1.Advances in targets of pharmacotherapy and discovery of new drugs for Alzheimer disease:do we have any novel strategies?
wei Wei HU ; qin Xue HOU ; jia Ru LIAO ; ting Han ZHANG
Chinese Journal of Pharmacology and Toxicology 2017;31(7):701-706
Alzheimer disease (AD), the most common dementia, is a chronic, progressive and neuro-degenerative disorder. With an increasing prevalence, AD has been the third cause of death after cardio-vascular diseases and cancer in the elderly population. However, the pathogenesis of AD remains unclear, which has led to a fairly slow development of drugs for AD and a dim view of future treatments of AD. It has been a hot spot and a big challenge to develop effective, therapeutic drugs for AD. Recently, this topic was discussed via WeChat by experts from the Neuropsychiatric WeChat Group, which consists of 300 Chinese-origin neuroscientists and neuropsychiatrists in China or overseas. The experts pointed out the problems that might have misled researches on drug discovery, such as the misleading but dominating AD pathology hypotheses and problems with the platforms for drug screening. Therefore, it is important to review the pathology of AD and the treatment strategies from big data and the overall view of the disease, which may shed new light on AD therapy to develop drugs for multiple targets, leading to omni-direc-tional, comprehensive treatments of AD. The development of AD can be further classified into different stages based on the upstream factors of AD pathology. Interestingly, it has been found that the AD brain has mitochondria damage and dysfunction; long-term exposure to low doses of ionizing radiation can also cause AD-like pathological changes. These provide novel views and ideas in terms of the path-ological process and preventive and therapeutic strategies for AD.
2.The impact of platelet membrane autoantibodies on high-dose dexamethasone therapy in patients with idiopathic thrombocytopenic purpura.
Rui WANG ; Ping QIN ; Xue-bin JI ; Ming HOU
Chinese Journal of Hematology 2009;30(9):619-621
OBJECTIVETo evaluate the impact of platelet membrane glycoprotein (GP)-specific autoantibodies on high-dose dexamethasone therapy in patients with idiopathic thrombocytopenic purpura (ITP).
METHODSModified direct monoclonal antibody immobilization of platelet antigen assay (MAIPA) was used to detect platelet GPIIb/IIIa and/or GPI b specific autoantibodies. All patients received oral dexamethasone 40 mg/d for 4 days.
RESULTSThe response rate of high-dose dexamethasone in GPIIb/IIIa and/or GPIb specific autoantibody-negative patients was significantly different from that of antibody-positive patients (P<0.05). The response rate of GPIIb/IIIa specific autoantibody-positive patients was lower than that of antibody-negative patients (P<0.05). GPIb specific autoantibody had no significant impact on the efficacy of high-dose dexamethasone (P>0.05).
CONCLUSIONPlatelet membrane GPIIb/IIIa-specific autoantibody can be a potential negative indicator for ITP patients'response to high-dose oral dexamethasone.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Autoantibodies ; blood ; Dexamethasone ; administration & dosage ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Platelet Glycoprotein GPIIb-IIIa Complex ; immunology ; Platelet Glycoprotein GPIb-IX Complex ; immunology ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; immunology ; Treatment Outcome ; Young Adult
3.Effect of maternal iron status on infant's iron level: a prospective study.
Chinese Journal of Pediatrics 2009;47(4):291-295
OBJECTIVETo investigate the effect of maternal iron levels in second trimester of pregnancy on the infants' early iron status, explore the relationship between maternal and infant's iron status, and analyze the main factor influencing anemia of the infants.
METHODSTotally 100 couples of mother-baby were followed up from the second trimester of the mothers' pregnancy till the babies were 3 - 5 months old in the Department of Primary Child Care from March 2006 to February 2007. The maternal venous blood samples were collected in the second and the third trimesters and were analyzed for Hb at the same time. The infants' venous blood samples were collected at the end of the follow-up visit and were analyzed for Hb. The values of sTfR of the infants were compared with the maternal iron status diagnostic criteria. The infant's weight was measured during the visits by two professional staff members. The physical growth was assessed with CDC2000 reference.
