The prognosis in patients with cerebral hemorrhage is poor. Studies have shown that cerebral microbleeds are closely related with intracerebral hemorrhage. Cerebral microbleeds may be a precursor to the occurrence or recurrence of intracerebral hemorrhage. This article reviews the relationship between cerebral microbleeds and intracerebral hemorrhage from the aspects of epidemiology, etiology, pathophysiology, clinical observation, and complications of cerebral hemorrhage.

Objective Medication for pituitary adenomas is mainly targeted on the prolactin-secreting and growth-hormone types and shows poor therapeutic effects on other adenomas .Therefore, new drugs urgently need to be developed for this purpose .This study was to investigate the effects of glivec and everolimus on mouse pituitary AtT-20 cells and their molecular mechanisms in vitro. Methods Mouse pituitary AtT-20 cells were incubated with glivec or everolimus or combination of both and their inhibitory effect on the proliferation of the cells was measured by CCK-8 assay.The mRNA levels of AKT and ERK were determined by q-PCR and the ex-pressions of the phosphorylated AKT (p-AKT) and ERK (p-ERK) were detected by Western blot. Results Used alone, both glivec and everolimus inhibited the proliferation of the AtT-20 cells in a time-and dose-dependent manner , but their combination produced a mutually antagonistic effect, with combination index values of 1.13 ±0.06, 1.12 ±0.03, and 1.07 ±0.03 respectively.The two a-gents , either used alone or in combination , induced no significantly inhibitory effects on the mRNA and protein expressions of AKT and ERK ( P >0.05 ).Both glivec and everolimus up-regulated the expressions of p-AKT and p-ERK, and their combination manifested an even stronger effect (P>0.05). Conclusion Both glivec and everolimus inhibit the proliferation of AtT-20 cells when administered alone, but their combination produces an antagonistic effect .Their action mechanism might be that when targeting some signaling path-ways to inhibit cell proliferation , glivec, as well as everolimus , in-duces a feedback activation of AKT and ERK .

OBJECTIVE: To investigate the association between transforming growth factor beta1(TGF-beta1)-800G>A polymorphism and cerebral infarction (CI). METHODS: The genotypes of 247 patients with atherosclerotic cerebral infarction and 167 sex- and age-matched healthy controls were detected by PCR-RFLP, and the frequency distribution of alleles calculated. RESULTS: TGF-beta1-800G>A polymorphism was found in Han population in Hunan Province, China. The distribution of -800G>A genotypes was consistent with Hardy-Weinberg balance in the CI and healthy control group. There was no significant difference between genotypes and allele frequency of TGF-beta1-800G>A in the CI and control group (P>0.05). Logistic regression analysis suggested that no genotypes could increase or reduce the risk of CI onset (P>0.05). CONCLUSION TGF-beta1-800G>A polymorphism is not associated with CI in Han population in Hunan Province.
Case-Control Studies ; Cerebral Infarction ; genetics ; China ; ethnology ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Polymorphism, Genetic ; genetics ; Polymorphism, Single Nucleotide ; Transforming Growth Factor beta1 ; genetics

OBJECTIVETo develop a new method to rapidly determine and identify Guizhi Fuling capsule by portable acousto-optic tunable filter-near infrared spectroscopy.

METHODThe qualitative model was set up using principal component analysis. The correlation models between the NIR spectra and the reference values of five major constituents were obtained with partial least squares method.

RESULTThe identifying model accurately identified Guizhi Fuling capsule, and quantitative analytical models could precisely predicted the content of ellagic acid, baicalin, benzoylpaenoniflorin, cinnamaldehyde, and paeonol. The correlation coefficients of the calibration models were 0.924 2, 0.938 4, 0.924 2, 0.933 6, 0.934 7, the validation set coefficients of the calibration were 0.924 2, 0.938 4, 0.924 2, 0.933 6, 0.934 7, and the RMSEP were 1.138%, 3.014%, 0.751%, 0.625%, 3.455%, 1.363%, respectively. The results of external validation showed no significant difference between the predictive and the determining values by t-test.

CONCLUSIONThe method is accurate, rapid and non-destructive, and can be used for determining and identifying Guizhi Fuling capsule.

Acetophenones ; analysis ; Acrolein ; analogs & derivatives ; analysis ; Calibration ; Capsules ; chemistry ; Drug Evaluation ; methods ; Drugs, Chinese Herbal ; analysis ; Ellagic Acid ; analysis ; Flavonoids ; analysis ; Least-Squares Analysis ; Models, Chemical ; Principal Component Analysis ; methods ; Spectroscopy, Near-Infrared ; methods

