Single Molecular Nanomedicines Based on Macrocyclic Carrier-Drug Conjugates for Concentration-Independent Encapsulation and Precise Activation of Drugs.

Nanomedicines often rely on noncovalent self-assembly and encapsulation for drug loading and delivery. However, challenges such as reproducibility issues due to the multicomponent nature, off-target activation caused by premature drug release, and complex pharmacokinetics arising from assembly dissociation have hindered their clinical translation. In this study, we introduce an innovative design concept termed single molecular nanomedicine (SMNM) based on macrocyclic carrier-drug conjugates. Through the covalent linkage of two chemotherapy drugs to a hypoxia-cleavable macrocyclic carrier, azocalix[4]arene, we obtained two self-included complexes to serve as SMNMs. The intramolecular inclusion feature of the SMNMs has not only demonstrated comprehensive shielding and protection for the drugs but also effectively prevented off-target drug leakage, thereby significantly reducing their side effects and enhancing their antitumor therapeutic efficacy. Additionally, the attributes of being a single component and molecularly dispersed confer advantages such as ease of preparation and good reproducibility for SMNMs, which is desirable for clinical applications.

An angel or a devil? Current view on the role of CD8+ T cells in the pathogenesis of myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) and the experimental autoimmune MG (EAMG) animal model are characterized by T-cell-induced and B-cell-dominated autoimmune diseases that affect the neuromuscular junction. Several subtypes of CD4+ T cells, including T helper (Th) 17 cells, follicular Th cells, and regulatory T cells (Tregs), contribute to the pathogenesis of MG. However, increasing evidence suggests that CD8+ T cells also play a critical role in the pathogenesis and treatment of MG. MAIN BODY: Herein, we review the literature on CD8+ T cells in MG, focusing on their potential effector and regulatory roles, as well as on relevant evidence (peripheral, in situ, cerebrospinal fluid, and under different treatments), T-cell receptor usage, cytokine and chemokine expression, cell marker expression, and Treg, Tc17, CD3+CD8+CD20+ T, and CXCR5+ CD8+ T cells. CONCLUSIONS: Further studies on CD8+ T cells in MG are necessary to determine, among others, the real pattern of the Vß gene usage of autoantigen-specific CD8+ cells in patients with MG, real images of the physiology and function of autoantigen-specific CD8+ cells from MG/EAMG, and the subset of autoantigen-specific CD8+ cells (Tc1, Tc17, and IL-17+IFN-γ+CD8+ T cells). There are many reports of CD20-expressing T (or CD20 + T) and CXCR5+ CD8 T cells on autoimmune diseases, especially on multiple sclerosis and rheumatoid arthritis. Unfortunately, up to now, there has been no report on these T cells on MG, which might be a good direction for future studies.

Salvage radiofrequency ablation followed by external beam radiotherapy for inoperable recurrent differentiated thyroid cancer.

PURPOSE: The treatment of recurrent thyroid cancer with critical organ invasion is challenging. The combination of radiofrequency ablation (RFA) and external beam radiation therapy (EBRT) has been proposed as an effective option. This study evaluates outcomes for inoperable residual/recurrent differentiated thyroid cancer (rDTC) patients treated with RFA followed by EBRT. MATERIALS AND METHODS: Patients with rDTC treated with RFA followed by EBRT were retrospectively studied. RFA was performed using a free-hand, 'moving-shot' technique under US or CT guidance. For lesions invading critical structures intolerant to 'en bloc' high-temperature RFA, limited-field EBRT using 6- or 10-MV photons was used for adjuvant treatment at a dose of 66 Gy in 33 daily fractions. Toxicities and outcomes were reviewed. RESULTS: Between April 2020 and January 2022, 11 patients with 14 rDTC lesions underwent RFA followed by EBRT. Five patients had metastatic lesions at rDTC diagnosis. With a median follow-up period of 33.7 months, all patients maintained locoregional control, while achieving a 2-year survival rate of 90.9%. This combined treatment achieved a volume reduction ratio of 92.1% ± 5.1%. The mean nadir thyroglobulin level in patients without initial distant metastases after treatment was 1.40 ± 0.81 ng/ml. Regarding treatment-related complications, one patient (9%) experienced temporary hoarseness after RFA, grade 2 radiation dermatitis occurred in 3 patients (27.2%), and grade 2 dysphagia was noted in 4 patients (36.4%). No grade 3 or greater toxicities occurred. CONCLUSIONS: Salvage RFA followed by EBRT is feasible, effective and safe for patients with rDTC.

