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Background: Since cytokine receptor-like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. Methods: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow-derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno-associated virus (AAV) or AAV containing CRLF1 was determined by morphological, histological, and micro computer tomography (CT) analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were determined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes using real-time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. Results: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondrogenic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and cardiotrophin-like Cytokine (CLC) stimulated catabolic events via STAT3 activation. Conclusion: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.

Purpose Surgery and nonoperative management (NOM) are the treatment modalities for acute appendicitis (AA). There is little evidence to indicate which treatment method should be performed according to the patient's condition or disease severity, surgical extension, and timing after an appendectomy. This study aimed to evaluate postoperative intra-abdominal abscess (PIAA) associated with these factors. Methods The medical records of 839 patients who underwent appendectomy after a diagnosis of AA between 2019 and 2020 at Gangneung Asan Medical Centre were reviewed retrospectively. The factors associated with PIAA were evaluated. Results Postoperative complications occurred in 92 patients. Following appendectomy, 16 (1.9%), 83 (9.9%), and three (0.4%) patients developed PIAA, surgical site infection, and incisional hernia, respectively. The American Society of Anesthesiologists class, complicated appendicitis on preoperative abdominal computed tomography, failure of NOM, and extensive surgery above appendectomy were associated with the development of PIAA. However, a laparoscopic approach, irrigation, indwelling drain, ultrasonic dissection, and use of sterile bags were not associated with the development of PIAA. Conclusion NOM for some patients with complicated AA is an attractive treatment modality. However, to reduce the incidence of PIAA, the application of NOM should be circumspect considering patient factors and the nature of acute appendicitis. Furthermore, appendectomy should be performed as early as possible for patients not indicated for NOM.

Background Radioactive iodine (RAI) remnant ablation is recommended in patients with papillary thyroid cancer (PTC) and extrathyroidal extension or central lymph node metastasis. However, there exists little evidence about the necessity of remnant ablation in PTC patients with low- to intermediate-risk, those have been increasing in recent decades. Methods This multicenter, prospective, non-randomized, parallel group clinical trial will enroll 310 eligible patients with low- to intermediate-risk of thyroid cancer. Inclusion criteria are patients who recently underwent total thyroidectomy for PTC with 3 or less tumors of size 1≤ to ≤2 cm with no microscopic extension and N0/x, or size ≤2 cm with microscopic extension and/or N1a (number of lymph node ≤3, size of tumor foci ≤0.2 cm, and lymph node ratio

Purpose The impact of postoperative complications on long-term oncologic outcome after radical colorectal cancer surgery is controversial. The aim of this study was to examine the risk factors and oncologic outcomes of surgery-related postoperative complication groups. Methods From January 2010 to December 2010, 310 patients experienced surgery-related postoperative complications after radical colorectal cancer surgery. These stage I–III patients were classified into 2 subgroups, minor (grades I, II) and major (grades III, IV) complication groups, according to extended Clavien-Dindo classification system criteria. Clinicopathologic differences between the 2 groups were analyzed to identify risk factors for major complications. The diseasefree survival rates of surgery-related postoperative complication groups were also compared. Results Minor and major complication groups were stratified with 194 patients (62.6%) and 116 patients (37.4%), respectively. The risk factors influencing the major complication group were pathologic N category and operative method. The prognostic factors associated with disease-free survival were preoperative perforation, perineural invasion, tumor budding, and receiving neoadjuvant therapy. With a median follow-up period of 72.2 months, the 5-year disease-free survival rates were 84.4% in the minor group and 78.5% in the major group, but there was no statistical significance between the minor and major groups (P = 0.392). Conclusion Advanced cancer and open surgery were identified as risk factors for increased surgery-related major complications after radical colorectal cancer surgery. However, severity of postoperative complications did not affect disease-free survival from colorectal cancer.

Abstract Background Febrile urinary tract infection (UTI) is one of the most common complications after ureteroscopic lithotripsy (URS). We evaluated the effect of secondary signs on preoperative computed tomography (CT) for febrile UTI after URS. Methods In total, 182 patients who underwent URS for ureteral stones from January 2013 to December 2015 were retrospectively included in this study. These patients were divided into two groups according to the presence of postoperative febrile UTI after URS. We compared the clinical factors, stone factors, and secondary signs between the groups. Predictive factors for febrile UTI after URS were analyzed using a multivariate logistic regression model. Results Febrile UTI occurred in 26 of the 182 patients. In univariate analysis, presence of comorbid chronic kidney disease (CKD) and stone size were significantly different between UTI and non-UTI groups. Among secondary signs, presence of hydroureter, perinephric fat stranding, periureteral fat stranding, and tissue rim sign were significantly different between the groups. In multivariate logistic regression analysis, comorbid CKD, stone size, perinephric fat stranding, and tissue rim sign were independent predictive factors for febrile UTI after URS. Conclusion This study demonstrated that secondary signs including perinephric fat stranding and tissue rim sign on preoperative CT, CKD, and stone size are independent predictive factors for febrile UTI after URS.

