OBJECTIVE:To observe clinical efficacy and safety of butylphthalide in the treatment of Alzheimer’s disease (AD). METHODS:94 AD patients selected from our hospital during Jan. 2013-Jun. 2014 were divided into control group(45 cas-es)and observation group(49 cases). Control group was given routine treatment as nourishing nerve,lowering blood lipid,taking Memantine hydrochloride tablet orally 5 mg,bid. Observation group was additionally given Butylphthalide soft capsule orally 0.2 g,tid,on the basis of control group. Both groups were treated for consecutive 1 year. Clinical efficacy of 2 groups were observed, and MMSE,ADL,the levels of TNF-α,IL-1,CRP and BDNF were observed before and after treatment;the incidence of ADR was compared. RESULTS:The total effective rate of observation group was 85.71%,which was significantly higher than that of control group(66.67%),with statistical significance(P<0.05). There was no statistical significance in MMSE and ADL between 2 groups before treatment (P>0.05);those of 2 groups increased significantly after treatment,the observation group was higher than the control group,with statistical significance (P<0.05). There was no statistical significance in the levels of TNF-α,IL-1, CRP and BDNF between 2 groups before treatment(P>0.05). Above indexes of 2 groups were improved significantly after treat-ment,the observation group was better than the control group,with statistical significance(P<0.05). There was no statistical dif-ference in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS:Butylphthalide is effective in the treatment of AD,can improve cognitive and life skills and reduce inflammatory level with good safety.

Objectiye To optimize the depth of the microchannel and the time point for sperm collection,and improve the efficiency of sperm screening on a microfluidic device. Methods Microchannels with four different depths of 25, 50, 100 and 200 μm were tested. Mice sperm were added to the inlet of the microchannel. The relative quantity and motility of sperm in the outlet were recorded at different collection times, i.e. ,5, 15, 30 and 60 min. Statistical method one-way ANOVA and appropriate post-hoc testing were applied to analyze differences between different groups, and further to select the best-fit depth of the microchannel and the time point for collection. Results In microchannels with depths of 25, 50, 100 and 200 μm, the sperm motilities measured in each outlet were (85.4 ± 2.3)%, (85.8 ± 5.8)%,( 87. 2 ± 2. 8 ) %, (76. 5 ± 2. 8 ) % respectively with statistical significance ( F = 5.8, P ＜ 0. 05 ). No obvious differences were found among 25-100 μm channels, however the motility dramatically decreased in the 200 μm group. The relative sperm quantities were (5.2 ±2.0)%, (7.2 ±2.5)%,(12.3 ±2.0)%,(7. 7 ± 1.1 ) % respectively with statistical significance ( F = 6. 9, P ＜ 0. 05), which increased with channel depth from 25 to 100 μm,while it decreased in the 200 μm channel Taking 2 indexes into account, 100 μmwas the most fit channel depth for sperm motility screening. The sperm motility in the outlet gradually decreased with time. At the time points of 5, 15, 30 and 60 min after adding sperm, the sperm motilities were (99. 6 ±0. 7)%, (87.2 ±2. 8)%, (79. 3 ±2. 2)% and (62. 6 ±8.0)% respectively with statistical significance ( F = 37. 3, P ＜ 0. 01 ). Yet the relative quantities of sperm in the outlet increased almost three times in this process. At the time points mentioned above, the relative quantities of sperm were (5.8±1.1)%, (10.6 ± 0.9)%, (12.1 ± 1.7)%, (17.9 ± 3.4)% respectively with statistical significance ( F = 17.8, P ＜ 0. 01 ). Thus 15-30 min was the ideal screening time. Conclusion An effective microdevice for sperm screening with optimized depth and collection time period is developed,which may contribute significantly for the screening of healthy sperm on microfluidic chips.

Glioma is a central nervous system tumor,which originates neuroderm and expresses the high malignant degree.Due to the particularity of the usual location,it makes the treatment of glioma difficult to achieve the desired effect.Interferon is a kind of important cytokines,and it has some biological characteristics,such as inducing apoptosis,inhibiting of tumor growth,and pathological angiogenesis,regulating immune function and so on.Studies have shown that there are many key molecules in the interferon signaling pathways,and these molecules play an important role in the occurrence and development of glioma cell apoptosis.Explore the key molecules and its mechanism of action in the process of Interferon inducing glioma,which may provide new clinical strategies for diagnosis and treatment of glioma.