The safety and short-term effect of mixed approach in laparoscopic right hemicolectomy for right colon cancer compared with middle approach: a retrospective study.

PURPOSE: To investigate whether the mixed approach is a safe and advantageous way to operate laparoscopic right hemicolectomy. METHODS: A retrospective study was performed on 316 patients who underwent laparoscopic right hemicolectomy in our center. They were assigned to the middle approach group (n = 158) and the mixed approach group (n = 158) according to the surgical approaches. The baseline data like gender、age and body mass index as well as the intraoperative and postoperative conditions including operation time, blood loss, postoperative hospital stay and complications were analyzed. RESULTS: There were no significant differences in age, sex, BMI, ASA grade and tumor characteristics between the two groups. Compared with the middle approach group, the mixed approach group was significantly lower in terms of operation time (217.61 min vs 154.31 min, p < 0.001), intraoperative blood loss (73.8 ml vs 37.97 ml, p < 0.001) and postoperative drainage volume. There was no significant difference in the postoperative complications like postoperative anastomotic leakage, postoperative infection and postoperative intestinal obstruction. CONCLUSIONS: Compared with the middle approach, the mixed approach is a safe and advantageous way that can significantly shorten the operation time, reduce intraoperative bleeding and postoperative drainage volume, and does not prolong the length of hospital stay or increase the morbidity postoperative complications.

Hypoxia and Matrix Metalloproteinase 13-Responsive Hydrogel Microspheres Alleviate Osteoarthritis Progression In Vivo.

The occurrence of osteoarthritis (OA) is highly associated with the inflammatory hypoxic microenvironment. Yet currently no attention has been paid to fabricating hypoxia-responsive platforms for OA treatment. Herein, an injectable hydrogel microsphere system (HAM-SA@HCQ) focusing on the hypoxic inflamed joint is prepared with methacrylate-modified sulfonated azocalix[4]arene (SAC4A-MA), methacrylated hyaluronic acid (HA-MA), and dithiol-terminated matrix metalloproteinase 13 (MMP-13) sensitive peptide via a microfluidic device and photo crosslinking technique, followed by encapsulation of the anti-inflammatory drug hydroxychloroquine (HCQ) through host-guest interaction. Owing to the hydrophobic deep cavity, phenolic units, and azo bonds of SAC4A-MA, the hydrogel microspheres show strong drug loading capacity, prominent reactive oxygen species (ROS) scavenging capability, and specific hypoxia-responsive drug release ability. In the OA tissue microenvironment, the hydrogel microspheres undergo degradation by excessive MMP-13 and release HCQ under the hypoxia condition, which synergizes with the ROS-scavenging calixarene to inhibit the inflammatory response of macrophages. After being injected into the OA-inflamed joint, the HAM-SA@HCQ can significantly attenuate the oxidative stress, downregulate the expression of hypoxia-induced factor-1α and inflammatory cytokines, and prevent the cartilage from being destroyed.

Analysis of enhanced CT imaging signs and clinicopathological prognostic factors in hepatoid adenocarcinoma of stomach patients with radical surgery: a retrospective study.

BACKGROUND: To investigate the association between CT signs and clinicopathological features and disease recurrence in patients with hepatoid adenocarcinoma of stomach (HAS). METHODS: Forty nine HAS patients undergoing radical surgery were retrospectively collected. Association between CT and clinicopathological features and disease recurrence was analyzed. Multivariate logistic model was constructed and evaluated for predicting recurrence by using receiver operating characteristic (ROC) curve. Survival curves between model-defined risk groups was compared using Kaplan-Meier method. RESULTS: 24(49.0%) patients developed disease recurrence. Multivariate logistic analysis results showed elevated serum CEA level, peritumoral fatty space invasion and positive pathological vascular tumor thrombus were independent factors for disease recurrence. Odds ratios were 10.87 (95%CI, 1.14-103.66), 6.83 (95%CI, 1.08-43.08) and 42.67 (95%CI, 3.66-496.85), respectively. The constructed model showed an area under ROC of 0.912 (95%CI,0.825-0.999). The model-defined high-risk group showed poorer overall survival and recurrence-free survival than the low-risk group (both P < 0.001). CONCLUSIONS: Preoperative CT appearance of peritumoral fatty space invasion, elevated serum CEA level, and pathological vascular tumor thrombus indicated poor prognosis of HAS patients.

