Cancer, also known as malignant tumor, is the second largest disease after heart disease, which is characterized by genomic instability and mutagenicity. Ataxia telangiectasia and RAD3-related kinase (ATR) are members of phosphatidylinositol 3-kinase (PIKK) family, belonging to serine/threonine kinase, one of the key kinases in DNA damage response (DDR) and DNA repair pathway. This paper reviews the latest progress in the ATR inhibitor field including mechanism of action (MOA), therapeutic applications, and the combination therapy from the perspective of medicinal chemistry. It also discusses the possible challenges and future directions of developing ATR inhibitor antitumor drugs, which could provide the scientists in this field the convenience for access the information and application guidance for clinical studies.

Objective To investigate the feature brain damage and clinical manifestations in neuromyelitis optica (NMO) patients; To investigate the relationship between serum NMO-IgG antibody and NMO brain damage. Methods Clinical data of 37 NMO patients and their head and spinal cord MRI by 1.5T superconducting MR scanner, were analyzed; serum NMO-IgG antibody were measured by immunofluorescence. Results 17 cases were found to have abnormal signals on MRI, which were mainly in the white matter, pons, medulla, ventricle, aqueduct, and around the corpus callosum; According to pathological changes, brain damage can be divided into scattered irregularity (13 cases), fusion (3 cases),multiple sclerosis-like (1 case) ,with scattered irregularity more common,5 cases had clinical manifestations of brain damage: somnolence, vomiting, diplopia, visual rotation, 11 cases patients with brainstem damage show positive serum NMO-IgG antibodies. Conclusions Brain damage can be seen in half of NMO patients, they often located in the high expression area of AQP4: brain white matter, periventricular,brainstem and so on. Clinical symptoms has nothing to do with the size of lesions but the location, they often occur when brainstem was involved. Serum NMO-IgG is helpful in differentiating NMO with brain damage and MS.

Objective To investigate the feature of regional grey matter volume changes in relapsing-remitting multiple sclerosis (RRMS) patients by voxel-based morphometry ( VBM) and presume the possible pathophysiological basis.Methods Conventional magnetic resonance imaging (MRI) and T1-weighted three-dimensional MRI were obtained from 32 RRMS and 32 sex- and age-matched normal controls.The comparison of grey matter volume between the two groups was analyzed by statistical analysis software SPM5 and VBM.A Pearson correlational analysis was used to assess correlation between gre matter loss and disease duration,expanded disability status scale (EDSS) and visible brain lesion volume.Results Compared with normal controls,RRMS patients had extensive bilateral grey matter atrophy in thalami (left 2031 and right 1711),caudate (left 815 and right 1031) and parahippocampal gyrus (left 313 and right 467),as well as several cortical regions in frontal,temporal,parietal,and occipital lobes (t value were between 8.853 and 11.163,all P ＜ 0.01).Regional grey matter loss in bilateral thalami ( r value were - 0.596 on left and were - 0.694 on right) and right caudate ( r = - 0.409 ) were strongly negatively correlated with visible brain lesion volume in RRMS (all P ＜ 0.05 ).Conclusions By means of VBM,extensive grey matter atrophy are found in RRMS patients,especially in deep grey matter.Axonal degeneration secondary to visible brain lesions may be a key pathogenesis of grey matter atrophy in RRMS.

