Comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for low-risk gestational trophoblastic neoplasia (FIGO Score 0-4): study protocol for a prospective, multicentre, randomized trial.

BACKGROUND: Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens. METHODS: We will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m2) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life. DISCUSSION: Previous clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020-9-24, version 1.0).

Study on the correlation between early three-dimensional gait analysis and clinical efficacy after robot-assisted total knee arthroplasty.

PURPOSE: Robot-assisted technology is a forefront of surgical innovation that improves the accuracy of total knee arthroplasty (TKA). But whether the accuracy of surgery can improve the clinical efficacy still needs further research. The purpose of this study is to perform three-dimensional (3D) analysis in the early postoperative period of patients who received robot-assisted total knee arthroplasty (RATKA), and to study the trend of changes in gait parameters after RATKA and the correlation with the early clinical efficacy. METHODS: Patients who received RATKA in the Center of Joint Surgery, the First Hospital Affiliated to Army Military Medical University from October 2020 to January 2021 were included. The imaging parameters, i.e., hip-knee-ankle angle, lateral distal femoral angle, medial proximal tibial angle, posterior condylar angle were measured 3 months post-TKA. The 3D gait analysis and clinical efficacy by Western Ontario Mac Master University Index (WOMAC) score were performed pre-TKA, 3 and 6 months post-TKA. The differences in spatiotemporal parameters of gait, kinetic parameters, and kinematic parameters of the operated limb and the contralateral limb were compared. The correlation between gait parameters and WOMAC scores was analyzed. Paired sample t-test and Wilcoxon rank-sum test were used to analyze the difference between groups, and Spearman correlation coefficient was used to analyze the correlation. RESULTS: There were 31 patients included in this study, and the imaging indexes showed that all of them returned to normal post-TKA. The WOMAC score at 3 months post-TKA was significantly lower than that pre-TKA, and there was no significant difference between at 3 and 6 months. The 3D gait analysis results showed that the double support time of the operated limb reduced at 3 and 6 months (all p < 0.05), the maximum extension and maximum external rotation of the knee joint increased at stance phase, and the maximum flexion angle, the range of motion and the maximum external rotation increased at swing phase. Compared with the preoperative data, there were significant improvements (all p < 0.05). Compared with the contralateral knee joint, the maximum external rotation of the knee joint at swing phase was smaller than that of the contralateral side, and the maximum flexion and extension moment was greater than that of the contralateral knee. The maximum external rotation moment of the joint was greater than that of the contralateral knee joint (p < 0.05). There was a negative correlation between the single support time pre-TKA and the WOMAC score at 3 months (p = 0.017), and the single support time at 3 months was negatively correlated with the WOMAC score at 6 months (p = 0.043). The cadence at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.031). The maximum knee extension at stance phase at 6 months was negatively correlated with the WOMAC score at 6 month (p = 0.048). The maximum external rotation at stance phase at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.024). CONCLUSION: The 3D gait analysis of RATKA patients is more sensitive than WOMAC score in evaluating the clinical efficacy. Trend of changes in gait parameters shows that the knee joint support, flexion and extension function, range of motion, external rotation and varus deformity moment of the patient were significantly improved at 3 months after surgery, and continued to 6 months after surgery. Compared with the contralateral knee, the gait parameters of the operated limb still has significant gaps in functionality, such as the external rotation and flexion and extension. The single support time, cadence, knee extension, and knee external rotation of the operated limb have a greater correlation with the postoperative WOMAC score. Postoperative rehabilitation exercises should be emphasized, which is of great value for improving the early efficacy of RATKA.

MRI-derived radiomics analysis improves the noninvasive pretreatment identification of multimodality therapy candidates with early-stage cervical cancer.

