Identification and validation of a new target is one of the most important steps for new antituberculosis (TB) drug discovery. Researches have shown that Mycobacterium tuberculosis (Mtb) encodes 20 CYP450 enzymes which play important roles in the synthesis and metabolism of lipid, cholesterol utilization, and the electron transport of respiratory chain in Mtb. With the critical roles within the organism as well as the protein structures of six Mtb CYP450 enzymes being clarified, some of them have been highlighted as potential anti-tuberculosis targets. In this paper, the phylogenetic analysis, the structural features, and the enzymatic functions of Mtb CYPs, as well as the mechanism of interactions with selective inhibitors such as azole antifungal agents for the CYPs have been reviewed and summarized. The druggability of the CYPs has also been analyzed for their further utility as targets in high throughput screening and rational design of more selective inhibitors.
Antitubercular Agents ; chemistry ; pharmacology ; Azoles ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme Inhibitors ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Drug Delivery Systems ; methods ; Drug Discovery ; Humans ; Mycobacterium tuberculosis ; drug effects ; enzymology ; genetics ; Phylogeny ; Tuberculosis ; drug therapy ; microbiology

OBJECTIVETo assess the clinical outcomes of balloon kyphoplasty assisted with calcium phosphate cement (CPC) in treating osteoporotic vertebral fractures (OVF).

METHODSFrom January 2009 to January 2011, 26 patients with osteoporotic vertebral fractures were treated with balloon kyphoplasty assisted with CPC, including 31 vertebrae. There were 15 males and 11 females with an average age of (71.67 +/- 4.36) years old (ranged from 60 to 89 years). Course of disease was from 0.5 to 7 days with an average of 3.2 days. Clinical outcomes were assessed by the visual analogue scale (VAS) and the oswestry disability index (ODI). Vertebral height loss and kyphotic angle were measured by X-rays.

RESULTSAll patients were followed up for 10 to 24 months with an average of 18 months. Before operation, 24 hours after operation and at final follow-up, VAS scores were 7.91 +/- 1.20, 3.22 +/- 1.12, 1.92 +/- 0.83, respectively; ODI scores were 40.00 +/- 1.15, 17.00 +/- 2.12, 13.00 +/- 1.42, respectivesly; vertebral heights were (18.21 +/- 3.21), (23.82 +/- 3.10), (21.85 +/- 3.24) mm, respectivesly; vertebral kyphosis angles were (18.21 +/- 3.21) degrees, (7.42 +/- 3.13) degrees, (10.01 +/- 3.11) degrees, respectivesly. There was significant difference between preoperation and 24 hours after operation, and between final follow-up and preoperation (P < 0.05). There was no significant difference between final follow-up and 24 hours after operation (P > 0.05).

CONCLUSIONBalloon kyphoplasty assisted with calcium phosphate cement (CPC) is effective for the treatment of osteoporotic vertebral fractures (OVF), which can expeditiously relieve pain and effectively rebuild height of vertebral body and kyphotic angle, and also has advantages of minimal trauma and good security.

Aged ; Aged, 80 and over ; Bone Cements ; Calcium Phosphates ; therapeutic use ; Female ; Humans ; Kyphoplasty ; methods ; Male ; Middle Aged ; Osteoporotic Fractures ; surgery ; Spinal Fractures ; surgery ; Visual Analog Scale

Objective To investigate the proliferation inhibition of chlorpromazine combined with taxol on Hep-2 cells (human laryngeal carcinoma cell line) and the effects on cell cycle progression. Methods Hep-2 cells at logarithmic growth phase were divided into taxol groups(3.0,6.0 and 12.0 mg?L-1),chlorpromazine(12.0 mg?L-1) comined with taxol (4 mg?L-1)group and control group (100 mL culture fluid).MTT and flow cytometry were used to detect the proliferation inhibition rates of Hep-2 cells in various groups.Flow cytometry was also used to analyze the cell cycle progression of Hep-2 cells and apoptotic rate after administration.Results The proliferation inhibition rates in 3.0,6.0 and 12.0 mg?L-1 taxol groups were 14.0%,23.9% and 36.7%,respectively,there were significant differences between three groups(P

The author uses the database technique to manage the impedance spectroscopy data.In design of impedance spectroscopy database frame,ActiveX Data Object(ADO)technique is adopted to improve the agility and efficiency.It also enhances the efficiency to use data binding technique to avoid complex data type transformation in appending and amending.

