Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China's real world.

BACKGROUND: Endometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China's real world. METHODS: This retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤ 45 years old) and non-young (> 45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT) ± VBT. RESULTS: The study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT ± VBT and those who received VBT alone. CONCLUSIONS: In the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT.

Practice patterns of adjuvant radiotherapy in women with stage I to II endometrial carcinoma: a real-world multi-institutional analysis in China.

BACKGROUND: This study aimed to report clinical practice patterns of postoperative radiotherapy for stage I to II endometrial carcinoma (EC) patients treated in 13 Chinese medical centers. METHODS: We included early stage EC patients treated by hysterectomy and adjuvant RT between 2003 and 2017 from 13 institutions. Patients were classified into 4 risk groups based on ESMO-ESGO-ESTRO recommendations (2014). RESULTS: A total of 1,227 cases were analyzed. Along the 15 years of the study, an increasing tendency was found towards administration for vaginal brachytherapy (VBT) alone, while the proportion of external beam pelvic radiotherapy (EBRT) alone remained stable in the corresponding period. When radiation modalities were stratified by risk groups, proportion of VBT alone significantly increased in all risk groups. The higher the risk, the later VBT became the main adjuvant treatment modality. However, EBRT alone or with VBT remained the main adjuvant method for high-risk patients. There were 13 dose-fractionation schemes for VBT alone with the scheme of 30 Gy in 6 fractions prescribed at 0.5cm under the vaginal mucosa accounting for most. There were 17 schemes for VBT boost and the most common schedule was 10 Gy in 2 fractions. The upper 3-5cm part of vagina was the most frequent target. 89.6% of the practitioners performed two-dimensional VBT technique. The median dose for EBRT was 50 Gy. From 2003 to 2017, conventional radiotherapy was gradually replaced by three-dimensional conformal radiotherapy modality and intensity modulated radiotherapy. CONCLUSION: We report a significant shift from EBRT to VBT alone for high-intermediate-risk, intermediate-risk and low-risk EC patients from 2003 to 2017 while EBRT remained the main radiation modality for high-risk early stage patients. There has been remarkable heterogeneity among VBT dose fractionation schedules across China. TRIAL REGISTRATION: The clinical trial ID was ChiCTR-PRC-17010712. It was authorized by the Institutional Review Board of Peking Union Medical College Hospital (N0. S-K139).

Overview of adjuvant radiotherapy on survival, failure pattern and toxicity in stage I to II endometrial carcinoma: a long-term multi-institutional analysis in China.

BACKGROUND: This research aimed to provide an overview of the impact of adjuvant vaginal brachytherapy (VBT) and external beam pelvic radiotherapy (EBRT) with or without VBT on survival in stage I to II EC patients in China from a long-term multi-institutional analysis. METHODS: We retrospectively analyzed stage I to II EC patients from 13 institutions treated between 2003 and 2015. All patients underwent surgical staging and received adjuvant RT. Patients were divided into groups of low-risk (LR), intermediate-risk (IR), high-intermediate-risk (HIR) and high-risk (HR). Survival statistics, failure pattern, and toxicity of different radiation modalities in different risk groups were analyzed. RESULTS: A total of 1048 patients were included. HR disease represented 27.6%, HIR 17.7%, IR 27.7% and LR 27.1%, respectively. Endometrioid adenocarcinoma (EAC) and non-endometrioid carcinoma (NEC) accounted for 92.8 and 7.2%. A total of 474 patients received VBT alone and 574 patients received EBRT with or without VBT. As for EAC patients, the 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rate was: 94.6, 90.4, 93.0 and 91.6%, respectively. For LR patients, EBRT (with or without VBT) seemed to be a risk factor. With the higher risk category, the survival benefit of EBRT gradually became remarkable. EBRT (with or without VBT) significantly increased DFS, LRFS and DMFS compared to VBT alone in the HR group (p < 0.05). Distant metastasis was the main failure pattern for all risk groups. As for NEC patients, the 5-year OS, DFS, LRFS and DMFS rate was: 93.4, 87.2, 91.7 and 89.3%, respectively. As for toxicity, EBRT (with or without VBT) significantly increased the incidence of grade 1-2 gastrointestinal, urinary, and hematological toxicity. CONCLUSIONS: For stage I to II EC patients, EAC accounted for the majority and had better prognosis than NEC. For EAC patients, VBT alone resulted in comparable survival to EBRT in the LR, IR and HIR groups, while EBRT significantly increased survival in the HR group. EBRT had higher rate of toxicity than VBT.

