Mechanism of HES1 regulating herceptin resistance in gastric cancer cells by ferroptosis / 药学学报

Drug resistance of cancer cells is the main causes of chemotherapy failure, and gene mutation or function loss is key factor to induce drug resistance. Previous studies have shown that hairy and enhancer of split 1 (HES1) is up-regulated in herceptin-resistant gastric cancer cells, and inhibition of its activity can reverse its resistance while the potential mechanism has not yet been elucidated. In this study, we employed CRISPR/Cas9 to establish HES1 knock-out cell line (△HES1/NCI N87R) to investigate the functions of HES1 in herceptin resistance of NCI N87R cells and its potential mechanisms. We investigated proteomics profiling of △HES1/NCI N87R cells based on quantitative proteomics. Gene ontology analysis was conducted by GeneSet Enrichment Analysis (GSEA) and Metascape database, and pathway enrichment analysis was done using GeneAnalytics database. The selected molecules were quantified by Western blot and some pathways were verified by using inhibitors. The results showed that the resistance to herceptin of △HES1/NCI N87R cells decreased compared to NCI N87R cells. Proteomic data demonstrated that the expression of 1 263 genes changed significantly in △HES1/NCI N87R cells, among which 761 genes were up-regulated while 502 ones down-regulated comparing with NCI N87R cells. Pathway analysis showed that ferroptosis, fatty acid β-oxidation, autophagy and glutathione metabolism, etc. exhibited notable changes in △HES1/NCI N87R cells. The functional studies showed that the levels of iron ion and malondialdehyde increased, and glutathione decreased in △HES1/NCI N87R cells. It was further found that Fer-1, a ferroptosis inhibitor, could reverse the expression of pTP53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in △HES1/NCI N87R cell, and reduce the sensitivity of △HES1/NCI N87R cells to herceptin. It is suggested that HES1 regulated the resistance of NCI N87R cells to herceptin through TP53/SLC7A11/GPX4 signaling pathway, and targeting TP53/SLC7A11/GPX4 signal axis mediated by HES1 is a potential strategy to reverse herceptin resistance in gastric cancer.

RUNX3 regulates trastuzumab resistance of gastric cancer cells: a metabolomic analysis based on UPLC-Q Exactive Focus Orbitrap mass spectrometry / 南方医科大学学报

OBJECTIVE@#To explore the role of Runt-related transcription factor 3 (RUNX3) in metabolic regulation of trastuzumab-resistant gastric cancer cells and investigate the mechanism of RUNX3 knockdown-mediated reversal of trastuzumab resistance.@*METHODS@#We performed a metabolomic analysis of trastuzumab-resistant gastric cancer cells (NCI N87R) and RUNX3 knockdown cells (NCI N87R/RUNX3) using ultra performance liquid chromatography (UPLC) coupled with Q Exactive Focus Orbitrap mass spectrometry (MS). Multivariate combined with univariate analyses and MS/MS ion spectrums were used to screen the differential variables. MetaboAnalyst 5.0 database was employed for pathway enrichment analysis. Differential metabolites-genes regulatory relationships were constructed based on OmicsNet database. The changes in GSH/GSSG and NADPH/NADP ratios in NCI N87R/RUNX3 cells were measured using detection kits.@*RESULTS@#The metabolic profile of NCI N87R cells was significantly altered after RUNX3 knockdown, with 81 differential metabolites identified to contribute significantly to the classification, among which 43 metabolites were increased and 38 were decreased (P < 0.01). In NCI N87R cells, RUNX3 knockdown resulted in noticeable alterations in 8 pathways involving glutamine metabolism, glycolysis, glycerophospholipid, nicotinate-nicotinamide and glutathione metabolism, causing also significant reduction of intracellular GSH/GSSG and NADPH/NADP ratios (P < 0.01). The differential metabolites-genes network revealed a regulatory relationship between the metabolic molecules and genes.@*CONCLUSION@#RUNX3 reverses trastuzumab resistance in gastric cancer cells by regulating energy metabolism and oxidation-reduction homeostasis and may serve as a potential therapeutic target for trastuzumab-resistant gastric cancer.