OBJECTIVES: To develop and validate a clinical-radiomics model that incorporates radiomics signatures and pretreatment clinicopathological parameters to identify multimodality therapy candidates among patients with early-stage cervical cancer. METHODS: Between January 2017 and February 2021, 235 patients with IB1-IIA1 cervical cancer who underwent radical hysterectomy were enrolled and divided into training (n = 194, training:validation = 8:2) and testing (n = 41) sets according to surgical time. The radiomics features of each patient were extracted from preoperative sagittal T2-weighted images. Significance testing, Pearson correlation analysis, and Least Absolute Shrinkage and Selection Operator were used to select radiomic features associated with multimodality therapy administration. A clinical-radiomics model incorporating radiomics signature, age, 2018 Federation International of Gynecology and Obstetrics (FIGO) stage, menopausal status, and preoperative biopsy histological type was developed to identify multimodality therapy candidates. A clinical model and a clinical-conventional radiological model were also constructed. A nomogram and decision curve analysis were developed to facilitate clinical application. RESULTS: The clinical-radiomics model showed good predictive performance, with an area under the curve, sensitivity, and specificity in the testing set of 0.885 (95% confidence interval: 0.781-0.989), 78.9%, and 81.8%, respectively. The AUC, sensitivity, and specificity of the clinical model and clinical-conventional radiological model were 0.751 (0.603-0.900), 63.2%, and 63.6%, 0.801 (0.661-0.942), 73.7%, and 68.2%, respectively. A decision curve analysis demonstrated that when the threshold probability was > 20%, the clinical-radiomics model or nomogram may be more advantageous than the treat all or treat-none strategy. CONCLUSIONS: The clinical-radiomics model and nomogram can potentially identify multimodality therapy candidates in patients with early-stage cervical cancer. KEY POINTS: • Pretreatment identification of multimodality therapy candidates among patients with early-stage cervical cancer helped to select the optimal primary treatment and reduce severe complication risk and costs. • The clinical-radiomics model achieved a better prediction performance compared with the clinical model and the clinical-conventional radiological model. • An easy-to-use nomogram exhibited good performance for individual preoperative prediction.

Dexmedetomidine inhibits inflammatory response and oxidative stress through regulating miR-205-5p by targeting HMGB1 in cerebral ischemic/reperfusion.

OBJECTIVE: To investigate effects of dexmedetomidine (DEX) on miR-205-5p/HMGB1 axis in cerebral ischemic/reperfusion (I/R) injury. METHODS: Both in vivo I/R rat model and in vitro hypoxia/reoxygenation (H/R) cell model using rat hippocampal neurons cells were established. miR-205-5p was overexpressed or inhibited by transfection of miR-205-5p mimics or inhibitor. HMGB1 was overexpressed by transfection overexpression plasmids (OE-HMGB1). TTC staining was used for measurement of infraction volume. Oxidative stress was evaluated by measurement of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) and inflammation was evaluated by measurement of IL-1ß, IL-6 and TNF-α. Dual luciferase reporter assay was performed to confirm binding between miR-205-5p and HMGB1. The expression levels of miR-205-5p, and HMGB1 were measured using RT-qPCR. Western blotting was used to test the protein expression levels of HMGB1, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase (GPx), glutathione reductase (GR), heme oxygenase 1 (HO-1) and catalase (CAT). RESULTS: Treatment of DEX significantly reduced brain infraction volume, decreased Longa's neurological function score and inhibited oxidative stress and inflammation in brain tissues of I/R rats, which were all reversed by inhibition of miR-205-5p. Both treatment of DEX or overexpression of miR-205-5p restricted oxidative stress and inflammation in H/R rat hippocampal neurons cells. The inhibition of miR-205-5p reversed the effects of DEX, while the overexpression of HMGB1 reversed the effects of miR-205-5p overexpression in H/R rat hippocampal neurons cells. Dual luciferase reporter assay showed miR-205-5p directly targeted HMGB1. CONCLUSION: DEX improved I/R injury by suppressing brain oxidative stress and inflammation DEX improved I/R injury by suppressing brain oxidative stress and inflammation through activating miR-205-5p/HMGB1 axis through activating miR-205-5p/HMGB1 axis.

Oncofertility outcomes after fertility-sparing treatment of bilateral serous borderline ovarian tumors: results of a large retrospective study.

