Age-Dependent Female Survival Advantage in Hepatocellular Carcinoma: A Multicenter Cohort Study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a higher incidence in males, but the association of sex with survival remains controversial. This study aimed to examine the effect of sex on HCC survival and its association with age. METHODS: Among 33,238 patients with HCC from 12 Chinese tertiary hospitals, 4175 patients who underwent curative-intent hepatectomy or ablation were analyzed. Cancer-specific survival (CSS) was analyzed using Cox regression and Kaplan-Meier methods. Two propensity score methods and multiple mediation analysis were applied to mitigate confounding. To explore the effect of estrogen, a candidate sex-specific factor that changes with age, female participants' history of estrogen use, and survival were analyzed. RESULTS: There were 3321 males and 854 females included. A sex-related disparity of CSS was present and showed a typical age-dependent pattern: a female survival advantage over males appeared at the perimenopausal age of 45 to 54 years (hazard risk [HR], 0.77; 5-year CSS, 85.7% vs 70.6%; P = .018), peaked at the early postmenopausal age of 55 to 59 years (HR, 0.57; 5-year CSS, 89.8% vs 73.5%; P = .015), and was not present in the premenopausal (<45 y) and late postmenopausal groups (≥60 y). Consistent patterns were observed in patients after either ablation or hepatectomy. These results were sustained with propensity score analyses. Confounding or mediation effects accounted for only 19.5% of sex survival disparity. Female estrogen users had significantly longer CSS than nonusers (HR, 0.74; 5-year CSS, 79.6% vs 72.5%; P = .038). CONCLUSIONS: A female survival advantage in HCC depends on age, and this may be associated with age-dependent, sex-specific factors.

FHL3 promotes the formation of fast glycolytic muscle fibers by interacting with YY1 and muscle glycolytic metabolism.

The proportions of the various muscle fiber types are important in the regulation of skeletal muscle metabolism, as well as animal meat production. Four-and-a-half LIM domain protein 3 (FHL3) is highly expressed in fast glycolytic muscle fibers and differentially regulates the expression of myosin heavy chain (MyHC) isoforms at the cellular level. Whether FHL3 regulates the transformation of muscle fiber types in vivo and the regulatory mechanism is unclear. In this study, muscle-specific FHL3 transgenic mice were generated by random integration, and lentivirus-mediated gene knockdown or overexpression in muscles of mice or pigs was conducted. Functional analysis showed that overexpression of FHL3 in muscles significantly increased the proportion of fast-twitch myofibers and muscle mass but decreased muscle succinate dehydrogenase (SDH) activity and whole-body oxygen consumption. Lentivirus-mediated FHL3 knockdown in muscles significantly decreased muscle mass and the proportion of fast-twitch myofibers. Mechanistically, FHL3 directly interacted with the Yin yang 1 (YY1) DNA-binding domain, repressed the binding of YY1 to the fast glycolytic MyHC2b gene regulatory region, and thereby promoted MyHC2b expression. FHL3 also competed with EZH2 to bind the repression domain of YY1 and reduced H3K27me3 enrichment in the MyHC2b regulatory region. Moreover, FHL3 overexpression reduced glucose tolerance by affecting muscle glycolytic metabolism, and its mRNA expression in muscle was positively associated with hemoglobin A1c (HbA1c) in patients with type 2 diabetes. Therefore, FHL3 is a novel potential target gene for the treatment of muscle metabolism-related diseases and improvement of animal meat production.

20(S)-Ginsenoside Rh2 inhibits hepatocellular carcinoma by suppressing angiogenesis and the GPC3-mediated Wnt/ß­catenin signaling pathway.

