Specifically differentiated cells exhibit greater therapeutic efficacy than mesenchymal stem cells (MSCs), and extracellular vesicles (EVs) present therapeutic benefits similar to those of parental cells and fewer safety issues. Ovarian granulosa cells (OGCs) play a critical role in the pathogenesis of premature ovarian insufficiency (POI), a common gynecological disease that can cause infertility and has no effective treatment. Here, we investigated whether umbilical cord mesenchymal stem cells (UCMSCs) can differentiate into ovarian granulosa-like cells (GLCs) and whether GLC-EVs are more effective in restoring ovarian function than UCMSC-EVs are in POI model rats. Here, we differentiated rat UCMSCs (rUCMSCs) into GLCs in vitro using cytokines and hormones and isolated GLC-EVs. We then used chemotherapy-induced POI model rats to verify the ability of GLC-EVs to repair ovarian function. We found that GLCs/GLCs-EVs expressed granulosa cell markers (FOXL2 and FSHR). We demonstrated that GLC-EVs outperformed rUCMSC-EVs by restoring the estrous cycle and ovarian morphology, increasing the number of follicles, regulating serum hormone levels, and restoring fertility in POI model rats. Mechanistically, GLC-EVs showed enhanced ovarian tropism. Proteomic analysis identified PLAU as a key component of GLC-EVs, and subsequent antibody blockade experiments demonstrated that PLAU contributes to primordial follicle activation through promoting FOXO3A phosphorylation (pFOXO3A). This study provides the first proof that EVs derived from differentiated cells enhance therapeutic precision for POI, improve the tissue targeting of EV therapy, and provide a generalized strategy for clinical cell-free therapy.
Premature ovarian insufficiency (POI), which is defined as the loss of ovarian activity before the age of 40 leading to amenorrhea and infertility, is often induced in female patients treated with alkylating agents such as cyclophosphamide (CTX). Currently, the standard clinical management for POI is hormone replacement therapy, which alleviates symptoms but does not restore fertility. Although multiple previous studies have demonstrated that mesenchymal stem cells and their derived extracellular vesicles can protect ovarian function and restore fertility, whether concurrent EV intervention during chemotherapy can preserve ovarian reserve remains unclear. The rat umbilical cord mesenchymal stem cells derived extracellular vesicles (rUCMSC-EVs) in this study were isolated from the culture supernatant of rat umbilical cord mesenchymal stem cells (rUCMSC), and POI rat model was established via intraperitoneal injection of CTX and subcutaneous administration of busulfan. Concurrently with the chemotherapeutic drug injection, rUCMSC-EVs were injected into the ovaries. ELISA, histological assessment and mating experiments were used to evaluate ovarian function and reproductive outcomes. Additionally, ovarian granulosa cells were isolated and co-treated with CTX and rUCMSC-EVs to assess apoptosis and DNA repair capacity via flow cytometry and gene expression assays. Treatment with rUCMSC-EVs effectively counteracted CTX-induced ovarian damage, as evidenced by restored ovarian weight, improved follicular reserve (increased antral follicles and reduced atreic follicles), and elevated serum anti-Müllerian hormone (AMH) and estradiol (E2) levels. Consequently, EV-treated rats exhibited reduced ovarian fibrosis and apoptosis, resulting in improved pregnancy and live birth rates. Furthermore, in ovarian granulosa cells, compared to cells treated with CTX alone, co-treatment with CTX and EVs significantly reduced apoptosis and DNA damage, while upregulating the expression levels of key DNA repair molecules (including BRCA1, BRCA2, MRE11 and RAD51). Our study demonstrates that the combined intervention of rUCMSC-EVs and chemotherapy drugs can alleviate the apoptosis of ovarian granulosa cells, thereby preserving the ovarian function and improving the fertility of the POI rats. The reduction in granulosa cell apoptosis may be related to the enhancement of DNA damage repair capacity.