STUDY QUESTION: What are the oncofertility outcomes of young women (≤40 years old) with bilateral serous borderline ovarian tumors (SBOTs) after fertility-sparing surgery? SUMMARY ANSWER: Fertility preservation with the bilateral ovarian cystectomy procedure is feasible for bilateral SBOTs, with an acceptable oncological outcome and worthwhile pregnancy rates. WHAT IS KNOWN ALREADY: Fertility-sparing approaches are becoming the standard management of young patients with unilateral SBOTs and other borderline histological subtypes. However, there is a paucity of evidence to dictate the best management in bilateral SBOTs. STUDY DESIGN, SIZE, DURATION: This was a retrospective observational study performed at the Peking Union Medical College Hospital in Beijing, China, between January 1999 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ninety-four women (≤40 years old) with pathologically confirmed bilateral SBOTs were included. Following preoperative counseling, patients self-selected into one of three treatment modalities: bilateral ovarian cystectomy (n = 48), unilateral adnexectomy plus contralateral cystectomy (UAC; n = 31), and radical surgery (n = 15). Univariate and multivariate analyses were used to determine the clinical and pathological features associated with disease-free survival and reproductive outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: During the median follow-up of 64 months (range, 4-243 months), 61 patients (65%) developed relapse, including 3 (20%) in the radical group, 26 (84%) in the UAC group and 32 (67%) in the bilateral cystectomy group. In the multivariate analyses, preoperative CA-125>300 U/mL, fertility preservation and micropapillary pattern were independently associated with adverse disease-free survival (P = 0.001, 0.03 and 0.026, respectively). Fourteen patients (15%) experienced invasive recurrence, and three (3%) died of progressive disease. The micropapillary pattern was significantly associated with invasive evolution risk (P = 0.006). Of the 49 patients who attempted to conceive, 23 (47%) achieved 27 pregnancies (24 spontaneous and three after IVF-ET), resulting in 19 live births. There was no significant difference in disease-free survival (P = 0.13) or pregnancy rate (41 vs. 50%, P = 0.56) between the UAC and bilateral procedures. LIMITATIONS, REASONS FOR CAUTION: As a retrospective study conducted in a referral center, inherent biases exist. The nonrandom allocation to treatment groups and relatively small number of patients attempt to conceive might limit the statistical power of our findings. Only 41 patients (43.6%) received complete staging during their initial surgeries, so an underestimation bias in terms of the FIGO stage and extraovarian implants might have occurred. WIDER IMPLICATIONS OF THE FINDINGS: The ultraconservative bilateral ovarian cystectomy procedure should be proposed in bilateral SBOTs when technically feasible. Invasive evolution occurs frequently in these women, and intense follow-up and oncofertility counseling are warranted, especially for those with micropapillary patterns. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Reproductive outcomes after floxuridine-based regimens for gestational trophoblastic neoplasia: A retrospective cohort study in a national referral center in China.

OBJECTIVE: To analyze the reproductive outcomes of gestational trophoblastic neoplasia (GTN) patients who were cured only by floxuridine-based regimens. METHODS: This was a retrospective analysis of 464 patients who were treated with only floxuridine-based regimens at Peking Union Medical College Hospital between January 2002 and December 2013 and retained their reproductive ability. Their reproductive outcomes were analyzed. The factors affecting pregnancy intention were identified by logistic regression. RESULTS: Of the 464 patients (average age, 28.0 ± 5.7 years; median follow-up = 85 months), the livebirth rate was 72.2%, while the rates of spontaneous abortion, induced abortion and ectopic pregnancy were 9.2% (n = 41), 8.7% (n = 39) and 1.8% (n = 8), respectively. The GTN recurrence rate was 2.1%. The time from chemotherapy completion to first conception in the induced abortion group was significantly shorter than those in spontaneous abortion, full-term/premature, and ectopic pregnancy groups (P ≤ 0.001, <0.001, =0.015, respectively). The logistic analysis showed that the age at onset of GTN (OR = 0.899, 95% CI 0.851-0.951, P < 0.001), parity at onset of GTN (parity = 1, OR = 0.123, 95% CI 0.068-0.225, P < 0.001; parity = 2-3, OR = 0.058, 95% CI 0.014-0.232, P < 0.001) and interval from the index pregnancy to chemotherapy were independent factors affecting pregnancy intention. Among the 36 pregnancies occurring within 12 months postchemotherapy, only one choriocarcinoma occurred, and 20 culminated in induced abortions (55.6%). CONCLUSIONS: After floxuridine-based chemotherapy, the pregnancy rate of GTN patients after fertility-preserving treatment is comparable to that of the normal population. Pregnancy losses within one year after chemotherapy completion are mainly caused by induced abortion.

Three-dimensional turbo-spin-echo amide proton transfer-weighted mri for cervical cancer: A preliminary study.

BACKGROUND: Amide proton transfer-weighted (APTw) imaging has shown great potential in the diagnosis of cancer, but has yet not been well studied in cervical cancer. PURPOSE: To evaluate the image quality and clinical feasibility of APTw MRI for cervical cancer. STUDY TYPE: Prospective. POPULATION: In all, 75 patients with cervical lesions and 49 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0 T, 3D turbo spin echo (TSE) APTw sequence. ASSESSMENT: Three radiologists, blinded to the clinical data, independently evaluated APTw image quality with a 5-point Likert scale on 64 patients with pathologically confirmed cervical cancer. APT values, calculated based on asymmetry of acquired Z-spectrum with respect to water frequency, using 3D turbo spin echo volume acquisition with B0 correction, were independently measured by two radiologists, twice for each observer, on 52 cervical cancer lesions and 49 normal cervical stroma with a mean region of interest area of 638.6 mm2 and 557.5 mm2 , respectively. STATISTICAL TESTS: Interobserver agreement was evaluated by Kendall's W test. Intra- and interobserver interclass correlation coefficients (ICC) were computed. Student's t-test was used to compare the differences of APT values between cervical cancer and normal cervix; receiver operating characteristic analysis was performed. RESULTS: Most cases revealed good APTw image quality with excellent agreement (Kendall's W = 0.850, P < 0.001). APT values of cervical cancer and normal cervical stroma were 2.745 ± 0.065 and 1.853 ± 0.059, respectively, with a significant difference (P < 0.0001). Intraobserver ICCs were 0.963 and 0.960 for two readers. Interobserver ICC was 0.993. Area under the curve (AUC) for differentiating cervical cancer from normal cervical stroma was 0.927. The feasible threshold value for AUC was determined as 2.221 with sensitivity of 84.62% and specificity of 83.66%. DATA CONCLUSION: 3D TSE APTw MRI is feasible in cervical cancer. Cervical cancer showed significantly higher APT values than normal cervix. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1318-1325.