20(S)-Ginsenoside Rh2 has significant anti-tumor effects in various types of cancers, including human hepatocellular carcinoma (HCC). However, its molecular targets and mechanisms of action remain largely unknown. Here, we aim to elucidate the potential mechanisms by which Rh2 suppresses HCC growth. We first demonstrate the role of Rh2 in inhibiting angiogenesis. We observe that Rh2 effectively suppresses cell proliferation and induces apoptosis in HUVECs. Furthermore, Rh2 significantly inhibits HepG2-stimulated HUVEC proliferation, migration and tube formation, accompanied by the downregulation of VEGF and MMP-2 expressions. We also reveal that Rh2 inhibits HCC growth through the downregulation of glypican-3-mediated activation of the Wnt/ß-catenin pathway. We observe a dose-dependent inhibition of proliferation and induction of apoptosis in HepG2 cells upon Rh2 treatment, which is mediated by the inhibition of glypican-3/Wnt/ß-catenin signaling. Moreover, downregulation of glypican-3 expression enhances the effects of Rh2 on the glypican-3/Wnt/ß-catenin signaling pathway, resulting in greater suppression of tumor growth in HepG2 cells. Collectively, our findings shed light on the molecular mechanisms through which Rh2 modulates HCC growth, which involve the regulation of angiogenesis and the glypican-3/Wnt/ß-catenin pathway. These insights may pave the way for the development of novel therapeutic strategies targeting these pathways for the treatment of HCC.

Congo Red-Derived Carbon Dots: Simultaneously as Fluorescence Probe for Protein Aggregates, Inhibitor for Protein Aggregation, and Scavenger of Free Radicals.

The pathological aggregation of some proteins is claimed to be highly related to several human diseases, such as ß-amyloid 1-42 (Aß42 ) to Alzheimer's disease (AD), islet amyloid polypeptide, and insulin to type 2 diabetes mellitus. Therefore, it is in desperate need to develop effective methods for detection of protein aggregates and inhibition of abnormal aggregation. Herein, to construct all-in-one probe with both diagnosis and treatment potentials for protein aggregation diseases, Congo red (CR), a classical staining reagent with red fluorescence signal output for protein aggregates, is deliberately adopted to react with three different reductive carbon sources and ammonium persulfate to generate three CR-derived carbon dots (CDs). The obtained CDs exhibit the capabilities of turn-on red fluorescence imaging of protein aggregates, and/or inhibition of protein aggregation as well as scavenging of free radicals. Among them, CA-CDs, using citric acid as the reductive carbon source, demonstrate the superiority to the other two studied CDs in integrating all of these functions, and particularly exert excellent cytoprotection effect against toxic Aß42 species, possessing tremendous potential in diagnosis and treatment of AD for future study. The present study paves a new way to develop all-in-one CDs for the protein disease research.

Safety and efficacy of microwave ablation for the treatment of low-risk papillary thyroid microcarcinoma: a prospective multicenter study.

OBJECTIVES: To assess the safety and efficacy of ultrasound-guided thermal ablation for low-risk papillary thyroid microcarcinoma (PTMC) via a prospective multicenter study. METHODS: From January 2017 through June 2021, low-risk PTMC patients were screened. The management details of active surveillance (AS), surgery, and thermal ablation were discussed. Among patients who accepted thermal ablation, microwave ablation (MWA) was performed. The main outcome was disease-free survival (DFS). The secondary outcomes were tumor size and volume changes, local tumor progression (LTP), lymph node metastasis (LNM), and complication rate. RESULTS: A total of 1278 patients were included in the study. The operation time of ablation was 30.21 ± 5.14 min with local anesthesia. The mean follow-up time was 34.57 ± 28.98 months. Six patients exhibited LTP at 36 months, of whom 5 patients underwent a second ablation, and 1 patient received surgery. The central LNM rate was 0.39% at 6 months, 0.63% at 12 months, and 0.78% at 36 months. Of the 10 patients with central LNM at 36 months, 5 patients chose ablation, 3 patients chose surgery and the other 2 patients chose AS. The overall complication rate was 1.41%, and 1.10% of patients developed hoarseness of the voice. All of the patients recovered within 6 months. CONCLUSIONS: Thermal ablation of low-risk PTMC was observed to be safe and efficacious with few minor complications. This technique may help to bridge the gap between surgery and AS as treatment options for patients wishing to have their PTMC managed in a minimally invasive manner. CLINICAL RELEVANCE STATEMENT: This study proved that microwave ablation is a safe and effective treatment method for papillary thyroid microcarcinoma. KEY POINTS: Percutaneous US-guided microwave ablation of papillary thyroid microcarcinoma is a very minimally invasive treatment under local anesthesia during a short time period. The local tumor progression and complication rate of microwave ablation in the treatment of papillary thyroid microcarcinoma are very low.

SMALL PLANT AND ORGAN 1 (SPO1) Encoding a Cellulose Synthase-like Protein D4 (OsCSLD4) Is an Important Regulator for Plant Architecture and Organ Size in Rice.