Protection of Addition and Subtraction Therapy of Ditantang Combined with Taohong Siwutang to Brain Nerve of Patients with Cerebral Infarction and （Syndrome of Phlegm and Blood Stasis Blocking Collaterals） During Early Recovery / 中国实验方剂学杂志

Objective:To discuss clinical effect of addition and subtraction therapy of Ditantang combined with Taohong Siwutang to cerebral infarction and syndrome of phlegm and blood stasis blocking collaterals during early recovery， and to study protection to brain nerve. Method:One hundred and fifty-two patients were randomly divided into control group （76 cases） and observation group （76 cases） by random number table， 71 patients in control group completed the therapy （5 patients were falling off， missing visit or eliminated）， and 70 patients in observation group completed the therapy. Both groups' patients got comprehensive rehabilitation measures. Patients in control group got Zhongfeng Huichun pills， 1.5 g/time， 3 times/day. Patients in observation group got addition and subtraction therapy of Ditantang combined with Taohong Siwutang in the morning and at night， 1 dose/day. The treatment was continued for 12 weeks. Before and after treatment， scores of degree of neurological deficit， Barthel （BI） index， Fugl-Meyer scale （FMA）， modified Rankin scale （MRS） and syndrome of phlegm and blood stasis blocking collaterals were graded. And levels of malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， advanced oxidation protein products （AOPP）， vascular endothelial growth factor （VEGF）， brain-derived neurotrophic factor （BDNF） and neuron specific enolase （NSE）. And cerebral hemodynamics were detected， and peak flow velocity （VS）， vascular resistance index （RI）， pulsatility index （PI） and cerebrovascular reserve function （CVR） were recorded. Safety was evaluated. Result:After the 6th week and 12th week of treatment， scores of degree of neurological deficit， BI， FMA， MRS， syndrome of phlegm and blood stasis blocking collaterals， AOPP， MDA， NSE， RI and PI were lower than those in control group （P<0.01）， levels of SOD， GSH-Px， BDNF， VEGF， Vs and CVR were higher than those in control group （P<0.01）. The clinical effect was better than which in control group （Z=2.109， P<0.05）. Besides， there was no adverse reaction caused by Ditantang combined with Taohong Siwutang. Conclusion:Ditantang combined with Taohong Siwutang can ameliarate the hemodynamics， reduce the lipid peroxidation damage， regulate the neurovascular repair factor， so it can promote the repair of nerve tissue and function， clinically reduce the degree of nerve function defect， improve the ability of daily life and exercise when it used to cerebral infarction and syndrome of phlegm and blood stasis blocking collaterals during early recovery， and it is good for clinical effect and safe using.

Study on protective effect of pedunculoside on acute myocardial ischemia/reperfusion injury in rats / 中国药理学通报

Aim To explore the protective effect of pedunculoside (PE) on myocardial ischemia/reperfusion injury. Methods Rat model of acute myocardial ischemia reperfusion injury was prepared by ligating the left anterior descending coronary artery (LAD) of the heart for 30 min and reperfusion for 24 h, and the rats were randomly divided into seven groups (re = 10): sham group (Sham), acute myocardial ischemia reperfusion injury model group (M), captopril group (Capt), metoprolol group (MT), PE low, medium and high dosage groups (2. 5, 5 and 10 mg · kg

Label-free quantitative proteomic study of RUNX3 regulating Herceptin resistance in gastric cancer cells / 药学学报