RESULTS(1) Among 100 couples of mother-baby, none of the Hb values was lower than 90 g/L during the whole period of survey. The prevalence of ID in the babies at the ages of 3-5 months was 39%. Among them 36 cases (36/39, 92.31%) were born to the mother with ID during pregnancy; 26 couples of mother-infant had normal iron status during the following study. (2) The ID' prevalence in the infants born to the mothers with ID was higher than in the babies born to the healthy mothers (chi(2) = 11.567, P < 0.005). The ID' prevalence in the infants born to the mothers with IDA was higher than in the babies born to the mothers with LID (chi(2) = 7.356, P < 0.01). (3) The sTfR values of infants born to the mother with ID during pregnancy were increased significantly (P < 0.01); the iron nutritional status did not show any significant difference between babies whose mothers were IDA and LID (P > 0.05). (4) The SF value of maternal venous blood was negatively correlated with the sTfR value of infant (r = -0.7552, P < 0.01).
CONCLUSIONS(1) The anemia of the infants aged 3 - 5 months was correlated with the iron shortage during the fetal stage. (2) The mild iron deficiency in the pregnant women during the second trimester could decrease the iron storage of fetus and then also could affect the iron status of the early infancy and cause anemia.
Adult ; Anemia, Iron-Deficiency ; epidemiology ; Female ; Fetal Blood ; chemistry ; Humans ; Infant ; Iron ; deficiency ; metabolism ; Maternal Nutritional Physiological Phenomena ; Mothers ; Nutritional Status ; Pregnancy ; Pregnancy Trimester, Second ; Prevalence ; Prospective Studies ; Receptors, Transferrin ; blood ; Young Adult
4.Thinking and Methods for Demonstrating the Effectiveness of Chinese Herbal Compounds from the Perspective of Pharmacokinetics.
Ru-yu SU ; Lei ZHANG ; Yu ZHANG ; Rong YAN ; Xue-qin HOU ; Zhao QU ; Cong YANG ; Yun-bo CHEN ; Qi WANG
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(1):111-115
To exert pharmacological effects, no matter therapeutic effect or toxic/side effect, it's necessary to achieve enough plasma concentration. Chinese medical compounds, which contain various ingredients, influence the metabolism of some active ingredients through the interaction of ingredients to improve curative effects or reduce toxic/side effects. Pharmacokinetics can be used to explore how Chinese medical compounds influence the in vivo metabolism of some active ingredients to achieve better curative effects.
Drugs, Chinese Herbal
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pharmacokinetics
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pharmacology
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Humans
5.Isolation and identification of Borrelia burgdorferi sensu lato from ticks in six provinces in China
Zhen GENG ; Xue-Xia HOU ; Kang-Lin WAN ; Qin HAO
Chinese Journal of Epidemiology 2010;31(12):1346-1348
Objective To understand the carrying status of Borrelia burgdorferi in ticks from the mountain areas from six representative provinces, including Jilin, Shanxi, Gansu, Qinghai,Guizhou and Hunan in China. Methods Flagging and trapping methods were used to collect ticks in forest area and culture medium was used to isolate the pathogen. Nested-PCR was used to detect the gem-carrying rate of ticks. Results More than 2200 ticks from six representative provinces were collected and 1000 ticks were used to isolate the pathogen. 13 Lyme disease spirochetes from ixodes persulcatus in Changbai, Jilin province and 9 Lyme disease spirochetes from ixodes granulatus in Daozhen, Guizhou province were identified. There were 1255 ticks used for PCR testing. Specific fragments of the Borrelia burgdorferi in ticks were found from the six representative provinces in China. The carrier rate was higher in Jilin (Changbai 27.08%, Tonghua 20.41% ), Qinghai (Huzhu 25.06%, Huangnan 21.11%)and Guizhou (Daozhen 25.63% ), than in Shanxi (Yuanqu 4.72%,Jiaocheng 3.64% ). Result from the sequence analysis showed that the genotype belong to Borrelia garinii in Jilin, Qinghai, Gansu, Shanxi provinces but Borrelia valaisiana in Guizhou and Hunan provinces. Conclusion Our data showed that there existed Lyme disease spirochetes in all the six representative provinces in China, but the carriying rates of ticks were different. Borrelia garinii was found in Shanxi province, and Borrelia valaisiana in Hunan province.
6.Cloning and expression of flagellin gene from a Chinese Borrelia burgdorferi PD91 strain.
Bing LÜ ; Kang-lin WAN ; Xue-xia HOU ; Qin HAO ; Zhen GENG
Chinese Journal of Epidemiology 2004;25(9):783-786
OBJECTIVETo study the cloning and expression of flagellin gene from Chinese Borrelia burgdorferi, PD91 strain and to evaluate the feasibility of using recombinant protein as diagnostic antigen when comparing the gene sequence with flagellin gene from North American Borrelia burgdorferi B31.