Directional atherectomy and drug-coated balloon angioplasty vs. bare nitinol stent angioplasty for femoropopliteal artery lesions.

Background: The present study evaluated the prognosis of directional atherectomy (DA)+drug-coated balloon (DCB) angioplasty for femoropopliteal artery lesions compared with bare nitinol stent (BNS). Patients and methods: This retrospective cohort study included patients with femoropopliteal artery lesions who underwent percutaneous endovascular surgery between January 2016 and June 2019. The primary outcome was the primary patency rate after 12, 24, and 36 months; the secondary outcomes comprised incidence of flow-limiting dissections, technical success, limb salvage, and all-cause death. Results: During the study period, 110 (44%) patients underwent DA+DCB, and 140 (56%) patients underwent bare nitinol stent (BNS). There were no differences in the 12- and 24-month patency rates of the two groups (98.2% vs. 93.6% and 68.2% vs. 60.0%, both p>.05). The 36-month primary patency rate in the DA+DCB group was significantly higher than that of the BNS group (27.3% vs. 15.7%, p=.003). The technical success rate and all-cause death were similar between groups (p>.05). Flow-limiting dissections occurred more frequently in the BNS group than in the DA+DCB group (27.9% vs. 10.9%, p=.033). After adjustment for potential confounders, such as sex, smoking, hypertension, hyperlipidemia, ABI after surgery, TASC II B, lesion length ≥15 cm, two-vessel runoff, and three-vessel runoff, the HR for primary patency rate comparing BNS to DA+DCB was 2.61 (95%CI: 1.61-4.25). Conclusions: In this retrospective cohort study, DA+DCB was associated with a higher 30-month primary patency rate and a lower flow-limiting dissection incidence than BNS.

Treatment optimization of pelvic external beam radiation and/or vaginal brachytherapy for patients with stage I to II high-risk Endometrioid adenocarcinoma: a retrospective multi-institutional analysis.

BACKGROUND: For stage I to II high-risk endometrioid adenocarcinoma patients, the optimal adjuvant radiotherapy modality remains controversial. The present study sought to optimize the treatment of pelvic external beam radiation (EBRT) with/or vaginal brachytherapy (VBT) for high-risk endometrioid adenocarcinoma patients in multiple radiation oncology centers across China. METHODS: This article retrospectively reviewed stage I to II patients with resected endometrioid adenocarcinoma treated at 13 radiation centers from 1999 to 2015. Patients were eligible if they had high-risk features (stage IB Grade 3 disease or stage II Grade 1-3 disease) on the basis of ESMO-ESGO-ESTRO risk group consensus. RESULTS: A total of 218 patients were included. Fifty-one patients received EBRT, 25 patients received VBT, and 142 patients were administered EBRT combined with VBT. The three groups were comparable in baseline characteristics, except the proportion of stage IB and Grade 3 disease in the VBT group was significantly higher and their age was older. Survival analysis showed that OS, DFS, LRFS and DMFS were significantly different among the three groups. Two out of three groups were compared with each other, and results demonstrated that DFS, LRFS and DMFS were worse in the VBT group than in the EBRT or EBRT + VBT group. The 3-year OS rates were 95.2, 85.2 and 95.1% in the EBRT, VBT and EBRT + VBT groups, respectively (p = 0.043). There was no significant difference in survival outcomes between EBRT group and EBRT + VBT group. A propensity matching analysis was performed to eliminate group differences. The results demonstrated that DFS and LRFS were significantly improved in the pelvic radiation group compared to the VBT group. Distant failure accounted for most of the failure patterns. Patients in the VBT group had significantly increased local and regional recurrence rates than patients in the EBRT or EBRT + VBT group. Acute and chronic radiation-induced toxicities were well tolerated for all patients. CONCLUSION: For patients with postoperative stage I to II high-risk endometrioid adenocarcinoma, compared with VBT alone, radiotherapy modalities including EBRT significantly improved DFS, LRFS and DMFS with tolerable adverse effects. Overall survival was not significantly different between EBRT and EBRT + VBT modalities.