Bacterial cell division is strictly regulated in the formation of equal daughter cells. This process is governed by a series of spatial and temporal regulators, and several new factors of interest to the field have recently been identified. Here, we report the requirement of gluconate 5-dehydrogenase (Ga5DH) in cell division of the zoonotic pathogen Streptococcus suis. Ga5DH catalyzes the reversible reduction of 5-ketogluconate to D-gluconate and was localized to the site of cell division. The deletion of Ga5DH in S. suis resulted in a plump morphology with aberrant septa joining the progeny. A significant increase was also observed in cell length. These defects were determined to be the consequence of Ga5DH deprivation in S. suis causing FtsZ delocalization. In addition, the interaction of FtsZ with Ga5DH in vitro was confirmed by protein interaction assays. These results indicate that Ga5DH may function to prevent the formation of ectopic Z rings during S. suis cell division.
Bacterial Proteins ; chemistry ; genetics ; metabolism ; Cell Division ; Cell Shape ; Cytoskeletal Proteins ; chemistry ; genetics ; metabolism ; Mutation ; Oxidoreductases ; deficiency ; genetics ; metabolism ; Protein Binding ; Streptococcus suis ; enzymology

Objective:To analyze the inflammatory mechanism and potential intervention drugs related to angiotensin converting enzyme 2 (ACE2) inhibitory mutations in order to provide reference for the treatment of corona virus disease 2019 (COVID-19).Methods:The data of lung adenocarcinoma with ACE2 mutations were screened from the cancer genome atlas (TCGA) database. The data were analyzed by R program language edgeR package and cluster Profiler package, gene ontology (GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Using String online analysis website for protein-protein interaction (PPI) network analysis, screening out the core genes, and finally using the Epigenomic Precision Medicine Prediction Platform (EpiMed) for multi-group association analysis of key genes, and drug candidates prediction.Results:A total of 1 005 differential genes were obtained, of which 91 were up-regulated and 914 down-regulated. A total of 71 GO were enriched, including 45 items related to biological processes, 16 items related to cell components, and 10 items related to molecular function. A total of 13 KEGG pathways were enriched, mainly in inflammatory pathways, various viral infectious diseases, transcriptional regulation, drug metabolism and protein digestion and absorption pathways. The differentially expressed genes were introduced into String online analysis website for PPI network analysis, a total of 252 proteins were obtained, and 10 core genes were H2A clustered histone 16(HIST1H2AL), H3 clustered histone 2 (HIST1H3B), H3 clustered histone 7 (HIST1H3F), H3 clustered histone 11 (HIST1H3I), H3 clustered histone 3 (HIST1H3C), H2B clustered histone 3 (HIST1H2BB), H2B clustered histone 6 (HIST1H2BI), H4 clustered histone 2 (HIST1H4B), H1-4 linker histone (HIST1H1E), H2A clustered histone 4 (HIST1H2AB). Interferon-α, resveratrol, celecoxib, heartleaf houttuynia herb, weeping forsythia capsule, dexamethasone, Chinese pulsatilla root, tumor necrosis factor-α inhibitors, liquorice root and famciclovir might be drugs for the treatment of ACE2 mutation-related inflammation.Conclusions:Inflammation associated with ACE2 inhibitory mutations is similar to the pathogenesis of COVID-19, which could lead to disease by promoting the activation of inflammatory pathways such as mitogen-activated protein kinase (MAPK), the Janus kinase signal transducer and activator of transcription (JAK/STAT), mammalian target of rapamycin (mTOR). Celecoxib, interferon and resveratrol may have the potential therapeutic effects on COVID-19.

