy alone without recurrence after 16 years: a case report and literature review.

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.

Applying Item Response Theory to the Student Adaptation to College Questionnaire: Examining Psychometric Characteristics and Developing Computerized Adaptive Testing Version.

Incoming students have many difficulties adjusting to college, and selecting appropriate measures to effectively screen them is indispensable, especially in China, where there is insufficient research in this area. To enrich domestic research, this study seeks to examine psychometric characteristics and develop a computerized adaptive version of the Student Adaptation to College Questionnaire (SACQ-CAT) based on a sample of Chinese students. Under the framework of item response theory, the item bank of student adaptation to college was formulated after uni-dimensionality testing, model comparison, item fit testing, and local independence testing. Subsequently, a CAT simulation, including three termination rules, was performed using real data to evaluate and verify the SACQ-CAT. The results showed reliability values exceeding 0.90 when participants' latent traits were between -4 and 3, covering majority of the subjects. The SACQ-CAT administered an average of fewer than 10 items to participants compared to 67 items on the original scale. The correlation coefficient between latency estimated by the SACQ-CAT and the SACQ is greater than .85, whereas the correlation coefficient with the Symptom Checklist 90 (SCL-90) scores ranges from -.33 to -.55 (p < .001). The SACQ-CAT largely reduced the number of items administered to the participants and avoided losing measurement precision.

Emissions, Isomer-Specific Environmental Behavior, and Transformation of OBS from One Major Fluorochemical Manufacturing Facility in China.

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS), a novel alternative to perfluorooctane sulfonic acid (PFOS), has been widely used in various fields in China and has certain toxic effects similar to PFOS. This study monitored OBS and 15 legacy PFASs in surface water, sediment, soil, and crucian carp near a fluorochemical manufacturing factory (FMF) in Suqian, China, focusing on the emission, isomer-specific environmental fate, and transformation of OBS. One to four orders of magnitude higher concentrations of OBS than other polyfluoroalkyl substances (PFASs) in all samples indicate that industrial emission is an important point source of OBS in the surrounding environment. The concentrations of OBS in surface water, sediment, and soil decreased exponentially as the distance from the FMF increases. The proportions of OBS-c, the dominant isomer, increased in the order: water (75.5 ± 6.4%), sediment (85.7 ± 10%), fish (muscle: 94.1 ± 0.99%; blood: 93.5 ± 1.4%), suggesting its preferential accumulation in sediment and fish than other isomers. Mono-hydroxylated transformation products of OBS were first identified in water, sediment, and fish, suggesting its hydroxylation may exist in the real environment. The transformation of OBS may explain its significantly lower bioaccumulation than PFOS in fish. However, considering the higher BAF of OBS than the regulatory bioaccumulation criterion and the possible stronger toxicity of its transformation products, further studies on its bioaccumulation and transformation are warranted.

Penetration of Organophosphate Triesters and Diesters across the Blood-Cerebrospinal Fluid Barrier: Efficiencies, Impact Factors, and Mechanisms.

The penetration of organophosphate triesters (tri-OPEs) and diesters (di-OPEs) across the blood-brain barrier and their influencing factors remain unclear in humans. In this study, 21 tri-OPEs and 8 di-OPEs were measured in 288 paired serum and cerebrospinal fluid (CSF) samples collected in Jinan, China. Six tri-OPEs were frequently detected in both serum and CSF, with median concentrations ranging from 0.062 to 1.62 and 0.042-1.11 ng/mL, respectively. Their penetration efficiencies across the blood-CSF barrier (BCSFB) (RCSF/serum, CCSF/Cserum) were calculated at 0.667-2.80, and these efficiencies first increased and then decreased with their log Kow values. The reduced penetration efficiencies of triphenyl phosphate (TPHP) and 2-ethylhexyl diphenyl phosphate (EHDPP) may be attributed to their strong binding affinities for human serum albumin and p-glycoprotein due to their high hydrophobicity and aryl structure, as indicated by molecular docking. This suggests that active efflux transport may be involved in the penetration of TPHP and EHDPP in addition to passive diffusion similar to the other four tri-OPEs. Di-OPEs were found in few serum samples and even fewer CSF samples, indicating their limited BCSFB permeability. This may be due to their high polarity, low hydrophobicity, and ionic state in blood. This study has important implications for understanding the neurotoxicity of tri-OPEs and di-OPEs and the underlying mechanisms.