Trans-Septal Myocardial Biopsy in Hypertrophic Cardiomyopathy Using the Liwen Procedure: An Introduction of a Novel Technique.

OBJECTIVE: The purpose of this study was to evaluate the feasibility and safety of myocardial biopsy using a new approach, the Liwen procedure. BACKGROUND: Myocardial biopsy is essential when other methods could not differentiate other etiologies from hypertrophic obstructive cardiomyopathy (HOCM). Our previous work using intramyocardial radiofrequency ablation for hypertrophic obstructive cardiomyopathy (Liwen procedure) may provide another approach to obtain the myocardial samples. METHOD: Seventeen patients with HOCM were enrolled for biopsies through percutaneously accessed intramyocardial septum and evaluated possible complications. RESULTS: We obtained 31 specimens from 17 patients with a success rate of sample acquisition 100.0%. The number of myocardial samples taken per patient was 1.8 ± 0.8, and the average length of all samples was 16.7 ± 5.6 mm which could be used for pathological diagnosis. The complications included pericardial effusion with and without tamponade in one patient (5.9%), and no incidence of nonsustained and sustained ventricular tachycardia, conduction abnormity, perforation, stroke, and pneumothorax. The inhospital and 30-day mortality was 0%. CONCLUSION: This study has shown that myocardial biopsy of the Liwen procedure is relatively safe and technically feasible with adequate tissue sampling, which may help pathological diagnosis and further research of HOCM of diverse etiologies. This trial is registered with NCT04355260.

Potentialities of multi-b-values diffusion-weighted imaging for predicting efficacy of concurrent chemoradiotherapy in cervical cancer patients.

BACKGROUND: To testify whether multi-b-values diffusion-weighted imaging (DWI) can be used to ultra-early predict treatment response of concurrent chemoradiotherapy (CCRT) in cervical cancer patients and to assess the predictive ability of concerning parameters. METHODS: Fifty-three patients with biopsy proved cervical cancer were retrospectively recruited in this study. All patients underwent pelvic multi-b-values DWI before and at the 3rd day during treatment. The apparent diffusion coefficient (ADC), true diffusion coefficient (Dslow), perfusion-related pseudo-diffusion coefficient (Dfast), perfusion fraction (f), distributed diffusion coefficient (DDC) and intravoxel diffusion heterogeneity index(α) were generated by mono-exponential, bi-exponential and stretched exponential models. Treatment response was assessed based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1) at 1 month after the completion of whole CCRT. Parameters were compared using independent t test or Mann-Whitney U test as appropriate. Receiver operating characteristic (ROC) curves was used for statistical evaluations. RESULTS: ADC-T0 (p = 0.02), Dslow-T0 (p <  0.01), DDC-T0 (p = 0.03), ADC-T1 (p <  0.01), Dslow-T1 (p <  0.01), ΔADC (p = 0.04) and Δα (p <  0.01) were significant lower in non-CR group patients. ROC analyses showed that ADC-T1 and Δα exhibited high prediction value, with area under the curves of 0.880 and 0.869, respectively. CONCLUSIONS: Multi-b-values DWI can be used as a noninvasive technique to assess and predict treatment response in cervical cancer patients at the 3rd day of CCRT. ADC-T1 and Δα can be used to differentiate good responders from poor responders.

An approach for mechanical property optimization of cell-laden alginate-gelatin composite bioink with bioactive glass nanoparticles.