Plant architecture and organ size are considered as important traits in crop breeding and germplasm improvement. Although several factors affecting plant architecture and organ size have been identified in rice, the genetic and regulatory mechanisms remain to be elucidated. Here, we identified and characterized the small plant and organ 1 (spo1) mutant in rice (Oryza sativa), which exhibits narrow and rolled leaf, reductions in plant height, root length, and grain width, and other morphological defects. Map-based cloning revealed that SPO1 is allelic with OsCSLD4, a gene encoding the cellulose synthase-like protein D4, and is highly expressed in the roots at the seedling and tillering stages. Microscopic observation revealed the spo1 mutant had reduced number and width in leaf veins, smaller size of leaf bulliform cells, reduced cell length and cell area in the culm, and decreased width of epidermal cells in the outer glume of the grain. These results indicate the role of SPO1 in modulating cell division and cell expansion, which modulates plant architecture and organ size. It is showed that the contents of endogenous hormones including auxin, abscisic acid, gibberellin, and zeatin tested in the spo1 mutant were significantly altered, compared to the wild type. Furthermore, the transcriptome analysis revealed that the differentially expressed genes (DEGs) are significantly enriched in the pathways associated with plant hormone signal transduction, cell cycle progression, and cell wall formation. These results indicated that the loss of SPO1/OsCSLD4 function disrupted cell wall cellulose synthase and hormones homeostasis and signaling, thus leading to smaller plant and organ size in spo1. Taken together, we suggest the functional role of SPO1/OsCSLD4 in the control of rice plant and organ size by modulating cell division and expansion, likely through the effects of multiple hormonal pathways on cell wall formation.

A multicenter 10-year oncologic outcome of ultrasound-guided percutaneous microwave ablation of clinical T1 renal cell carcinoma: will it stand the test of time?

OBJECTIVES: We updated the experience on percutaneous microwave ablation for renal cell carcinoma with five-center data and long-term follow-up. METHODS: This retrospective study reviewed the T1N0M0 renal cell carcinoma patients who underwent microwave ablation between April 2006 and December 2019. Clinicopathological and procedural data were collected. Technical effectiveness and complications were assessed, and the Kaplan-Meier method was used for cancer-specific survival, disease-free survival, overall survival, and local neoplastic process analyses. RESULTS: A total of 323 consecutive patients (mean age, 62.9 years ± 14.0) with 371 biopsy-proved tumors (mean diameter, 2.9 cm ± 1.2) were enrolled, and 42.6% of the tumors were located adjacent to collecting system/bowel and technical effectiveness was achieved in 360 (97.0%) tumors. For 275 cT1a patients, during median follow-up time of 66.0 months (IQR, 58.4-73.6), 10-year local neoplastic processes, cancer-specific survival, disease-free survival, and overall survival rates were 1.9%, 87.4%, 71.8, and 67.5%, respectively. For 48 cT1b patients, during the median follow-up time of 30.4 months (IQR, 17.7-44.8), 5-year local tumor progression, cancer-specific survival, disease-free survival, and overall survival rates were 11.3%, 91.4%, 69.1, and 89.2%, respectively. Major complications showed no differences between cT1a (3.5%) and cT1b (6.9%) patients (p = 0.28). A clinical risk stratification system was developed based on multivariable model to predict DFS and CSS with c-indexes of 0.78 (95% CI: 0.71-0.85) and 0.77 (95% CI: 0.65-0.90), respectively. CONCLUSIONS: With matured follow-up at five institutions, ultrasound-guided percutaneous microwave ablation is a reliable treatment option for cT1a renal cell carcinoma even in dangerous location and appears to be promising for cT1b tumors. KEY POINTS: • To our knowledge, this is the first multicenter cohort of long-term oncologic outcomes with percutaneous MWA of cT1 RCC. • The predicting model we developed is accurate to predict the long-term DFS and CSS, which can help to provide a better MWA prognostication over routinely available clinical information. • The available evidence shows that microwave ablation of clinical stage T1 RCC is safe and reliable with promising long-term oncologic outcomes, especially for cT1a RCC with excellent 10-year results.

Efficacy and safety of azathioprine, mycophenolate mofetil, and reduced dose of rituximab in neuromyelitis optica spectrum disorder.