An Antitumor Dual-Responsive Host-Guest Supramolecular Polymer Based on Hypoxia-Cleavable Azocalix[4]arene.

The exploitation of specific guests which can respond to external stimuli is the main approach for the construction of stimuli-responsive supramolecular polymers (SPs) based on host-guest interactions. Most functional guests, however, fail to manifest stimuli-responses. Herein, a hypoxia-responsive dimeric azocalixarene (D-SAC4A) with outstanding hosting properties was used as the macrocyclic building block for the preparation of host stimuli-responsive SPs. Since azocalixarenes can also be compatible with stimuli-responsive guests, an antitumor drug, camptothecin (CPT), was chosen and linked via a disulfide-containing linker to afford a glutathione (GSH)-responsive ditropic guest (D-CPT). A unique dual-responsive SP was obtained by 1 : 1 mixing of D-SAC4A and D-CPT in water, which further assembled into SP nanoparticles (DSPNs). DSPNs displayed outstanding stability against dilution and biological interferants, as well as precise CPT-release under GSH and hypoxia conditions. In vitro and in vivo experiments demonstrated the good biosafety and tumor-suppressive effects of DSPNs.

Effect of the transanal drainage tube on preventing anastomotic leakage after laparoscopic surgery for rectal cancer: a systematic review and meta-analysis.

PURPOSE: Anastomotic leakage (AL) is a common postoperative complication of rectal cancer, and transanal drainage tube (TDT) efficacy is still contentious. This study aimed to evaluate the TDT effect on AL prevention. METHODS: All relevant papers were searched by using a predefined search strategy (two randomized controlled trials (RCTs), one prospective study, and four retrospective studies). Meta-analysis was conducted to estimate AL and re-operation pooled rates. RESULTS: A total of 7 studies (1556 patients) were included: No significant statistic difference was found between two groups on AL rate (odds ratio (OR) 0.61, P = 0.11) and re-operation rate (OR 0.52, P = 0.10). For subgroup analysis, significant statistic difference was found between two groups on AL rate (OR 0.29, P = 0.002) and re-operation rate (OR 0.15, P = 0.04) in patients without neoadjuvant therapy. As for patients without diverting stoma, the AL rate (OR 0.35, P = 0.002) was significantly lower than that in patients without TDT. CONCLUSIONS: TDT may reduce AL morbidity and re-operation rate for patients without high risk of AL, but may be useless for those in high-risk situations.

Efficacy and safety of radiofrequency ablation for primary and secondary hyperparathyroidism with or without previous parathyroidectomy: a retrospective study.

INTRODUCTION: This study aimed to investigate and compare the therapeutic efficacy and safety of ultrasound-guided radiofrequency ablation (RFA), between primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT) patients, with or without previous parathyroidectomy (PTX). SUBJECTS AND METHODS: A total of 21 patients (7 PHPT, 14 SHPT) underwent RFA for hyperparathyroidism (HPT) at Kaohsiung Chang Gung Memorial Hospital, Taiwan. Five of the 14 SHPT patients had previously received PTX. The laboratory data, volume change of each parathyroid nodule, symptomatic scores, and complications were analyzed and compared between all groups at 1 and 7 days, and at 1, 3, 6, and 12 months after RFA. RESULTS: After RFA, the volume reduction ratio (VRR) for all patients at the last follow-up was 93.76%, and clinical symptoms significantly improved. At 12 months, all PHPT patients achieved successful treatment of intact PTH (iPTH). In SHPT patients, the mean iPTH value significantly decreased 1-day post-RFA, subsequently exhibiting a transient rebound which proceeded to decrease, with 57.1% reaching successful treatment standards. SHPT patients with PTX showed a lower complication score, shorter ablation time, higher iPTH baseline and outcomes, and lower VRR, compared to patients without PTX. The serum calcium level significantly decreased to normal range in 85.7% of all patients at 12 months. Severe hypocalcemia occurred in 23.8% at 1 week, and all were corrected with calcium supplements. CONCLUSIONS: RFA demonstrates a therapeutic efficacy similar to PTX. It can thus be considered an effective alternative treatment for PHPT, SHPT, or post-PTX patients who are unsuitable for another PTX.