OBJECTIVES:To investigate the inhibitory effect of Escherichia coli outer membrane vesicles (E. coli-OMVs) on glioma proliferation and the underlying mechanism. METHODS:CCK-8 assay and EdU incorporation assay were used to determine the optimal concentrations of E. coli-OMVs and chlorpromazine (CPZ) for cell treatment. C6 glioma cells treated with 10 μg/mL E. coli-OMVs and 10 μmol/L CPZ were examined for PCNA and Ki67 expressions and cell cycle distribution using qRT-PCR, Western blotting, immunocytochemistry and flow cytometry. The expressions of β-catenin, cyclin D1, and c-Myc proteins in C6 cells were detected following treatment with OMVs in the presence or absence of CHIR99021. In a SD rat model bearing orthotopic glioma, the effects of intranasal PBS or OMVs (0.25, 0.5, 1.0 mg/kg) administration on tumor growth and PCNA and Ki67 expressions were observed using fluorescence imaging and immunohistochemistry. RESULTS:E. coli-OMVs within the concentrations of 2.5-10 μg/mL dose-dependently inhibited C6 cell viability, and such inhibitory effect was attenuated by 2.5, 5, and 10 μmol/L CPZ, which was the most effective at 10 μmol/L. The OMVs at 10 μg/mL significantly reduced EdU-positive cells, downregulated mRNA and protein expressions of PCNA and Ki67, and increased G0/G1-phase and decreased S-phase cell populations. These alterations were largely reversed by 10 μmol/L CPZ. Treatment with OMVs downregulated cellular expressions of β‑catenin, Cyclin D1, and c-Myc, which were partially restored by application of CHIR99021. In the tumor-bearing mice, intranasal OMVs administration dose-dependently decreased the relative fluorescence signals, slowed tumor growth, and reduced PCNA and Ki67 expressions. CONCLUSIONS:E. coli-OMVs inhibit glioma cell proliferation and delay orthotopic tumor growth in rats likely via endocytic uptake of the OMVs to cause suppression of Wnt/β-catenin signaling and cell cycle arrest.
Purpose: To develop a shorter version of the uterine fibroid symptom and quality of life (UFS-QoL) questionnaire and evaluate its psychometric properties, aiming to provide a more efficient instrument for symptom and quality-of-life assessment. Patients and Methods: Items were selected using classical test theory (CTT) and item response theory (IRT), and the standardized response mean was used to identify inconsistent items and to evaluate their ability to detect change. The short-form was evaluated for dimensionality, internal consistency reliability, and criterion and known-group validity. Data were obtained from a 20-center prospective cohort of premenopausal Chinese women with symptomatic uterine fibroids who underwent hysterectomy, myomectomy, or HIFU (n = 1939; development n = 969, validation n = 970). Results: To improve adaptability and clinical application, we removed the self-consciousness subscale and retained only one item in the sexual functioning subscale. The resulting 11-item UFS-QoL (UFS-QoL-11) reduced the administrative burden by 70% (from 37 items to 11 items) compared to the original version. It exhibited a strong correlation with UFS-QoL in each domains (all exceeding 0.7). Exploratory factor analysis accounted for 64.22% of total variance, slightly higher than the original scale (63.60%). UFS-QoL-11 demonstrated excellent internal consistency and reliability, and sensitivity in detecting varying levels of current health status. The responsiveness of UFS-QoL-11 was comparable to that of UFS-QoL, with all effect sizes > 0.45. Conclusion: The UFS-QoL-11 demonstrated comparable psychometric performance to the original scale while substantially reducing the number of items. It offers a more efficient instrument for assessing symptom severity and quality of life and shows potential for use in clinical and research settings, although further validation in independent populations is warranted.