Resistance of tumor cells is a complex biological process involving multiple mechanisms and factors, in which anti-apoptosis is the most important cause of drug resistance. Previous studies have shown that the DNA binding activity of Runt related transcription factor 3 (RUNX3) increased prominently in Herceptin resistant gastric cancer cells (NCI N87R) while the relevance of which to drug resistance has not yet been confirmed. In this study, we employed CRISPR/Cas9 to establish RUNX3 knock-out cell line (△RUNX3/NCI N87R) to investigate the functions of RUNX3 in Herceptin resistance of NCI N87R cells and its potential mechanisms. We investigated proteomics profiling of △RUNX3/NCI N87R cells based on label free quantitative proteomics. Differentially expressed proteins were screened out according to fold change and significance level between △RUNX3/NCI N87R and NCI N87R cells. Pathway enrichment analysis was done using GeneAnalytics database, and gene ontology analysis was conducted by DAVID Bioinformatics Resources database. Protein-protein interaction networks were constructed based on STRING database. The results showed that △RUNX3/NCI N87R cells increased the sensitivity to Herceptin. Proteomic data demonstrated that the expression of 577 genes changed significantly in △RUNX3/NCI N87R cells, among which 191 genes were up-regulated while 386 ones down-regulated comparing with NCI N87R cells. Pathway analysis showed that autophagy, cell cycle, apoptosis, mitochondrial fatty acid β oxidation, neurogenic locus notch homolog protein 1 (NOTCH1), mammalian target of rapamycin (mTOR), Hedgehog and DNA damage response pathways exhibited notable changes based on pathway enrichment ratio and significance level (P < 0.05). These results indicated that RUNX3 knock-out altered multiple signaling pathways of NCI N87R cells. Western blotting manifested that the expression of autophagy regulatory molecules autophagy-related protein (ATG) 13, 7 and BECN1 increased remarkably while cell cycle molecules serine/threonine-protein kinase Chk2 (CHEK2) and apoptosis regulator Bcl-2 (BCL2) decreased prominently in △RUNX3/NCI N87R cells. The p-AKT expression decreased significantly in △RUNX3/NCI N87R cells compared with NCI N87R cells (P < 0.01) and was suppressed by Herceptin. These results indicated that RUNX3 knock-out altered cell cycle, increased inhibition to p-AKT by Herceptin, promoted autophagy and induced cell apoptosis of NCI N87R cells. These results suggested that RUNX3 may be a potential therapeutic target for reversing or reducing Herceptin resistance in gastric cancer cells.

Fingerprint analysis and Q-marker prediction of processed liquorice products / 中国中药杂志

Licorice has long been regarded as one of the most popular herbs, with a very wide clinical application range. Whether being used alone or as an ingredient in prescription, it has an important role which cannot be ignored. However, the efficacy and chemical constituents of licorice will change after honey-processing. Therefore, it is necessary to find quality markers before and after honey-processing to lay the foundation for a comprehensive evaluation of the differences between raw and processed licorice pieces. HPLC-DAD was employed to establish fingerprints of raw and processed licorice. Multivariate statistical analysis methods including principal component analysis(PCA) and orthogonal partial least squares discrimination analysis(OPLS-DA) were applied to screen out the differential components before and after processing of licorice. Based on network pharmacology, the targets and pathways corresponding to the differential components were analyzed with databases such as Swiss Target Prediction and Metascape, and the "component-target-pathway" diagram was constructed with Cytoscape 3.6.0 software to predict the potential quality markers. A total of 17 common peaks were successfully identified in the established fingerprint, and seven differential components were selected as potential quality markers(licoricesaponin G2, glycyrrhizic acid, liquiritigenin, liquiritin, isoliquiritin, liquiritin apioside and isoliquiritigenin). The HPLC fingerprint method proposed in this study was efficient and feasible. The above seven differential chemical components screened out as potential quality markers of licorice can help to improve and promote the overall quality. These researches offer more sufficient theoretical basis for scientific application of licorice and its corresponding products.