One year follow-up of US-Guided radiofrequency ablation for low-risk papillary thyroid microcarcinoma: The first experience in Taiwan.

BACKGROUND: The incidence of papillary thyroid microcarcinoma (PTMC) has increased rapidly in recent decades, with a favorable overall prognosis. We aimed to evaluate the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for treating low-risk PTMC in Taiwan. METHODS: This prospective study included patients with PTMC who were ineligible or refused surgery and underwent US-guided RFA between October 2018 and June 2020. US and computed tomography (CT) were performed before RFA to assess tumor lesions and exclude cervical lymph node metastasis. Sequential US follow-up following RFA was performed after 1, 3, 6, and 12 months, and yearly thereafter. Volume reduction ratio (VRR) and complete disappearance rate of tumor at one year were evaluated. RESULTS: 13 PTMCs in 12 patients were enrolled with a mean follow-up of 16.2 ± 8.1 months (range, 1-24 months). The median largest tumor diameter and tumor volume before RFA were 0.76 cm and 0.15 ml (range, 0.02-0.37 ml). The median (interquartile range, IQR) volume and VRR at 12 months post-RFA were 0 (0, 0.03) ml (p = 0.033) and 100% (84.26%, 100%) (p = 0.008). Eight tumors (61.54%) were completely disappeared at 12 months post-RFA and no tumor recurrence, lymph nodes, or distant metastasis were noted. All tumors were successfully treated without complications. CONCLUSION: Minimally invasive US-guided RFA is an effective and safe alternative for low-risk PTMC, resulting a satisfied VRR.

Decreased Expression of Estrogen Receptors Is Associated with Tumorigenesis in Papillary Thyroid Carcinoma.

Papillary thyroid carcinomas (PTC), which is derived from thyroid follicular cells, is the most commonly differentiated thyroid cancer with sex disparity. However, the role of estrogen receptors (ERs) in the pathogenesis of PTC remains unclear. The present study aimed to determine the association of ER mRNA expression levels with clinicopathologic features in PTC. To that aim, the mRNA levels of ESR1 (ERα66), ESR1 (ERα36), ESR2, and G-protein-coupled estrogen receptor 1 (GPER1) in snap-frozen tissue samples from PTCs and adjacent normal thyroid tissues were determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the correlation between ER mRNA expression levels and clinicopathologic features was analyzed. The expression of ERα66, ERα36, ERß, and GPER1 was lower in PTC specimens than in adjacent normal thyroid tissues. Moreover, low GPER1 expression was associated with extrathyroidal extension. There was no obvious difference in expression of ERs between PTC specimens from male and female patients. In conclusion, our findings highlight the importance of ERs in PTC tumorigenesis.

Efficacy and safety of single-session radiofrequency ablation for intrathoracic goiter: preliminary results and short-term evaluation.

BACKGROUND: An intrathoracic goiter (ITG) is defined as a thyroid extension below the sternal notch. Compared to cervical goiters, surgery for ITG is more challenging, with a higher risk of an extracervical approach. Ultrasound (US)-guided radiofrequency ablation (RFA) is a minimally invasive treatment modality. The purpose of this study was to prospectively evaluate the safety and efficacy of RFA in patients with ITG. METHODS: From a total of 324 patients who underwent thyroid RFA at a single medical center, 15 patients (mean age 52.2 years; 73.3% female) with 16 ITGs were included and classified into three grades and three types using the cross-section imaging CT system. Clinical features and demographics, degree of extension, RFA details, goiter volume, and complications were analyzed. RESULTS: Mean pre- and post-RFA goiter volumes as measured by US were 106.62 ± 61.82 and 25.09 ± 14.22 mL respectively, with a volume reduction rate (VRR) of 75.5% (p < 0.001) at 6 months. The VRR as measured by CT/MRI was 57.0 ± 10.0% (p < 0.001) at 6 months. The intrathoracic length reduction rate at 6 months was 44.9 ± 39.2% (p = 0.001). In addition, 4 (25%) ITGs had total regression of the intrathoracic extension, with a downgrade from grade 1 to cervical goiter. Mean pre- and post-RFA symptom and cosmetic scores were 1.53 and 0.15 (p = 0.001), and 2.67 and 2.00 (p = 0.001), respectively. One patient had transient vocal cord palsy and another had perithyroidal and mediastinal hemorrhage. CONCLUSION: US-guided RFA is an effective treatment for ITG in terms of both cervical and intrathoracic reductions with an acceptable complication rate.

