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

Objective To discuss the effects and influence of preoperative and postoperative adjunctive intravitreal conbercept in 23G vitrectomy for proliferative diabetic retinopathy (PDR).Methods A retrospective research was performed on 42 PDR eyes from January 2015 to February 2016 in the Second Affiliated Hospital of Nanchang University,who received either intravitreal 0.05 mL conbercept injection 7 days before 23G vitrectomy (group A,n =22) or intravitreal 0.05 mL conbercept injection at the end of 23 G vitrectomy (group B,n =20).The operative time,postoperative vitreous hemorrhage (VH),intraoperative and postoperative other differences of clinical indicators and postoperative best-corrected visual acuity (BCVA) between the two groups were compared.Results The average operation time,intraoperative electric coagulation hemostasis rate,iatrogenic hiatal incidence and intraoperative hemorrhage rate of group A were lower than those of group B (all P ＜ 0.05).BCVA at 6 months after surgery did not differ significantly between two groups (P ＞ 0.05),but the difference was statistically significant between pre-operation and post-operation (P ＜ 0.05).The incidences of early (≤ 1 month) postoperative VH were 18.2％ (4 eyes) and 15.0％ (3 eyes) in group A and B,respectively (P ＞ 0.05).The incidences of later (＞ 1 month) postoperative VH were 27.3％ (6 eyes) and 0 in group A and B,respectively,the difference was statistically significant (P ＜0.05).The percentages of reoperation were 13.6％ (3eyes with postoperative VH) and 10.0％ (2 eyes with traction retinal detachment) respectively in group A and B.The average times of supplementary laser photocoagulation were (2.3 ± 1.0) times and (1.4 ±0.6) times in group A and B,respectively in follow-up period (P ＜ 0.05).Conclusion The adjunctive use of intraoperative intravitreal injection of conbercept can prevent effectively postoperative VH and decrease conveniently the time of supplementary laser photocoagulation in 23G vitrectomy for PDR,as well as the preoperative adjunctive use can decrease the operation time,intraoperative complications and incidences of early postoperative VH.

Bacterial resistance has always been a challenge in the field of antibacterials research. As one of the most problematic pathogens causing nosocomial infections, Acinetobacter baumannii (A. baumannii) was a severe threaten to public health. In recent years, as the rate of multidrug-resistant, extensively drug-resistant, and even pan drug-resistant A. baumannii has been increasing, there is an urgent need to develop new strategies to combat this pathogen. Iron is an essential element for the survival and the infection process of A. baumannii. Bacteria have developed a series of iron uptake strategies to survive in conditions of the host iron starvation, including the secretion of siderophore for iron chelation, the uptake of ferroheme, and the transport of ferrous by Feo system. Developing antibacterial strategies to inhibit the iron uptake is an effective way to deal with A. baumannii infection. This article will review the mechanisms of iron uptake by A. baumannii and the antimicrobial strategies developed based on them.

A breakthrough in molecular biology for the twenty-first century is CRISPR/Cas gene editing, which has been used in a variety of fields due to its simplicity, adaptability, and targeting. Given the current global challenge of severe bacterial resistance, difficulties in detecting antimicrobial resistance, and slow development of antimicrobial drugs, CRISPR/Cas gene-editing technology offers a promising avenue for the development of antibacterial treatments. On the one hand, CRISPR/Cas gene editing technology helps advance the study of bacterial functions and serves as a toolbox. For instance, Cas proteins and exogenous repair systems enable efficient and precise gene editing, nCas proteins and deaminase systems facilitate template-free and single base precision editing, dCas proteins and reverse transcriptase allow for repair-free gene editing, and dCas proteins and modified sgRNA enable gene expression level regulation and gene function analysis. On the other hand, its specific gene recognition and targeted DNA cleavage characteristics can be used for pathogen detection, elimination of drug-resistant bacteria and genes, and hold promise as a new strategy for clinical diagnosis and treatment.

