To research the structure-activity relationship (SAR) of glycinamide-bearing compounds that used as inhibitors of dipeptidyl peptidase IV (DPP-IV), P32/98 and compound A were chosen as the leading compounds, heterocycles containing nitrogen atom were introduced to form amide, and different residues on a-position of carbonyl were designed. The nineteen designed compounds were synthesized by a simple route and were evaluated as inhibitors of DPP-IV. All of the structures were characterized by 1H NMR and HRMS. The preliminary SAR result was obtained.

In recent studies some urea derivatives have been identified as potent anti-tuberculosis agents by targeting mycobacterial membrane protein large 3 (MmpL3). However, this compound series as exemplified by AU1235 exhibited poor in vitro pharmacokinetic profile. With AU1235 as the lead, we have identified a novel benzimidazole series as potential anti-tuberculosis agents by using scaffold hopping approach. Among these synthesized compounds, 2-aminobenzimidazole derivative 8b showed the potent anti-tuberculosis activity with the MIC value of 0.03 microg x mL(-1). This compound also showed improved metabolic stability compared to AU1235. Our investigation indicated that benzimidazole derivatives are the promising lead for further optimization as anti-tuberculosis agents.

BACKGROUND:The osteogenic differentiation of mesenchymal stem cells is regulated by a variety of molecules.Long non-coding RNA(lncRNA)has attracted much attention because they can participate in regulating a variety of biological processes,but the regulatory role of lncRNA on osteogenic differentiation of mesenchymal stem cells has not been fully explored. OBJECTIVE:To explore the effect of lncRNA Gm16104 on osteogenic differentiation of C3H10T1/2 mesenchymal stem cells. METHODS:The C3H10T1/2 mesenchymal stem cells were induced into osteogenic differentiation by bone morphogenetic protein-2.Alkaline phosphatase staining was performed to identify the osteogenic differentiation of the cells 5 days after osteogenic induction.Expression levels of alkaline phosphatase and lncRNA Gm16104 were detected by qRT-PCR after 0,1,3,and 5 days of osteogenic differentiation.After transfection of the overexpression plasmid of pcDNA-Gm16104,the osteogenic differentiation was identified by alkaline phosphatase staining and qRT-PCR 4 days after osteogenic induction.The expression levels of osteogenesis-related signalling pathway proteins were detected by western blot assay. RESULTS AND CONCLUSION:(1)After 5 days of osteogenic induction,alkaline phosphatase activity was significantly increased.(2)Compared with 0 days,expression levels of the osteogenic marker gene alkaline phosphatase increased and expression levels of Gm16104 decreased after 1,3,and 5 days of osteogenic induction.(3)Transfection of C3H10T1/2 cells with pcDNA-Gm16104 plasmid significantly increased the expression level of Gm16104.(4)Overexpression of Gm16104 inhibited alkaline phosphatase activity,the expression levels of the osteogenic marker gene alkaline phosphatase and the osteogenesis-related transcription factor Osterix.(5)Overexpression of Gm16104 inhibited phosphorylated protein expression of PI3K and Akt.(6)The above results suggest that overexpression of Gm16104 may inhibit osteogenic differentiation of C3H10T1/2 mesenchymal stem cells through the PI3K/Akt signaling pathway.

INTRODUCTIONThis study aims to evaluate the predictive factors affecting the clinical outcome of Below Knee Amputations (BKA) performed in diabetic foot patients admitted to National University Hospital (NUH) Multi-Disciplinary Diabetic Foot Team.

MATERIALS AND METHODSThis is a prospective cohort study of 151 patients admitted to the Department of Orthopaedic Surgery, NUH, for Diabetic Foot Problems (DFP) from January 2006 to January 2010. All had undergone BKA performed by NUH Multi-Disciplinary Diabetic Foot Team. Statistical analyses (univariate and multivariate analysis with logistic regression) were carried out using SPSS version 18.0, for factors such as demographic data, diabetic duration and control, clinical findings and investigations, indications for surgery, preoperative investigations and evaluation, microbiological cultures, and these were compared to the clinical outcome of the patient. A good clinical outcome is defined as one not requiring proximal re-amputation and whose stump healed well within 6 months. The ability to ambulate with successful use of a prosthesis after 1 year was documented. Statistical significance was set at P <0.050.

RESULTSMean age of study population was 55.2 years with a male to female ratio of about 3:2. Mean follow up duration was 36 months. Of BKAs, 73.5% gave a good outcome. Univariate analysis showed that smoking, previous limb surgery secondary to diabetes, high Total White Count (TW), Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Urea, Creatinine (Cr), Neutrophils, absence of posterior tibial and popliteal pulses, low Ankle Brachial Index (ABI) and Toe Brachial Index (TBI) were associated with poor clinical outcome. Multivariate analysis showed that high CRP, ESR, Neutrophils, absence of popliteal pulse and low ABI were associated with poor clinical outcome. Of patients, 50.3% attained mobility with prosthesis after 1 year. Mortality rate was 21.2% within 6 months of operation, with sepsis being the most significant cause of death.

CONCLUSIONSuccess rate of BKA was 73.5%, with mortality rate being 21.2% within 6 months. In this cohort, 50.3% were able to attain eventual mobility with prosthesis after 1 year. Sepsis was the most significant cause of death. Markers of infection such as high CRP, ESR, neutrophils; and indicators of poor vascularity such as absence of popliteal pulse and low ABI were significantly associated with poor clinical outcome.

Adult ; Aged ; Aged, 80 and over ; Amputation ; methods ; Diabetic Foot ; surgery ; Female ; Humans ; Knee ; Male ; Middle Aged ; Prospective Studies ; Treatment Outcome

OBJECTIVE To analyze the dose-adjusted concentrations of Posaconazole oral suspension in patients undergoing hematopoietic stem cell transplantation （HSCT） and their influential factors. METHODS Data were collected from hospitalized HSCT patients admitted to the First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital） from January 2021 to April whtwhm@yeah.net 2023 who took Posaconazole oral suspension for the prevention of invasive fungal disease （IFD） and received blood concentration of posaconazole. The rate of concentration attainment and clinical failure rate of posaconazole for the prevention of IFD were evaluated， and one-way and multiple linear regression analyses were performed for the influential factors of dose-adjusted concentrations （C0/D） of posaconazole. RESULTS A total of 44 patients were enrolled； the mean C0 of posaconazole in patients was （0.99±0.94） µg/mL， and 20 patients had a C0≥0.7 μg/mL， with a concentration attainment rate of 45.45% for the prevention of IFD； 13 cases were clinical failures， with a clinical failure rate of 29.55%. Of 24 patients who did not achieve C0/D of posaconazole for IFD prophylaxis， one patient was a clinical failure despite timely dose adjustment of posaconazole in seven patients； seven of the thirteen patients who did not undergo dose adjustment were clinical failures； and the remaining four patients were switched to other antifungal agents. The results of univariate analysis showed that gender， body mass index （BMI）， renal function， combined use of sodium phenytoin， omeprazole and metoclopramide had a significant effect on the C0/D of posaconazole （P＜0.05）； the results of multivariate linear regression analysis showed that gender， BMI and combined use of sodium phenytoin were the independent factors affecting the C0/D of posaconazole （P＜0.05）. CONCLUSIONS Significant individual differences are reflected in the blood concentration of Posaconazole oral suspension； gender， BMI and combined use of sodium phenytoin are independent factors affecting the C0/D of posaconazole.