Objective:To investigate the transcriptomic mechanisms and clinical efficacy of D-CAG regimen for the treatment of acute myeloid leukemia (AML) after failure to initial induction of remission.Methods:The transcriptome data of AML cells before and after the use of dexitabine before August 28, 2021 was searched in Gene Expression Omnibus (GEO) database with "decitabine" as the search term. The R language package was used for differential expression analysis and Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis of the data. Protein-protein interaction network (PPI) analysis was conducted on the STRING online analysis website. The accurate treatment prediction platform designed based on logistic omics theory (EpiMed) was used to make drug-disease-target correlation analysis. The clinical data of 18 AML patients treated with D-CAG regimen after failure to induction of remission with standard anthracycline and cytarabine regimen ("3+7" regimen) in the 305th Hospital of Chinese PLA from October 8, 2015 to July 9, 2018 were searched and analyzed, and the curative effect was evaluated. The effects of the dose and duration of each drug on the efficacy were analyzed.Results:The transcriptome data of AML cells before and after the use of decitabine in GSE40442 dataset of the GPL5188 platform were finally selected, updated on July 10, 2014. A total of 366 differentially expressed genes were screened, including 201 up-regulated genes and 165 down-regulated genes. The differential genes were mainly related to cell cycle regulation, bone marrow leukocyte migration and differentiation, transcriptional regulation, bone marrow hematopoiesis and other signaling pathways. Ten core genes such as ANXA5, IL-10, THBS1, TLR4, JUN and CXCL12 were screened by PPI analysis. Drug-disease-target analysis showed that dexitabine had a potential therapeutic effect on various blood diseases such as diffuse large B-cell lymphoma, thrombocytopenia, T-cell acute lymphocytic leukemia, aplastic anemia, and AML. Of the 18 patients, after initial induction of remission, 7 (38.8%) patients achieved partial remission (PR), and 11 (61.2%) patients had no response (NR); after one cycle of re-induction remission therapy, 9 patients had complete remission (CR), 5 patients had PR, 4 patients had NR, and the overall response rate (ORR) was 77.8% (14/18). Compared with patients with NR, the CR rate was higher in patients with PR after initial induction therapy, which were 85.7% (6/7) and 27.3% (3/11), and the difference was statistically significant ( χ2=5.84, P = 0.025). The median duration of cytarabine in CR patients was longer than that in NR patients [10 d (7-14 d) vs. 5 d (2-8 d), Z = 3.89, P = 0.002] and the median ratio of the number of bone marrow blast cells to the duration cytarabine was lower in CR patients than that in NR patients [2.29 (0.89-9.10) vs. 8.10 (3.00-38.50), Z = -2.19, P = 0.006]; the median dose of cytarabine in CR patients was lower than NR patients, which were 50 mg·m -2·d -1 (30-150 mg·m -2·d -1) and 100 mg·m -2·d -1 (50-500 mg·m -2·d -1), and the difference was not statistically significant ( Z = -1.80, P = 0.074). Conclusions:AML patients with PR after initial induction and failure to initial induction of remission may be more likely to achieve CR after the treatment of D-CAG regimen, and this change may be related to the epigenetic regulation of decitabine.

Objective: To investigate the effect of transcatheter arterial chemoembolization(TACE) combined with three dimensional conformal radiotherapy(3-DCRT) and hyperthermia on inoperable primary hepatic carcinoma. Methods: This study retrospectively analyzed 96 patients with hepatic carcinoma in the Third Hospital of Chengde between 2014 and 2017 who received TACE or combined therapy (TACE combined with 3-DCRT and hyperthermia). Kaplan-Meier curve was used to compare the overall survival(OS) of the two groups. Results: There were 50 cases in the combined therapy group, 46 cases in the TACE group.The effective rate of the combined therapy group was 76.1%, and that of TACE group was 45.6%, the difference was statistically significant(P=0.028). The overall 6-, 12- and 18-month survival rates of the combined therapy group were 98.0%, 89.9% and 63.1%, respectively, which in the TACE group were 91.3%, 67.3% and 46.8%, respectively, the difference between the two groups was significant(χ²=7.836, P=0.005). The incidence of adverse effect of the combined therapy group was low, only 2 patients(4.0%) developed radiation-induced liver disease(RILD), and the liver function recovered to the normal level after 8 weeks. Conclusion TACE combined with 3-DCRT and hyperthermia is more effective than TACE alone for inoperable primary hepatic carcinoma, and with a low incidence of adverse effect.

Objective:To investigate the omics mechanism of SARS-related immune injury and predict targeted therapeutic drugs through clinical bioinformatics analysis of the transcriptome data of SARS virus in order to provide reference for clinical treatment of COVID-19.Methods:The transcriptome data of SARA virus were collected from the Gene Expression Oibus (GEO) and used to screen differential genes. Enrichment analysis and protein interaction analysis were performed to investigate the mechanism of immune damage associated with SARS. A platform of epigenetics in precision medicine (EpiMed) was established to predict potential therapeutic drugs.Results:The mechanism of SARS-related immune injury was complex, involving affecting the function of immune cells through signaling pathways such as Toll-like receptors, increasing cytokines in plasma through Th17 signaling pathway and inducing autoimmune responses after autoantibodies were generated by molecules such as IL-6, NF-κB, and TNF. Drugs such as Chuanqiong and Etanercept might have therapeutic effects on SARS-related immune damage.Conclusions:SARS virus could cause abnormal expression of many immune-related molecules and signaling pathways. Drugs such as Chuanqiong and Etanercept might have therapeutic effects on SARS-related immune damage. This study might provide reference for clinical treatment of COVID-19.