Pancreatic cancer remains among the most treatment-refractory solid malignancies worldwide. High-intensity focused ultrasound (HIFU) surgery is a treatment option with the advantage of providing cancer pain relief. However, there has been limited research addressing the trends in pancreatic cancer treatment utilizing HIFU surgery. Publications on pancreatic adenocarcinoma treatment utilizing HIFU surgery in the Web of Science Core Collection (WoSCC) were identified and analyzed by visualization software VOSviewer and CiteSpace. This approach provides comprehensive insights into the knowledge structure of the field. A total of 1172 articles published from 1999 to 2024 were identified in the WoSCC, showing a consistent rise in the publication volume and average annual citation frequency related to pancreatic adenocarcinoma treatment utilizing HIFU surgery. The United States and China contributed the most publications. There were six clusters summarized including descriptions of clinical trials of pancreatic cancer, basic research, mechanisms of HIFU surgery, combined therapy effect of pancreatic cancer, attenuated symptom of pancreatic cancer, and metastatic pancreatic cancer. Based on this bibliometric analysis of the publications over the last twenty years, it is the first scholarly visualization in the domain of pancreatic cancer treated with HIFU surgery. The clinical research regarding the efficacy of this technology should be developed in the future. It provides clinicians and researchers with a reliable synopsis, changes, and evolution regarding the field, offering a reference point for existing research and suggesting new avenues for future investigations.
OBJECTIVE:This study aimed to evaluate the efficacy of ultrasound-guided high-intensity focused ultrasound ablation (USgHIFU) for uterine fibroids with different blood flow grading based on Alder classification. MATERIALS AND METHODS:A total of 353 patients with solitary uterine fibroid who underwent USgHIFU from July 2014 to July 2019 were enrolled. The patients were classified as four groups based on blood flow grading in fibroids. The relevant factors influencing the therapeutic effect were analyzed. RESULTS:Significant differences were observed in treatment time, irradiation time, irradiation intensity, nonperfusion volume (NPV), NPV ratio and energy efficiency factor (EEF) among the four groups (p < 0.05). As the level of blood flow increased, the treatment time, irradiation time, irradiation intensity and energy efficiency factor (EEF) of USgHIFU were increased, but the NPV ratio was decreased. No major complication occurred in any patient of the four groups. Overall, 318 patients completed long-term follow-up, and 55 of 318 patients underwent re-intervention (17.2%). Univariate analysis indicated that increased menstruation, uterine volume, type of fibroids, signal intensity on T2-weighted imaging, NPV ratio were factors related to reinterventin (p < 0.05). Multivariate analysis revealed that the type of fibroids and NPV ratio were independent risk factors for re-intervention (p < 0.05). CONCLUSIONS:Our results suggested that the difficulty of USgHIFU treatment for uterine fibroids could be evaluated using Alder classification. The fibroids with more blood flow were more difficulty to treat. However, satisfactory NPV ratio could be achieved even fibroids with abundant blood supply, and the long-term intervention rate was not increased.
Mesenchymal stem cells (MSCs) are adult stem cells with the capacity to differentiate into several cell types, including hepatocyte-like cells, neural-like cells, islet-like clusters and so on. However, the differentiation into ovarian-related cells such as ovarian granulosa cells (OGCs) has not been well studied. Here, we established an efficient culture system to differentiate human umbilical cord mesenchymal stem cells (HUCMSCs) into pre-granulosa cells, which can further mature into granulosa-like cells. HUCMSCs were cocultured with hormones (E2, FSH) and cytokines (TGF-β), a simple differentiation method was used to induce morphological changes and positive expression of forkhead transcription factor (FOXL2). In the process of further mature, the cells differentiated into mature granulosa-like cells, expressed mature granulosa cell markers (FSHR, AMHR2, CYP19A1) and likely possesses some granulosa cell hormone secretion capacity. In conclusion, we successfully established an efficient protocol to generate pre-granulosa cells from HUCMSCs that can further differentiate into mature granulosa-like cells, opening a new avenue for the further study of therapies for female reproductive health.