Emerging and Legacy Per- and Polyfluoroalkyl Substances in an Elderly Population in Jinan, China: The Exposure Level, Short-Term Variation, and Intake Assessment.

Human exposure to per- and polyfluoroalkyl substances (PFASs) has gained worldwide attention due to their widespread presence in the environment and adverse health effects, but the exposure assessment in the elderly is still lacking. This study aimed to assess exposures to 3 emerging PFASs (chlorinated polyfluoroalkyl ether sulfonic acids, Cl-PFESAs) and 15 legacy PFASs. The temporal variability of internal exposures and intake amounts of these PFASs were evaluated among a population of 76 healthy elderly adults (age: 60-69) in Jinan, China over 5 consecutive months. Fifteen PFASs were detected in whole blood with the mean total concentration (ΣPFAS) at 20.1 ng/mL (range: 5.0-135.9 ng/mL) dominated by perfluorooctanoic acid (PFOA) (9.0 ng/mL), perfluorooctanesulfonic acid (PFOS) (5.3 ng/mL), and 6:2 Cl-PFESA (1.6 ng/mL). Across the 5 month assessment period, significant variation was only observed for short-chain (C4-C7) perfluoroalkyl carboxylic acids, and their variations ranged from 53 to 334%. The median intake of PFOA and PFOS was estimated to be 1.46 and 0.92 ng/kg bw/day, respectively. Regression analysis showed that dietary ingestion, especially fish, was likely an important exposure pathway for PFASs among the elderly adults. Various pathways (e.g., dietary, water, air, and dust) should thus be considered to fully understand human exposure to PFASs.

Presence of organophosphate flame retardants (OPEs) in different functional areas in residential homes in Beijing, China.

The production and application of organophosphate esters (OPEs) have dramatically increased in recent years due to their use as a replacement for brominated flame retardants. In this study, 13 OPEs (Σ13OPEs) were analyzed in indoor air samples from kitchens and living rooms in 14 residential homes in Beijing, China. The concentrations of Σ13OPEs in kitchen air samples (mean: 13 ng/m3) were significantly (p < 0.05) higher than in living room air samples (5.0 ng/m3). In addition, paired window surface organic film samples were collected and analyzed to investigate film-air partitioning, exhibiting a mean concentration of Σ13OPEs of 4100 ng/m2. The congener profiles showed that tris(2-chloroisopropyl) phosphate (TCPP) was the predominant compound in both window film samples (48%) and the corresponding indoor air sample (56%). The estimated daily intakes (EDI) of OPEs via indoor air inhalation were 2.8 and 1.4 ng/kg/day for infants and adults, respectively, both of which are below the reference dose values (RfDs). Overall, these findings indicate that OPEs in the indoor air environment of residential homes in Beijing are not likely to pose a health risk to the general population.

TRIM44 facilitates ovarian cancer proliferation, migration, and invasion by inhibiting FRK.

Ovarian cancer (OC) is the leading cause of gynecologic cancer-related death in the world. Accumulating evidence indicated the important role of TRIM44 in cancer development. However, how TRIM44 displays in OC and the underlying mechanism remained unclear. TRIM44 and FRK expression in OC tissues and cell lines were investigated by western blot and RT-qPCR. Histotype of tissue samples and patients' data were analyzed. Kaplan-Meier Curve was performed to validate the effect of TRIM44. Colony formation assay, MTT assay, Transwell assay, and wound-healing assay were applied to elucidate the function of TRIM44 in OC cells. CHIP assay was used to explore the association between TRIM44 and FRK. Finally, we performed SKOV3 xenografts in Balb/c nude mice to further confirm the involvement of TRIM44 in OC development. We found TRIM44 highly expressed while FRK displayed low expression in OC cell lines and tissues. Moreover, analysis of histotype of tissues and patients' data and Kaplan-Meier Curve implied the important role of TRIM44 and FRK in tumor progression. Further in vitro study suggested that knocking down TRIM44 inhibited OC cells proliferation, migration, and invasion. Besides, FRK was identified as the target gene of TRIM44 in OC, and TRIM44 promoted OC cells proliferation, migration, and invasion by inhibiting FRK. Finally, in vivo animal experiment further confirmed the promotive effect of TRIM44 on OC progression. Our findings demonstrated that TRIM44 facilitated OC proliferation, migration, and invasion by inhibiting FRK, providing new insights for theoretical research and therapy of OC.

[Clear Cell Carcinoma of Cervix in a 12-Year-Old Girl: A Case Report].