METHODSThe piece of genes coding flagellin from Chinese Borrelia burgdorferi PD91 by polymerase chain reaction (PCR) method was obtained, and constructed recombinant plasmid, before transformed into E. coli BL21 strain, and induced. The recombinant plasmid was identified with enzyme cutoff and gene sequence comparison. Efficient expression strain was selected and the expression product was analyzed with sodium amplified polymorphic-polyacrylamide gel electrophoresis (SDS-PAGE) and Western-blot method.
RESULTSThe recombinant protein (r-flagellin) expressed in host bacteria was successful. By means of western-blot assay, the immunological response showed the same antigenicity between r-flagellin and PD91 flagellin. The piece of genes coding flagellin of PD91 was 1011 bp, but when comparing with that of North American Borrelia burgdorferi it showed 94.70% homology. Homology between the sequence of amino acid of the r-flagellin and that of B31 flagellin was 95.85%.
CONCLUSIONFlagellin gene of Borrelia garinii of Chinese Lyme disease spirochete was successfully cloned and expressed for the first time. It was proved that the immunoreactivity of r-flagellin was the same as the natural flagellin.
Amino Acid Sequence ; Base Sequence ; Borrelia burgdorferi ; genetics ; isolation & purification ; Cloning, Molecular ; Escherichia coli ; genetics ; metabolism ; Flagellin ; biosynthesis ; genetics ; Humans ; Lyme Disease ; microbiology ; Molecular Sequence Data ; Plasmids ; genetics ; Recombinant Proteins ; biosynthesis ; genetics
7.Clinical characteristics and surgical treatment of 18 cases of duodenal gastrointestinal stromal tumors.
Yi-Hong SUN ; Xue-Fei WANG ; Ying-Yong HOU ; Xin-Yu QIN
Chinese Journal of Gastrointestinal Surgery 2007;10(1):26-28
OBJECTIVETo investigate the clinical characteristics, surgical procedures and prognosis of duodenal gastrointestinal stromal tumors (GISTs).
METHODSThe clinical data of 18 GIST patients, collected from 1995 to 2004, were retrospectively analyzed.
RESULTSThe lesions of duodenal GISTs mainly located in the descending duodenum (13/18), unusually in the horizontal part (2/18), ascending part (1/18), and the bulb (2/18). Pathological examination revealed 1 case of benign tumor, 2 cases of borderline tumors and 15 cases of malignant tumors, Microscopically, the tumors were composed of spindle cells (14 cases), epithelial cell (1 case), and mixed cell types (3 cases). The clinical manifestations were non-specific, mostly was melena (7/18), as well as abdominal pain (6/18), fullness (5/18), and anemia (3/18). The diagnoses were performed by upper gastrointestinal radiography, gastroscopy, endoscopic ultrasonography and CT scan. All of the 18 patients received surgical treatment, including 9 pancreaticoduodenectomies, 5 local resections, 3 segmental resections of duodenum, and 1 distal subtotal gastrectomy. 1 and 3 year survival rates were 100% and 86.7% respectively.
CONCLUSIONMost duodenal GISTs are malignant, and the choices of surgical procedures are mainly determined by the location and size of the tumors.
Adult ; Aged ; Duodenal Neoplasms ; diagnosis ; pathology ; surgery ; Female ; Gastrointestinal Stromal Tumors ; diagnosis ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Retrospective Studies
8.Cloning and analysis of psaB cDNA of Dunaliella salina.
Hong-Tao LIU ; Wei-Dong ZANG ; Zhao-Ming LU ; Ning WANG ; Gui-Qin HOU ; Shen-Ke LI ; Le-Xun XUE
Chinese Journal of Biotechnology 2005;21(4):642-645
One pair of degenerate primer was designed according to conserved motifs of the psaB (A2 subunit of photosystem I) of Chlamydomonas reinhardtii, Chlamydomonas moewusii, Chlorella vulgaris and Mesostigma viride, and a total RNA of Dunaliella salina (D. salina) was extracted with TRIzol reagent. A cDNA fragment, about 1.8kb in length, from green algal D. salina was obtained through RT-PCR method. The resulting PCR product was cloned into T-vector and screened to determine its sequence. Homologous analysis of the deduced amino acid sequence was performed by BLAST and subsequeqtly compared with GenBank data. The obtained cDNA sequence was 1815 bp long, which encodes 605 amino acids (GenBank accession number: AY820754). The sequence shared high homologue with the following psaB: Chlamydomonas reinhardtii 92%, Chlamydomonas moewusii 91%, Chlorella vulgaris 86%, Mesostigma viride 85%, Physcomitrella patens subsp. Patens 85% and Nephroselmis olivacea 84%. It can be concluded that the cloned sequence is psaB cDNA fragment from D. salina.