Alginate-gelatin (Alg-Gel) composite hydrogel is extensively used in extrusion-based bioprinting. Although Alg-Gel blends possess excellent biocompatibility and printability, poor mechanical properties have hindered its further clinical applications. In this study, a series of design by incorporating bioactive glass nanoparticles (BG) (particle size of 12 and 25 nm) into Alg-Gel hydrogel have been considered for optimizing the mechanical and biological properties. The composite Alg-Gel-BG bioink was biophysically characterized by mechanical tests and bioprinting practice. Biocompatibility of Alg-Gel-BG bioink was then investigated by bioprinting mouse dermal fibroblasts. Mechanical tests showed enhanced stiffness with increasing concentration of incorporated BG. But the maximum concentration of BG was determined 1.0 wt% before blends became too viscous to print. Meanwhile, the incorporation of BG did not affect the highly porous structure and biodegradation of Alg-Gel hydrogel, while the mechanical strength and printability were enhanced. In addition, the cellular proliferation and adhesion in the bioprinted constructs were significantly enhanced by BG (12 nm), while extension was not affected. Therefore, our strategy of incorporating BG in Alg-Gel composite hydrogel represents an easy-to-use approach to the mechanical reinforcement of cell-laden bioink, thus demonstrating their suitability for future applications in extrusion-based bioprinting.

Low-Dose X-ray Excited Photodynamic Therapy Based on NaLuF4:Tb3+-Rose Bengal Nanocomposite.

X-ray excited photodynamic therapy (X-PDT), which utilizes X-rays as the energy source and X-ray luminescent nanoparticles (XLNPs) as the transducer to excite photosensitizers (PS), resolves the penetration problem of light in traditional PDT to enable the treatment of deep-seated tumors. Nevertheless, the high X-ray dosage used in X-PDT hampers its potential applications in clinics. In this study, to alleviate the dose problem, ß-NaLuF4:Tb3+ spherical nanoparticles (NPs) with ultrastrong green X-ray excited optical luminescence (XEOL) due to the less nonradiative relaxation probability and high X-ray absorption mass coefficient, which perfectly matches the absorption spectrum of a photosensitizer named rose bengal (RB), were synthesized and employed as the energy transducer for X-PDT. After covalent conjugation of NPs with RB, high Förster resonant energy transfer (FRET) efficiency up to 94.29% was achieved, leading to high production of singlet oxygen. In vivo X-PDT efficacy was evaluated by nude mice with a HepG2 tumor xenograft. With excellent biocompatibility, the synthesized NPs-RB nanocomposite showed significant antitumor efficiency up to 80 ± 12.3% with a total X-ray dose of only 0.19 Gy, demonstrating the feasibility of low-dose X-PDT in vivo for the first time. The present work provides a promising platform for X-PDT in deep-seated tumors.

Vaginal dose of radical radiotherapy for cervical cancer in China: a multicenter study.

BACKGROUND: The posterior-inferior border of symphysis (PIBS) point system is a novel vaginal dose-reporting method and is a simple and reliable method proposed by the Medical University of Vienna proposed for both external-beam radiotherapy (EBRT) and brachytherapy (BT). In this multicenter study, we sought to first evaluate the vaginal radiation dose in Chinese cervical cancer patients according to the PIBS point system and then to analyze the factors influencing the dose distribution. METHODS: We collected data from the medical records of 936 cervical cancer patients who underwent concurrent radiochemotherapy at 13 different institutions in China. Radiation doses at points A, PIBS+ 2 cm, PIBS and PIBS-2 cm, International Commission on Radiation Units (ICRU)-R and ICRU-B were measured. RESULTS: The median total doses in EQD2α/ß = 3 at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 82.5 (52.7-392.1) Gy, 56.2 (51.4-82.1) Gy and 2.6 (0.9-7.4) Gy, respectively. The median total doses in EQD2α/ß = 3 at ICRU-R and ICRU-B were 77.5 (54.8-132.4) Gy and 79.9 (60.7-133.7) Gy, respectively. The mean vaginal reference length (VRL) was 4.6 ± 1.0 cm (median, 4.5 cm). In patients with VRL ≤4.5 cm, the mean total doses in EQD2α/ß = 3 at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 128.5, 60.7 and 0.8 Gy, respectively. In patients with VRL > 4.5 cm, the mean total doses at these three points were 68.9, 0.5 and 54.5 Gy, respectively. Classification of patients revealed significant differences (P < 0.05) between these two groups. CONCLUSIONS: With the PIBS point system, Chinese patients with a shorter VRL of < 4.5 cm received higher radiation doses at the PIBS+ 2 cm, PIBS and PIBS-2 cm points than European and American patients. Further studies are required to establish the dose-effect relationships with these points as references. The study was registered as a clinical trial (NCT03257475) on August 22, 2017.