The 12-year-old patient was admitted to the hospital on September 19, 2019 for "vaginal bleeding for 2 + months and pelvic mass to be diagnosed". The patient and her family explicitly denied any previous history of diethylstilbestrol exposure. After admission, relevant examinations were conducted and hysteroscopic exploration was performed under general anesthesia. During the procedure, cervical neoplasms were extracted and pathology results indicated cervical cancer. Then, extensive transabdominal hysterectomy+bilateral salpingectomy+bilateral ovarian transposition+pelvic lymph node dissection+para-aortic lymph node sampling were performed. Postoperative pathology analysis of the removed tissue showed that clear cell carcinoma of cervix (CCAC) had infiltrated into 1/3 of the cervical stroma and there was downward involvement of the vaginal wall; the cancer metastasized to the left obturator lymph node and the left internal and external iliac lymph nodes. Immunohistochemical staining of the removed tissue showed the following results: cytokeratin 7 (+), cytokeratin 20 (-), Napsin-A (+), cell adhesion molecule CD15 (+), heatocyte nuclear factor-1 ß (+), Sal-like protein 4 (-), tumor suppressor gene P16 protein (+), estrogen receptor (+), progesterone receptor (-), tumor suppressor gene P53 protein (focal positive), tumor suppressor gene WT-1 protein (-) and Ki67 antigen (about 40% positive). The patient was diagnosed with CCAC stage ⅢC1p. Four cycles of postoperative systemic chemotherapy (fluorouracil+cisplatin) and 25 times of three-dimensional afterloading radiotherapy were performed. The patient did follow-up visits and did not show obvious signs of recurrence. The clinical manifestations of this disease are basically the same as those of cervical squamous cell carcinoma, and if the patient is younger, it can be easily misdiagnosed as dysfunctional uterine bleeding, indicating the need for differential diagnosis.

Association between genital mycoplasmas infection and human papillomavirus infection, abnormal cervical cytopathology, and cervical cancer: a systematic review and meta-analysis.

BACKGROUND: Some studies demonstrated that female genital mycoplasmas play important roles in human papillomavirus (HPV) infection, abnormal cervical cytopathology, and cervical cancer. However, those results remained inconclusive. We aimed to perform a systematic review and meta-analysis to investigate the association between female genital mycoplasmas and those disorders. METHODS: Computerized databases were comprehensively searched before 26 January 2017. Pooled odd radios (ORs) and correlative 95% confidence intervals (CIs) were adopted to evaluate the strength of association. RESULTS: Our meta-analysis included 22 studies with 16,181 participants. Ureaplasma urealyticum and Ureaplasma parvum were associated with a significantly increased risk of overall HPV infection (OR 1.57, 95% CI 1.05-2.34; OR 3.02, 95% CI 2.10-4.33, respectively), and U. urealyticum and Mycoplasma genitalium were associated with a significantly increased risk of high-risk HPV infection (OR 1.37, 95% CI 1.05-1.80; OR 1.50, 95% CI 1.11-2.02, respectively). In addition, U. urealyticum, U. parvum, and Mycoplasma hominis were associated with a significantly increased risk of abnormal cervical cytopathology (OR 1.51, 95% CI 1.23-1.85; OR 1.41, 95% CI 1.10-1.80; OR 1.48, 95% CI 1.10-1.99, respectively). CONCLUSION: We found that U. urealyticum and M. genitalium may increase the risk of high-risk HPV infection, while U. urealyticum, U. parvum, and M. hominis may increase the risk of abnormal cervical cytopathology.

Organophosphorus Flame Retardants and Plasticizers in Building and Decoration Materials and Their Potential Burdens in Newly Decorated Houses in China.

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.

[Studies on the lymphatic tropism and lymph cells apoptosis of cisplatin-nano carbon suspension in the rats].