The information encoded in a single copy of DNA is processed into a plethora of protein molecules via the cascade of transcription and translation. Thus, the molecular process of gene expression can be considered an efficient biological amplifier from the viewpoint of synthetic biology. Cell-free protein synthesis (CFPS) enables the implementation of this amplification module for in vitro analysis of important biomolecules and avoids many of the problems associated with whole cell-based approaches. Here, we developed a method to analyze indole by using a combination of enzymatic conversion of indole and amino acid-dependent CFPS. In this method, indole molecules in the assay sample are used to generate tryptophan, which is incorporated into signal-generating proteins in the subsequent cell-free synthesis reaction. The activity of cell-free synthesized proteins was successfully used to estimate the indole concentration in the assay sample. In principle, the developed method could be extended to analyses of other important bioactive compounds.

Anterior mediastinal teratomas are congenital tumors containing derivatives of all three germ layers. They usually grow slowly and are often detected incidentally by imaging studies. We describe the case of a 38-year-old man with an anterior mediastinal teratoma extending to the anterior neck, which resulted in a cystic neck mass.

Purpose: Ureteroscopic lithotripsy (URS) is gaining popularity for the management of ureteral stones and even renal stones, with high efficacy and minimal invasiveness. Although this procedure is known to be safe and to have a low complication rate, febrile urinary tract infection (UTI) after URS is not rare. Therefore, we aimed to analyze the risk factors and causative pathogens of febrile UTI after URS. Materials and Methods: Between January 2013 and June 2015, 304 patients underwent URS for ureteral or renal stones. The rate of postoperative febrile UTI and the causative pathogens were verified, and the risk factors for postoperative febrile UTI were analyzed using logistic regression analysis. Results: Of 304 patients, postoperative febrile UTI occurred in 43 patients (14.1%). Of them, pathogens were cultured in blood or urine in 19 patients (44.2%), and definite pathogens were not identified in 24 patients (55.8%). In patients with an identified pathogen, Pseudomonas aeruginosa had the highest incidence. Multivariate analysis showed that the operation time (p

BackgroundThe ongoing Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) aims to observe the natural course of papillary thyroid microcarcinoma (PTMC), develop a protocol for active surveillance (AS), and compare the long-term prognosis, quality of life, and medical costs between the AS and immediate surgery groups.MethodsThis multicenter prospective cohort study of PTMC started in June 2016. The inclusion criteria were suspicious of malignancy or malignancy based on fine needle aspiration or core needle biopsy, age of ≥18 years, and a maximum diameter of ≤1 cm. If there was no major organ involvement, no lymph node/distant metastasis, and no variants with poor prognosis, the patients were explained of the pros and cons of immediate surgery and AS before selecting AS or immediate surgery. Follow-up visits (physical examination, ultrasonography, thyroid function, and questionnaires) are scheduled every 6 months during the first 2 years, and then every 1 year thereafter. Progression was defined as a maximum diameter increase of ≥3, ≥2 mm in two dimensions, suspected organ involvement, or lymph node/distant metastasis.ResultsAmong 439 enrolled patients, 290 patients (66.1%) chose AS and 149 patients (33.9%) chose immediate surgery. The median follow-up was 6.7 months (range, 0.2 to 11.9). The immediate surgery group had a larger maximum tumor diameter, compared to the AS group (7.1±1.9 mm vs. 6.6±2.0 mm, respectively; P=0.014).ConclusionThe results will be useful for developing an appropriate PTMC treatment policy based on its natural course and risk factors for progression.

Amyloidosis has a wide spectrum of manifestations in numerous abdominal organs. It can be categorized into primary or secondary disease according to the presence of accompanying conditions, such as rheumatoid arthritis, tuberculosis, or neoplasms. Herein, we present a rare case of amyloidosis associated with renal cell carcinoma that showed nonspecific radiologic features such as diffuse bowel wall thickening, ascites and peritoneal thickening.