Health-related quality of life in locally advanced cervical cancer patients treated with neoadjuvant therapy followed by radical surgery: A single-institutional retrospective study from a prospective database.

OBJECTIVE: To evaluate the health-related quality of life (HRQOL) in locally advanced cervical cancer (LACC) patients treated with neoadjuvant concurrent chemoradiation (CCRT) or radiation (RT) alone followed by radical surgery (RS). METHODS: In a single-center retrospective study from a prospective database, 275 FIGO Stage IB2-IIIB patients who underwent CCRT/RT + RS were included. HRQOL was prospectively assessed by EORTC QLQ-C30 and EORTC QLQ-CX24 prior to any treatment (baseline) and 6 months after surgery, respectively. RESULTS: A statistically significant and clinically relevant improvement in physical functioning (P < 0.001) and role functioning (P = 0.002, P = 0.031) was observed in patients receiving either CCRT+RS or RT + RS at follow-up. In addition, quality of life (QoL), physical functioning, and social functioning were better in the RT + RS group than the CCRT+RS group after treatment (P = 0.028, P = 0.010, P = 0.014). Symptom scores of fatigue decreased in both groups over time (P < 0.001, P = 0.004) while insomnia decreased only in the RT + RS group (P = 0.042). Worsened menopausal symptoms were documented in both groups at follow-up (P = 0.001, P = 0.047), while lymphedema was deteriorated only in patients receiving CCRT + RS (P < 0.001). Sexuality scores did not differ between groups or over time with the exception of sexual worry, which was deteriorated in patients receiving RT + RS (P = 0.042). CONCLUSIONS: QLQ-C30 functioning and tumor-related symptoms scores improved while lymphedema and menopausal symptoms worsened 6 months after neoadjuvant CCRT or RT alone followed by RS in LACC patients. Patients treated with RT + RS had a generally better HRQOL compared with those receiving CCRT+RS, though further validation with prospective randomized clinical trials is warranted.

Quantitative dual-channel FRET microscopy.

Acceptor-sensitized quantitative Förster resonance energy transfer (FRET) measurement (E-FRET) is mainly impeded by donor emission crosstalk and acceptor direct excitation crosstalk. In this paper, we develop a novel E-FRET approach (Lux-E-FRET) based on linear unmixing (Lux) of the fluorescence intensity ratio between two detection channels with each excitation of two different wavelengths. The two detection channels need not to selectively collect the emission of donor or acceptor, and the excitation wavelengths need not to selectively excite donor or acceptor. For a tandem FRET sensor, Lux-E-FRET only needs single excitation wavelength. We performed Lux-E-FRET measurements on our dual-channel wide-field fluorescence microscope for FRET constructs in living cells, and obtained consistent FRET efficiencies with those measured by other methods. Collectively, Lux-E-FRET completely overcomes all spectral crosstalks and thus is applicable to the donor-acceptor pair with larger spectral overlapping.

The Prognosis and Risk Stratification Based on Pelvic Lymph Node Characteristics in Patients With Locally Advanced Cervical Squamous Cell Carcinoma Treated With Concurrent Chemoradiotherapy.