BACKGROUND AND PURPOSE: Data regarding the efficacy and safety of currently widely available preventive therapies in neuromyelitis optica spectrum disorder (NMOSD) are needed. We compared the efficacy and safety of azathioprine (AZA), mycophenolate mofetil (MMF), and reduced dose of rituximab (RTX) in NMOSD based on a large multicenter retrospective cohort. METHODS: Patients with aquaporin 4 (AQP4) antibody-positive NMOSD with AZA (n = 167), MMF (n = 131), or RTX (n = 55) as initial preventive treatment were included. The main outcome was the occurrence of relapse after the initiation of immunotherapy. Secondary outcomes were annual relapse rate, disability accumulation, drug persistence, and adverse events. RESULTS: The median follow-up time of the 353 patients was 30.3 months. The regimen of RTX was 100 mg on Day 1 and 500 mg on Day 2, followed by 500 mg every 6 months. The proportions of patients with concomitant steroid therapy at baseline were 96.4%, 95.4%, and 76.4% in the AZA, MMF, and RTX groups. Risk of relapse was significantly reduced in patients treated with RTX compared with those treated with AZA (hazard ratio [HR] = 4.40, 95% confidence interval [CI] = 1.41-13.80, p = 0.011) or MMF (HR = 5.20, 95% CI = 1.60-16.86, p = 0.006) after adjusting for potential confounding variables. Drug discontinuations were less likely on RTX than AZA (HR = 2.22, 95% CI = 1.34-3.66, p = 0.002). RTX exhibited lower incidence of adverse events (32.7%) than AZA (62.3%, p < 0.001). CONCLUSIONS: We provide Class III evidence that reduced dose of RTX is superior to AZA and MMF as initial treatment to reduce the risk of relapse and is better tolerated than AZA in Chinese patients with AQP4 antibody-positive NMOSD.

Effect of steaming process on the structural characteristics and antioxidant activities of polysaccharides from Polygonatum sibiricum rhizomes.

Polygonatum sibiricum (P. sibiricum) rhizomes are widely used as a tonic and functional food, and are often processed to enhance their tonic function by repeated steaming and drying. As the most important constituent, the polysaccharide from P. sibiricum rhizomes (PSP) has demonstrated various activities, but the alteration of structural characteristics and activities of the purified PSPs during steaming process was rarely investigated. To well understand the effect of steaming process on the polysaccharides of P. sibiricum, neutral polysaccharides from P. sibiricum rhizomes (PSP0 ~ PSP9) after steaming were first isolated and purified, and then the chemical properties and antioxidant activities were determined. The results showed that the molar ratios of monosaccharides in PSPs were different. The molecular weights of PSPs were increased significantly after the fourth steaming. Morphological studies showed that the surface of PSPs became much tighter during the steaming process. Fourier transform infrared spectroscopy spectra displayed the polysaccharides had similar backbones and chemical groups. Furthermore, the antioxidant activity of PSPs was measured through radical scavenging tests. It was found that the radical scavenging activity of PSPs was elevated strikingly after steaming, and increased gradually with numbers of steaming process. The biological and chemical variance of PSPs revealed considerable segregation of PSP0, PSP1 ~ PSP4 and PSP5 ~ PSP9. In conclusion, our results proposed the fourth time as the optimal number of steaming to extract functional polysaccharide from P. sibiricum rhizomes.

Application of marine natural products in drug research.

New diseases are emerging as the environment changes, so drug manufacturers are always on the lookout for new resources to develop effective and safe drugs. In recent years, many bioactive substances have been produced in the marine environment, which represents an alternative resource for new drugs used to combat major diseases such as cancer or inflammation. Many marine-derived medicinal substances are in preclinical or early stage of clinical development, and some marine drugs have been put on the market, such as ET743 (Yondelis®). This review presents the sources, activities, mechanisms of action and syntheses of bioactive substances based on marine natural products in clinical trials and on the market, which is helpful to understand the progress of drug research by application of marine natural products.

Volume reduction for ≥2 cm benign breast lesions after ultrasound-guided microwave ablation with a minimum 12-month follow-up.