Abstract Background A variety of anticancer chemotherapeutics induce adverse side effects including myelotoxicity. Dried roots of Phragmites communis Trinius, Phragmitis rhizoma, have been clinically used in traditional folk medicine to relieve various symptoms like fever. In this study, we evaluated the protective effect of the aqueous extract of Phragmitis rhizoma (EPR) against docetaxel-induced myelotoxicity in vitro and in vivo. Methods The in vitro myelo-protective effect of EPR was evaluated using the colony forming unit (CFU) assay with hematopoietic progenitor cells. The in vivo efficacy of EPR was evaluated in myelosuppressed C57BL/6 male mice which were induced by repeated intraperitoneal injections of 30 mg/kg docetaxel for 3 times. EPR was orally administered for 4 days to docetaxel-induced myelosuppressed C57BL/6 male mice which were induced by intraperitoneal injection of 30 mg/kg docetaxel for 3 times: Group 1 (vehicle control, n = 10), Group 2 (docetaxel plus vehicle, n = 10), Group 3 (docetaxel plus EPR 30 mg/kg, n = 10), Group 4 (docetaxel plus EPR 100 mg/kg, n = 10) and Group 5 (docetaxel plus EPR 300 mg/kg, n = 10). Whole blood counts were measured automatically, and immune organs were histologically examined. Expression of immunomodulatory cytokines was measured by quantitative real-time polymerase chain reaction or enzyme-linked immunosorbent assay. The toxicity of EPR itself was evaluated in normal human cell lines including IMR-90, foreskin fibroblast and human umbilical vein endothelial cells. The hepatotoxicity of EPR was predicted by multi-parametric assays involving cell viability, caspase 3/7 activity, GSH contents and LDH leakage using the HepaRG hepatic cell line. Results Co-treatment of EPR or its major component, p-hydroxycinnamic acid, increased the numbers of hematopoietic CFU counts in the docetaxel-induced in vitro myelotoxicity assay system. The in vitro protective effect of EPR against docetaxel toxicity was replicated in a myelosuppressed animal model: white blood cells, neutrophils, lymphocytes and red blood cells rebounded; bone marrow niche and structural integrity of the thymus were preserved; and the expression of immune-stimulating cytokines including IL3, IL6, SCF and GM-CSF was enhanced. Furthermore, EPR and p-hydroxycinnamic acid promoted the proliferation of primary splenocytes and thymocytes. In the toxicity assays, no remarkable signs related with toxicity were observed in all tested normal human cells and HepaRG. Conclusions EPR has the potential to ameliorate docetaxel-mediated myelotoxicity in both in vitro and in vivo models. However, the identification of the responsible active components and the precise underlying myelo-protective mechanism of EPR need to be elucidated before novel drug development using EPR can precede.

Purpose: Based on the experiences of our center, we sought to verify the necessity of actively removing stones during retrograde intrarenal surgery (RIRS) for the management of renal stones. Materials and Methods: From March 2010 to March 2015, 248 patients underwent RIRS at our center. We classified these patients into 2 groups according to the performance of active stone removal; group A (n=172) included the patients whose stones were actively removed using a stone basket, and group B (n=76) included the patients whose stones were fragmented with laser lithotripsy without active removal of the fragments. We retrospectively compared the operation time, success rate, and complication rate between the 2 groups. Results: There were no significant differences between groups A and B in terms of mean age (56.1 years vs. 58.6 years), male to female ratio (115:57 vs. 46:30), mean body mass index (24.5 kg/m2 vs. 25.0 kg/m2 ), mean preoperative size of stone (11.1 mm vs. 11.1 mm), the ratio of unilateral and bilateral stones (136:36 vs. 64:12), success rate (89.0% vs. 86.8%), operation time (82.5 minutes vs. 82.1 minutes), overall complication rate (9.9% vs. 11.8%), incidence of febrile urinary tract infection (6.4% vs. 2.6%), gross hematuria (1.7% vs. 2.6%), or postoperative de novo hydronephrosis (2.9% vs. 5.3%). Conclusions: This study demonstrated that during RIRS, fragmentation only, without the active removal of stones, is a safe and effective technique in which the surgical outcomes are comparable to those of procedures involving the active removal of stones.

Purpose: The aim of this study was to assess the advantages of robotic surgery, comparing perioperative and oncological outcomes between robot-assisted radical cystectomy (RARC) and open radical cystectomy (ORC). Materials and Methods: Between August 2008 and May 2014, 112 radical cystectomies (42 RARCs and 70 ORCs) were performed at a single academic institution following Institutional Review Board approval. Patient demographics, perioperative variables (e.g., complications), and oncologic outcomes including metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were reported using the Kaplan-Meier analyses. Results: The median follow-up period was 40 months (range, 0–70 months) vs. 42 months (range, 0–74 months) in RARC and ORC, respectively. Baseline characteristics of both groups were balanced. Blood loss (median, [range]; 300 mL [125–925 mL] vs. 598 mL [150–2,000 mL], p=0.001) and perioperative transfusion rates (23.8% vs. 45.7%, p=0.020) were significantly lower in the RARC group than in the ORC group. The overall complication rates were greater in the ORC group, but this was not statistically significant (65.7% vs. 64.3%, p=0.878). However, there were significantly higher major complication rates in the ORC group (45.7% vs. 26.2%, p=0.040). No significant differences were found with regards to MFS, CSS, and OS. Conclusions: While histopathological findings, overall complications, and survival rates do not reveal definite differences, RARC has more advantages compared to ORC in terms of estimated blood loss, perioperative transfusion rates and fewer perioperative major complications. We propose that RARC is a safer treatment modality with equivalent oncological outcomes compared to ORC.