Radiofrequency ablation for treatment of thyroid follicular neoplasm with low SUV in PET/CT study.

OBJECTIVES: To evaluate the feasibility of radiofrequency ablation (RFA) on follicular neoplasm with low standard uptake value (SUV) in a Positron emission tomography (PET/CT) study. METHODS: From January 2018 to July 2019, 86 consecutive patients were diagnosed with follicular neoplasm. Of the patients, 28 with PET/CT scans were enrolled in this study. All patients received ultrasound, fine/core needle aspiration, and PET/CT scan prior to treatment. In accordance with previous studies, we recommended 6 patients who had follicular neoplasm with SUVmax ≥5 undergo surgical resection due to an elevated suspicion of malignancy. For 22 patients SUVmax <5, RFA was performed using the moving shot technique. Ultrasound was performed 6 to 12 months after each procedure. RESULTS: Statistically significant volume reductions during follow-up between values prior to RFA and 12 months post RFA were demonstrated (12.6 ± 20.9 vs. 2.4 ± 3.0 cm3, p < 0.001). Volume reduction ratios at 6-12 months (mean: 10.1 months) after RFA were 73.3% ± 17.7%. One patient presented with vocal cord palsy and recovered within 3 months after RFA. No postprocedural hypothyroidism occurred in the RFA patients. CONCLUSIONS: By using PET/CT, we can select patients with low SUV follicular neoplasm. RFA offers a safe and feasible alternative treatment option for patients unsuitable or unwilling to undergo surgery.KEY POINTSBy using positron emission tomography-computed tomography, we can distinguish low SUV follicular neoplasm for radiofrequency ablation.For low SUV follicular neoplasm, RF ablation offers a safe and effective alternative treatment option for patients unsuitable or unwilling to undergo surgery.

The diagnostic value of the combination of hemoglobin, CA199, CA125, and HE4 in endometriosis.

BACKGROUND: We aimed to analyze the differences in the peripheral blood cells and tumor biomarkers between the patients with endometriosis and healthy people, and establish a more efficient combined diagnostic model. METHODS: We retrospectively analyzed the differences in the peripheral blood cells and tumor biomarkers between the patients with endometriosis and healthy people. Binary logistic regression analysis was used to establish a combined diagnostic model. We plotted the receiver operator characteristic (ROC) curve to analyze the diagnostic efficiency of different diagnostic indexes. RESULTS: Compared with patients in the control group, patients in the endometriosis group had significantly lower eosinophil% (p = 0.045), neutrophil (p = 0.001), lymphocyte (p < 0.001), red blood cells (RBCs) (p < 0.001), and hemoglobin (HGB) (p < 0.001), and had significantly higher monocyte% (p = 0.008), monocyte-to-lymphocyte ratio (MLR) (p = 0.001), platelet-to-lymphocyte ratio (PLR) (p < 0.001), carbohydrate antigen (CA)-199 (p < 0.001), CA125 (p < 0.001), human epididymis protein (HE)-4 (p < 0.001), and the risk of ovarian malignancy algorithm (ROMA) (p < 0.001). The combined diagnostic model of HGB, CA199, CA125, and HE4 was established by binary logistic regression analysis. The ROC curve showed that the combined diagnostic model reached a sensitivity of 85.4%, a specificity of 78.83%, and an area under the curve of 0.900, which was significantly higher than that of the individual index in endometriosis diagnosis. CONCLUSION: The combined diagnostic model of HGB, CA199, CA125, and HE4 may provide a new approach for the early non-invasive diagnosis of endometriosis.

Association Between Oral Corticosteroid Bursts and Severe Adverse Events : A Nationwide Population-Based Cohort Study.