BACKGROUND:Electronic patient-reported outcomes (ePROs)-based cancer symptom management presents an opportunity to improve patient outcomes by optimizing symptom detection and prompting clinician interventions in tertiary hospitals. However, real-world evidence is limited, especially in primary health care (PHC) settings, which are accompanied by more complex and unknown influencing factors. OBJECTIVE:We conducted a qualitative study to identify facilitators and barriers associated with the implementation of ePRO-based symptom management in China's PHC settings under the implementation science (IS) framework. We further developed strategies and recommendations for real-world practices and health policies. METHODS:This qualitative study was conducted from October to December 2023 in 9 purposively selected PHC institutions (5 urban and 4 rural) across 5 administrative districts of Yangzhou, Jiangsu Province, China. Community-dwelling patients with cancer, PHC providers, and medical supervisors participated in semistructured interviews and focus group discussions. We used 2 subframeworks under the IS framework-the Consolidated Framework for Implementation Research and Expert Recommendations for Implementing Change-to conduct data analysis and generate strategies. RESULTS:A total of 72 individuals were invited to participate in this study, including 35 community-dwelling patients with cancer (median 66, IQR 60-71.5 years; n=21, 60% men) and 23 PHC personnel (median 45, IQR 27-51 years; n=12, 52.17% men) who participated in semistructured interviews, and 14 medical supervisors (median 47.5, IQR 36.5-54 years; n=10, 71.43% men) who participated in focus group discussions. This study identified 29 barriers and 21 facilitators, and then developed 13 strategies. Crucial challenges include PHC providers' low self-efficacy and unclear role identification, coupled with community-dwelling patients' mistrust of primary care, cancer stigma, and fatalistic beliefs, which further reduce motivation; poor integration of ePRO with existing workflows and the absence of performance incentive mechanisms; a lack of nationwide standardized implementation guidelines and quality evaluation criteria; and outdated medical equipment and a limited range of medications. Common challenges included weak collaborative relationships and insufficient funding. CONCLUSIONS:Grounded in the IS framework, our study identifies 3 critical priorities for implementing ePRO-based cancer symptom management in PHC settings, including addressing individual-level motivational deficiencies among community-dwelling patients with cancer and PHC providers by resolving misconceptions, bridging knowledge gaps, and establishing supportive incentives; developing supportive medical partnerships and advancing tiered management systems to empower PHC settings; and creating standardized operational guidelines with clear workflows and implementing real-world data-driven regulatory feedback mechanisms to ensure quality control.
Background:Glypican-3 (GPC3), which is a membrane-associated antigen that is overexpressed in hepatocellular carcinoma (HCC). hGC33, a humanized anti-GPC3 antibody, has been validated as a potential antibody drug with good antitumor activity by preclinical studies and the Phase II clinical trial. However, free drug usually lack good tumor penetration. Outer membrane vesicles (OMVs) that are secreted by Escherichia coli function as natural vectors for molecule delivery and mediators of biological signals across tissues. Our study aimed to engineer E. coli for use as a platform to precisely deliver the hGC33 single-chain variable fragment (hGC33-scFv) for the targeted treatment of HCC. Methods:In this study, we utilized E. coli BL21(DE3) to express Hbp-hGC33-scFv fusion protein and generated E. coli hGC33-OMVs. After isolation and characterization, we assessed their chemotaxis toward HepG2 cells by Transwell, coimmunoprecipitation (co-IP) to confirm hGC33-GPC3 binding, and immunofluorescence (IF) to evaluate the localization of hGC33 on OMV membranes. The in vivo efficacy was assessed in BALB/c nude mice harboring HepG2 cell-derived xenografts, and tumor targeting was analyzed with Cy7-labeled OMVs and live imaging. Proliferation assays, cell cycle analysis, and Wnt pathway expression analysis were performed to elucidate the underlying mechanisms. Results:hGC33-OMVs exhibited spherical bilayered nanostructures and displayed hGC33-scFv on their surface. hGC33-OMVs preferentially accumulated in tumors, significantly reducing tumor volume compared with controls and downregulating the proliferation markers Ki67 and PCNA. Transwell assays revealed increased tropism of hGC33-OMVs toward HepG2 cells, while Co-IP confirmed the direct interaction between hGC33 and GPC3. Meanwhile, hGC33-OMVs suppressed HepG2 cell proliferation, induced G1-phase arrest, and reduced Wnt3a, β-catenin, Cyclin D1, and C-myc expression. Conclusion:Engineered E. coli hGC33-OMVs effectively target HCC via the hGC33-GPC3 interaction, inhibit tumor growth by suppressing Wnt signaling, and demonstrate potential for use as a versatile platform for antibody delivery.
