Protein kinases are intimately involved in the pathogenesis of many diseases such as cancer, inflammation, and autoimmune and neurological diseases. Therefore, kinases have been widely studied as drug targets over the past three decades. As of April, 2020, the FDA had approved 59 small molecule kinase inhibitors (SMKIs) in the emerging field of targeted drug therapy. This paper focuses on the biochemistry and pharmacology of these 59 SMKIs and 121 SMKIs for which structures can be retrieved and that are now in phase Ⅱ and Ⅲ clinical trials. In addition, this paper also conducts a simple analysis of several popular targets and their inhibitors.

Authors presented the serial changes of brain MRI findings in two cases of cryptococcal meningitis. The MRI findings of the first patient (53-year-old female) consisted of dilated Virchow-Robin spaces, leptomeningeal enhancement, cryptococcomas and hydrocephalus. Dilated Virchow-Robin spaces were noted on the first MR obtained 33 days after symptom onset. The size and number of dilated Virchow-Robin space gradually decreased since 119 days after symptom onset (62 days after treatment). Faint leptomeningeal enhancement was found at cerebellar region on the first MRI, which became more distinct and intense on the day 119, probably due to improper treatment. The leptomeningeal enhancement decreased on the day 156. Mild hydrocephalus was noted on MRI obtained 70 days after symptom onset, which markedly aggravated on the day 119. It decreased after steroid therapy alone. Enhancing crytococcomas of variable size were noted at the right temporal lobe and cerebellum on MRI of the day 119, which decreased in size and number on the day 156. On the day 295 MRI showed nearly disppearance of the dilated Virchow-Robin space, but faint leptomeningeal enhancement, cerebellar crytococcomas and hydrocephalus still remained. The MRI findings of the second patient (36-year-old female) showed the findings similar to those of the first patient. Initial MRI obtained 18 days after symptom onset showed no abnormal findings. Dilated Virchow-robin spaces were noted on the day 36 (13 days after treatment onset), which nearly disappeared on the day 109. Enhancing cryptococcomas in both basal ganglia and cerebral cortex and leptomeningeal enhancement were noted on MRI of the day 136. Both cryptococcomas and leptomeningeal enhancement decreased in size and enhancing degree on the day 157. Hydrocephalus was noted on the day 109.
Basal Ganglia ; Brain ; Cerebellum ; Cerebral Cortex ; Follow-Up Studies* ; Humans ; Hydrocephalus ; Magnetic Resonance Imaging* ; Meningitis, Cryptococcal ; Temporal Lobe

Authors presented the serial changes of brain MRI findings in two cases of cryptococcal meningitis. The MRI findings of the first patient (53-year-old female) consisted of dilated Virchow-Robin spaces, leptomeningeal enhancement, cryptococcomas and hydrocephalus. Dilated Virchow-Robin spaces were noted on the first MR obtained 33 days after symptom onset. The size and number of dilated Virchow-Robin space gradually decreased since 119 days after symptom onset (62 days after treatment). Faint leptomeningeal enhancement was found at cerebellar region on the first MRI, which became more distinct and intense on the day 119, probably due to improper treatment. The leptomeningeal enhancement decreased on the day 156. Mild hydrocephalus was noted on MRI obtained 70 days after symptom onset, which markedly aggravated on the day 119. It decreased after steroid therapy alone. Enhancing crytococcomas of variable size were noted at the right temporal lobe and cerebellum on MRI of the day 119, which decreased in size and number on the day 156. On the day 295 MRI showed nearly disppearance of the dilated Virchow-Robin space, but faint leptomeningeal enhancement, cerebellar crytococcomas and hydrocephalus still remained. The MRI findings of the second patient (36-year-old female) showed the findings similar to those of the first patient. Initial MRI obtained 18 days after symptom onset showed no abnormal findings. Dilated Virchow-robin spaces were noted on the day 36 (13 days after treatment onset), which nearly disappeared on the day 109. Enhancing cryptococcomas in both basal ganglia and cerebral cortex and leptomeningeal enhancement were noted on MRI of the day 136. Both cryptococcomas and leptomeningeal enhancement decreased in size and enhancing degree on the day 157. Hydrocephalus was noted on the day 109.
Basal Ganglia ; Brain ; Cerebellum ; Cerebral Cortex ; Follow-Up Studies* ; Humans ; Hydrocephalus ; Magnetic Resonance Imaging* ; Meningitis, Cryptococcal ; Temporal Lobe

OBJECTIVETo investigate the resistant effect of houttuyfonate sodium (SH) combined with imipenem (IMP) against Pseudomonas aeruginosa (Pa) biofilms.

METHODThe two-fold dilution method was used to examine the minimum inhibitory concentration (MIC) of the tested drug. The crystal violet staining was applied to detect the effect of the combination of 1/2MIC, 1MIC, 2MIC of SH, single IMP, 1/2MIC of SH and IMP of various concentrations on the clearance rate of adherent bacteria, growth of biofilms and alginate production. Fluorescein diacetate (FDA)-propidium iodide (PI) doubling staining assay was employed to observe the bacterial viability and morphological changes after membrane dispersion of each drug group.

RESULTSodium houttuyfonate could enhance the effect of IMP against pseudomonas aeruginosa biofilms. Particularly, the combination group with the concentration of 2MIC showed the highest effect, with P < 0.001 compared with the negative control group. The above results were proved by the bacterial viability and biofilm morphology under fluorescence microscope.