Curcumin inhibits proliferation,migration and invasion of gastric cancer cells via Wnt3a/β-catenin/EMT signaling pathway / 中国中药杂志

The aim of this paper was to investigate the effects of curcumin on the proliferation,migration,invasion and apoptosis of human gastric cancer cells and to explore the potential mechanisms. SGC7901,MKN45 and NCI N87 cells lines were cultured under different concentrations of curcumin( 2. 5,5,10,20,40,80 and 160 μmol·L~(-1)) at different time points( 12,24,48 and 72 h),and the effect of curcumin on cell proliferation was detected by CCK-8 assay. The migration and invasiveness of cells were determined by wound healing and Transwell assays,the apoptosis rate was assessed by flow cytometry,the expression of N-cadherin,E-cadherin,snail1,Wnt3 a,p-β-catenin,p-LRP6,Bcl-2 and Bax were detected by Western blot,and the enzymatic activity of caspase-3,caspase-8 and caspase-9 was evaluated via caspase kit. RESULTS:: indicated that the proliferation of MKN45 cells was significantly inhibited by curcumin in a dose-and time-dependent manner( IC50= 21. 93 μmol·L~(-1)). Moreover,curcumin could inhibit the migration and invasion of MKN45 cells,downregulate the expression of N-cadherin,snail1,Wnt3 a,p-β-catenin,p-LRP6 and Bcl-2,and upregulate the expression of E-cadherin and Bax,it could increase the activity of caspase-3,caspase-8,caspase-9 and induce apoptosis as well. The potential mechanism is through inhibiting the Wnt3 a/β-catenin/EMT pathway,regulating Bcl-2 signaling and caspase pathway,which might provide new potential strategies for gastric cancer treatment.

Preparation of Inclusion Complex of Camptothecin with Cucurbit7uril and Exploration of the Properties of Inclusion Complex System / 中国药学杂志

OBJECTIVE: To prepare and verify the anticancer drug camptothecin(CPT) and its inclusion complex with cucurbit[7]uril(CB[7]). METHODS: Camptothecin-cucurbit[7]uril inclusion complex was prepared by the lyophilization. The complex was characterized by fluorescence spectroscopy, Fourier transformation-infrared spectroscopy(FI-IR), differential scanning calorimetry(DSC), X-ray diffraction(XRD) and 1H-NMR. The dissolution properties of the inclusion complex was analyzed by ultraviolet spectrum. RESULTS: The formation of 1:2 complex with CB[7] in aqueous solution was confirmed by fluorescence spectroscopy and the apparent stability constant was 3.95×1012 L2•mol-2.The stability and solubility of camptothecin was significantly improved after it was included with cucurbit[7]uril. CONCLUSION: Stable complex can be formed between camptothecin and cucurbit[7]uril,and the solubility of camptothecin is increased by CB[7] significantly.

Mechanisms of curcumin to reverse herceptin resistance in gastric cancer cells / 药学学报

This study is aimed to investigate the potential mechanisms of herceptin-acquired resistance and curcumin to reverse resistance in NCI N87/R gastric cancer cells. Western blot was used to evaluate the effect of curcumin on the expression of IκBα, NF-κBp65, HER-2, caspase-3, Bcl-2 and Bax in herceptin resistant cells; Annexin V-FITC/PI was exploited to analyze the effect of curcumin on cell apoptosis; Caspase kit was used to evaluate the effect of curcumin on the enzymatic activity of caspase-3, 8 and 9. The results showed a low expression of IκBα in the cytoplasm and a high expression of NF-κBp65 in the nucleus of NCI N87/R cells. Correspondingly, inhibition of NF-κB pathway by EVP4593, a specific NF-κB inhibitor, preferentially reduced cell viability of NCI N87/R cells, indicating the activation of NF-κB pathway in NCI N87/R cells. Curcumin preferentially reduced cell proliferation and inhibited NF-κB signaling pathway of NCI N87/R cells, downregulated the expression of HER-2 and Bcl-2, upregulated the expression of Bax, increased the activity of caspase-3, 8 and 9. Taken together, our study demonstrates the correlation between herceptin resistance acquirement of NCI N87 cells and the activation of NF-κB pathway. Moreover, curcumin reverses herceptin resistance of NCI N87 cells possibly by inhibiting NF-κB pathway and inducing cell apoptosis.