This study aims to prepare bacterial outer membrane vesicles (OMVs) with anti-glypican-3 (GPC3) single-chain antibody and analyze their targeting effects on Hep G2 hepatocellular carcinoma (HCC) cells and tissue. The recombinant plasmid pET28a-Hbp-hGC 33-scFv was constructed by ligating Hbp-hGC 33-scFv to pET28a. Western blotting was employed to determine the prokaryotic expression of the fusion protein Hbp-hGC 33-scFv, on the basis of which the optimal induction conditions were determined. Hbp-hGC 33-OMVs secreted from the recombinant expressing strains were collected by ultrafiltration concentration and then characterized. The localization of Hbp-hGC 33-scFv in bacteria and Hbp-hGC 33-OMVs was analyzed by immune electron microscopy. The binding of Hbp-hGC 33-scFv to Hep G2 cells was observed by immunofluorescence. The Hep G2 tumor-bearing mouse model was established, and the targeted retention of Hbp-hGC 33-OMVs in the tumor site of mice was observed by a fluorescence imaging system in vivo. The results showed that the actual molecular weight of the fusion protein was 175.3 kDa, and the optimal induction conditions were as follows: OD600=0.5, IPTG added at a final concentration of 0.5 mmol/L, and overnight induction at 16 ℃. The prepared Hbp-hGC 33-OMVs were irregular spherical structures with an average particle size of (112.3±4.6) nm, expressing OmpC, OmpA, and the fusion protein Hbp-hGC 33-scFv. The Hbp-hGC 33-OMVs prepared in this study demonstrated stronger ability of binding to Hep G2 cells than the wild-type OMVs (P=0.008). All the data indicated that Hbp-hGC 33-OMVs with anti-GPC3 single-chain antibody were successfully prepared and could be used for research on the targeted therapy of hepatocellular carcinoma.
Tumor cell-derived extracellular vesicles (EVs) play a crucial role in mediating immune responses by carrying and presenting tumor antigens. Here, we suggested that melanoma EVs triggered cytotoxic CD8 T cell-mediated inhibition of tumor growth and metastasis. Our results indicated that immunization of mice with melanoma EVs inhibited melanoma growth and metastasis while increasing CD8 T cells and serum interferon γ (IFN-γ) in vivo. In vitro experiments showed that melanoma EV stimulates dendritic cells (DCs) maturation, and mature dendritic cells induce T lymphocyte activation. Thus, tumor cell-derived EVs can generate anti-tumor immunity in a prophylactic setting and may be potential candidates for cell-free tumor vaccines.
Objectives: To investigate all pregnancies and analyze the factors influencing pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound (HIFU). Materials and methods: A total of 231 patients with adenomyosis who completed HIFU and wished to conceive were enrolled. The symptom improvement and information of pregnancy were recorded during the follow-up period. Factors influencing pregnancy outcomes were analyzed using multivariate regression analysis and survival analysis. Results: After HIFU, 100 of 231 (43.3%) patients became pregnant within 96 months, including 77 (77/194, 39.7%) in natural and 23 (23/37, 62.2%) in vitro fertilization and embryo transfer (IVF-ET) pregnancies following gonadotropin-releasing hormone agonist (GnRHa). Among the 108 (46.8%, 108/231) infertile patients (defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse, 40 primary infertility and 68 secondary infertility), 31 (28.7%) became pregnant. At the end of the follow-up, 70 successfully delivered 71 healthy babies. No uterine rupture occurred during pregnancy and delivery. Patients with pelvic adhesion and infertility history had a lower pregnancy chance than that of patients without pelvic adhesion and infertility history (OR < 1, p < 0.05). Patients with small adenomyotic lesion volume had a greater pregnancy chance than that of patients with large lesion volume (OR < 1, p < 0.05). IVF-ET following GnRHa had a better pregnancy chance (p < 0.05). Conclusions: HIFU seems to have a beneficial effect on fertility of patients with adenomyosis. Pelvic adhesion, infertility history, and large adenomyotic lesion volume have adverse effects on pregnancy, but IVF-ET following GnRHa after HIFU could increase the pregnancy chance.