CONCLUSIONAfter being combined with imipenem, sodium houttuyfonate shows a higher effect against biofilms. It is expected that the combination of the two drugs could improve the clinical efficacy of associated infections.

Alkanes ; pharmacology ; Biofilms ; drug effects ; growth & development ; Drug Synergism ; Imipenem ; pharmacology ; Microbial Sensitivity Tests ; Microbial Viability ; drug effects ; Pseudomonas aeruginosa ; drug effects ; physiology ; Sulfites ; pharmacology

0.05)and the TNM staging (P=0.55).A mild elevated compared other pathological classification was found in small cell lung cancer (0.191?0.275).Conclusions The results showed that RFQ-PCR was suitable for measurement of the mRNA level of PLKI in bronchoscopic bioptic specimens.This study suggest elevated expression of PLK1 might play a important role in development of lung cancer,so that PLK1 might be a potential tumor marker for Lung cancers.Advanced studies will be needed to clarify that PLKI mRNA level do not relate to TNM staging and pathological classification.

The production technology for the first generation of biofuels has been made great achievements and some countries, such as USA, EU countries, and Brazil, have formed successful biofuel industrial chains. Cellulose ethanol, a representative of the second generation of biofuels and a kind of more promising alternative fuels, has not yet got enough key technological breakthroughs and its large scale commercial production still needs rather some time to realize. Now it is in the early stage of transition to the second generation of biofuels. Taking the development of second generation of biofuels as their national policies, many countries have developed long-term development plans and objectives, and provided a good policy environment and strong support for it. Thus institutes and enterprises are engaging and successing in addressing key issues relating to the development of biofuels. At the mean time, some important issues relating to the sustainable development of biofuels have attracted people's attention.

Biomass resources are strategically vital for the sustainable development of a country.The United States has recently made a variety of plans or roadmaps and taken significant actions in order to promote the R&D of biomass resources.These plans and actions for the key issues in the development of biomass resources were analysed.

AIM:To study the visual acuity and refractive status of students pupils and middle school students in Shenzhen, and to provide a scientific basis for the prevention and control of myopia.
METHODS:A cluster sampling method was used to select five primary school students(6 737) and three junior middle school students(1 925) from Shenzhen. The visual acuity, anterior segment, fundus, eye position, and refractive status were measured. Information on associated factors for poor vision were also obtained using a questionaire. The risk factors of poor vision and the rate of myopia between grade or gender were analysed by Chi-square test.
RESULTS:The rate of poor vision was 67. 0%. Female, family history of high myopia, long time of continuous look near, short time of outdoor activities were the main risk factors. The rate of emmetropia, hyperopia, astigmatism and myopia were 15. 1%, 11. 3%, 11. 0% and 62. 6% respectively. Emmetropia, hyperopia and astigmatism incidenece rate decreased with age growing, but myopia incidence rate was increased. There were significant differences between adjacent two grades in myopia(χ2=7. 338-45. 018, P<0. 05 ) except the primary grade six and the junior grade one. There were significant differences between boys ( 61. 0%) and girls ( 65. 5%) in myopia(χ2=17. 180, P<0. 05).
CONCLUSION:The rate of poor vison is pretty high in students of Shenzhen aged between 5 to 16 years old, and myopia is the main reason. The development rate of myopia is increased with age. Early management of myopia may play an important role in controlling poor vision in students.

This study was conducted to investigate the relationship of body fatness indicators and serum lipids (total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein(LDL) cholesterol, triglycerides, myocardial infarction(MI) index) to find anthropometric indicators of body fat distribution that are strongly associated with serum lipids. 347 adult male workers of an industry in Kyungpook province were selected and data on the general characteristics were obtained using questionnaire from June 26 to June 29, 1991. Serum lipids were tested with 5 ml fasting blood and height, weight, circumferences of waist, hip and mid-thigh, five subcutaneous fat thickeness(biceps, triceps, supscapular, suprailiac, thigh) were mea sured using Ultrasound type A TATT. Waist circumference, waist/hip circumference ratio and subcutaneous fat thickness of suprailiac area are significantly increased with increasing age, but thigh circumference is significantly decreased (P< 0.05). These results suggest that central obesity is closely related to age and waist circumference may be the best indicator of body fatness or body fat distribution in men. In younger age group(below 40 year old), the result of canonical correlations analysis suggests that circumferences(0.501) was slightly closely related to serum lipids than subcutaneous fat thickness(0.493), however, in older age group (above 40 year old), subcutaneous fat thickness(0.528) were more strongly associated with serum lipids than circumferences(0.419). Weighted canonical analyses suggest that biceps and suprailiac areas in younger age group and sub scapular area in older age group are stronger indicators of serum lipids among .subcutaneous fatness measurements. Of the circumferences, waist is the most strongest indicator of serum lipids in both age groups. Therefore, it is recommended that circumference of waist and subcutaneous fat thickness of subscapular area should be measured to estimate the degree of central obesity for preventing cardiovascular disease in men.
Adipose Tissue* ; Adult ; Body Fat Distribution* ; Cardiovascular Diseases ; Cholesterol ; Fasting ; Gyeongsangbuk-do ; Hip ; Humans ; Lipoproteins ; Male ; Obesity, Abdominal ; Subcutaneous Fat ; Thigh ; Triglycerides ; Ultrasonography ; Waist Circumference ; Surveys and Questionnaires

No abstract available.
Coronary Artery Disease* ; Coronary Vessels* ; Risk Factors*