A prognostic immune predictor,HLA-DRA,plays diverse roles in non-muscle invasive and muscle invasive bladder cancer

BackgroundThere is an increasing demand for prognostic immune biomarkers of cancer. The prognostic significance of immune markers has been shown for various cancers, but biomarkers of bladder cancer (BCa) have not been fully evaluated. To clarify the role of human leukocyte antigen DR alpha chain (HLA-DRA) in BCa development, we examined expression of HLA-DRA mRNA in tissue samples of non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC).Materials and MethodsTissues of 96 NMIBC, 43 MIBC and 59 controls comprising noncancerous BCa surrounding tissues were used to examine the expression of HLA-DRA gene by real-time polymerase chain reaction. The expression of up-stream genes regulating HLA-DRA were also measured to explain the role of HLA-DRA in BCa.ResultsPatients with high grade NMIBC showed higher expression of HLA-DRA than those with low grade NMIBC (P < 0.05). In addition, NMIBC patients who progressed to MIBC showed high expression of HLA-DRA mRNA. Kaplan-Meier analysis showed that NMIBC patients with low expression of HLA-DRA had better progression-free survival than those with high expression (P = 0.004). Moreover, the expression of genes regulating HLA-DRA varied in NMIBC and MIBC, indicating a different immunoregulation effect of HLA-DRA in both cancers.ConclusionsHigh expression of HLA-DRA in NMIBC patients has implications for patient stratification strategies, as well as for BCa tumor immunology.     

Computed Tomography Evaluation of Forearm and Hand Muscles in Patients With Distal Radius Fracture

Introduction: Computed tomography (CT) can be used to assess bone status with measurement of Hounsfield unit (HU). The objective of this study was to evaluate whether HU of muscle might be associated with parameters of bone and muscle status. Methods: We reviewed 71 women aged over 50 yr of age who had distal radius fracture and underwent CT evaluation of affected wrist. We assessed HUs of forearm flexor muscles (flexor digitorum superficialis) and thenar muscles and bone HUs at the capitate and the ulnar head. Other parameters included femur neck and lumbar bone mineral density (BMD), upper extremity lean mass, hand grip strength, and muscle fiber cross-sectional area. We performed correlation analyses to determine associations between variables. Results: Thenar and forearm muscle HUs were significantly correlated with each other, but not with other parameters. HUs of the capitate and ulnar head were positively correlated with femur neck and lumbar BMDs and inversely correlated with age. Ulnar head HU was positively correlated hand grip strength. Conclusions: HUs of forearm and thenar muscles did not show significant correlations with bone or muscle parameters, although bone HUs correlated well with bone mineral densities. These results support the opportunistic use of CT for evaluating bone fragility. Clinical usefulness of muscle HU measurement needs further studies.     

Culture-Expanded Autologous Adipose-Derived Mesenchymal Stem Cell Treatment for Osteonecrosis of the Femoral Head

BackgroudOutcomes of traditional treatment for osteonecrosis of the femoral head (ONFH) are not always satisfactory. Hence, cell-supplementation therapy has been attempted to facilitate necrotic-tissue regeneration. Adipose-derived mesenchymal stem cell (ADMSC) transplantation is potentially advantageous over bone marrow-derived MSC implantation, but its outcomes for ONFH remain unclear. The aim of this study was to determine 2-year radiological and clinical outcomes of culture-expanded autologous ADMSC implantation for ONFH.MethodsEighteen hips with necrotic lesions involving ≥ 30% of the femoral head were included. ADMSCs were harvested by liposuction and culture expanded for 3 passages over 3 weeks. With a 6-mm single drilling, ADMSCs were implanted into the necrotic zone. All patients underwent magnetic resonance imaging (MRI), single-photon emission computed tomography/computed tomography (SPECT/CT) at screening and 6 months, 12 months, and 24 months postoperatively. The primary outcome was the change in the size of necrotic area on MRI. Secondary outcomes were changes in clinical scores and radioisotope uptake on SPECT/CT. Conversion total hip arthroplasty (THA) was defined as the endpoint.ResultsPreoperatively, the necrotic lesion extent was 63.0% (38.4%–96.7%) of the femoral head. The mean Harris hip score was 89.2, the University of California at Los Angeles (UCLA) score was 5.6, and Western Ontario and McMaster Universities Arthritis index (WOMAC) was 79.4. Three patients underwent THA and 1 patient died in an accident. Finally, 11 patients (14 hips) were available for ≥ 2-year follow-up. At the last follow-up, no surgery-related complications occurred, and 14 of 17 hips (82%) were able to perform daily activities without THA requirement. There was no significant decrease in lesion size between any 2 intervals on MRI. However, widening of high signal intensity bands on T2-weighted images inside the necrotic lesion was observed in 9 of 14 hips (64%); 11 of 14 hips (79%) showed increased vascularity on SPECT/CT at 2 years postoperatively. No significant differences were observed between preoperative and 24-month mean Harris hip score (89.2 vs. 88.6), WOMAC (79.4 vs. 75.7), and UCLA score (5.6 vs. 6.2).ConclusionsOur outcomes suggest that culture-expanded ADMSC implantation is a viable option for ONFH treatment without adverse events.     