Safety and fertility outcomes after the conservative treatment of endometrioid borderline ovarian tumours.

BACKGROUND: Because of the rarity of endometrioid borderline ovarian tumours (EBOTs), there is a paucity of data concerning the natural history and prognosis of this condition. Thus, the objective of our study was to establish the feasibility of fertility preservation in young women with EBOTs, as well as their oncological and reproductive outcomes. METHODS: Consecutive patients with EBOTs, treated at a tertiary referral centre during a span of 22 years, were retrospectively analysed. Recurrence-free interval, as well as its association with the type of surgery and with other clinical and pathological features, was assessed using the Kaplan-Meier and Cox proportional hazards methods. RESULTS: Of the 59 patients studied, the median follow-up time was 30 months (range, 6-177 months). Nine (15.3%) patients developed 13 recurrences 6-137 months after the initial surgeries, including three patients (5.1%; n = 3/59) who developed six invasive recurrences 8, 18 and 68 months after their initial surgeries. Conservative surgery showed a tendency towards a high recurrence rate (17.2% versus 13.3%); however, this difference was not significant (p = 0.45). The 5-year recurrence-free survival rate was significantly higher in the oophorectomy group than in the cystectomy group (p = 0.001). Cox regression analysis showed that none of the variables assessed were associated with an increased hazard ratio for recurrence, except for a younger age at diagnosis (p = 0.021). Of 20 patients who attempted to conceive, three pregnancies among two patients (10.0%) resulted in two live births. CONCLUSIONS: Conservative surgery with unilateral adnexectomy can be proposed for young women with EBOTs with fertility desire; however, the reproductive result is not satisfactory. In addition, careful evaluations of the endometria should be offered during the initial surgery and follow-up period. TRIAL REGISTRATION: Retrospectively registered.

Evaluation and suggestions for improving the FIGO 2000 staging criteria for gestational trophoblastic neoplasia: A ten-year review of 1420 patients.

BACKGROUND: To re-evaluate the efficacy of the prognostic factors currently employed in the treatment of malignant gestational trophoblastic neoplasia. METHODS: Clinical data from the Gestational Trophoblastic Disease (GTD) Center at Peking Union Medical Hospital (PUMCH) collected between January 2002 and December 2013 were retrospectively analyzed. Univariate and multivariate analyses of prognostic factors were performed using the Cox proportional hazards model. A new hazard ratio (HR)-based prognostic scoring scale was established and compared with the original scoring system. RESULTS: In total, 1420 cases were included in the study (median follow-up=40months, overall complete remission (CR) rate=95.8%, relapse rate=7.1%, mortality rate=5.5%, median disease-free survival (DFS)=36months). Low-risk (0-6 points) and high-risk (≥6 points) patients exhibited CR rates of 99.8% (915/917) and 88.5% (445/503) and mortality rates of 0.3% and 15.1% (P<0.001), respectively. Univariate and multivariate analyses showed that age, pretreatment serum levels of human chorionic gonadotropin beta-subunit (ß-hCG) and maximum tumor diameter were not independent prognostic risk factors. Antecedent pregnancy, the interval from the index pregnancy, the number of metastases and a history of failed chemotherapy treatments were independent prognostic risk factors. By modifying the scoring system based on the variables identified in a Cox analysis, we significantly increased the area under the receiver operating characteristics (ROC) curve. CONCLUSION: Though effective, the accuracy of the International Federation of Gynecology and Obstetrics (FIGO) 2000 Trophoblastic Neoplasia Staging System requires improvement. Irrelevant prognostic factors should be removed, and the weights of other factors should be adjusted appropriately.

Transcriptome analysis in Cucumis sativus identifies genes involved in multicellular trichome development.