OBJECTIVE: To research the lymphatic tropism and lymph cell apoptosis of cisplatin-nano carbon suspension in rats with the aim of proposing a new way for chemotherapy. METHODS: A total of 72 Wistar rats were randomly divided into two groups. For the experimental group, cisplatin-nano carbon suspension 0.3 ml (4 mg/ml) was injected subcutaneously into Wistar rats' plantar. For the control group, cisplatin 0.3 ml (4 mg/ml) was injected intravenously. Cisplatin concentration in the inguinal lymphatic tissue and plasma was determined by high performance liquid chromatography (HPLC) at 1, 2, 3, 4, 5 and 6 hours after drug administration. The apoptosis of lymph cell was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay (TUNEL). Targeting ability were evaluated and compared by targeting index (TI), selecting index (SI) and relative extraction efficiency (RE). SPSS 17.0 statistical software was used to analyze the differentiation of the cisplatin concentration and apoptosis index (AI) among various groups. DAS software was used to evaluate the lymphatic tropism. RESULTS: The cisplatin concentration of lymphatic tissue in experimental group were respectively (1.03± 0.32), (3.00±0.91), (2.20±0.73), (1.56±0.38), (1.30±0.74) and (0.78±0.34)µg/g after administration 1, 2, 3, 4, 5 and 6 hours, while in control group were (0.49±0.21), (1.02±0.70), (0.59±0.50), (0.56±0.21), (0.47±0.18) and (0.36±0.13)µg/g, in which there were significant difference at every times (all P < 0.05)except at 1 hour(P = 0.173). The cisplatin concentration in plasma were significant higher in the experimental group than those in the control group at various times(all P < 0.05), the former were respectively (0.57±0.28), (1.22 ± 0.45), (0.61 ± 0.18), (0.51 ± 0.13), (0.45 ± 0.13) and (0.40 ± 0.07) µg/ml, while the latter were respectively (3.12±0.33), (4.09±0.48), (2.56±0.38), (2.05±0.13), (1.81±0.28) and (1.44±0.40) µg/ml. Values of TI were respectively 2.12, 2.93, 3.73, 2.78, 2.76 and 2.19 and SI were 1.80, 2.45, 3.63, 3.07, 2.86 and 1.93. Value of RE was 2.86. The AI in experimental group were respectively (16.5±5.2)%, (30.2±2.8)%, (51.7 ± 4.3)%, (69.8 ± 3.2)%, (80.1 ± 4.3)% and (89.7 ± 8.5)% , while in control group were respectively(1.3±0.8)%, (2.4±1.7)%, (3.2±1.1)%, (3.9±2.6)%, (5.1±2.1)% and (6.3±2.3)%, in which there were significant difference at every points(all P < 0.05). CONCLUSIONS: The nano carbon has the character of lymphatic tropism, and could send cisplatin to lymphatic tissue to achieve a higher concentration. The trait may break a new way for chemotherapy targeting lymph metastasis.

[Pathological characteristics and prognosis of 664 patients with epithelial ovarian cancer: a retrospective analysis].

OBJECTIVE: To analyze clinicopathologic features and risk factors associated with the recurrence and prognosis of epithelial ovarian cancer (EOC). METHODS: 710 EOC patients treated at the West China University Second Hospital from Jan. 2006 to Jun. 2011 were recruited in this study retrospectively. Univariate and multivariate logistic regression models were constructed to evaluate the risk of factors. Kaplan-Meier and log-rank methods were adopted for survival analyses. RESULTS: The final sample included 664 patients with complete and well-documented data. The participants had a mean age of (49.35 +/- 11.58) yr. and 79.07% (525/664) were older than 40 year-old. CA125 was tested in 550 patients before surgery and 82.55% showed abnormal values. Over half (55.57%) of the patients were classified as serious EOC, which was followed by clear cell EOC (12.35%), endometrioid EOC (10. 09%), mucinous EOC (7.68%), and others (14.31%). Stage I (FIGO) comprised 30. 72% of the cases. The patients were followed up on average of (37.48 +/- 12.51) months and 303 died with a mean survival length of (28.54 +/- 9.56) months. Recurrence was found in 126 patients at a median of (26.10 +/- 5.75) months. For the 361 survived, 81. 72% lived without detectable cancer. All patients received surgical operations, including 483 undergoing retroperitoneal lymphadenectomy. The univariate analysis identified older age, advanced FIGO stage, suboptimal debulking, abnormal CA125 values before surgery, undifferentiated, mixed type and serous pathologic subtypes, poor-differentiation and pathogenesis of tumor as risk factors associated with survival prospect. The multivariate logistic regression models confirmed that poor prognosis was associated with older age, advanced FIGO stage, suboptimal debulking and undifferentiated, mixed type and serous pathologic subtype. CONCLUSION: Older age, advanced FIGO stage, high grade differentiation, suboptimal debulking, lymphnode metastasis, and type II EOC are associated with poor prognosis of EOC patients.

Association Between Pelvic Inflammatory Disease and Risk of Endometriosis: A Systematic Review and Meta-Analysis.