Objective To investigate the molecular characteristics of H5 subtype avian influenza viruses (AIV) in Weining, Guizhou Province. Methods Nine representative strains were randomly select-ed from H5 subtype AIV that were identified by real-time PCR in Weining, Guizhou Province from 2015 to 2017. Nucleic acid was extracted from each sample and hemagglutinin (HA) genes were amplified and then sequenced. Homology, genetic evolution and the sites related to pathogenicity, receptor binding regions as well as potential glycosylation of H5 AIV were analyzed by bioinformation software. Results Homology analysis revealed that there was 96. 1%-99. 9% and 95. 7%-100% similarity among the nine strains in nu-cleotide and amino acid of HA gene, respectively. These strains belonged to two branches, H5-1 and H5-2. The cleavage site motifs were PLREKRRKR↓GLF for five strains in H5-1 branch and PQRERRRKR↓GLF for four strains in H5-2 branch, which made them high pathogenic. QSG and QRG at the key receptor bind-ing sites were found in H5-1 and H5-2 branch strains, respectively. They were responsible for receptor bind-ing specificity of AIV. Mutations of 138Q, 139G and 53K were all detected in the nine strains. 129K, 189T, 140K and 282V mutations were discovered in the five strains of H5-1 branch, while 189N, 140M and 282I mutations were found in the four strains of H5-2 branch. Results of the glycosylation motif analysis showed that six sites were conservative, but there was an addition of 124NHT site in two strains of H5-2 branch isolated in 2017. Conclusion Two high pathogenic H5 subtypes of AIV could be epidemic in Wein-ing, Guizhou Province during 2015 to 2017. Although H5 subtype AIV did not possess specific receptor binding regions like human influenza viruses, they were in continuous variation with an increase in glycosyla-tion motifs, which might enhance their virulence and pathogenicity to human beings. Hence, surveillance and study on the molecular properties of H5 subtype AIV should be strengthened.

Objective The aim of this study was to investigate the effects of Rad9 mutants with impaired DNA mismatch repair ( MMR) function on the tumorigenesis of colorectal cancer. Methods The colorectal cancer tumor samples were collected from 100 patients. The mutation profiles of human Rad9 ( hRad9) gene in these samples were detected by reverse transcriptase?polymerase chain reaction ( RT?PCR) and sequencing. The plasmid of pFLAG?hRad9 ( L101M ) was constructed following the QuickChange mutagenesis procedure and transfected into mRad9?deleted mouse cells ( mRad9-/- cells) . The expression of hRad9 protein was measured by western blot analysis. The MMR activity in live cells was detected by flow cytometry using the reporter plasmid for MMR function. Results Mutation from Leu to Met at the residue 101 ( L101M) of hRad9 gene was detected in 7 of the 100 samples. The mismatch repair efficiency of mRad9-/-+L101M cells ( mRad9?deleted mouse cells with ectopic expression of L101M hRad9 gene) was (34.0± 5. 6)%, which was significantly lower than that in the mRad9-/-+ hRad9 cells [ mRad9?deleted mouse cells with ectopic expression of hRad9 gene, (48.0±7.5)%, P<0.05]. After N?nitroso?N?methylurea (MNU) treatment, the survival rate of mRad9-/-+L101M cells was (33.7±5.9)%, which was significantly higher than that in the mRad9-/-+ hRad9 cells [(21.3±4.7)%, P<0.05]. Thus, ectopic expression of L101M hRad9 gene resulted in significantly reduced MMR activity and increased resistance to MNU. Furthermore, ectopic expression of hRad9 gene with mutation at the target residues of post?translational modification in mRad9-/- cells also led to a reduced MMR activity. Conclusion Rad9 mutants with impaired DNA mismatch repair function may promote tumorigenesis of colorectal cancer.

Objective The aim of this study was to investigate the effects of Rad9 mutants with impaired DNA mismatch repair ( MMR) function on the tumorigenesis of colorectal cancer. Methods The colorectal cancer tumor samples were collected from 100 patients. The mutation profiles of human Rad9 ( hRad9) gene in these samples were detected by reverse transcriptase?polymerase chain reaction ( RT?PCR) and sequencing. The plasmid of pFLAG?hRad9 ( L101M ) was constructed following the QuickChange mutagenesis procedure and transfected into mRad9?deleted mouse cells ( mRad9-/- cells) . The expression of hRad9 protein was measured by western blot analysis. The MMR activity in live cells was detected by flow cytometry using the reporter plasmid for MMR function. Results Mutation from Leu to Met at the residue 101 ( L101M) of hRad9 gene was detected in 7 of the 100 samples. The mismatch repair efficiency of mRad9-/-+L101M cells ( mRad9?deleted mouse cells with ectopic expression of L101M hRad9 gene) was (34.0± 5. 6)%, which was significantly lower than that in the mRad9-/-+ hRad9 cells [ mRad9?deleted mouse cells with ectopic expression of hRad9 gene, (48.0±7.5)%, P<0.05]. After N?nitroso?N?methylurea (MNU) treatment, the survival rate of mRad9-/-+L101M cells was (33.7±5.9)%, which was significantly higher than that in the mRad9-/-+ hRad9 cells [(21.3±4.7)%, P<0.05]. Thus, ectopic expression of L101M hRad9 gene resulted in significantly reduced MMR activity and increased resistance to MNU. Furthermore, ectopic expression of hRad9 gene with mutation at the target residues of post?translational modification in mRad9-/- cells also led to a reduced MMR activity. Conclusion Rad9 mutants with impaired DNA mismatch repair function may promote tumorigenesis of colorectal cancer.