Objective To explore the value of wound blush in predicting patients' ulcer healing whom with critical limb ischemia after revascularization.Methods Retrospectively analyze the clinical data of 173 cases of critical limb ischemia with ischemic ulcers under thetreatment of endovascular therapy followed the concept of angiosome.According to the condition of wound blush after endovascular therapy,by compared the difference of limb salvage rate and ulcer healing time,and try to analyze the value of wound blush in predicting ulcer healing in patients.Results Included in the study with a total of 173 cases (173 limbs),group wound blush(+) 109 patients,group wound blush (-) 64 cases,the age,proportion of male patients,smoking history,diabetes,coronary heart disease,chronic renal insufficiency,pre and post operative ankle brachial index,were no statistical difference between the two groups.The ulcer healing time of group wound blush (+) was significantly shorter than that of group wound blush(-) (P ＜ 0.05).The rate of ulcer healing in group wound blush(+) was significantly higher than that in group wound blush(-) (P ＜ 0.05).In group wound blush(+),the cumulative rate of limb salvage was statisticallyhigher than group wound blush (-) (P ＜ 0.05).By logistic regression analysis,wound blush(-) (OR =4.5,P ＜ 0.05),IRc revascularization (OR =2.6,P ＜ 0.05) were independent risk factors of ulcer healing.Conclusions The resoult of wound blush(+) shows a good distal perfusion of foot.It can be used as a predictive factor for critical limb ischemia ischemic ulcer healing,and wound blush (-) was an independent risk factor for ulcer nonhealing.

OBJECTIVETo explore the effect of high fat diet on the expression of sterol regulatory element binding protein-1 (SREBP-1), transforming growth factor-beta1 (TGF-beta1) and alpha-smooth muscle actin (alpha-SMA) in renal tubular cells and extracellular matrix accumulation in Wistar rats.

METHODSThe Wistar rats were treated with high fat diet for 12 weeks and renal lipid deposit was detected by the method of Oil Red O staining. The immunohistochemistry and Western blot were used to investigate the expression of SREBP-1, TGF-beta1, alpha-SMA and fibronectin (FN) protein. The expression of SREBP-1 mRNA was determined with in situ hybridization. Masson staining was for the detection of extracellular matrix (ECM) accumulation.

RESULTSThe weight of rats raised by high fat diet increased, in company with the high serum glucose, serum triglyceride and serum insulin. The Oil Red O staining revealed that the renal proximal tubular epithelial cells showed significant lipid droplet in high fat diet rats. SREBP-1 protein and mRNA were located in the renal tubular cells and the expressions of high fat diet rats were higher than those of normal control rats. They were respectively 1.88 times and 1.85 times than those of normal control group. TGF-beta1 and alpha-SMA protein were also located in renal tubular cells and high fat diet up-regulated the expression of them. ECM accumulation was detected with Masson staining and the result showed that high fat diet treatment increased interstitial ECM product and FN protein was found high expression.

CONCLUSIONHigh fat diet may induce lipid droplet deposit in renal tubular cells by up-regulation of the expression of SREBP-1, which causes ECM accumulation by increasing the expression of TGF-beta1 and alpha-SMA.

Actins ; metabolism ; Animals ; Diet, High-Fat ; Extracellular Matrix ; metabolism ; Kidney Tubules ; cytology ; metabolism ; Male ; Rats ; Rats, Wistar ; Sterol Regulatory Element Binding Protein 1 ; metabolism ; Transforming Growth Factor beta1 ; metabolism

Because of different display parameters and other factors, digital medical images present different display states in different section offices of a hospital. Based on CPI integration profile of IHE, this paper implements the consistent presentation of medical images, and it is helpful for doctors to carry out medical treatments of teamwork.
Computer Simulation ; Diagnostic Imaging ; Integrated Advanced Information Management Systems ; Medical Informatics Computing ; standards

The positioning error in radiotherapy is one of the most important factors that influence the location precision of the tumor. Based on the CT-on-rails technology, this paper describes the research on measuring the positioning error in radiotherapy by comparing the planning CT images with the treatment CT images using 3-dimension (3D) methods. It can help doctors to measure positioning errors more accurately than 2D methods. It also supports the powerful 3D interaction such as drag-dropping, rotating and picking-up the object, so that doctors can visualize and measure the positioning errors intuitively.
Humans ; Imaging, Three-Dimensional ; Radiotherapy ; methods

OBJECTIVETo put forward a revised scheme on LeFort classification for the upper jaw fractures.