Extended-spectrum beta-lactamases (ESBLs), mediated by plasmids, can hydrolyze and cause resistance to penicillins, broad spectrum-cephalosporins, and monobactams. Most ESBLs are derived from the widespread broad-spectrum beta-lactamases TEM-1 and SHV-1. There are also other families of ESBLs, including CTX-M and OXA-type enzymes as well as novel unrelated beta-lactamases. This article reviews recent advances in the classification, characteristics, and other molecular biological aspects of ESBLs.
Molecular Biology ; beta-Lactamases ; classification ; genetics

Persistent Muellerian duct syndrome (PMDS) is a rare form of male pseudohermaphrodism without the feature of ambiguous genitalia. We present a case of PMDS with transverse testicular ectopia (TTE).
Abnormalities, Multiple ; Adult ; Disorders of Sex Development ; pathology ; surgery ; Hernia, Inguinal ; surgery ; Humans ; Male ; Mullerian Ducts ; abnormalities ; surgery ; Testicular Hydrocele ; surgery ; Testis ; abnormalities ; surgery

OBJECTIVETo compare and assess the effectiveness of leukocyte-filtered platelet and standard platelet concentrates transfusion in preventing platelet transfusion refractoriness (PTR) and human leukocyte antigen (HLA)-alloimmunization.

METHODSRandomized controlled trials (RCTs) or quasi-RCTs comparing leukocyte-filtered platelet with standard platelet concentrates transfusion (up to December 31, 2009) were searched and identified from Medline, EMBASE, The Cochrane Library, and CBM. A meta-analysis was conducted with Cochrane Collaboration's RevMan 5. 0.

RESULTSThe search identified 558 citations in total, in which 7 articles in English were finally included in the meta-analysis. The analysis showed that compared with standard platelet concentrates transfusion, leukocyte-filtered platelet transfusion significantly decreased PTR [ RR = 0. 59, 95% CI (0. 42, 0. 82) , P = 0. 002 ] and HLA-alloimmunization [ RR = 0. 49,95% CI (0. 33, 0. 74) , P =0. 0006]. Subgroup analysis showed that HLA-alloimmunization was significantly reduced by leukocyte-filtered platelet transfusion among the patients with acute myelocytic leukemia [ RR =0.42, 95% CI (0.32, 0.56), P <0. 00001], while no significant difference was detected in patients with acute lymphoblastic leukemia because of the limited sample size [ RR = 0. 50, 95% CI (0. 10, 2.41) , P =0. 39].

CONCLUSIONSThe current evidence shows that leukocyte-filtered platelet transfusion can prevent PTR and HLA-alloimmunization more effectively than standard platelet transfusion. Well-designed large-scale RCTs are still needed to further confirm this finding.

Filtration ; HLA Antigens ; immunology ; Humans ; Leukocytes ; immunology ; Platelet Transfusion ; methods ; Randomized Controlled Trials as Topic

Objective To demonstrate the feasibility and necessity of constructivist pedagogy for teaching biomedical electronics so as to create a new instructional mode. Methods The new mode for teaching biomedical electronics was discussed from two aspects of teaching thought and practice with considerations on constructivist pedagogy connotation as well as the actualities of teaching resources and object. Results Instructional thoughts which boosted students' thinking ability,learning habits and confidence were developed.The instructional practice,which included integrated teaching units, problem-based discussion,task-driven experiment content,was also been achieved.Conclusion The reform of instructional mode gains high practical effect, and provides pedagogical implications to other specialized courses of biomedical engineering.

BACKGROUNDHyperbaric oxygen preconditioning (HBO) is a new method of ischemia preconditioning. In this study, we examined its effects on skin flap survival and the mechanisms involved.

METHODSThirty-six rats were divided into three groups: HBO preconditioning, control, and sham groups. An extended epigastric adipocutaneous flap based on the right superficial epigastric artery and vein was raised. A 3-hour period of flap ischemia was induced by clamping the pedicle vessels with a microvascular clamp. At the end of ischemia induction, the clamp was removed and the flap was resutured. Rats in the HBO preconditioning group were treated with HBO four times before surgery. Microcirculation in the skin flap was measured on postoperative days 1, 3 and 5. The size of the flap was measured on postoperative day 5, before the animals were sacrificed. Samples of the skin flap were prepared and stained with hematoxylin and eosin. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the flap samples were measured.