Background: Endometriosis is a common chronic disorder, which leads to dysmenorrhea, dyspareunia, pelvic chronic pain, and infertility. It affects ∼6% to 10% of the general female population. However, the etiology of endometriosis remained unclear. We aimed to systematically assess the association between pelvic inflammatory disease (PID) and the risk of endometriosis. Materials and Methods: Eligible studies published until May 21, 2022, were retrieved from the PubMed, EMBASE, and Web of Science databases. The studies were included based on the following criteria: (1) original articles on the association between PID and risk of endometriosis; (2) randomized controlled trials and cross-sectional, case-control, and cohort studies; and (3) studies involving humans. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the studies included in this systematic review. The association between PID and risk of endometriosis was evaluated using the overall odds ratio (OR) and correlative 95% confidence interval (CI). Results: The meta-analysis included 14 studies with 747,733 patients. The mean prevalence of PID in women with endometriosis was 33.80%. Our quantitative synthesis revealed that endometritis was associated with a significantly increased risk of endometriosis (OR: 1.63, 95% CI: 1.53-1.74, I2 = 59%). Conclusion: We study a statistically significant association between PID and the risk of endometriosis. In particular, endometritis might play an important role in endometriosis, based on the lower heterogeneity of the subgroup analysis. This finding suggests that reducing the incidence of endometritis might aid in the prevention and treatment of endometriosis.

Occurrence, distribution, sources, and risk assessment of organophosphate esters in typical coastal aquaculture waters of China.

This study monitored 20 organophosphate esters (OPEs) in water and sediment from three typical mariculture bases (Yunxi Marine Ranching (YX), Hangzhou Bay (HZB), and Zhelin Bay (ZLB)) and Meiliang Bay (MLB) of Taihu Lake in China, focusing on the spatial distribution and sources of OPEs. Moreover, the occurrence and risk of OPEs in fishes from ZLB were evaluated. The ∑OPE concentrations in waters followed the order MLB (591 ng/L) > YX (102 ng/L) > HZB (70.0 ng/L) > ZLB (37.4 ng/L), with tri(1-chloro-2-propyl) phosphate (TCIPP), triethyl phosphate (TEP), and tri(2-chloroethyl) phosphate (TCEP) being the dominant OPEs. Significantly higher ∑OPE concentrations were found in sediment in MLB compared to the other three areas with similar levels. The decreasing concentrations of OPEs from nearshore to offshore areas in HZB and MLB indicated that terrigenous input is the main source of OPEs. The even distribution of OPEs in YX and ZLB combined with PCA analysis suggested ship traffic or aquaculture activities are also potential sources. The ∑OPE concentrations in fishes ranged from 0.551-2.45 ng/g wet weight, with TCIPP, tri-phenyl phosphate (TPHP), and TCEP being the main OPEs. Hydrophobicity was a key factor affecting the sediment-water distribution coefficients and the bioaccumulation factors of OPEs. The human exposure to OPEs through consumption of fishes from ZLB had a low health risk.

Clinicopathologic characteristics, treatment, prognosis and pregnancy outcomes in rhabdomyosarcoma of the uterine cervix: a case series.

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.

Patient-derived organoids facilitating individual therapy in an adolescent with embryonal rhabdomyosarcoma of the cervix: a case report and literature review.

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.

m6A-modified circNFIX promotes ovarian cancer progression and immune escape via activating IL-6R/JAK1/STAT3 signaling by sponging miR-647.

BACKGROUND: Ovarian cancer (OC) is one of the most common gynecological malignant cancers. Our previous work confirmed that circNFIX acted as an oncogene in OC, which could promote malignant proliferation, metastasis and angiogenesis. However, the role and mechanism of circNFIX in OC immune escape remain unclear. METHODS: The RNA and protein levels were determined by qRT-PCR and western blot assays. The malignant phenotypes were tested by cell count kit-8, EdU staining, flow cytometry and transwell assays. The immune cytokines levels were measured by ELISA analysis. Molecular interactions were verified employing RNA immunoprecipitation, meRIP and dual luciferase methods. In vivo validation was performed by xenograft tumor and lung metastasis model. Hematoxylin & eosin and immunohistochemistry staining were used to observe the pathological changes. RESULTS: The levels of circNFIX, PD-L1, and IL-6R were upregulated in OC tissues and cell lines, while miR-647 was downregulated. Functional assays showed that loss of circNFIX suppressed the growth, metastasis and immune escape of OC cells both in vitro and in vivo. On the molecular level, the m6A modification of circNFIX was elevated in OC cells, and its expression was positively correlated to m6A modification and depended on IGF2BP1 âˆ¼ 3 recognition. Moreover, circNFIX acted as a competing endogenous RNA for miR-647 to upregulate IL-6R expression, thereby activating JAK/STAT3 signaling and elevating PD-L1 expression. Rescue assays revealed that co-silencing of miR-647 reversed the antitumor effects of circNFIX knockdown on cell proliferation, metastasis and immune escape of OC cells. CONCLUSION: This study provided a comprehensive understanding of the molecular mechanism about circNFIX in OC, demonstrating m6A activated-circNFIX accelerated OC development and immune escape via regulating miR-647/IL-6R/PD-L1 pathway.