OBJECTIVE： To screen active fractions of Xiaozhong zhitong lotion that are able to reduce swelling， promote ulcer healing and analgesia， and to provide reference for it’s secondary development of ointment preparation. METHODS： Water elution fraction and 20％， 40％， 60％， 95％ ethanol elution parts were separated by D101 macroporous resin from Xiaozhong zhitong lotion. 120 SD rats were randomly divided into normal group （n＝8） and modeling group （n＝112）. Rats in the normal group were not treated. Hemorrhoids model was established in the model group by injecting 75％ glacial acetic acid into the perianal skin to induce perianal ulcer. 96 model rats were randomly divided into model group [blank ointment matrix 0.51 g/（kg·d）]， positive group [Mayinglong ointment， 0.51 g/（kg·d）]， high-dose and low-dose groups of Xiaozhong zhitong lotion and it’s water elution fraction and 20％， 40％， 60％ ethanol elution parts [8.34， 2.78 g/（kg·d） by crude drug， all make into containing drug ointment]， with 8 rats in each group. The periphery of the anus was smeared with relevant medicine， twice a day， for consecutive 7 d. The local symptoms around the anus of rats 3 and 7 days after administration and the pathological morphology of the local mucosa around the anus of rats 7 days after administration were observed and scored respectively. The effects of each elution part for reducing swelling and promoting ulcer healing were investigated. 120 ICR mice were randomly divided into model group [blank ointment matrix 1.03 g/（kg·d）]， positive group [Mayinglong ointment 1.03 g/（kg·d）]， high-dose and low-dose groups of Xiaozhong zhitong lotion and it’s each elution part [16.65， 5.55 g/（kg·d） by crude drug， all make into containing drug ointment]， with 10 mice in each group. Transdermal administration， twice a day， for consecutive 7 d. After 30 min of last administration， the latency time and 15 min writhing times of mice were detected by designing acetic acid writhing test； pain threshold of mice was determined by hot-plate pain test so as to investigate systemic and local analgesic effects of each elution part. RESULTS： In the detumescence and ulcer healing test， compared with normal group， the score of local symptoms around anus at 3rd and 7th day of administration as well as pathological score of hemorrhoids local mucosa were increased significantly in model group （P＜0.01）. Compared with model group， above scores of positive group， 40％ ethanol elution high-dose and low-dose groups were decreased significantly （P＜0.05 or P＜0.01）. The scores of local symptoms around anus in 20％ ethanol elution part high-dose group at 3rd and 7th day after medication as well as 60％ ethanol elution part group at 7th day after medication were decreased significantly （P＜0.05）. In analgesia test， compared with model group， writhing latency time was shortened significantly and 15 min writhing times was decreased significantly in positive group， 40％ ethanol elution part high-dose and low-dose groups as weel as 60％ ethanol elution part high-dose group （P＜0.05 or P＜0.01）； writhing latency time of 20％ ethanol elution part high-dose group was shortened significantly （P＜0.05）. Pain threshold of mice was increased significantly in positive group， 40％ ethanol elution part high-dose and low-dose groups after medication （P＜0.05 or P＜0.01）. CONCLUSIONS： The 40％ ethanol elution part from Xiaozhong zhitong lotion is the effective part that can reduce swelling， promote ulcer healing and analgesia.

OBJECTIVE： To analyze chemical components in active fraction of Xiaozhong zhitong lotion， to clarify the material basis of its efficacy， and to provide reference for the second development of ointment preparation. METHODS： UPLC-Q-TOF-MS was adopted to analyze the chemical components of active fraction （40％ ethanol elution site separated by D101 macroporous resin） of Xiaozhong zhitong lotion. The determination was performed on Hypersil GOLD aQ C18 column with mobile phase consisted of 0.1％ formic acid acetonitrile （A）-0.1％ formic acid water （B） （gradient elution） at the flow rate of 0.4       mL/min. The sample size was 4 μL， and the column temperature was 30 ℃. The condition of mass spectrometry was ESI detection in positive and negative scanning ion mode （ESI+/ESI－）. The scanning range was 100-2 000 Da. The collision energy was 45/－45 eV， and the energy of the extended collider was 10/15 eV. The accurate molecular weight， retention time and multi-stage fragment ion information of the compounds were collected after obtaining the chromatogram， and the chemical components were identified by comparing with the mass spectrum information of reference materials and references. RESULTS： A total of 48 compounds were identified， and 9 and 39 compounds were identified under ESI+/ESI－ ion mode， mainly including 10 phenolic acids， 8  phenylpropanoids， 9 anthraquinones， 3 flavones， 7 alkaloids， 5 tannins and 6 other categories. CONCLUSIONS： UPLC-Q-TOF- MS method is rapid， efficient and accurate for identify chemical components from active fraction of Xiaozhong zhitong lotion. Main chemical components of the active fraction are phenolic acids， phenylpropanoids， anthraquinones， alkaloids and tannins.