RESULTSSurviving flap size was significantly higher in the HBO preconditioning group compared with controls, with a reduced inflammatory response and increased perfusion. IL-1, TNF-α, and IL-6 levels in the HBO preconditioning group were lower than in controls.

CONCLUSIONSHBO preconditioning improved flap survival in this ischemia-reperfusion rat model. The mechanisms responsible for this effect may relate to attenuation of the inflammatory response and increased flap perfusion following HBO preconditioning.

Animals ; Graft Survival ; Hyperbaric Oxygenation ; methods ; Ischemia ; surgery ; Male ; Microcirculation ; physiology ; Rats ; Rats, Sprague-Dawley ; Skin ; Surgical Flaps

OBJECTIVEPeriventricular leukomalacia (PVL), the principal form of brain injury in the premature infant, is characterized by overt focal necrotic lesions in periventricular white matter and diffuse cerebral white matter injury. The early detection of the disease is not consistently possible with cranial ultrasonography or conventional magnetic resonance imaging (MRI). Recently, diffusion-weighted imaging (DWI) has been shown to be highly sensitive in detecting acute ischemic cerebral injury. This study aimed to evaluate possible role of DWI in early diagnosis of PVL.

METHODSImages and clinical data from 12 preterm infants with PVL diagnosed in our NICU from August, 2005 to April, 2007 were reviewed. MRI using conventional and diffusion-weighted imaging, as well as the assays of blood routine test, serum bilirubin, C-reactive protein (CRP), blood culture, blood gas analysis, blood sugar and serum ions were performed in these preterm infants. All examinations were performed on a 3.0-T MRI system (Philips Intera Acheva Magnetom Vision) with echo-planar imaging capability with the use of a standard protocol. The imaging protocol for all the patients contained diffuse weighted images (EPI-SE, TR = 2144 ms, TE = 56 ms), T1-weighted images (TR = 389 ms; TE = 15 ms; slice thickness = 4 mm) as well as T2-weighted images (TR = 3035 ms; TE = 100 ms; slice thickness = 4 mm). The first MR examinations were performed in all these twelve preterm infants (mean age 4.5 days, range 2 - 7 days). Conventional MRI and DWI sequences obtained in the acute phase were compared. All the neonates underwent another two MRI examinations up to 2 and 4 weeks after delivery; five subjects also underwent MRI follow-up for up to 4 - 8 months (in 3 for 4 months, in 1 for 7 months, and in another for 8 months). Qualitative evaluations were performed to assess the presence of DWI changes compatible with PVL.

RESULTSThe gestational ages of these twelve patients were from 31 to 35 weeks. None of them had intrauterine distress or birth asphyxia. None of the patients had localized neurological signs in the early course except for abnormal muscular tone of some extent, but seizure and apnea were their major symptoms. No other positive signs of nervous system was found in these preterm infants with PVL. First DWI detection (on the average of 4.5 days) in all these infants showed bilateral, symmetric, diffuse high signal intensity (including genu and plenum of corpus callosum), while conventional MRI showed normal images on both T1- and T2-weighted imaging; two weeks later, DWI showed irregularly high, low mixed signals while conventional MRI showed punctate high signal intensity on T1-weighted imaging and slightly lower signal on T2-weighted imaging. Four weeks later, DWI showed cystic low signal intensity where conventional MRI showed low signal intensity on T1-weighted imaging and high signal intensity on T2-weighted imaging (cystic PVL). Four months later, DWI showed that the cystic cava became diminished and disappeared, while conventional MRI showed reduced cerebral white matter and dilation of ventricle.

CONCLUSIONBilateral, symmetric, diffuse high signal intensity on DWI seems to be the earliest evidence of PVL; diffusion-weighted imaging performed in the acute phase of the disease may have a higher correlation with later evidence of PVL than does conventional MR imaging. DWI is likely to be a considerable technique in the early assessment of white matter injury and later PVL in preterm infants.

Diffusion Magnetic Resonance Imaging ; methods ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Leukomalacia, Periventricular ; diagnosis ; pathology ; Male ; Prognosis ; Retrospective Studies