OBJECTIVE: To prospectively evaluate the efficacy of microwave ablation (MWA) for benign breast lesions (BBLs) ≥2 cm and explore the possible factors associated with the volume reduction rate (VRR) of ablated lesions. MATERIALS AND METHODS: From November 2013 to December 2017, a total of 80 patients with 104 biopsy-proved BBLs larger than 2 cm in size underwent MWA. After the procedure, patients were followed up via physical and imaging examination consisting of contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI). Possible factors associated with 12-month VRR were assessed, including basic patient characteristics, index lesions and parameters of ablation technique. RESULTS: The mean tumor size was 2.6 ± 0.6 cm (ranging 2.0-6.3 cm). Of the 104 lesions, 70 were fibroadenomas, 27 adenosis and 7 fibrocystic changes. Post-procedure CEUS or contrast-enhanced MRI showed that all lesions were completely ablated. No immediate or delayed complications were observed. All patients were followed up for more than 12 months (median follow-up 12.5 months). After MWA, the ablated lesion volume decreased significantly by 12 months (p < 0.001), with a mean volume reduction of 80.2 ± 13.1%. Multiple linear regression analysis showed that location adjacent to areola (ß = 7.5, 95%CI: 1.0-13.9, p = 0.025) and location adjacent to skin (ß = -7.4, 95%CI: -12.7 to -13.9, p = 0.007) were independent factors respectively associated with the increased and decreased 12-month VRR. CONCLUSION: For BBLs larger than 2 cm, US-guided MWA is a favorable treatment modality, with BBLs adjacent to the areola being associated with more significant 12-month VRR after MWA.

Direct oxidative coupling of N-acyl pyrroles with alkenes by ruthenium(ii)-catalyzed regioselective C2-alkenylation.

Ruthenium(ii)-catalyzed oxidative coupling by C2-alkenylation of N-acyl pyrroles with alkenes has been described. The acyl unit was found to be an effective chelating group for the activation of aryl C-H bonds ortho to the directing group. The alkenylation reaction of benzoyl pyrroles occurred regioselectively at the C2-position of the pyrrole ring, without touching the benzene ring. The reaction provides exclusively monosubstituted pyrroles under the optimized conditions. Disubstituted pyrroles could be obtained using higher loadings of the ruthenium(ii)-catalyst and the additives.

Comprehensive N-Glycome Profiling of Cells and Tissues for Breast Cancer Diagnosis.

Aberrant protein glycosylation is observed in the progression of many types of diseases, including different cancers. In this study, we assess differential N-glycan patterns of human breast cancer cells and tissues by PGC-ESI-MS/MS. Compared with mammary epithelial cells, high-mannose glycans were significantly elevated in breast cancer cells. However, the alteration of N-glycans in tissues was more obvious than that in cells. Sixty-three kinds of different N-glycans were stably identified, and 38 types of them exhibited significant differences between para-carcinoma and breast cancer tissues. High-mannose glycans and core-fucosylated glycans were increased in the breast cancer tissues, while bisected glycans and sialylated glycans were decreased. Moreover, a total of 27 types of N-glycans displayed evident differences between benign breast tumor and breast cancer tissues, and most of them including bisected and sialylated glycans exhibited decreased relative abundances in cancer tissues. Overall, three high-mannose N-glycans (F0H6N2S0, F0H7N2S0, F0H8N2S0) exhibited significant diagnostic accuracy in both breast cancer cells and tissues, suggesting their potential role in biomarkers. Furthermore, a negative correlation between sialylated glycans and age of patients was identified. In conclusion, our results may be beneficial to understand the role that N-glycan plays on the progression of breast cancer and propose potential diagnostic biomarkers.

Gangliosides profiling in serum of breast cancer patient: GM3 as a potential diagnostic biomarker.

Gangliosides altered during the pathological conditions and particularly in cancers. Here, we aimed to profile the gangliosides in breast cancer serum and propose potential biomarkers. LC-FTMS method was first used to identify all the ganglioside species in serum, then LC-MS/MS-MRM method was employed to quantitate the levels of gangliosides in serum from healthy volunteers and patients with benign breast tumor or breast cancer. 49 ganglioside species were determined, including GM1, GM2, GM3, GD1, GD3 and GT1 species. Compared to healthy volunteers, the levels of GM1, GM2, GM3, GD1 and GD3 displayed a rising trend in breast cancer patients. In particular, as the major glycosphingolipid component, GM3 showed excellent diagnostic accuracy in cancer serum (AUC > 0.9). PCA profile of the GM3 species showed clear distinction between normal and cancer serum. What's more, ROC curve proved great diagnostic accuracy of GM3 between cancer and benign serum. In addition, GM3 was discovered as a diagnostic marker to differentiate luminal B subtype from other subtypes. Furthermore, a positive correlation between GM3 and Ki-67 status of patients was identified. In conclusion, our results introduced the alteration patterns of serum gangliosides in breast cancer and suggested serum GM3 as a potential diagnostic biomarker in breast cancer diagnosis and luminal B subtype distinction.

