HIV and AIDS remain as the crucial global health concern, therefore, research and development of novel anti-HIV-1 chemical therapeutics is still of paramount significance, which may be illuminated by cases of successful marketed drugs. Herein, we document the discovery and biological profile of new anti-HIV-1 drugs approved by FDA between 2005 and 2008 and some drug candidates are also discussed.

BACKGROUND: Whether horizontal and vertical impacts cause craniocerebral injury of the same degree, and whether serum myelin basic protein (MBP) changes is associated with the direction of impact have been scarcely addressed in previous studies.OBJECTIVE: To observe the change in the serum MBP levels and morphological changes of the brain tissue rabbits with craniocerebral injury resulting from impacts from different directions.DESIGN: A randomized controlled experiment.SETTING: Department of Neurosurgery of a hospital affiliated to a medical university.MATERIALS: This study was conducted in the Central Laboratory of Shenyang Medical College between October 2003 and January 2004. Totally 30 healthy rabbits of either sex were randomly divided into two equal groups to receive vertical and horizontal impact on the head.METHODS: All the rabbits were anesthetized and fixed in prone position onto a table equipped with a device for inducing impact on the head from different directions. Venous blood of 1 mL was taken from the edge of the ear of each rabbit for detecting MBP before injury. The rabbits in vertical impact group received the impact of a hammer falling directly on the parietal bone of the skull. In the horizontal group, the rabbits were subjected to horizontal impact on the lateral side of the skull. Forty-eight hours after the injury, venous blood were again taken for MBP measurement. The rabbits were then killed for pathological examination of the brain.MAIN OUTCOME MEASURES: Changes in serum MBP and pathomorphology of the brain tissues in the two groups after the impact.RESULTS: ① According to intention to treat analysis, all the 30 animals were involved in the experiment. There was no significant difference in serum MBP levels between the two groups before the impact, nor 48 hours after the impact( P ＞ 0.05). In the vertical impact group, serum MBP levels before the impact was( 1.68 ± 0. 86) μg/L, which was significantly lower than that after the impact[ (5.25 ± 1.96) μg/L, t = 3. 226, P ＜ 0. 05]. ② In the horizontal strike group, serum MBP also significantly increased from the level of( 1.70 ± 0.91 ) μg/L before impact to(5.73 ± 2.07) μg/L after that( t = 3. 080, P ＜ 0.05) . ③ After the impact, vasodilation and congestion in the cortex near the midline of the bilateral parietal region and edema in the deep layer of the white matter were observed in the vertical impact group, along with significant enlargement of the extravascular and extracellular space. In the horizontal group, similar changes except those near the midline of the bilateral parietal region took place after the impact; the same pathological changes were also observed in the basal plane, with nearly identical pathological changes in the deep layer of the white matter.CONCLUSION: Vertical and horizontal impacts can both result in almost identical brain injuries demonstrated by similar changes in serum MBP and the pathomorphology of the brain tissues after the impacts.

Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. Phosphotyrosine (pTyr) is the substrate for PTP1B dephosphorylation. Malonic acid moiety was used herein as a mimic of the phosphate group in pTyr, and novel malonic acid derivatives 1-7 were designed, synthesized and evaluated as PTP1B inhibitors. Results from enzymatic assays indicated that compounds 3 and 4 exhibited potent inhibition against human recombinant PTP1B with IC50 values of 7.66 and 1.88 micromol x L(-1), respectively.

Objective To discuss the feasibility of positioning the acetabular center,fixing acetabular implant correctly and reconstructing hip rotation center according to Harris fossa and the remaining anatomical markers of acetabular notch in revision hip arthroplasty.Methods Twenty-eight patients underwent revision hip arthroplasty from April 2007 to June 2009.Based on Paprosky type,3 cases with type Ⅰ were treated with biological fixed acetabular component;8 cases with ⅡA and ⅡB were reconstructed with using of morselized bone grafting and large diameter cemented acetabular prosthesis;17 cases with type ⅡC,ⅢA and ⅢB were treated with using of morselized bone grafting and fixation of acetabular reinforcement ring.Among them,5 patients with massive bone loss in acetabular wall were reconstructed with the use of the structural and morselized bone grafting.The center of the original acetabulum was believed to be in the lunate cartilage surface which was closed to Harris fossa.During the operation,the center was located in the site which was 25-28 mm above in line with perpendicular bisector of acetabular notch connecting line.The acetabular center was the point of positioning acetabular prosthesis (Ⅰ type) or making new acetabulum by impaction bone grafting.Acetabular reinforcement ring (Ⅱ,Ⅲ type) was fixed in accordance with proper transverse angle and anteversion angle.The vertical distance from hip rotation center to teardrop connection and the horizontal distance from hip rotation center to teardrop were measured on preoperative and postoperative radiograph.And the outcomes of reconstruction of rotation center were evaluated.Results The vertical distance was changed from (14.22±3.39) mm preoperatively to (32.64±4.51) mm postoperatively.The difference was statistically significant (t=3.65,P＜ 0.05).The horizontal distance was changed from (25.13±3.46)mm preoperatively to (32.87±4.73) mm postoperatively.The difference was statistically significant (t=2.72,P＜0.05).Conclusion Using residual Harris fossa and acetabular notch as the anatomical markers in revision hip arthroplasty,the restoration of the anatomical hip center has shown to be favorable.

Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. We have previously identified the benzoyl sulfathiazole derivative II as a non-competitive PTP1B inhibitor with in vivo insulin sensitizing effects. Preliminary SAR study on this compound series has been carried out herein, and thirteen new compounds have been designed and synthesized. Among them, compound 10 exhibited potent inhibition against human recombinant PTP1B with the IC50 value of 3.97 micromol x L(-1), and is comparable to that of compound II.

OBJECTIVETo investigate the influence of electroporation on the immunogenicity of the DNA vaccine pVAX- tG250FcGB.

METHODSThe DNA vaccine pVAX-tG250FcGB was constructed by inserting the coding gene of tG250 fusion genes into the expression vector pVAX. The DNA vaccine was delivered in BALB/c mouse by electroporation or intramuscular injection, and the induced antigen specific immune responses were compared.

RESULTSThe vaccine delivered by electroporation and intramuscular injection both induced immune responses in BALB/c mouse, but electroporation produced an obviously stronger effect than intramuscular injection.

CONCLUSIONElectroporation-mediated DNA vaccine delivery can produce strong immune response in mice and is an effective means for studying the immunogenic effect of DNA vaccine pVAX-tG250FcGB.

Animals ; Antibody Formation ; Antibody Specificity ; Antigens, Neoplasm ; genetics ; immunology ; Electroporation ; Gene Fusion ; Granulocyte-Macrophage Colony-Stimulating Factor ; genetics ; immunology ; HEK293 Cells ; Humans ; Injections, Intramuscular ; Male ; Mice ; Mice, Inbred BALB C ; Plasmids ; Random Allocation ; Recombinant Fusion Proteins ; genetics ; immunology ; Transfection ; Vaccines, DNA ; genetics ; immunology

Objective:To explore the effects of the scaffolding-based flipped classroom approach in the teaching of Infectious Disease Nursing. Methods:We assigned 152 students of nursing and midwifery majors of grade 2018 (experimental group) to be taught using the scaffolding-based flipped classroom approach and 182 students of grade 2017 (control group) to be taught using the traditional lecture method. Teaching effects were evaluated through students' exam performance and a questionnaire survey. Numerical data were analyzed using the χ2 test and t test with the use of SPSS 18.0, and text data were processed using NVivo 11 for thematic analysis. Results:The experimental group and control group showed significant differences in the interim exam score (83.19±7.96 vs. 79.62±3.14, P<0.001) and final exam score (78.47±6.92 vs. 73.16±8.24, P<0.001). The students of grade 2018 had a high level of participation in online learning. The questionnaire results showed that the scaffolding-based flipped classroom was well recognized in terms of students' overall perception, perceived course quality, perceived value of learning, and satisfaction and the open-ended question, with low scores for learner complaints and loyalty. Conclusions:The scaffolding-based flipped classroom is feasible in the teaching of Infectious Disease Nursing, which can improve students' academic performance and overall competence.

To investigate the effect of adipose-derived stem cells (ADSCs) on radiation-induced skin injury in SD rats.
 Methods: Radioactive particles 192Ir were used to irradiate the left medial thigh skin of SD rats, and the irradiation dose was at 90 Gy. Then, the rats were randomly allocated into a control group and a treatment group (each n=9). After the irradiation, the control group was injected with 60 μL PBS and the treatment group was injected with 60 μL ADSCs in irradiated skin. The progress of skin damage and healing was observed and photographed every day. Twenty-eighth days after the irradiation, the irradiated skin tissue was taken from the left thigh, and then fixed with formaldehyde fixative solution. At the same time, the skin tissue of the corresponding part of the normal group (n=9) that was not irradiated was also taken. After sampling, embedding and slicing, immunohistochemical staining was used to compare the levels of α-smooth muscle actin (α-SMA), and HE staining was used to compare pathological features of the skin.
 Results: Radioactive particle 192Ir caused the development of III or IV radioactive skin damage. The score of the treatment group was significantly lower than that of the control group. The wounds of the treatment group were basically healed at 28 days, while the ulcer of the control group was unhealed. So, the healing time was shorter in the treatment group. The expression of α-SMA in the skin of the two groups was increased after the radiotherapy. By analyzing the pathological microstructure image, we found that the thickness of epidermis in the control group was greater than that in the treatment group, while the vascular density in the treatment group was greater than that in the control group (all P<0.05).
 Conclusion: Radioactive particles 192Ir can cause skin damage, while the adipose-derived stem cells might alleviate radiation-induced skin injury and promote ulcer healing by promoting angiogenesis.
Adipocytes ; Animals ; Iridium Radioisotopes ; Rats ; Rats, Sprague-Dawley ; Skin ; Stem Cells

Based on a non-competitive and selective PTP1B inhibitor reported by us previously, thirty-nine benzamido derivatives were designed and synthesized as novel PTP1B inhibitors. Among them, twelve compounds exhibited IC values at micromolar level against human recombinant PTP1B, and most of them exhibited significant selectivity to PTP1B over TC-PTP and CD45. Further evaluation of the most potent compound on high-fat diet (HFD)-induced insulin-resistant (IR) obese mice indicated that could modulate glucose metabolism and ameliorate dyslipidemia simultaneously.