Label-free quantitative proteomic analysis of acquired herceptin resistance in gastric cancer cells / 药学学报

This study was designed to explore proteins differentially expressed in HER2 positive gastric cancer N87 cells and N87/R cells with an acquired resistance to herceptin based on label-free quantitative proteomics. The extracted proteins were reduced and alkylated, then digested using filter aided sample preparation (FASP); peptides were separated via small manual reversed phase column, analyzed by LC-MS/MS, and identified with protein database 2.1 search engine. Proteins were quantified by intensity based quantification (IBQ) to search for differential proteins by comparison with relatively quantified proteins. The enrichment and network construction in gene ontology (GO) terms, genes-disease and Wikipathway of differential proteins were established through Web Gestalt. A total of 8 509 proteins were detected, among them, 7 163 proteins were further analyzed by bioinformatics, of which 110 proteins were up-regulated and 70 were down-regulated in N87/R cells. The differential proteins showed a significant difference in cellular component, biological process and molecular function in GO terms, respectively. Genes-disease network analysis indicated the association of these differential proteins with neoplasm metastasis, neoplasm invasiveness and inflammation, etc. Wikipathway enrichment analysis revealed the relevance of several signaling pathways to herceptin resistance, which included IL-2, MAPK/ERK, mTOR, aurora A, Ret, NF-κB, immune-regulatory and metabolic pathway. Western blot showed a significant increase of ERK1/2 activities in N87/R cells compared with N87 cells. Correspondingly, SCH772984, a MAPK/ERK inhibitor, preferentially reduced the viability of N87/R cells. Taken together, our data suggested that the MAPK/ERK signaling pathway is one of the key pathways that mediate herceptin resistance. This study provides the basic information for exploring the mechanisms of acquired resistance to herceptin in gastric cancer cells.

Effects of different doses of caffeine in the treatment of neonatal apnea / 中国基层医药

Objective To investigate the therapeutic effect of different doses of caffeine on premature apnea.Methods 80 patients with apnea were divided into observation group and control group,each group in 40cases.The two groups applicated caffeine citrate.The control group received the basal dose, first application of 20 mg/kg, intravenous injection, intravenous injection of 5 mg/kg after 24 h.The observation group was treated with intravenous injection of 10 mg/kg after 24 h.The treatment period was 7 d.The therapeutic effect, blood gas and oxygenation index and adverse reactions were observed in the two groups.Results The effective rate of the observation group was 92.5%,which was significantly higher than 75.0% of the control group(x2=4.501,P0.05).Conclusion In the treatment of premature apnea, advanced caffeine citrate treatment can better improve the clinical symptoms and blood gas index, the curative effect is reliable.

Clinical effect of minimally invasive operation that alteplase assisted for the patients with moderate amount of cerebral basilar hemorrhage / 临床神经病学杂志

Objective To investigate the clinical effect and safety of the treatment of cerebral hemorrhage of basal ganglia regionin middle volume with minimally invasive surgery combined with alteplase .Methods Sixty-three patients with moderate amount of cerebral basilar hemorrhage and their GCS scores were between 8 to 10 in our hospital from 2012 to 2016 were divided into experimental group and control group .The experimental group were taken by minimally invasive surgery for intracranial hematoma combined with alteplase , otherwise, the patients in the control group were treated by medical conservative treatment .GCS,NIHSS,activities of daily living ( ADL), mRS were used to evaluated the efficacy ,the results were compared .Results The amount of bleeding in two groups had no significant difference before treatment .However, the experimental group of hematoma was neaely clear up or almost all absorped , the control group was not significantly reduced after treatment according to review of CT , there was statistical significance between the two groups (P<0.05).In the experimental group, NIHSS score was significantly decreased after treatment than before treatment ( P<0.05 ) , while there was no statistically significant difference in the control group .In the experimental group , GCS score was significantly decreased after treatment than before treatment(P<0.05).Three months after discharge, the ADL score of the experimental group was significantly higher than that of the control group ( P<0.05 ) , the mRS score of the experimental group after 3 months was significantly lower than that of the control group ( P<0.05 ) .Conclusion Treatment to basal ganglia cerebral hemorrhage of minimally invasive surgery combined with alteplase is more safe and effective by removing intracranial hematoma quickly , reducing brain damage caused by hematoma compression and thereby deseasing morbidity and mortality.