Fast reversed-phase liquid chromatographic separation of proteins by flow-through poly(styrene-co-divinylbenzene) microspheres.

With the explosive growth of the bioscience and biopharmaceuticals, the demand for high efficient analysis and separation of proteins is urgent. High-performance liquid chromatography is an appropriate technology for this purpose, and the stationary phase is the kernel to the separation efficiency. In this study, flow-through poly(styrene-co-divinylbenzene) microspheres characteristic of the binary pores, i.e. flow-through pores and mesopores, were synthesized; this special porous structure would benefit the convective mass transfer while guarantee the high specific surface area. Owing to the hydrophobic nature, poly(styrene-co-divinylbenzene) microspheres were suitable as the reversed-phase stationary phase for separation of proteins. For the high permeability of the poly(styrene-co-divinylbenzene) microspheres packed column, fast separation of the studied six proteins in ∼2 min was achieved. The recoveries of studied proteins were acceptable in the range of 79.0-99.4%. The proposed column had good pH stability of 1-13 and repeatability. Moreover, the column was applied for egg white fast separation, further demonstrating its applicability for complex bio-sample separation. The flow-through poly(styrene-co-divinylbenzene) microspheres were promising for fast separation of large molecules.

Profiling and Structural Characterization of High Neu5Gc or Sulfate-containing O-glycans from Hyla Rabbit Intestinal Mucin.

Intestinal mucins constitute the major component of the mucus covering the epithelium of the gastrointestinal tract, thereby forming a barrier against microbial colonization. Rabbits are bred in large numbers worldwide, with little known about intestinal O-glycosylation despite this insight being crucial to the understanding of host-pathogen interactions. In the present study, a major mucin-type glycopeptide (RIF6) of hyla rabbit intestine was isolated and the O-glycans were extensively characterized based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with bioinformatics approaches. Thirty-three O-glycans were identified, and most of them were sulfated or sialylated glycans. It was worth noting that Neu5Gc-containing structures within sialylated O-glycans accounted for 91%, which were extremely different from that of other species including humans, mice, chickens, etc. Sulfated glycans accounted for 58%, unique disufated and sulfated-sialylated glycans were also detected in rabbit intestinal mucin. These structural characterization reflected species diversity and may provide deeper insights into explaining the adaptability of hyla rabbit to the environment.

Microwave ablation of benign breast tumors: a prospective study with minimum 12 months follow-up.

PURPOSE: This prospective study was to evaluate clinical outcomes of microwave ablation (MWA) of benign breast tumors with minimum 12 months follow up. METHODS: With approval of the institutional ethics committee and written informed consent, 56 patients with 107 biopsy-proved breast benign tumors were recruited from November, 2013 to April, 2017. MWA with ultrasound (US) guidance was performed under local anesthesia. During the procedure, pull-back technique was used for tumors larger than 1.0 cm in diameter and hydro-dissection technique was used for tumors adjacent to skin, pectoralis and areola. Clinical outcomes were followed up by physical examination and medical images including US, contrast enhanced US and MR. RESULTS: The maximum diameter of these tumors was 1.6 ± 0.8 cm. MWA was successfully performed with the median 120 s of duration (ranging 20-1100 s). Technical success was achieved in all patients. At the median follow-up of 20.5 months (ranging 12-53 months), the mean volume reduction ratios (mVRRs) of tumors were 77.1 ± 8.2%, 84.3 ± 10.6%, 93.3 ± 8.2% at follow-up of 12, 18, 24 months (p < .0001), respectively. Compared with 92% of masses were palpable before ablation, mass palpabilities were 40%, 11%, 5% at follow-up of 12, 18, 24 months (p < .001), respectively. Cosmetic satisfaction was reported excellent or good in 100% of patients. CONCLUSIONS: As a safe and effective minimally invasive modality for inactivating benign breast tumors in situ, MWA achieved optimistic clinical outcomes on volume reduction and cosmetic satisfaction after minimum 12 months follow-up.