BACKGROUND: The purpose of this study is to determine the prognostic significance of pelvic lymph node (PLN) characteristics and perform risk stratification in patients undergoing concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma. METHODS: We retrospectively reviewed the records of 609 patients with Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stage II to IVa who underwent concurrent chemoradiotherapy, compared overall survival (OS), distant metastasis-free survival (DMFS), and pelvic recurrence-free survival between patients with or without PLN involvement. We further analyzed prognostic factors for OS and DMFS including FIGO stage, tumor volume, and lymph node (LN) characteristics in 300 patients with PLN involvement. RESULTS: The 3-year OS rate was 81.7% versus 92.8% (P = 0.002) and the 3-year DMFS rate was 79.3% versus 92.7% (P = 0.006) in patients with or without PLN involvement, respectively. With univariable analysis, FIGO stage, LN-volume, LN-number, LN-diameter, and matted/necrotic LN affected both OS and DMFS. Based on multivariable analysis, we created a risk stratification model. For OS, the independent risk factors were FIGO stage III or IVa, LN-volume of 3 cm or more, LN-diameter of 1.5 cm or more, and matted/necrotic LN. The low-risk group (no risk factors), mid-risk group (1 or 2 risk factors), and high-risk group (3 or 4 risk factors) had a 3-year OS of 96.6%, 84.9%, and 64.7%, respectively (P = 0.005). For DMFS, LN-diameter of 1.5 cm or more, LN-number of 3 or more, and matted/necrotic LN were the independent risk factors. The subgroups for DMFS were the low-risk group (no risk factors), the mid-risk group (1 risk factor), and the high-risk group (2 or 3 risk factors), and the 3-year DMFS was 92.4%, 76.2%, and 64.6%, respectively (P = 0.001). CONCLUSIONS: The prognosis was significantly poorer for patients with high-risk lymph node characteristics. Using this risk stratification, we should select the most appropriate and individualized treatment modality to improve outcomes in those patients with a poorer prognosis.

Prognostic values of tumor size and location in early stage endometrial cancer patients who received radiotherapy.

OBJECTIVE: To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. METHODS: Data of patients who had been treated for stage I-II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failure-free survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell's C-index, calibration curves and receiver operating characteristic (ROC) curves. RESULTS: The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2-15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. CONCLUSION: Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

Downregulation of miR-181c-5p in Alzheimer's disease weakens the response of microglia to Aß phagocytosis.

Alzheimer's disease (AD) is an age-associated neurodegenerative disease. Recently, studies have demonstrated the potential involvement of microRNA-181c-5p (miR-181c-5p) in AD. However, the mechanism through which miR-181c-5p is responsible for the onset and progression of this disease remains unclear, and our study aimed to explore this problem. Differential expression analysis of the AD dataset was performed to identify dysregulated genes. Based on hypergeometric analysis, AD differential the upstream regulation genes miR-181c-5p was found. We constructed a model where SH-SY5Y and BV2 cells were exposed to Aß1-42 to simulate AD. Levels of tumor necrosis factor-alpha, interleukin-6, and IL-1ß were determined using enzyme-linked immunosorbent assay or reverse transcription quantitative polymerase chain reaction. Phosphorylation levels of p-P38 and P38 were detected by Western blot. The level of apoptosis in BV2 cells under Aß1-42 stress was exacerbated by miR-181c-5p mimic. Downregulated miR-181c-5p impaired the phagocytosis and degradation of Aß by BV2 cells. The release of proinflammatory cytokines in BV2 cells with Aß1-42 stress was alleviated by miR-181c-5p upregulation. Additionally, miR-181c-5p downregulation alleviated the phosphorylation of P38 in Aß1-42-induced SH-SY5Y cells. In conclusion, miR-181c-5p improves the phagocytosis of Aß by microglial cells in AD patients, thereby reducing neuroinflammation.

Efficacy and safety of bevacizumab in neoadjuvant and concurrent chemoradiotherapy for refractory cervical cancer patients.