In the search for novel herbal-based anticancer agents, we isolated a new angular-type pyranocoumarin, (+)-cis-(3′S,4′S)-3′-angeloyl-4′-tigloylkhellactone (1) along with 12 pyranocoumarins (2–13), two furanocoumarins (14, 15), and a polyacetylene (16) were isolated from the roots of Peucedanum praeruptorum using chromatographic separation methods. The structures of the compounds were determined using spectroscopic analysis with nuclear magnetic resonance (NMR) and high-resolution-electrospray ionization-mass spectrometry (HR-ESI-MS). The multidrug-resistance (MDR) reversal and anti-inflammatory effects of all the isolated compounds were evaluated in human sarcoma MES-SA/Dx5 and lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among the 16 tested compounds, two (2 and 16) downregulated nitric oxide (NO) production and five (1, 7, 8, 11, and 13) inhibited the efflux of drugs by MDR protein, indicating the reversal of MDR. Therefore, these compounds may be potential candidates for the development of effective agents against MDR forms of cancer.

A new tetrahydrofuran lignan, (7S,8R,7'S,8'S)-3-methoxy-3',4'-methylenedioxy-7,9'-epoxylignane-4,7',9-triol (1), and 21 known compounds 2–22 were isolated from the roots of Asiasarum heterotropoides by chromatographic separation methods. The structures of all compounds 1–22 were elucidated by spectroscopic analysis including 1D- and 2D-NMR. Fourteen of these compounds (1–3, 7, 10, 12–17, 19, 21, and 22) were isolated from this species in this study for the first time. All of the isolates were evaluated for their anticancer activities using in vitro assays. Among the 22 tested compounds, two (compounds 5 and 7) induced the downregulation of NO production, FOXP3 expression, and HIF-1α transcriptional activity.

BackgroundShivering is a frequent event during spinal anesthesia and meperidine is a well-known effective drug for prevention and treatment of shivering. Nefopam is a non-opiate analgesic and also known to have an anti-shivering effect. We compared nefopam with meperidine for efficacy of prevention of shivering during spinal anesthesia.MethodsSixty five patients, American Society of Anesthesiologists physical status I or II, aged 20-65 years, scheduled for elective orthopedic surgery under spinal anesthesia were investigated. Patients were randomly divided into two groups, meperidine (Group M, n = 33) and nefopam (Group N, n = 32) groups. Group M and N received meperidine 0.4 mg/kg or nefopam 0.15 mg/kg, respectively, in 100 ml of isotonic saline intravenously. All drugs were infused for 15 minutes by a blinded investigator before spinal anesthesia. Blood pressures, heart rates, body temperatures and side effects were checked before and at 15, 30, and 60 minutes after spinal anesthesia.ResultsThe incidences and scores of shivering were similar between the two groups. The mean arterial pressures in Group N were maintained higher than in Group M at 15, 30, and 60 minutes after spinal anesthesia. The injection pain was checked in Group N only and its incidence was 15.6%.ConclusionsWe conclude that nefopam can be a good substitute for meperidine for prevention of shivering during spinal anesthesia with more stable hemodynamics, if injection pain is effectively controlled.

BACKGROUND:In recent years, some reports have suggested that papillary thyroid cancers are more frequently associated with lymphocytic thyroiditis or Hashimoto's thyroiditis. This study investigated a potential increase in the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients. MATERIALS AND METHODS:We used national epidemiological survey data on thyroid cancer patients diagnosed in 1999, 2005, and 2008. A retrospective medical record survey was conducted by representative sampling of a national cancer incidence database. The analysis included 5,378 papillary thyroid cancer patients aged 20-79 years. We calculated the age-standardized prevalence and age-adjusted prevalence ratios using a binomial regression model with a log link for the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients by sex for each year. RESULTS:The prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients was 4.0% and 12.8% for men and women in 1999, 6.5% and 24.6% in 2005, and 10.7% and 27.6% in 2008, respectively. Between 1999 and 2008, the age-standardized prevalence of chronic lymphocytic thyroiditis increased 4.1-fold in male patients and 2.0-fold in female patients with papillary thyroid cancer. The prevalence of other thyroid diseases, however, did not increase in either gender. CONCLUSIONS:Among Korean papillary thyroid cancer patients, the prevalence of chronic lymphocytic thyroiditis increased between 1999 and 2008, whereas the prevalence of other thyroid disorders did not change.