Algal Proteins
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genetics
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Amino Acid Sequence
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Animals
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Chlamydomonas reinhardtii
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genetics
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Chlorophyta
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genetics
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metabolism
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Cloning, Molecular
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DNA, Complementary
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genetics
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Molecular Sequence Data
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Photosystem I Protein Complex
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genetics
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Sequence Analysis, Protein
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Sequence Homology, Amino Acid
9.Protective effect of penehyclidine hydrochloride in cerebral ischemia-reperfusion injury rats
Tie XU ; Tao PANG ; Xue-Mei ZONG ; Gao-Yong LIANG ; Zhi-Ping WANG ; De-Qin GENG ; Xian-Liang YAN ; Hou-Qing WANG ;
Chinese Journal of Emergency Medicine 2006;0(09):-
Objective To investigate the effect of a selective muscarinic receptor antagonist (penehyclidine hydrochloride) in three vessel occlusion model of acute global cerebral ischemia-reperfusion in rats.Method One hundred and forty-four male SD rats were randomly divided into four groups:sham operated group,vehicle treated group (saline 1 ml,i.p.),scopolamine treated group (0.01 mg/kg,i.p.) and penehyclidine hydrochloride treated group (0.01 mg/kg,i.p.) with drugs injected 40 minutes before ischemia respectively.The ischemic duration was 10 minutes.The animals were subjected to motor activity tests (open field activity test,beam-walking test and grip test) at 24 hours or on the 3rd and 7th day after reperfusion.HE staining,TUNEL staining and immunohistochemical reactions of bax and bel-2 were carried out at the time points of 2,12,24 hours,3 and 7 days after reperfusion.TTC staining was carried out in some rats for assessment of infarction volume on the 4th day after reperfusion.Results As compared with the vehicle treated group,both penehyclidine hydrochloride treatment and scopolamine treatment decreased the numbers of apeptotie neurons (P
10.Clinicopathological features of small gastrointestinal stromal tumors.
Xiaodong GAO ; Anwei XUE ; Yong FANG ; Ping SHU ; Jiaqian LING ; Jianwei HU ; Yingyong HOU ; Kuntang SHEN ; Jing QIN ; Yihong SUN ; Xinyu QIN
Chinese Journal of Gastrointestinal Surgery 2015;18(4):338-341
OBJECTIVETo investigate the clinicopathological features of small gastrointestinal stromal tumors(GISTs) and to evaluate the efficacy of endoscopic therapy for GISTs.
METHODSClinicopathological and follow-up data of 418 patients with GISTs undergoing endoscopic therapy in the Zhongshan Hospital between January 2009 and July 2014 were analyzed retrospectively. All the cases were evaluated by the NIH risk classification and AIFP classification, and were grouped according to the tumor size and location. Nuclear atypia and mitotic count were used to evaluate the biological behavior of small GIST. Efficacy of endoscopic therapy was analyzed with follow-up data.
RESULTSOut of 418 patients, GISTs located in the esophagus was 14(3.3%), in the stomach 389(93.1%), in the duodenum 5(1.2%), in the rectum 10(2.4%). A total of 412(98.6%) patients were mainly spindle cells, and mitosis was not found in 320(76.5%) patients. In 389 small stomach GIST, 245(58.6%) were in fundic region. Cases were divided into four groups according to the size and the result revealed the bigger the size, the more the mitotic count. Nuclear atypia in the 1.5-1.9 cm group was significantly higher compared to other groups. Cases were divided into four groups according to the location and the result revealed the mitotic count was not associated to the location. While the nuclear atypia of stomach GIST was significantly higher than that of esophageal GIST and the nuclear atypia of rectum GIST was significantly higher than that of other positions. The median follow-up was 32(4-69) months. One case(gastric fundus GIST, >1.5 cm) presented local recurrence 23 months after operation and underwent endoscopic resection again. No recurrence or metastasis was found in other patients.
CONCLUSIONSEndoscopic resection technique is effective for small GISTs patients. The small GISTs with 0.4 cm diameter or less are often benign and should be followed up for long time. The small GISTs with 0.5 cm diameter or more possess the risk of malignancy, then surgical resection should be performed. Rectum small GISTs (except for 0.4 cm diameter or less) have worse biological behavior and should be removed.
Gastrointestinal Neoplasms ; Gastrointestinal Stromal Tumors ; Humans ; Neoplasm Recurrence, Local ; Retrospective Studies