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.

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

Fatty Liver ; Humans ; Proteomics ; methods

OBJECTIVETo evaluate the early diagnostic significance of diffusion weighted imaging (DWI) compared with conventional magnetic resonance imaging (MRI) and to find the dynamic pattern of DWI and conventional MRI in newborn infants with neonatal cerebral infarction (NCI).

METHODSThe imaging studies and clinical records of six newborn infants with NCI admitted to our ward between April 2004 and October 2005 were reviewed. 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), T(1)-weighted images (TR = 389 ms; TE = 15 ms; slice thickness = 4 mm) as well as T(2)-weighted images (TR = 3035 ms; TE = 100 ms; slice thickness = 4 mm). Except the magnetic resonance image examination mentioned above, the following examinations were performed in all patients: whole blood cells count, serum total calcium and ionized calcium, blood glucose, C-reactive protein (CRP), blood culture, prothrombin time and partial thromboplastin time, chest radiograph (CR), cardiac color Doppler, conventional MRI and DWI of brain.

RESULTSAll the patients were full term infants. One had severe asphyxia and the other five had neither intrauterine distress nor birth asphyxia. Five of the patients had no localized neurological signs in the early course except for abnormal muscular tone to some extent, but just seizure as their major symptom. A seizure episode was the most common sign and no other positive signs of nervous system was found in the newborn with NCI. All the patients had normal white blood cells, red blood cells, blood platelet, blood glucose, serum total calcium and ionized calcium, prothrombin time and partial thromboplastin time, CRP and cardiac color Doppler. The first MRI was performed from 18 hours to 4 days after the onset of illness when four patients showed abnormal findings on routine MRI (T(1)WI hypointensity, T(2)WI hyperintensity) and the other two showed normal results while all the six showed abnormal hyperintensty on DMI. On following up, all the patients showed T(1)WI hypointensity and T(2)WI hyperintensity on routine MRI while hypointensity was shown on DWI. There were cortical and subcortical white matter damage with obvious high signal intensity on DWI in left temporal lobe and parietal-occipital lobes of 4 cases and in left frontal-parietal lobes of one patient and in left basal ganglia of another patient, but lesions of hypointensity on T(1)W and hyperintensity on T(2)W in only 3 patients between 2nd day and 3rd day after onset; two weeks later there were the lesions of hypointensity on T(1)W and on DWI and hyperintensity on T(2)W seen in all patients in the areas similar to those found before on DWI. Lesions of hypointensity on T(1)W and DWI and of hyperintensity on T(2)W remained in two patients at sixth month and in one patients at 15th month.

CONCLUSIONSeizure was the most common sign of newborn infants with NCI and seizures in the neonatal period may be the single symptom of acute ischemic cerebral infarction. It was difficult to establish the diagnosis in the acute phase by the use of ultrasound, CT, and conventional MRI because of the high water content of the immature brain.. DWI seems to be a sensitive early diagnostic measure for NCI. Hyperintensity was shown on DWI at the early stage of the disease. Two weeks later, the hyperintensity turned to hypointensity and lasted long with the same signal characters and lesions on T(1)WI. The lesions of hypointensity on T(1)W and DWI and hyperintensity on T(2)W appeared at 2 weeks and remained for more than 1 year. T(2)-weighted sequences should supplement DW images to reliably detect subacute ischemic infarctions in the neonatal period.

Brain ; pathology ; C-Reactive Protein ; metabolism ; Cerebral Infarction ; diagnosis ; Diffusion ; Diffusion Magnetic Resonance Imaging ; methods ; Echo-Planar Imaging ; methods ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; methods ; Stroke ; diagnosis