Exosomal circNFIX promotes angiogenesis in ovarian cancer via miR-518a-3p/TRIM44 axis.

Ovarian cancer (OC) is a gynecological cancer with high mortality. OC-derived exosomal circRNAs can regulate angiogenesis. This study aims to explore the role and mechanism of exosomal circRNA nuclear factor I X (CircNFIX) derived from OC cells in angiogenesis. Quantitative real-time polymerase chain reaction was employed to evaluate the levels of circNFIX, miR-518a-3p, and tripartite motif protein 44 (TRIM44) in OC and adjacent tissues. Exosomes from the ovarian surface epithelial cell (HOSEpiC) and OC cells (SKOV3 or OVCAR3) were isolated by differential centrifugation. Exosomes were cocultured with the human umbilical vein endothelial cells (HUVECs). The angiogenesis capacity was analyzed by Tube formation assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays were used to determine the cell viability and migration ability. The dual-luciferase report, RNA immunoprecipitation (RIP), and RNA pull-down assays were applied to validate the gene's interaction. CircNFIX and TRIM44 expression were higher and miR-518a-3p was lower in OC tissues than in the adjacent tissues. Upregulated circNFIX and TRIM44 were significantly correlated with the tumor size and International Federation of Gynecology and Obstetrics (FIGO) stage of OC patients. HUVECs treated OC-derived exosomes had higher proliferation, migration, and angiogenesis capacities than the control group. While OC-derived exosomal circNFIX silencing restrained HUVECs' proliferation, migration, and angiogenesis, compared with the OC-derived exosomes group. OC-derived exosomal circNFIX positively regulated TRIM44 expression by targeting miR-518a-3p in HUVECs. OC-derived exosomal circNFIX promoted angiogenesis by regulating the Janus-activated kinase/signal transducer and activator of transcription 1 (JAK/STAT1) pathway via miR-518a-3p/TRIM44 axis in HUVECs.

CircNFIX stimulates the proliferation, invasion, and stemness properties of ovarian cancer cells by enhancing SH3RF3 mRNA stability via binding LIN28B.

We aimed to study the regulatory roles and mechanism of circular nuclear factor IX (circNFIX) in cancer growth and stemness properties of ovarian cancer (OC). CircNFIX and SH3RF3 levels in OC tissues and cells were tested by quantitative real-time PCR. RNase R treatment quantified circNFIX RNA stability. Molecular interaction among circNFIX, LIN28B, and SH3RF3 was predicted by bioinformatics software and validated through RNA immunoprecipitation (RIP) assay. The gain- or loss-experiments of circNFIX on capabilities of metastasis and stemness in vitro were assessed using Cell Counting Kit-8, Transwell, western blot, and sphere-formation assays. CircNFIX and SH3RF3 were markedly elevated in OC tissues and OC cells. Knocking down circNFIX repressed the proliferation, migration, invasion, and stemness properties of A2780 and SKOV3 cells. The RIP assay verified the direct binding relationship between LIN28B, circNFIX, and SH3RF3. Additionally, overexpression of circNFIX elevated the SH3RF3 expression, while this effect was reversed by LIN28B silence. Rescue experiments demonstrated that the overexpression of SH3RF3 reversed the knockdown of circNFIX on OC cells' proliferation, metastasis, and stemness properties. CircNFIX improved the mRNA stability and translation of SH3RF3 via recruiting LIN28B, thus promoting the proliferation, invasion, and stemness properties of OC cells in vitro.

Association between Organophosphate Ester Exposure and Insulin Resistance with Glycometabolic Disorders among Older Chinese Adults 60-69 Years of Age: Evidence from the China BAPE Study.

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. https://doi.org/10.1289/EHP11896.