In the tissue impedance spectroscopy measurements ,four-electrode method are normally used. A measurement error caused by stray capacitance between lines of drive electrode and receive electrode is not a trivial problem. This paper studied this error and reached the results This stray capacitance introduces errors which increase with frequency and has more effect on the imaginary part than on the real part in the measurement frequency range.

Objective:To observe the clinical efficacy of Yi Jin Jing (Sinew-transforming Qigong Exercises) for primary osteoporosis in the elderly.Methods:Eighty old patients with primary osteoporosis were randomized into a Yi Jin Jing group and a medication group,40 cases in each group.The Yi Jin Jing group was intervened by Yi Jin Jing (Sinew-transforming Qigong Exercises) training,while the medication group was intervened by oral administration of alendronate sodium tablet.Prior to and after 6-month intervention,the bone mineral density (BMD) of the proximal femur,visual analog scale (VAS) and activities of daily living (ADL) were estimated.Results:There were no significant differences in the BMD of the proximal femur,and VAS and ADL scores between the two groups before the intervention (P＞0.05).After 6-month intervention,the above items all improved significantly in both groups (both P＜0.01);the improvements in VAS and ADL scores in Yi Jin Jing group were more significant than those in the medication group (P＜0.01),while the between-group difference in the BMD of the proximal femur was statistically insignificant (P＞0.05).Conclusion:Practice of Yi Jin Jing (Sinew-transforming Qigong Exercises) can effectively ameliorate the BMD in the elderly with primary osteoporosis,and it can reduce the pain and improve ADL,with a better general effect compared to oral administration of alendronate sodium tablet.

Objective To explore the molecular mechanisms of primary amenorrhea by using arrayCGH technology. Methods Ten patients with primary amenorrhea and 10 female volunteers with regular menstrual cycles as healthy controls were selected. All patients and control samples were analyzed by conventional chromosome analysis (G-banding technology) and array-CGH technology, respectively. ArrayCGH was performed using Affymetrix Cytogenetic 2. 7M arrays following the manufacturer's standard protocol. Results Both the patient group and control group analyzed by conventional G-banding karyotype technology showed a negative result with a normal female karyotype: 46, XX. The result of array-CGH analysis demonstrated a microdeletion of approximately 110 000 bp located at the end of the short arm of X chromosome [46, X, del (X) (p22. 33 )] were identified in 5 patients, which was not detected in the control group. All healthy control samples by array-CGH analysis showed no pathological DNA copy number variation. Conclusions Array-CGH technology can improve the diagnosis rate of chromosomal disease at the DNA level. It is necessary to provide array-CGH for higher resolution genetic analysis of idiopathic primary amenorrhea patient who can not be identified by conventional technology.

Objective To investigate the relationship between peripheral inflammatory cytokines and anxiety symptoms in patients with the first?episode generalized anxiety disorder. Methods 48 patients diagnosed with the first?episode generalized anxiety disorder according to ICD?10 criteria and 48 healthy sub?jects were recruited. Peripheral levels of IL?1, IL?2, IL?4, IL?5, IL?6, IL?8, IL?10, IL?12p70, GM?CSF and IFN?γ of both groups were evaluated by enzyme?linked immunosorbent assay ( ELISA) ,and CRP was evalua?ted by immunoturbidimetric method. Generalized Anxiety Disorder Scale( GAD?7) and State?Trait Anxiety Inventory ( STAI ) were used to assess the levels of overall anxiety, state anxiety and trait anxiety. Results The levels of CRP ( ( 1. 19 ± 0. 80 ) mg/L vs ( 0. 68 ± 0. 70 ) mg/L, t=3. 31 ) , IL?1α( ( 70. 34 ± 3.60)pg/ml vs (16.94±3.42)pg/ml, t=74.50),IL?2((7.25±3.42)pg/ml vs (4.95±2.31)pg/ml, t=3.85), IL?4((102.02±73.14)pg/ml vs (75.55±32.78)pg/ml, t=2.29),IL?6((12.55±2.37)pg/ml vs (2.71±1.35) pg/ml, t=14.79),IL?8((44.64±16.21)pg/ml vs (35.69±11.70)pg/ml, t=3.10),IL?12((18.16±24.17) pg/ml vs (10.82±4.72)pg/ml, t=2.06),IFN?γ((23.32±15.52)pg/ml vs (16.48±6.80)pg/ml, t=2.79), GM?CSF((19.07±11.12)pg/ml vs (13.40±8.54)pg/ml, t=2.80) in patients with the first?episode general?ized anxiety disorder were significantly higher than normal controls(P<0.05) . Both SAI and TAI had signifi? cantly positive correlation with the levels of IL?1α, IL?2, IL?6, IL?8, IL?12, IFN?γ and GM?CSF ( r=0.24?0.76, P<0.05) . Conclusion The levels of some peripheral inflammatory cytokines in patients with the first?episode generalized anxiety disorder are significantly increased,and they have positive correlation with gener?al anxiety,state anxiety and trait anxiety,which may suggest some immune system defects in the patients.