The regulatory gene network of unicellular trichome development in Arabidopsis thaliana has been studied intensively, but that of multicellular remains unclear. In the present study, we characterized cucumber trichomes as representative multicellular and unbranched structures, but in a spontaneous mutant, mict (micro-trichome), all trichomes showed a micro-size and stunted morphologies. We revealed the transcriptome profile using Illumina HiSeq 2000 sequencing technology, and determined that a total of 1391 genes exhibited differential expression. We further validated the accuracy of the transcriptome data by RT-qPCR and found that 43 genes encoding critical transcription factors were likely involved in multicellular trichome development. These 43 candidate genes were subdivided into seven groups: homeodomain, MYB-domain, WRKY-domain, bHLH-domain, ethylene-responsive, zinc finger and other transcription factor genes. Our findings also serve as a powerful tool to further study the relevant molecular networks, and provide a new perspective for investigating this complex and species-specific developmental process.

[The negative enrichment by immunomagnetic beads for tumor cells from malignant pleural effusions].

OBJECTIVE: To establish a method (negative enrichment by immunomagnetic beads) for detection of tumor cells in pleural effusions and to evaluate the sensitivity and specificity of the method for clinical application. METHODS: Five, 10, 20, 50 and 100 A549 (lung adenocarcinoma) cells were labeled with DAPI and added into 20 ml pleural effusions [containing (1 - 10)×10(6)cells] from heart failure patients, followed by immunomagnetic negative enrichment method. Recovered cancer cells were enumerated using a fluorescent microscope. Tumor cells were enriched from pleural effusion samples by means of density gradient centrifugation and negative enrichment by immunomagnetic beads method, followed by identification with cytology analysis (Wright's Giemsa's staining), immunofluorescence staining (IF) and fluorescence in situ hybridization (FISH) using centromere DNA probes of chromosome 7 and 8. Cytology, IF and FISH evaluations were performed in 53 pleural effusion samples, including 36 cases of malignant disease (25 male and 11 female patients aging 40 to 78 years, mean age (63 ± 9) and 17 cases of benign disease (8 male and 9 female patients aging 25 to 81 years, mean age (53 ± 18). RESULTS: After DAPI staining and mixing with pleural effusions from heart failure patients, the cell recovery rates of A549 cells evaluated under fluorescence microscope were 75%, 78%, 82%, 85%, 88%, and the average recovery rate was 81.6%. Using negative enrichment method and density gradient centrifugation combined with cytology analysis, the positive rates of tumor cells in 36 malignant pleural effusion samples were 81% (29/36) and 61% (22/36), respectively (χ(2) = 4.00, P = 0.039). Using negative enrichment method combined with IF, the positive rate of CK18(+), DAPI(+), CD(45)(-) cells was 100%. Moreover, using negative enrichment method combined with FISH analysis, the positive rate of tumor cells was 86% (31/36), much higher than that using density gradient centrifugation combined with cytology analysis (χ(2) = 5.818, P = 0.012). In 17 cases of benign pleural effusions, using negative enrichment method combined with IF, the positive rate was 100%. But other methods didn't find cancer cells from benign pleural effusions. CONCLUSIONS: It was applicable to enrich tumor cells from pleural effusions using negative enrichment method by immunomagnetic beads. This method combined with cytology analysis or FISH significantly enhanced the sensitivity and specificity of tumor cell detection in pleural effusions. But it was difficult to distinguish cancer cells from mesothelial cells using immunofluorescence staining with CK18, DAPI and CD(45) label. More specific markers were needed to recognize tumor cells from pleural effusions.

The impact of pulmonary metastases on therapeutic response and prognosis in malignant gestational trophoblastic neoplasia patients: a retrospective cohort study.

AIM: The lung is the most common site of metastasis for gestational trophoblastic neoplasia (GTN). However, the level of influence of lung metastases on the prognosis of GTN and the degree to which lung metastases are considered in assessments of disease treatment options are unclear. Moreover, it is unclear which characteristics of lung metastases impact the disease. In this study, we evaluated the influence of lung metastases on the clinical course of GTN and identified lung imaging characteristics that impact treatment outcomes. METHODS: A retrospective cohort study was conducted on GTN patients treated at Peking Union Medical College Hospital between 2002 and 2018. The baseline characteristics, first-line treatment outcomes and final outcomes of patients with lung metastases (Group 1) and those without lung metastases (Group 2) were compared. RESULTS: The emergence of resistance occurred significantly more frequently in Group 1 (n = 994) than in Group 2 (n = 570) (19.52% versus 14.56%, p = 0.019), and the death rate was higher in Group 1 (0.91% versus 0%, p = 0.031). Among the patients treated with multi-agent chemotherapy, the rate of resistance and the number of treatment courses were significantly higher in Group 1 than in Group 2 (p = 0.002 and < 0.001, respectively). The lung imaging characteristics that impacted prognosis included the number of nodules, whether there were multiple nodules or a single nodule, and the number of nodules sized >1 cm. Multivariate analysis showed that a nodule measuring ≥1.8 cm was an independent risk factor for first-line treatment resistance and recurrence. CONCLUSION: Although pulmonary metastases do not affect overall survival in GTN patients, the presence of lung metastases before treatment is associated with increased risk of disease recurrence and resistance to first-line multidrug chemotherapy, especially when pulmonary nodules are larger than 1.8 cm. CLINICAL TRIAL REGISTRATION: N.A.