BACKGROUND: Long-term use of oral corticosteroids has known adverse effects, but the risk from brief oral steroid bursts (≤14 days) is largely unknown. OBJECTIVE: To examine the associations between steroid bursts and severe adverse events, specifically gastrointestinal (GI) bleeding, sepsis, and heart failure. DESIGN: Self-controlled case series. SETTING: Entire National Health Insurance Research Database of medical claims records in Taiwan. PARTICIPANTS: Adults aged 20 to 64 years with continuous enrollment in the National Health Insurance program from 1 January 2013 to 31 December 2015. MEASUREMENTS: Incidence rates of severe adverse events in steroid burst users and non-steroid users, as well as incidence rate ratios (IRRs) for severe adverse events within 5 to 30 and 31 to 90 days after initiation of steroid therapy. RESULTS: Of 15 859 129 adult participants, 2 623 327 who received a single steroid burst were included. The most common indications were skin disorders and respiratory tract infections. The incidence rates per 1000 person-years in steroid bursts were 27.1 (95% CI, 26.7 to 27.5) for GI bleeding, 1.5 (CI, 1.4 to 1.6) for sepsis, and 1.3 (CI, 1.2 to 1.4) for heart failure. Rates of GI bleeding (IRR, 1.80 [CI, 1.75 to 1.84]), sepsis (IRR, 1.99 [CI, 1.70 to 2.32]), and heart failure (IRR, 2.37 [CI, 2.13 to 2.63]) significantly increased within 5 to 30 days after steroid therapy initiation and attenuated during the subsequent 31 to 90 days. LIMITATION: Persons younger than 20 years or older than 64 years were not included. CONCLUSION: Oral corticosteroid bursts are frequently prescribed in the general adult population in Taiwan. The highest rates of GI bleeding, sepsis, and heart failure occurred within the first month after initiation of steroid therapy. PRIMARY FUNDING SOURCE: National Health Research Institutes, Ministry of Science and Technology of Taiwan, Chang Gung Medical Foundation, and Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Investigate the improvement of facial skin texture with the VISIA system after total thyroidectomy.

BACKGROUND: During clinical practice we have noticed that some patients with hyperthyroidism have finer skin with less wrinkles, pores, and spots after thyroidectomy, and the improvement can be observed within a few weeks after the operation. However, there is no evidence or study in the literature to proof this finding. AIM AND OBJECTIVE: This study was designed to evaluate and quantify the skin characters of patients with hyperthyroidism before and after thyroidectomy. MATERIAL AND METHODS: This is a prospective study to include patients with hyperthyroidism who received total thyroidectomy between March 1st, 2018 and February 28th, 2019. The patients received blood test for T4 and TSH analysis and VISIA measurements for skin texture quantification, at the preoperative stage, three, and six months postoperatively. A total of 8 patients were included. Repeated measurement was used to determine the lab data and VISIA measurement changes before and after the operation. Mauchly's sphericity test was performed to determine whether the violation of sphericity occurs, and the Greenhouse-Geisser correction was used when the violation of sphericity occurs. RESULTS: All the patients were female and generally healthy without systemic medical disease except the hyperthyroidism. The T4 and TSH levels were not significantly different before and after the thyroidectomy. In terms of the skin character measurements, the wrinkles, texture, pores, UV spots, and brown spots were not improved after thyroidectomy. A trend of improvement in spots, red area, and porphyrin was noted, although not statistically significant. CONCLUSIONS: Surgical removal of the thyroid gland in patients with hyperthyroidism does not improve the skin quality and texture in examinations via the VISIA system.

R-Loops and Its Chro-Mates: The Strange Case of Dr. Jekyll and Mr. Hyde.

Since their discovery, R-loops have been associated with both physiological and pathological functions that are conserved across species. R-loops are a source of replication stress and genome instability, as seen in neurodegenerative disorders and cancer. In response, cells have evolved pathways to prevent R-loop accumulation as well as to resolve them. A growing body of evidence correlates R-loop accumulation with changes in the epigenetic landscape. However, the role of chromatin modification and remodeling in R-loops homeostasis remains unclear. This review covers various mechanisms precluding R-loop accumulation and highlights the role of chromatin modifiers and remodelers in facilitating timely R-loop resolution. We also discuss the enigmatic role of RNA:DNA hybrids in facilitating DNA repair, epigenetic landscape and the potential role of replication fork preservation pathways, active fork stability and stalled fork protection pathways, in avoiding replication-transcription conflicts. Finally, we discuss the potential role of several Chro-Mates (chromatin modifiers and remodelers) in the likely differentiation between persistent/detrimental R-loops and transient/benign R-loops that assist in various physiological processes relevant for therapeutic interventions.

Short to mid-term outcome of total hip arthroplasty with cementless implants in patients younger than 25 years old.

