Chondrogenic differentiation of mesenchymal stem cells (MSCs) is accurately regulated by essential transcription factors and signaling cascades. However, the precise mechanisms involved in this process still remain to be defined. MicroRNAs (miRNAs) regulate various biological processes by binding target mRNA to attenuate protein synthesis. To investigate the mechanisms for miRNAs-mediated regulation of chondrogenic differentiation, we identified that miR-145 was decreased during transforming growth factor beta 3 (TGF-β3)-induced chondrogenic differentiation of murine MSCs. Subsequently, dual-luciferase reporter gene assay data demonstrated that miR-145 targets a putative binding site in the 3′-UTR of SRY-related high mobility group-Box gene 9 (Sox9) gene, the key transcription factor for chondrogenesis. In addition, over-expression of miR-145 decreased expression of Sox9 only at protein levels and miR-145 inhibition significantly elevated Sox9 protein levels. Furthermore, over-expression of miR-145 decreased mRNA levels for three chondrogenic marker genes, type II collagen (Col2a1), aggrecan (Agc1), cartilage oligomeric matrix protein (COMP), type IX collagen (Col9a2) and type XI collagen (Col11a1) in C3H10T1/2 cells induced by TGF-β3, whereas anti-miR-145 inhibitor increased the expression of these chondrogenic marker genes. Thus, our studies demonstrated that miR-145 is a key negative regulator of chondrogenic differentiation by directly targeting Sox9 at early stage of chondrogenic differentiation.
Generating kidney models of T1N0M0 tumors with 3D printing are feasible with refinements to be performed. Face and content validity was obtained when those models were presented to experienced urologists for making practical planning and training. Understandings of the disease and procedure from patients were well appreciated with this novel technology.
ObjectiveThis study assessed the characteristics of pathogens identified in clinical isolates from patients with urinary tract infection (UTI) and their in vitro sensitivity to commonly used antibiotics in the clinical setting in China.Design and settingMulticenter study was conducted between January and December 2011 in 12 hospitals in China.ParticipantsUrine samples were collected from 356 symptomatic patients treated in the study hospitals for acute uncomplicated cystitis, recurrent UTI or complicated UTI.Primary and secondary outcome measuresMinimal inhibitory concentrations (MICs) were measured using broth microdilution according to the Clinical and Laboratory Standards Institute 2011 guidelines. Thirteen antimicrobial agents were tested: fosfomycin tromethamine, levofloxacin, moxifloxacin, cefdinir, cefixime, cefaclor, cefprozil, cefuroxime, amoxicillin/clavulanic acid, cefotaxime, azithromycin, nitrofurantoin and oxacillin. Escherichia coli isolates were screened and extended spectrum β-lactamases (ESBL) production was confirmed by a double-disk synergy test.Results198 urine samples were culture-positive and 175 isolates were included in the final analysis. E coli was detected in 50% of cultures, followed by Staphylococcus epidermidis (9%), Enterococcus faecalis (9%) and Klebsiella pneumoniae (5%). The detection rate of ESBL-producing E coli was 53%. Resistance to levofloxacin was the most common among all the isolates. Nitrofurantoin and fosfomycin tromethamine had the greatest activity against E coli; overall, 92% and 91% of isolates were susceptible to these antimicrobials. E faecalis had the highest susceptibility rates to fosfomycin tromethamine (100%).ConclusionsThe most frequently identified pathogens in our patients were ESBL-producing E
coli and E faecalis. Fosfomycin tromethamine and nitrofurantoin showed a good antimicrobial activity against UTI pathogens. They may represent good options for the empiric treatment of patients with UTI.
ObjectiveTo evaluate the clinical and microbiological efficacy and safety of three doses of 3 g fosfomycin tromethamine administered orally to treat lower urinary tract infections.Design and participantsThis prospective, uncontrolled, open-label study was conducted in 12 medical centres in China, between January and December 2011. According to the diagnosis criteria of Chinese Guidelines on Urological Infections, patients (18–70 years) with acute uncomplicated cystitis, recurrent lower urinary tract infection or complicated lower urinary tract infection received three doses of 3 g fosfomycin tromethamine orally, at days 1, 3 and 5.Primary and secondary outcome measuresEfficacy endpoints (clinical efficacy, microbiological efficacy and overall efficacy) were evaluated on day 15. Clinical symptoms, physical signs, urinalysis, liver and kidney function, patient records and evaluation of adverse events (AEs) and serious AEs up to day 15 were evaluated for analysis of safety.Results361 patients were included in the full analysis set, 356 in the safety analysis set and 335 in the per-protocol set (PPS). In the PPS, the clinical efficacy rates at day 15 for acute uncomplicated cystitis, recurrent lower urinary tract infection and complicated lower urinary tract infection were 94.71% (179/189), 77.22% (61/79) and 62.69% (42/67), respectively. The microbiological efficacy rates (day 15) were 97.65% (83/85), 94.44% (34/36) and 83.87% (26/31), respectively. The overall efficacy rates (day 15) were 95.29% (81/85), 77.78% (28/36) and 64.52% (20/31), respectively. 20/356 (5.6%) patients reported drug-related AEs, the most common being diarrhoea. No serious drug-related AEs were reported.ConclusionsThis fosfomycin tromethamine dosing regimen showed clinical and microbiological efficacy with some AEs and good tolerability in patients with acute uncomplicated cystitis, recurrent lower urinary tract infection and complicated lower urinary tract infection.
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