Prognosis and Prognostic Factors of Serous Borderline Tumor-Micropapillary Variant: Retrospective Study of 200 Patients with Long-Term Follow-Up.

Objective: To determine the oncofertility outcomes and prognostic factors in a large series of serous borderline ovarian tumor-micropapillary variant (SBOT-M) with a long-term follow-up. Methods: Consecutive patients with SBOT-Ms treated from two affiliated hospitals of the Chinese Academy of Medical Sciences were retrospectively reviewed. Prognostic factors on invasive recurrence, disease-free survival (DFS), and overall survival were analyzed, and outcomes of patients treated with conservative and radical surgery were compared. Results: From 2000 to 2020, 200 patients were identified and followed. After a median follow-up of 68 months, 81 patients relapsed. In the multivariate analyses, younger age at diagnosis and conservative surgery that preserved fertility potential were independently associated with worse DFS (p = 0.018 and <0.001, respectively). Twenty-three patients experienced invasive recurrence, and seven died of progressive disease. Multivariate analysis showed that nulliparous and advanced FIGO stage were independently adversely associated with lethal recurrence (p = 0.022 and 0.029, respectively). Only advanced FIGO stage at diagnosis was associated with worse overall survival at univariate analysis (p = 0.02). Among 61 patients attempting conception, 37 achieved 44 pregnancies and resulted in 32 live births. Conclusions: In this series, patients with SBOT-M have an acceptable oncofertility outcomes. The use of conservative surgery was independently associated with worse DFS, but without an impact on neither invasive relapse nor on overall survival. Patients with advanced FIGO stages had a significantly higher risk of lethal recurrence and worse overall survival, suggesting that adequate staging surgery and intensive postoperative surveillance should be warranted.

Large-scale synthesis of ultrafine Fe3C nanoparticles embedded in mesoporous carbon nanosheets for high-rate lithium storage.

Fe3C modified by the incorporation of carbon materials offers excellent electrical conductivity and interfacial lithium storage, making it attractive as an anode material in lithium-ion batteries. In this work, we describe a time- and energy-saving approach for the large-scale preparation of Fe3C nanoparticles embedded in mesoporous carbon nanosheets (Fe3C-NPs@MCNSs) by solution combustion synthesis and subsequent carbothermal reduction. Fe3C nanoparticles with a diameter of ∼5 nm were highly crystallized and compactly dispersed in mesoporous carbon nanosheets with a pore-size distribution of 3-5 nm. Fe3C-NPs@MCNSs exhibited remarkable high-rate lithium storage performance with discharge specific capacities of 731, 647, 481, 402 and 363 mA h g-1 at current densities of 0.1, 1, 2, 5 and 10 A g-1, respectively, and when the current density reduced back to 0.1 A g-1 after 45 cycles, the discharge specific capacity could perfectly recover to 737 mA h g-1 without any loss. The unique structure could promote electron and Li-ion transfer, create highly accessible multi-channel reaction sites and buffer volume variation for enhanced cycling and good high-rate lithium storage performance.

Correction: Large-scale synthesis of ultrafine Fe3C nanoparticles embedded in mesoporous carbon nanosheets for high-rate lithium storage.

[This corrects the article DOI: 10.1039/D1RA08516F.].

MRI-based radiomics analysis improves preoperative diagnostic performance for the depth of stromal invasion in patients with early stage cervical cancer.

BACKGROUND: The depth of cervical stromal invasion is one of the important prognostic factors affecting decision-making for early stage cervical cancer (CC). This study aimed to develop and validate a T2-weighted imaging (T2WI)-based radiomics model and explore independent risk factors (factors with statistical significance in both univariate and multivariate analyses) of middle or deep stromal invasion in early stage CC. METHODS: Between March 2017 and March 2021, a total of 234 International Federation of Gynecology and Obstetrics IB1-IIA1 CC patients were enrolled and randomly divided into a training cohort (n = 188) and a validation cohort (n = 46). The radiomics features of each patient were extracted from preoperative sagittal T2WI, and key features were selected. After independent risk factors were identified, a combined model and nomogram incorporating radiomics signature and independent risk factors were developed. Diagnostic accuracy of radiologists was also evaluated. RESULTS: The maximal tumor diameter (MTD) on magnetic resonance imaging was identified as an independent risk factor. In the validation cohort, the radiomics model, MTD, and combined model showed areas under the curve of 0.879, 0.844, and 0.886. The radiomics model and combined model showed the same sensitivity and specificity of 87.9% and 84.6%, which were better than radiologists (sensitivity, senior = 75.7%, junior = 63.6%; specificity, senior = 69.2%, junior = 53.8%) and MTD (sensitivity = 69.7%, specificity = 76.9%). CONCLUSION: MRI-based radiomics analysis outperformed radiologists for the preoperative diagnosis of middle or deep stromal invasion in early stage CC, and the probability can be individually evaluated by a nomogram.