A platinum-based concurrent chemoradiotherapy (CCRT) is the standard treatment for refractory cervical cancer (CC). However, the recurrence of disease and the occurrence of metastasis remain prevalent. We observed the long-term efficacy and safety of bevacizumab combined with neoadjuvant chemotherapy (NACT) and CCRT in refractory CC. A total of 62 patients with refractory CC were enrolled in this study from January 2016 to December 2019. The NACT regimen included bevacizumab (7.5 mg/kg), docetaxel (75 mg/m2), and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. The CCRT regimen included bevacizumab (7.5 mg/kg) and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. A dose of 45-50 Gy was prescribed for external beam radiotherapy (EBRT), while 30-35 Gy in 4-5 fractions was prescribed for brachytherapy (BT). Among the patients, 21 patients (33.9%) were at stages IIB-IIIB, 8 patients (12.9%) were at stage IIIC1, 19 patients (30.6%) were at stage IIIC2, and 14 patients (22.6%) were at stage IVB. Pelvic, para-aortic, supraclavicular, and inguinal lymph node metastases were discovered in 41 patients (66.1%). The median follow-up was 49.8 months (12.3-82.7 months). The median tumor volumes pre-treatment, after NACT, and before BT were 84.64 ± 53.15 cm3, 1.64 ± 13.15 cm3, and 0 ± 1.5 cm3, respectively. Complete clinical response (cCR) rates after NACT and EBRT were 35.5% and 66.1%, respectively. Four years after the diagnosis, the overall survival (OS) rate was 78.6%, the local region-free survival (LRFS) rate was 91.3%, the disease-free survival (DFS) rate was 70.6%, and the distant metastasis-free survival (DMFS) rate was 81.4%. A total of 29 patients (46.8%) experienced grade 3/4 hematological toxicity, 3 patients (4.8%) experienced grade 3 gastrointestinal toxicities, and none experienced grade 5 adverse events. Bevacizumab combined with NACT and CCRT significantly improved cCR and OS in refractory CC with acceptable toxicity.

A survey on brachytherapy training of gynecological cancer focusing on the competence of residents in China.

BACKGROUND: The brachytherapy is an indispensable treatment for gynecological tumors, but the quality and efficiency of brachytherapy training for residents is still unclear. METHODS: An anonymous questionnaire was designed to collect information on gynecological brachytherapy (GBT) training for radiation oncology residents from 28 training bases in China. The questionnaire content was designed based on the principle of competency based medical education (CBME). The Likert scale was employed to evaluate self-reported competence and comprehension regarding GBT. A total of 132 senior residents were included in the final analysis. RESULTS: 53.79% (71/132) of senior residents had experience in performing image-guided GBT, whereas 76.52% (101/132) had observed the procedure during their standardized residency training. The proportion of senior residents who reported having the self-reported competence to independently complete the GBT was 78.03% for intracavity GBT, 75.00% for vaginal stump GBT, and 50.03% for interstitial GBT, respectively. The number of successful completion of Interstitial, intracavity and vaginal GBT was correlated with the self- confidence of trainees after standardized training. In particular, the independent completion of interstitial GBT for more than 20 cases was an independent factor for the self-reported competence of senior residents. During the training period, 50.76% and 56.82% of the residents had not participated in the specialized examinations and professional GBT courses. CONCLUSIONS: The study revealed that the self-confidence of residents to independently complete brachytherapy was relatively high, and the specialized curriculum setting and training process assessment for brachytherapy training still need to be strengthened in the future.

BTG2 inhibits the proliferation, invasion, and apoptosis of MDA-MB-231 triple-negative breast cancer cells.

