Purpose To investigate the expression of the protein of CD151 and MT1-MMP in adenocarcinoma of esophagogastric junc-tion tissues and to explore their relationship with the invasiveness and metastasis of the tumor. Methods CD151 and MT1-MMP pro-tein were detected by immunohistochemical staining respectively in 15 cases of paraneoplastic normal gastric mucosa tissue, 40 cases dysplasia and 172 cases of adenocarcinoma of esophagogastric junction tissues. Results All of the expression level of CD151 and MT1-MMP protein were increasing according to the order of normal-dysplsia-carcinoma. The expression rate of CD151 was 6. 67%, 20. 0% and 78. 3%, while the rate of MT1-MMP with 13. 3%, 22. 5% and 79. 1% in the normal, dysplasia and carcinoma subgroup. The expression rate of each protein were significant difference among the three goroups (P<0. 05). In the adenocarcinoma of esopha-gogastric junction tissues, the expression of them in the subgroup of poorly-differentiated with serosa invasion and lymph nodes metasta-sis was significantly higher than the other subgroup of well-differentiated with non serosa invasion or lymph nodes metastasis ( P <0. 05 ) . There was a positive correlation between the expression of CD151 and MT1-MMP protein in adenocarcinoma of esophagogastric junction tissues ( P<0. 05 ) . Conclusions CD151 and MT1-MMP assuredly and highly express in the adenocarcinoma of esopha-gogastric junction tissues and they have close relationships, which could involved in the invasiveness and metastasis synergistically in this tumor.

OBJECTIVETo observe analgesic effect of scalp acupuncture on labor.

METHODSSeventy primiparae with term pregnancy and monocyesis were randomly divided into scalp acupuncture group treated by acupuncture at the Shengzhi area of scalp, and control group by no treatment. Pain grades before and after scalp acupuncture were evaluated with the pain 4-grade rating criteria stipulated by WHO, and the active stage and the second birth process, the Apgar scores of new-born and postpartum hemorrage amount were compared between the two groups.

RESULTSThe labor pain with 1 to approximately 2 grades was found in 33 cases in the scalp acupuncture group, and 2 cases in the control group with very significant difference between the two groups (P < 0.01); the active stage was (130.70 +/- 74.16 ) min and the second birth process was (40.70 +/- 21.65) min in the scalp acupuncture group, and (166.15 +/- 62.65) min and (53.30 +/- 26.93) min in the control group, respectively, with significant differences between the two groups (all P < 0.05); and there were no significant differences in Apgar score of new-born and postpartum hemorrhage amount.

CONCLUSIONScalp acupuncture has a better analgesic effect in vaginal delivery with no adverse effect on the mother and infant.

Acupuncture Analgesia ; Adult ; Analgesia, Obstetrical ; Apgar Score ; Female ; Humans ; Infant, Newborn ; Pregnancy ; Scalp

OBJECTIVETo investigate the changes of thrombospondin 1(TSP1) level and von Willebrand factor cleaving protease(ADAMTS13) activity in the patients with hematologic malignancies before and after treatment and to evaluate their clinical significance.

METHODSEighty-two patients with hematologic malignancies were enrolled in this study, among them 20 patients were with acute leukemia, 48 patients were with lymphoma and 14 patients were with multiple myeloma. The plasma samples of 82 patients with hematologic malignancies and 45 healthy controls were collected. The activities of ADAMTS13 were evaluated by residue collagen binding assay(R-CBA), the levels of TSP1 and vWF antigen were measured by enzyme-linked immunosorbent assay(ELISA).

RESULTSThe activity of plasma ADAMTS13 in patients with hematologic malignancies was lower than that of normal controls(P<0.05). The levels of vWF antigen and TSP1 in the patients with hematologic malignancies were higher than those in normal controls(P<0.05). After standard induction chemotherapy, the ADAMTS13 activity of the patients with hematologic malignancies at the complete remission was higher than that before therapy(P<0.05); the vWF antigen level was significantly lower than that in the patients with hematologic malignancies before therapy(P<0.05), but still higher than that in controls(P<0.05). There were 25 infection patients in 82 cases of hematologic malignancies, and the ADAMTS13 activity in the patients with newly diagnosed hematologic malignancies complicated with infection before therapy was obviously lower than that in the patients with hematologic malignancies without infection(P<0.05), the levels of vWF antigen and TSP1 were significantly lower than that in patients without infection (P<0.05). In the process of treatment, 8 patients have been speculated to suffer from thrombus, and the ADAMTS13 activity in the patients with thrombus was obviously lower than that in the patients without thrombus(P<0.05).

CONCLUSIONLow ADAMTS13 activity and high TSP1 level may participate in the progress of hematologic malignancies, the infection and thrombotic events may lead to further reduction of the ADAMTS13 activity. Assaying the level of ADAMTS13 activity in the patients with malignant tumor may be helpful to prevent the infection and thrombosis in the patients with hematologic malignancies.

OBJECTIVETo evaluate the clinicopathologic features of gastrointestinal stromal tumor (GIST) with synchronous carcinoma and the treatment principle.

METHODSNineteen cases of GIST with synchronous carcinoma were collected from 113 cases of GIST from 2002 to 2008. The clinicopathologic features were studied and the expression of CD117, CD34, smooth muscle actin and S-100 protein were detected by immunohistochemistry using EliVision method. The expression of proliferation marker Ki-67 was also studied. GIST with synchronous carcinoma and those without carcinoma were compared.