[Relationship between MTA1 expression and invasive and metastatic ability of cervical cancer cell].

OBJECTIVE: To investigate the relationship between metastasis-associated gene 1 (MTA1) expression and invasive and metastatic ability of cervical cancer cell. METHODS: Three kinds of plasmids pcDNA3 (control group), pcDNA3-MTA1 (MTA1 group) and pSilencer3.1-MTA1-siRNA (MTA1-siRNA group) were transfected into human cervical cancer cell line CaSki cells. Reverse transcription (RT)-PCR and western blot were used to detected MTA1 mRNA and protein expressions. The effects of MTA1 expression on CaSki cell growth and proliferation, cell migration, adhesion and invasion, and cell cycles were tested by methyl thiazolyl tetrazolium (MTT), clone formation experiment, wound-healing assay, transwell assay, adhesion assay and flow cytometry, respectively. In animal experiment, three groups of cells were inoculated to BALB/c nude mouse subcutaneously to observe tumor formation ability. RESULTS: Compared with control group, MTA1 mRNA and protein were significantly overexpressed in MTA1 group, while MTA1-siRNA group showed lower MTA1 expression. Compared with control group, MTA1 group showed significantly accelerated cell growth; while MTA1-siRNA group showed decreased cell growth since the second day (P < 0.05). Clone formation number in control, MTA1 and MTA1-siRNA group were 133 ± 6, 169 ± 10 and 57 ± 5, respectively. MTA1 group showed accelerated cell formation, while MTA1-siRNA group showed the reverse effect compared with that in control group (P < 0.05). At 24, 48 and 72 hours after wounding, the healing ability of MTA1-siRNA group significantly lagged behind that in the control group, while MTA1 group showed accelerated cell healing ability. The adhesion rate of control, MTA1 and MTA1-siRNA group were (69.3 ± 3.6)%, (80.4 ± 5.6)% and (39.2 ± 7.4)% separately at 90 minutes after cell seeding. In contrast with control group, MTA1 group promoted the adhesion of CaSki cell to matrigel matrix, while MTA1-siRNA group inhibited the adhesion process (P < 0.05). In the migration assay, the number of cells migrated to the bottom side of the membrane in control, MTA1 and MTA1-siRNA group were 153 ± 17, 247 ± 38 and 82 ± 10, respectively. The number of cells in the invasion assay were 231 ± 19, 354 ± 36 and 76 ± 7, respectively. Compared with the control group, MTA1 group significantly increased the migration and invasion ability, while MTA1-siRNA group showed lower cell migration and invasion ability (P < 0.05). In cell cycle experiment, no significant differences of cell proportions including G(1), S and G(2) stage were found among three groups (P > 0.05). In animal experiment, compared with control group, MTA1 group showed accelerated tumor formation and growth, while the MTA1-siRNA group showed the reverse effect (P < 0.05). CONCLUSIONS: MTA1 may play its roles to promote cervical cancer cell invasion, migration, adhesion, as well as cell growth and colony formation, while RNA interference against MTA1 may decrease the malignant phenotypes. This study shows that it will be an effective beginning to explore metastasis mechanisms and cancer gene therapy strategy targeting MTA1 in cervical cancer.

Higher Red Blood Cell Distribution Width is a Poor Prognostic Factor for Patients with Chronic Myeloid Leukemia.

PURPOSE: Red blood cell distribution width (RDW) has been considered as a potential indicator of the effects of treatment or as a prognostic indicator for various malignancies. Most chronic myeloid leukemia (CML) patients are in the chronic phase, but some have transformed to accelerated phase or blast phase (blast crisis). However, the clinical significance of RDW in CML remains limited. PATIENTS AND METHODS: In the present study, detailed clinical information and the RDW of 168 healthy people and 153 CML patients (106 patients for the training cohort and 47 patients for the validation cohort) were retrospectively assessed. RESULTS: Multivariate analysis demonstrated that patient age (OR, 1.081; 95CI% 1.039~1.125; p < 0.001), platelet counts (OR, 0.997; 95CI% 0.994~0.999; p = 0.001) and RDW at admission (OR,1.469; 95CI% 1.121~1.925; p = 0.005) were significantly associated with the patients with advanced phase. Among CML patients in the chronic phase, higher RDW was significantly associated with overall survival (OS; p = 0.0008) and the event-free survival (EFS; p = 0.0221) among CML patients with chronic phase, but not with Transformation-free survival (TFS; p = 0.0821). Furthermore, higher RDW was associated with higher mortality compared to patients with low RDW (CML-associated deaths; p < 0.0001). In addition, a decline in RDW is associated with the treatment of CML patients with tyrosine kinase inhibitors, especially at 6 and 12 months after the start of treatment. CONCLUSION: Higher RDW is a potential prognostic biomarker for chronic CML patients.