The purposes of this study were to investigate the effects of B cell translocation gene 2 (BTG2) on the proliferation, apoptosis, and invasion of triple-negative breast cancer and to provide an experimental basis for the future treatment of human triple-negative breast cancer. A pcDNA3.1-BTG2 eukaryotic expression vector was constructed and transfected into the MDA-MB-231 human triple-negative breast cancer cell line using lipofection. Then, relevant changes in the biological characteristics of the BTG2-expressing cell line were analyzed using MTT (tetrazolium blue), flow cytometry, and Transwell invasion chamber assays. Additionally, the effects of BTG2 expression on cyclin D1, caspase 3, and matrix metalloproteinases 1/2 (MMP-1/-2) expression were analyzed. Cell proliferation was significantly lower in the pcDNA3.1-BTG2-transfected group compared to the empty vector and blank control groups (p<0.05). There was no significant difference between the empty vector and blank control groups. FCM results demonstrated that there were significantly more cells in the G1 phase of the cell cycle and fewer S phase cells in the pcDNA3.1-BTG2 group than in the empty vector and blank control groups (p<0.05). Additionally, the proportion of cells that migrated across the membrane was significantly lower in the pcDNA3.1-BTG2 group than in the empty vector and blank control groups (p<0.05). Cyclin D1 and MMP-1/-2 expression were significantly lower in MDA-MB-231 cells transfected with pcDNA3.1-BTG2 as compared to the empty vector and blank control groups (p<0.05). Caspase 3 expression was significantly higher in MDA-MB-231 cells from the pcDNA3.1-BTG2 group compared to the empty vector and blank control groups (p<0.05). In conclusion, BTG2 may inhibit MDA-MB-231 proliferation and promote apoptosis. Additionally, BTG2 may also inhibit the invasion of MDA-MB-231 human triple-negative breast cancer cells.

Ultrasound-guided brachial plexus nerve block in a patient with a left palmar schwannoma: A case report.

RATIONALE: Ultrasound-guided brachial plexus block is a common anesthetic procedure used in upper extremity surgery. However, it may not be a suitable option for some patients. PATIENT CONCERNS: A 17-year-old woman with the left palmar schwannoma scheduled for surgical treatment received ultrasound-guided brachial plexus block. The anesthesia modalities of the disease were discussed. DIAGNOSES: Based on the patient's complaints and clinical appearance, provisional diagnosis of neurofibroma was considered. INTERVENTIONS: In this case, we present a case of ultrasound-guided axillary brachial plexus block used for upper extremity surgery in this patient. It was not easily and painlessly reduced in the surgery, although the visual analogue scale score was 0 and no motor movements of the left arm and palm were observed. The pain was relieved by intravenous injection of 50 mcg remifentanil. OUTCOMES: Immunohistochemically labeled pathological examination confirmed the mass to be a schwannoma. There was no need to apply additional analgesia after surgery, although the patient felt numbness in the left thumb for 3 days follow up. LESSONS: Even if there is painless when skin-cutting after implementation of brachial plexus block, the patient is painful when pulls the nerve around the tumor during excision. It is necessary to give an analgesic drug or anesthetize a single terminal nerve as a supplement for brachial plexus block in patients with schwannoma.

Bilateral visual loss after selective artery embolization in the neck for hemorrhage of malignant tumor.

INTRODUCTION AND IMPORTANCE: Currently, selective arterial embolization (SAE) has been widely applied for the treatment of many diseases due to its minimal invasiveness. But the complications caused by SAE can be serious. CASE PRESENTATION: Here, we report a case of a patient who experienced bilateral blindness 4 h after selective arterial embolization (SAE). A 67-year-old man, with a 13-year history of nasopharyngeal carcinoma, was admitted to our hospital for nasopharyngeal carcinoma hemorrhage and was scheduled for SAE. The patient did not have any thromboembolic complications. His had a platelet count of 43 × 109/L (range 150-400 × 109/L) and a prothrombin time (PT) of 9.3 s. The surgery was completed under local anesthesia. However, 4 h after the surgery, the patient complained of visual loss. We performed a fundoscopy examination, which showed bilateral ophthalmic artery embolism. CLINICAL DISCUSSION: Bilateral ophthalmic artery embolism is fatal to vision. When this occurs, it would be difficult to save the eyes. So, the relevant selection of the optimal properties of the used PVA and coil embolization materials is important during SAE. CONCLUSION: It is important to improve the existing understanding of the involvement various vessels during embolization of head and neck tumors. Furthermore, special and paramount attention is to be paid to the specific pre-operative angio-architecture, particular patient condition, and the prudent choice of embolic material to prevent the occurrence of ectopic embolization.