Background: Electronic symptom monitoring via patient-reported outcome in surgical oncology is limited owing to lengthy instruments and non-specific items in common patient-reported outcome instruments. To establish electronic symptom monitoring through a clinically relevant and fit-for-purpose core set of patient-reported outcome in patients undergoing lung cancer surgery. Materials and methods: One qualitative (Cohort 1) and two prospective studies (Cohorts 2 and 3) were conducted between 2018 and 2023. Patients undergoing lung cancer surgery were recruited. Items of symptoms and daily functioning were generated through extensive interviews in Cohort 1 and incorporated into a smartphone-based platform to establish the electronic Perioperative Symptom Assessment for Lung surgery (ePSA-Lung). This tool was finalized and validated in Cohort 2. Patients in Cohort 3 were longitudinally monitored for the first year post-surgery using the validated ePSA-Lung. Results: In total, 1,037 patients scheduled for lung cancer surgery were recruited. The 11-item draft PSA-Lung was generated based on qualitative interview with 39 patients and input from a Delphi study involving 42 experts. A 9-item ePSA-Lung was finalized by assessing 223 patients in the validation cohort; the results supported the instrument's understandability, reliability, sensitivity, and surgical specificity. In Cohort 3 (n=775), compliance ranged from 63.21% to 84.76% during the one-year follow-up after discharge. Coughing, shortness of breath, and disturbed sleep were the most severe symptoms after discharge. Longitudinally, patients who underwent single-port video-assisted thoracic surgery had a lower symptom burden than those who underwent multi-port video-assisted thoracic surgery or thoracotomy (all symptoms, P<0.001). Conclusion: The ePSA-Lung is valid, concise, and clinically applicable as it supports electronic symptom monitoring in surgical oncology care. The need for long-term extensive care was identified for patients after discharge, even in early-stage cancer with potential curative treatment.
Transdermal drug delivery system (TDDS) has attracted much attention in the pharmaceutical technology area. However, the current methods are difficult to ensure penetration efficiency, controllability, and safety in the dermis, so its widespread clinical use has been limited. This work proposes an ultrasound-controlled monodisperse lipid vesicles (U-CMLVs) hydrogel dressing, which combines with ultrasound to form TDDS. Using microfluidic technology, prepare size controllable U-CMLVs with high drug encapsulation efficiency and quantitative encapsulation of ultrasonic response materials, and even uniform mix them with hydrogel to prepare the required thickness of dressings. The high encapsulation efficiency can ensure sufficient dosage of the drugs and further realize the control of ultrasonic response through quantitative encapsulation of ultrasound-responsive materials. Using high frequency (5 MHz, 0.4 W cm-2 ) and low frequency (60 kHz, 1 W cm-2 ) ultrasound to control the movement and rupture of U-CMLVs, the contents not only penetrate the stratum corneum into the epidermis but also break through the bottleneck of penetration efficiency, and deep into the dermis. These findings provide the groundwork for deep, controllable, efficient, and safe drug delivery through TDDS and lay a foundation for further expanding its application.