Three-dimensional turbo-spin-echo amide proton transfer-weighted and intravoxel incoherent motion MR imaging for type I endometrial carcinoma: Correlation with Ki-67 proliferation status.

BACKGROUND: To evaluate 3-dimensional amide proton transfer weighted (APTw) imaging for type I endometrial carcinoma (EC), and investigate correlations of Ki-67 labelling index with APTw and intravoxel incoherent motion (IVIM) imaging. METHODS: 54 consecutive patients suspected of endometrial lesions underwent pelvic APTw and IVIM imaging on a 3 T MR scanner. APTw values and IVIM-derived parameters (Dt, D*, f) were independently measured by two radiologists on 22 postoperative pathological confirmed of type I EC lesions. Results were compared between histological grades and Ki-67 proliferation groups. ROC analysis was performed. Pearson's correlation analysis was performed for APTw values and IVIM-derived parameters with Ki-67 labeling index. RESULTS: APTw values and Dt, D*, f of all type I EC were 2.9 ± 0.1%, 0.677 ± 0.027 × 10-3 mm2/s, 31.801 ± 11.492 × 10-3 mm2/s, 0.179 ± 0.050 with inter-observer ICC 0.996, 0.850, 0.956, 0.995, respectively. APTw values of Ki-67 low-proliferation group (<30%, n = 8) were 2.5 ± 0.2%, significantly lower than the high-proliferation group (>30%, n = 14) with APTw values of 3.1 ± 0.1% (p = 0.016). Area under the curve was 0.768. APTw values of type I EC were moderately positively correlated with Ki-67 labelling index (r = 0.583, p = 0.004). There was no significant difference of Dt (p = 0.843), D* (p = 0.262), f (p = 0.553) between the two groups. No correlation was found between IVIM-derived parameters and Ki-67 labelling index (Dt, p = 0.717; D* p = 0.151; f, p = 0.153). CONCLUSION: 3D TSE APTw imaging is a feasible approach for detecting type I EC. Ki-67 labeling index positively moderately correlates with APTw not with IVIM.

Non-invasive Differentiation of Endometrial Adenocarcinoma from Benign Lesions in the Uterus by Utilization of Amide Proton Transfer-Weighted MRI.

PURPOSE: To evaluate the utility of three-dimensional (3D) amide proton transfer-weighted (APTw) imaging for differentiation of endometrial adenocarcinoma and uterine benign lesions. PROCEDURES: This prospective study enrolled 22 normal volunteers and 113 patients with suspicious uterine lesions, including endometrial adenocarcinoma, leiomyoma, and adenomyosis. Pelvic APTw MRI was performed on a 3-T MRI scanner with default APTw parameters. Two radiologists blindly evaluated uterine lesion APTw image quality by a 3-point Likert scale and independently measured APTw values on images with excellent to good image quality. Inter-reader agreement was evaluated. The Mann-Whitney U test with Bonferroni correction was used to compare the differences among different types of uterine lesions. A receiver operating characteristic analysis was performed. RESULTS: A total of 111 lesions (33 endometrial adenocarcinoma, 26 leiomyoma, and 52 adenomyosis lesions) from 99 patients revealing a majority of good quality with excellent inter-reader agreement were included for the image quality evaluation. APTw values of endometrial adenocarcinoma were 2.9 ± 0.1 %, significantly higher than those of leiomyoma (1.9 ± 0.1 %), adenomyosis (2.2 ± 0.1 %), and normal uterine myometrium (1.9 ± 0.1 %) (all p < 0.0001). The area under the receiver operating characteristic curve for differentiating endometrial adenocarcinoma from leiomyoma, adenomyosis, and myometrium was 0.87, 0.85, and 0.91, respectively. Feasible threshold APTw values of each group were determined as 2.4 %, 2.7 %, and 2.4 % with a sensitivity of 83.3 %, 76.7 %, and 83.3 % and a specificity of 83.3 %, 81.6 %, and 86.4 %, respectively. CONCLUSIONS: Malignant endometrial adenocarcinoma had significantly higher APTw values than leiomyoma, adenomyosis, and normal uterine myometrium. Our study adds to the growing body of validation on 3D APTw imaging and uterine lesions.