Design, synthesis and anti-proliferative activity of novel coumarin derivatives linking Schiff base and aryl nitrogen mustard / 药学学报

To explore novel coumarin derivatives with more potent anti-proliferative activity, a series of novel compounds were designed and synthesized by linking Schiff base and N, N-bis (2-chloroethyl) amine pharmacophore of nitrogen mustards to the coumarin's framework. Their structures were confirmed by 1H NMR, MS and element analysis techniques. In vitro anti-proliferative activities were evaluated against HepG2, DU145 and MCF7 cell lines by the standard MTT assay. The results showed that some of the target compounds exhibited strong anti-proliferative activities against selected tumor cells, and compounds 7c, 7f, 7g, 7h and 7q were better than or equal to the activities of positive control, they deserved further development.

Synthesis and antitumor activity of 5-substituted-2-(pyridyl)benzothiazole compounds / 药学学报

Fifteen novel 5-substituted-2-(pyridyl)benzothiazole compounds were designed and synthesized by simple hydrolization and condensation reaction of the 2-amino-5-substituent benzothiazole. Activities of these synthesized compounds were evaluated on Bcap-37, HCT-15 and HepG2 tumor cells in vitro by standard MTT assay. 5-Fluorouracil (5-FU) was used as the positive control. The results revealed that most of the new compounds had potent effects on Bcap-37, HCT-15 and HepG2 tumor cells, and had no or less effect on 293T and L02 normal cells. Particularly, compounds 1c and 2e exhibited better activities on HCT-15 and HepG2 cells with IC50 values of 41.59 and 38.65 micromol x L(-1), and 1i showed excellent activities on Bcap-37 and HepG2 cells with IC50 values of 46.63 and 23.51 micromol x L(-1), respectively. The structure-activity relationship of 5-substituted-2-(pyridyl)benzothiazole compounds were also discussed preliminarily.

The preliminary study of HBV genotype distribution and the relationship with clinical manifestation / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the relationship between HBV genotypes distribution in hepatitis B patients and clinical manifestations in Beijing area.</p><p><b>METHODS</b>200 HBsAg positive serum were choosen from 1148 serum samples. useing of nested PCR amplification method, HBV DNA S genes were Sequencing and typing; genotype distribution and the relationship with the clinical manifestation were Statistical analysis.</p><p><b>RESULTS</b>In Beijing area, HBV has B, C, D three genotypes, including B gene type 17 cases (12. 5%), C genotype 116 cases (85.2%), D genotype 3 cases (0.02%); in the carriers, patients with chronic hepatitis B, cirrhosis, liver cancer, B type have been gradually falling, C type have been gradually rising trend.</p><p><b>CONCLUSION</b>Serious liver disease relate with C type, B type patients with HBV infection is better than C type patients in clinical prognosis and antivirus treatment response.</p>

Design, synthesis and activities of novel benzothiazole derivatives containing arylpiperazine / 药学学报

Twenty-four novel benzothiazole derivatives containing arylpiperazine were designed and synthesized by bioisosterism principle. Anti-proliferative effect of these synthesized compounds against four cancer cell and two normal cell lines were evaluated in vitro by the standard MTT assay. Pharmacological test showed that most of the compounds exhibited potent antitumor activity. Some of the compounds (II2, II3, II6, II7) showed strong anti-proliferation activities against HepG2 and HeLa229 cell lines with the IC 50 values of 1.6-4.5 micromol x L(-1) and 2.5-5.3 micromol x L(-1), respectively, and compounds having cyan in p-substituted benzene ring (I4, I8, I12, II4, II8 and II12) were found to have better antitumor activities against AsPC-1 cell lines with the IC50 values of 5.2-11.3 micromol x L(-1). The structure-activity relationship of benzothiazole derivatives containing arylpiperazine was also discussed preliminarily.