BACKGROUND: Total hip arthroplasty (THA) was once reserved for old patients with hip arthritis but has become more common in very young patients (≤25 years old) diagnosed with various joint disease that were not relieved with conservative treatment. The purpose of this study was to evaluate short to mid-term outcome of THA in patients younger than 25 years old. METHOD: This retrospective study included 45 patients younger than 25 years (mean age 21.8 ± 2.14 years) who underwent THA. The surgical indications, implant selection, leg length discrepancy, medication history, radiographic outcome, survival and clinical results including the modified Harris hip score (mHHS) and SF-36 score were assessed. RESULT: The mean follow-up period recorded for patients was 7.82 years (range 5-12 years). The most common diagnosis was avascular necrosis (37.7%) followed by ankylosing spondylitis (24.4%), developmental dysplasia of the hip (17.7%) and rheumatoid arthritis (8.8%). The preoperative leg length discrepancy (LLD), which ranged from 0.5-7 cm significantly improved after surgery ranging from 0-1 cm. The mean preoperative mHHS was 32.44 ± 18.90 compared with the postoperative score of 94.54 ± 5.81 (p < 0.001). The preoperative p-value of SF-36 was lower compared to the postoperative value in all subgroups of SF-36 (p < 0.001). At the latest follow-up there were no radiological signs of loosening and all the implants were classified as well-integrated. CONCLUSION: At present total hip arthroplasty is considered to be safe and a good solution for young patients below 25 years suffering from end-stage joint disease; however, longer follow-up is required to evaluate the long-term function and outcome of the prosthesis in order to restore the normal lifestyle of the patients.

Development of a highly efficient, strongly coupled organic light-emitting diode based on intracavity pumping architecture.

We report a highly efficient polariton organic light-emitting diode (POLED) based on an intracavity pumping architecture, where an absorbing J-aggregate dye film is used to generate polariton modes and a red fluorescent OLED is used for radiative pumping of emission from the lower polariton (LP) branch. To realize the device with large-area uniformity and adjustable coupling strength, we develop a spin-coating method to achieve high-quality J-aggregate thin films with controlled thickness and absorption. From systematic studies of the devices with different J-aggregate film thicknesses and OLED injection layers, we show that the J-aggregate film and the pump OLED play separate roles in determining the coupling strength and electroluminescence efficiency, and can be simultaneously optimized under a cavity design with a good LP-OLED emission overlap for effective radiative pumping. By increasing the absorption with thick J-aggregate film and improving the electron injection of pump OLED with Li2CO3 interlayer, we demonstrate the POLED with a large Rabi splitting energy of 192 meV and a maximum external quantum efficiency of 1.2%, a record efficiency of POLEDs reported so far. This POLED architecture can be generally applied for exploration of various organic materials to realize novel polariton devices and electrically pumped lasers.

Efficacy and safety of single-session radiofrequency ablation for benign thyroid nodules of different sizes: a retrospective study.

PURPOSE: To compare the effectiveness of radiofrequency ablation (RFA) for benign thyroid nodules (BTNs) among groups presenting with different nodule volumes. MATERIALS AND METHODS: This retrospective study evaluated 186 patients with BTNs who underwent ultrasound guided RFA treatment. The BTNs were categorized into small (≤10 ml); medium (10-30 ml); and large (>30 ml) according to the initial volume of BTNs before ablation. The RFA procedures were performed using the moving shot technique. The volume reduction ratio (VRR) of each nodule, cosmetic score, symptomatic score, and complications were analyzed at 1, 3, and 6 months after RFA treatment and the three groups compared. RESULTS: At 1-month follow-up, the large nodules group showed significantly greater VRR compared to the other two groups (small, 31.88% ± 37.91; medium, 38.9% ± 19.18; large, 48.7% ± 20.43, p = .03). At 6-month follow-up, there was no significant difference of VRR among the three groups (small, 74.6% ± 20.92; medium, 68.1% ± 17.07; large, 75.0% ± 11.88). The most common presented complication was temporary vocal palsy (6 patients; small, n = 1; medium, n = 1; large, n = 3). Additionally, one skin burn, one hematoma, and one nodular rupture of BTNs occurred after the procedures. The complication rate of the large nodules group was highest among the three groups and showed a considerable difference (8 patients; small, n = 1, 2.1%; medium, n = 2, 4.5%; large, n = 5, 11.4%, p = .061). CONCLUSIONS: RFA was confirmed as effective in patients with large thyroid nodule (>30ml), with therapeutic efficacy similar to patients with smaller thyroid nodules.