目的 分析子宫肌瘤超声指标与MRI T2WI信号强度的相关性,预测聚焦超声消融治疗的难易程度.资料与方法 回顾性分析 2020 年 5 月—2021 年 7 月遂宁市中心医院聚焦超声消融治疗前 238 例单发子宫肌瘤患者的经阴道超声及MRI T2WI图像,获取子宫肌瘤T2WI信号强度类型与超声指标;采用Logistic回归分析超声指标与T2WI信号强度的相关性,通过受试者工作特征曲线分析超声指标对T2WI高信号肌瘤的预测价值.结果 238例患者T2WI信号表现:高信号组 86 例、非高信号组152例.子宫肌层与肌瘤灰度值差(Z=6.025,P<0.001)、能量多普勒血流信号像素面积比率(Z=5.957,P<0.001)、黏膜下肌瘤(Z=15.882,P=0.047)是不同T2WI信号强度的相关因素;使用受试者工作特征曲线验证Logistic回归模型,曲线下面积为0.817,约登指数为0.51,敏感度为0.826,特异度为0.684.结论 超声指标可在聚焦超声消融术前预测MRI T2WI高信号子宫肌瘤,具有一定的临床实用价值.
PURPOSE To study sacral injuries and influencing factors after ultrasonic ablation of uterine fibroids no more than 30 mm from the sacrum. METHODS A total of 406 patients with uterine fibroids who underwent percutaneous ultrasound ablation were analyzed retrospectively. All patients underwent contrast-enhanced magnetic resonance imaging (MRI) scans before and after high-intensity focused ultrasound. The abnormal signal intensity (low signal intensity on T1WI and high signal intensity on T2WI) on the postoperative MRIs was indicative of a sacral injury. The patients were divided into a sacrum injury group and a sacrum non-injury group. The relationship between fibroid characteristics, ultrasound ablation parameters, and injury was analyzed using univariate and multivariate analyses. RESULTS There were 139 cases of sacral injury (34.24%). When the distance from the fibroid’s dorsal side to the sacrum was 0–10 mm, the risk assessment showed that the danger of sacral injury increased by 1.85 times and 3.03 times compared with that at a distance of 11–20 or 21–30 mm. Furthermore, the risk of sacral injury increased by 1.89 times and 3.23 times when the therapeutic dose (TD) of a fibroid was >500 KJ compared with that of a fibroid with TD= 250–500 KJ and <250 KJ. CONCLUSION A distance of 10 mm or less and a TD of >500 KJ were significantly correlated with sacral injury. The distance from the fibroid’s dorsal side to the sacrum and the TD were the main causes of injury to the sacrum. A distance of 10 mm or less and a TD of >500 KJ carried higher injury risks, while a distance of 21–30 mm and a TD of <250 KJ were the most appropriate circumstances to reduce the risk of sacral injury.
Polycystic ovary syndrome (PCOS) is a common age-related endocrinopathy that promotes the metabolic disorder of the liver. Growing evidence suggests that the pathophysiology of this disorder is closely associated with the interaction between the liver and its exosome. However, the underlying mechanism of the interactions remains unclear. In this study, we aimed to investigate the metabolite profiles of liver tissues and hepatic exosomes between normal (n = 11) and PCOS (n = 13) mice of young- and middle-age using gas chromatograph-mass spectrometry (GC-MS) based metabolomics analysis. Within the 145 identified metabolites, 7 and 48 metabolites were statistically different (p < 0.05, q < 0.05) in the liver tissue and exosomes, respectively, between PCOS and normal groups. The greater disparity in exosome indicated its potential to reflect the metabolic status of the liver. Based on hepatic exosome metabolome, the downregulations of glycolysis and TCA cycle were related to hepatic pathophysiology of PCOS independent of age. Fatty acids were the preferred substrates in young-age-PCOS liver while amino acids were the main substrates in middle-age-PCOS liver for the processes of gluconeogenesis. Overall, this study enables us to better understand the metabolic status of the PCOS liver at different ages, and exosome metabolomics shows its potential to gain the metabolic insights of parental cell or source organ.