METHODS193 consecutive cases with the primary diagnoses of upper jaw fractures were involved in this study, for each one of which water's and CT scan were available to decide the fracture site and pattern. Data were filed in term of classification items as LeFort I, II and III fracture, as well as sagittal fracture and alveolar fracture. Statistical analysis was done to validate the meliorating thought on and revised scheme on LeFort classification.

RESULTSIt was validated that of 185 cases with upper jaw fractures only 30.81% which presented single-line fracture and 34.06% which presented multiple-line fracture were covered with LeFort classification. Additional 13.51% with single-line fracture and 21.61% with multiple-line fracture could be included when LeFort classification was extended with increase of items of sagittal fracture and alveolar fracture. Further results revealed that among total 344 sites or fracture lines included in 193 cases, 81.10% could be diagnosed fracture pattern of LeFort classification. Of 65 fracture sites presenting LeFort III type, 92.31% were concomitant with LeFort II type or LeFort I and II type, very few being alone.

CONCLUSIONSA revised classification was proposeded that upper jaw fractures could be classified into four types as follows: (1) high horizontal fracture (corresponding to LeFort II and III type), (2) low horizontal fracture (corresponding to LeFort I type), (3) sagittal fracture (including midline and para-midline fracture) and (4) alveolar fracture.

Adolescent ; Adult ; Female ; Humans ; Male ; Maxillary Fractures ; classification ; Middle Aged ; Young Adult

A 14-year-old boy presented with coma and convulsion following a 3-day high fever of unknown origin was initially diagnosed with a central nervous system infection with uncertain pathogen. Direct microscopic examination of wet slides of cerebrospinal fluid cytology revealed active amoeboid trophozoites with different shapes. The amoeba trophozoite could be seen at high magnification after Wright′s-Giemsa staining. A diagnosis of primary amoebic meningoencephalitis was made according to the cellular morphology results of the cerebrospinal fluid, imaging data, and clinical symptoms. After high-throughput gene detection targeting the infection pathogen and specific PCR verification of amoeba species, it was confirmed that the infection was caused by Naegleria fowleri. Timely antiamoebic treatment and other related treatments were implemented, but the patient progressed to brain death after 50 days, leading to the discontinuation of treatment by the family.

OBJECTIVETo study the epidemiology and strain variations of astrovirus infection among children under 5 years of age, hospitalized for acute diarrhea in China.

METHODSInpatients under 5 years of age with acute diarrhea in hospitals of seven provinces between 1998 and 2005 were enrolled in the study Stool specimens were collected and tested for astrovirus using the Dako Amplified IDEIA Astrovirus kits or reverse-transcription polymerase chain reaction (RT-PCR). Genetic identities of the strains were determined using RT-PCR with serotype-specific primers and confirmed by sequencing of the RT-PCR products.

RESULTSA total of 1668 diarrheal stool samples tested for both rotavirus and calicivirus negative were examined. The detection rate of astrovirus infection was 5.5% (91/1668) and the diarrhea cases caused by astrovirus infection could be found in any season of the year but mainly occurred in cold season from October to next January. Astrovirus detection-rates were: 7.4% among infants aged 9-11 months followed by 6.1% in 12-17 month-olds, and 6-8 months 5.6% & 0-2 months 5.6% before 8 months. Over 95% of astrovirus infections occurred in children before 2 years of age. Among 49 strains, typed, serotype 1(45/91) was most commonly seen while serotype 5 was in two cases and serotype 3 and 8 were detected in only one case respectively.

CONCLUSIONAstrovirus seemed an important etiologic agent in young children with acute diarrhea in China and Serotype 1 was the most prevalent one.

Acute Disease ; Astroviridae ; classification ; isolation & purification ; Astroviridae Infections ; complications ; epidemiology ; Child, Preschool ; China ; epidemiology ; DNA, Viral ; analysis ; Diarrhea ; virology ; Humans ; Infant ; Infant, Newborn ; Inpatients ; Reverse Transcriptase Polymerase Chain Reaction ; Seasons ; Serotyping