OBJECTIVE:To evaluate the pharmacoeconomic characteristics of dapagliflozin combined with metformin in the treatment of type 2 diabetes mellitus systematically. METHODS:Retrieved from Health Technology Assessment(HTA),Cochrane Library,PubMed,Embase,CNKI,Wanfang and CBM during database establishment to Jul. 2017,published pharmacoeconomics literatures about dapagliflozin combined with metformin were collected,using"sodium-glucose-transporter-2 inhibitors""SGLT2 inhibitor""metformin""dapagliflozin""cost""benefit""utility""effectiveness""pharmacoeconomic""economic"as English retrieval words and"SGLT2 inhibitor""dage liejing""metformin""cost""benefit""utility""effectiveness"as Chinese retrieval words. Outcome indexes included incremental cost,incremental effect,cost-effectiveness ratio and incremental cost-effectiveness ratio(ICER).The results of the economic research in the included literatures were evaluated systematically. RESULTS:Totally of 4 literatures were included,and all of them were cost-effectiveness analysis. Dapagliflozin was more cost-effective than sulfonylurea because the ICER of dapagliflozin were €2 709/QALY,€10 494/QALY,€7 939/QALY,€5 433/QALY,€4 767/QALY and €6 094/QALY in the UK,Greece,Denmark,Finland,Norway and Sweden,respectively,which were all lower than willingness-to-pay threshold. Dapagliflozin was more cost-effective than DPP-4 inhibitor,and the ICER were €7 200/QALY and €15 120/QALY in the UK and Greece,respectively,which were all lower than willingness-to-pay threshold. CONCLUSIONS:Current economic research shows compared with sulfonylurea and DDP-4 inhibitor,dapagliflozin is a cost-effective treatment alternative for patients with T2DM whose metformin regimen does not provide sufficient glycemic control.

Objective: To explore the effect of aerobic plus resistance training on the intervention of adolescents with moderate mental retardation and to provide reference for healthy development among specific need population. Methods: Totally 29 adolescents with moderate mental retardation, aged 12-17 years from one middle school in Shunde district of Foshan, were divided into intervention group and control group (16/13) with random number table. The intervention group was subjected to aerobic combined resistance exercise for 11 weeks. The control group maintained the original activities. The changes in body composition, muscle strength, cardiorespiratory endurance and balance ability of the two groups of subjects before and after intervention were compared. Results: After the intervention, the intervention group s skeletal muscle (22.90±3.63)kg, muscle mass (39.75±5.57)kg, lean body mass (41.52±6.79)kg, sitting arm support (49.19±35.28)s, standing timing test (22.13±6.01)s, half crunches (20.12±6.48), grip strength [left (15.98±4.86)kg; right (16.37±5.46)kg], heart rate immediately after 2 min stepping exercise (91.43±13.44)frequency/min, Standing on one foot with eyes closed [left (5.82±5.20)s; right (6.02±5.56)s] compared with before exercise, the body fat decreased(t=2.57,2.72,2.07,2.10,3.31,2.92,2.76,3.44, 2.86,2.04,2.38, -2.92,P<0.05); after the intervention, the sitting arm support and closed eyes standing(right) improved(P<0.05). Conclusion Aerobic combined resistance exercise can improve muscle strength and endurance, aerobic endurance and balance ability in adolescents with moderate mental retardation and adaptability of teenagers with moderate mental retardation.