Structural Characterization and Interaction with RCA120 of a Highly Sulfated Keratan Sulfate from Blue Shark (Prionace glauca) Cartilage.

As an important glycosaminoglycan, keratan sulfate (KS) mainly exists in corneal and cartilage, possessing various biological activities. In this study, we purified KS from blue shark (Prionace glauca) cartilage and prepared KS oligosaccharides (KSO) through keratanase II-catalyzed hydrolysis. The structures of KS and KSO were characterized using multi-dimensional nuclear magnetic resonance (NMR) spectra and liquid chromatography-mass spectrometry (LC-MS). Shark cartilage KS was highly sulfated and modified with ~2.69% N-acetylneuraminic acid (NeuAc) through α(2,3)-linked to galactose. Additionally, KS exhibited binding affinity to Ricinus communis agglutinin I (RCA120) in a concentration-dependent manner, a highly toxic lectin from beans of the castor plant. Furthermore, KSO from dp2 to dp8 bound to RCA120 in the increasing trend while the binding affinity of dp8 was superior to polysaccharide. These results define novel structural features for KS from Prionace glauca cartilage and demonstrate the potential application on ricin-antidote exploitation.

Effectiveness of ultrasound-guided percutaneous microwave ablation for symptomatic uterine fibroids: a multicentre study in China.

PURPOSE: To evaluate the clinical efficacy of ultrasound-guided percutaneous microwave ablation (PMWA) therapy for symptomatic uterine fibroids in a multicentre study. MATERIALS AND METHODS: Patients with symptomatic uterine fibroids who underwent PMWA at multiple treatment centres in China between January 2013 and August 2015 were prospectively studied to compare the reduction rate of uterine fibroids, haemoglobin level and uterine fibroid symptom and health-related quality of life questionnaire (UFS-QOL) scores before and at 3, 6 and 12 months after ablation. RESULTS: A total of 311 patients (405 leiomyomas) from eight treatment centres underwent the treatment (age, 29-55 years; mean ± SD, 41 ± 5.11 years). The mean diameter of the myomas ranged from 2.03 to 12.50 cm (mean, 5.10 ± 1.28 cm) and the volume ranged from 4.40 to 1022.14 cm3 (mean, 95.01 ± 70.29 cm3). Forty-eight myomas were identified as FIGO type 1/2 fibroids, 256 as type 3/4 fibroids and 101 as type 5/6 fibroids. The mean ablation rate was 86.6% (54.0-100%). The mean reduction rate was 63.5%, 78.5% and 86.7% at 3, 6 and 12 months posttreatment, respectively. The haemoglobin level increased significantly from 88.84 ± 9.31 g/L before treatment to 107.14 ± 13.32, 116.05 ± 7.66 and 117.79 ± 6.51 g/L at 3, 6 and 12 months posttreatment, respectively (p = .000). The symptom severity score (SSS) and health-related quality of life (HRQL) scores were also significantly improved posttreatment compared with before treatment (p = .000). CONCLUSION: PMWA is an effective, minimally invasive treatment for symptomatic leiomyomas that can significantly improve the quality of life of patients.

Dietary Keratan Sulfate from Shark Cartilage Modulates Gut Microbiota and Increases the Abundance of Lactobacillus spp.

Keratan sulfate (KS) represents an important family of glycosaminoglycans that are critical in diverse physiological processes. Recently, accumulating evidence has provided a wealth of information on the bioactivity of KS, which established it as an attractive candidate for drug development. However, although KS has been widely explored, less attention has been given to its effect on gut microbiota. Therefore, given that gut microbiota plays a pivotal role in health homeostasis and disease pathogenesis, we investigated here in detail the effect of KS on gut microbiota by high-throughput sequencing. As revealed by heatmap and principal component analysis, the mice gut microbiota was readily altered at different taxonomic levels by intake of low (8 mg/kg) and high dosage (40 mg/kg) of KS. Interestingly, KS exerted a differing effect on male and female microbiota. Specifically, KS induced a much more drastic increase in the abundance of Lactobacillus spp. in female (sixteen-fold) versus male mice (two-fold). In addition, combined with alterations in gut microbiota, KS also significantly reduced body weight while maintaining normal gut homeostasis. Altogether, we first demonstrated a sex-dependent effect of KS on gut microbiota and highlighted that it may be used as a novel prebiotic for disease management.