Disease gene screening of known loci in a Chinese family with autosomal dominant retinitis pigmentosa / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To map the disease-causing gene in a Chinese family with autosomal dominant retinitis pigmentosa.</p><p><b>METHODS</b>Twenty-seven micro-satellite markers were randomly selected from the region around the known loci of causative genes, and haplotypes were determined by ABI3100 genetic analyzer. Two-point linkage analysis was performed using MLINK.</p><p><b>RESULTS</b>The Lod score of each marker vs adRP was below 1.</p><p><b>CONCLUSION</b>The phenotype of this family may not be caused by mutation of the known disease-causing genes.</p>

Primary application of identification-aided system for diagnosis and differential diagnosis of emerging infectious diseases / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To verify the rate of diagnostic fitting between the clinic and the indentification-aided for diagnosis and differential diagnosis system, for emerging infections diseases (EID) established.</p><p><b>METHODS</b>314 cases of 49 kinds of contagious diseases diagnosed and another 186 patients with fever who not diagnosed were tested by the system.</p><p><b>RESULTS</b>Preliminary verification was made in 314 cases diagnosed which classified to 49 kinds of contagious diseases of infectious diseases and the results showed that the coincidence rate of clinical diagnosis and first diagnosis of this system was 61.9%; the suggestive rate of first three diagnoses was 78.1%, and that of first five diagnoses was 86.6%. The diagnosis of another 186 patients with fever were diagnosed by the system and the results showed that the coincidence rate of clinical diagnosis and first diagnosis was 59.7%; the suggestive rate of first three diagnoses was 77.9%, and that of first five diagnoses was 85.4%.</p><p><b>CONCLUSIONS</b>The system can accurately suggest impossible diagnosis and differential diagnosis, and be useful for our medical work.</p>

Linkage analysis of one family with autosomal dominant high myopia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To map the high myopia gene in a Chinese family with autosomal dominant high myopia.</p><p><b>METHODS</b>A family with autosomal dominant high myopia in three generations was collected. Eighteen short-tandem-repeat markers on previously reported loci linked to high myopia were chosen for genotyping and two-point linkage analysis was carried out.</p><p><b>RESULTS</b>The spherical equivalent of affected individuals ranges from -6.00D to -20.00D and the genetic pattern is autosomal dominant. The LOD score was less than -1 in all 18 microsatellite markers, indicating that there was no linkage between these markers and the high myopia related genes in this family.</p><p><b>CONCLUSION</b>A novel myopia locus for high-grade myopia may exist in the kindred. Genome-wide scan will be needed to determine this novel locus.</p>

Clinical observation on yintang (Ex-HN 3) point-injection for treatment of obstinate hiccup / 中国针灸

<p><b>OBJECTIVE</b>To search for an effective method for treatment of obstinate hiccup.</p><p><b>METHODS</b>Ninety cases of obstinate hiccup secondary to cerebral diseases were randomly divided into 3 groups, 30 cases in each group. Group A were treated by injection of compound chlorpromazine into Yintang (Ex-HN 3), group B by intramuscular injection of compound chlorpromazine and group C by acupuncture at Yintang (Ex-HN 3). Their therapeutic effects were compared.</p><p><b>RESULTS</b>The effective rate was 93.3% in the group A, 10.0% in the group B and 30.0% in the group C, the group A being better than the group B and the group C (P < 0.01).</p><p><b>CONCLUSION</b>Injection of compound chlorpromazine into Yintang (Ex-HN 3) has a significant therapeutic effect on obstinate hiccup.</p>