The establishment of the Korean medical device safety information monitoring center: Reviewing ten years of experience

Medical devices may revolutionize healthcare delivery but can lead to serious adverse events for treated patients and users. While reporting of adverse events related to medical devices is an essential starting point for post-market surveillance, underreporting of medical device adverse events is a global problem. Korea introduced a voluntary medical device adverse event reporting system in 2010, called the Medical Device Safety Information Monitoring Center, which has led to an increase in adverse event reports. For 10 years, the Medical Device Safety Information Monitoring Center has analyzed medical device adverse events systematically and has provided active feedback to the manufacturers and education on safe use. Recently, the Medical Device Safety Information Monitoring Center contributed to harmonization of international medical device vigilance through the sharing of adverse events. This experience of Korea might contribute to improvements in medical device vigilance, which is a critical prerequisite for improving medical device policies and regulations.     

An efficient synthesis of 3-(E)-hydroxypropenyl cephem derivatives, key intermediates for 3-(E)-ammoniopropenylcephalosporin antibiotics

An efficient synthesis of 3-(E)-hydroxy- and 3-(E)-acetoxypropenylcephem derivatives, key intermediates for the synthesis of 3-(E)-propenylcephalosporins was achievedvia Stille coupling reaction of 3-trifloxycephem with 3-(E)-tributylstannylallylic alcohol.     

New flavonoids from the aerial parts of Aconitum chiisanense

The studies were carried out to evaluate the constituents in the aerial part of Aconitum chiisanense (Ranunculaceae). From the butanol fraction of the methanol extract, kaempferol 3- O-beta-glucopyranoside-7- O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (I), quercetin 3- O-beta-glucopyranoside-7- O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (II), kaempferol 3- O-beta-glucopyranoside-7- O-(6-trans-feruloyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (III), kaempferol 3- O-beta-glucopyranoside-7- O-(6-benzoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (IV), kaempferol 7- O-(6-trans)-caffeoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (V), and kaempferol 7- O-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (VI) were isolated and identified on the basis of their physicochemical and spectroscopic evidence (UV, IR, FAB(-)MS, (1)H-NMR, (13)C-NMR, (1)H- (1)H COSY, HMQC and HMBC). New compounds I-VI were named chiisanin (I), chiiribanin (II), chiiribaconin (III), chiirin (IV), chiiricanin (V), and chiirirhamnin (VI), respectively.     

Clonazepam release from core-shell type nanoparticlesin vitro

AB-type amphiphilic copolymers (abbreviated as LE) composed of poly (L-leucine) (PLL) as the A component and poly (ethylene oxide) (PEO) as the B component were synthesized by the ring-opening polymerization of L-leucine N-carboxy-anhydride initiated by methoxy polyoxyethylene amine (Me-PEO-NH₂) and characterized. Core-shell type nanoparticles were prepared by the diafiltration method. Particle size distribution obtained by dynamic light scattering was dependent on PLL composition and the size for LE-1, LE-2 and LE-3 was 369.6±267, 523.4±410 and 561.2±364 nm, respectively. Shapes of the nanoparticles observed by transmission electron microscope (TEM) were almostly spherical. The critical micelle concentration (CMC) of the nanoparticles determined by a fluorescence probe technique was dependent on the composition of hydrophobic PLL, and the CMC for LE-1, LE-2 and LE-3 was 2. 0×10⁻⁶, 1.7×10⁻⁶ and 1.5×10⁻⁶ (mol/l), respectively. Clonazepam release from core-shell type nanoparticles in vitro was dependent on PLL composition and drug loading content.