Aims To evaluate the long-term survival benefits of high intensity focused ultrasound (HIFU) ablation in patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombus (PVTT). Methods The data of patients with HCC-PVTT treated with HIFU from January 2014 to December 2019 were retrospectively analyzed. All patients received HIFU ablation for both PVTT and liver tumor in one session. Perioperative adverse events (AEs) were recorded, and follow-up was performed postoperatively. The Kaplan-Meier method was used for survival analysis. Results Median follow-up was 13.75 +/- 1.31 months. A total of 144 patients (male/female: 122/22, age: 54.15 +/- 11.84 years old) were included in the study. A total of 267 liver tumors (tumor number: 1.87 +/- 1.65, range 1-10) were treated with HIFU. The mean +/- SD diameter of viable liver tumors was 100.98 +/- 61.65 mm. The reported postoperative AEs of HIFU were skin edema (93.75%), local pain (69.44%) and fever (7.64%). There was no liver failure, gastrointestinal bleeding or perioperative death. The median overall survival (OS) time was 14 months, while the cumulative survival rates of 0.5, 1, 2 and 3 years were 79.0%, 58.6%, 33.3% and 5.9%, respectively. The median OS of PVTT types I, II and III was 22, 13 and 14 months, respectively, and the difference was not statistically significant (p > 0.05). Conclusion HIFU is a minimally invasive method for HCC-PVTT with fewer complications, which could prolong the OS. Patients with PVTT type III could benefit more from HIFU, compared to types I and II.
目的 探讨急性缺血性脑卒中(acute ischemic stroke,AIS)介入取栓治疗的预后及其影响因素.方法 选取2017-01至2019-07在医院神经内科接受介入取栓治疗的106例AIS患者,根据术后3个月患者改良Rankin评分评估预后水平,分为预后良好组和预后不良组,对两组患者各项临床资料进行分析,对比预后的相关因素及危险因素,并对认知功能和预后血清神经相关因子表达水平进行对比.结果 患者年龄大、合并冠心病、术前血清CRP及Hcy高、阻塞血管再通时间较长、术后36 h存在部分再通均为AIS介入治疗预后不良的危险因素(OR>1,P<0.05);预后良好组的认知功能、运动功能、语言功能均优于预后不良组,差异有统计学意义(P<0.05);两组患者吞咽功能差异无统计学意义.预后良好组血清神经相关因子表达水平均优于预后不良组,差异有统计学意义(P<0.05).结论 预后良好AIS患者各项功能与血清神经相关因子表达水平状态均较好,对年龄较大、发病至就诊时间较长、合并冠心病,且术前血清CRP、Hcy、NIHSS评分偏高,阻塞血管再通时间较长及术后36 h内仅达到部分再通的患者应给予充分重视,对危险因素积极预防,提高预后水平.
BackgroundThe study was conducted to explore whether high-intensity focused ultrasound (HIFU) can improve the effect of transcatheter arterial chemoembolization (TACE) in intermediate and advanced hepatocellular carcinoma (HCC).MethodsPubMed, Embase, Cochrane Library, Web of Science, Wanfang Data, CQVIP, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical (CBM) databases were searched for randomized controlled trials (RCTs) comparing the effect of TACE in combination with HIFU group (group A) to TACE alone group (group B) in treating intermediate and advanced HCC. The primary outcomes were overall survival (OS) rate and tumor response rate. The odds ratio (OR) and 95% confidence interval (CI) for each study were calculated and then pooled with fixed effects model or random effects model. Sensitivity analyses and subgroup analyses were conducted. A publication bias was also evaluated.ResultsAfter literature selection, eleven RCTs involving 803 patients were included in this meta-analysis. This meta-analysis revealed that group A was associated with an increased 6-month OS rate (OR = 0.20), 12-month OS rate (OR = 0.23), 24-month OS rate (OR = 0.32), and overall response rate (WHO criterion, OR = 0.22; RECIST criterion, OR = 0.30). Furthermore, subgroup analyses showed no bias in the result. Given the limited number of studies that reported major complications, no additional meta-analysis of complication was conducted. Despite no special treatment, any complication following HIFU treatment was found to subside within 3-7 days.ConclusionTACE in combination with HIFU is associated with increased OS and tumor response in intermediate and advanced HCC. Current evidence supports the use of HIFU after TACE treatment in intermediate and advanced HCC.