RESULTSNineteen cases (16.8%) of GIST with synchronous carcinoma were found, including 11 males and 8 females (male to female ratio 1.38: 1.00). The age of the patients ranged from 43 to 66 years (median age 57 years). Five of 19 cases were located in the inferior segment of esophagus and 14 were in the gastric wall. The diameter ranged from 0.6 to 3.8 cm [mean (1.91 ± 0.92) cm]. Three of 19 cases showed low grade dysplasia, and there was no dysplasia in the remaining 16 cases. The number of mitosis ranged from 0 to 4/50 HPF [mean (0.74 ± 1.07)/50 HPF]. The Ki-67 proliferative index (number of Ki-67 positive cell/HPF) ranged from 0 to 7.72% [mean (2.51 ± 2.20)%]. The synchronous carcinomas included two esophageal carcinomas and 17 gastric cancers.In contrast, patients of GIST without carcinoma included 52 males and 42 females (male to female ratio 1.24: 1.00). The age of patients ranged from 43 to 71 years (median age 55 years). Seventy-nine of the 94 cases were located in the stomach, 10 were in the intestine and 5 were in the esophagus. The diameter ranged from 2.4 to 15.5 cm [mean (5.42 ± 6.17) cm].Seventy-nine of the 94 cases showed variable degrees of dysplasia, and 12 cases were of high malignant potential. The number of mitosis ranged from 0 to 53/50 HPF [average (3.78 ± 10.22)/50 HPF]. The Ki-67 proliferative index ranged from 0 to 37.54% [mean (6.78 ± 12.45)%]. Comparing these two groups, the male to female ratio of GIST with synchronous carcinoma was higher than that of GIST without carcinoma. The average diameter of GIST with synchronous carcinoma was smaller than of those without carcinoma. The number of mitosis and Ki-67 proliferative index of GIST with synchronous carcinoma were significantly lower than those without carcinoma (t' = 2.809, P < 0.05; t' = 3.095, P < 0.05, respectively).

CONCLUSIONSSixteen point eight percent of GIST may be associated with synchronous carcinoma. There are no special clinical symptoms in most of GIST with synchronous carcinoma, as these GIST are usually incidental findings. The Ki-67 proliferative index of GIST with synchronous carcinoma is significantly lower than that of GIST without synchronous carcinoma. Most GIST with synchronous carcinoma can be treated by the standard treatment for the accompanying carcinoma, and do not require specific additional treatments.

Adenocarcinoma ; metabolism ; pathology ; therapy ; Adenocarcinoma, Mucinous ; metabolism ; pathology ; therapy ; Adult ; Aged ; Antigens, CD34 ; metabolism ; Carcinoma, Signet Ring Cell ; metabolism ; pathology ; therapy ; Carcinoma, Squamous Cell ; metabolism ; pathology ; therapy ; Chemotherapy, Adjuvant ; Esophageal Neoplasms ; metabolism ; pathology ; therapy ; Esophagectomy ; Female ; Follow-Up Studies ; Gastrectomy ; Gastrointestinal Stromal Tumors ; metabolism ; pathology ; therapy ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms, Multiple Primary ; metabolism ; pathology ; therapy ; Proto-Oncogene Proteins c-kit ; metabolism ; Radiotherapy, Adjuvant ; Stomach Neoplasms ; metabolism ; pathology ; therapy

BACKGROUND:Hepatocyte transplantation has attracted more and more attention as a therapeutic measure for liver failure and genetic metabolic liver diseases.OBJECTIVE:TO evaluate the efficacy and safety of human hepatocyte transplantation in treating hepatitis B related liver failure in one case by a 2-year follow-up.DESIGN:A case-report of 2-year follow-up.SETTING:No.9 Department of Infectious Diseases,Bioengineering Research Room,the 302 Hospital of Chinese PLA.PARTICI PANT:One inpatient with hepatitis B related liver failure was selected from the 302 Hospital of Chinese PLA.and she was diagnosed according the laboratory tests.The transplanted hepatocytes were originated frOm the healthy liver of a 24-year-old man,who had signed the protocol for liver donation before death.METHODS:The hepatocyte transplantation was completed in the Department of Radiology,the 302 Hospital of Chinese PLA in December 2004.Liver was isolated to obtain human primary hepatocytes, and then cryopreserved.The hepatocytes were transplanted into recipient spleen via femoral vein after resuscitation.The clinical symptoms,changes of blood biochemical indexes,and changes of spleen MRI signals were observed before and after operation.The patient was reexamined every half a year after operation, including liver function, blood coagulation function,B-mode ultrasonography,gastroscopy and MRI,and she was followed up for 2 years. MAIN OUTCOME MEASURES:Liver function,blood coagulation function, imaging indexes, immunological indexes,complication and rejection.RESULTS:①Totally(1-2)×1010 hepatocytes were harvested,and the viability of rewarmed hepatocytes was 60%,and finally 2×109 hepatocytes were transplanted.②Two months later,the clinical symptoms of the recipient were obviously ameliorated,and serum bilirubin and aspartate aminotransferase(AST)were obviously decreased,while prothrombin activity was markedly increased.20 months later,the MRI results showed that there was hepatocyte image in spleen.Two years after operation.the total bilirubin level was 20 μmol/L,direct bilirubin level was 7 μmol/L, alanine aminotransferase was 416.75 nkat/L,AST was 533.44 nkat/L,albumin was 37 g/L,prothrombin activity was 90%,which were all obviously ameliorated as compared with those before operation(474.5 μmol/L,340.3 μmol/L,400.08 nkat/L,1 200.24 nkat/L,38 g/L,25%).The patient left the hospital 2 months later and could do light-burdened job.No complications of hydroperitonia and liver function failure, etc.were observed,and no rejection occurred.Several reexaminations by B-mode ultrasonography all indicated the further aggravations of liver cirrhosis and esophageal varices.She was admitted to hospital for twice because of esophageal varices bleeding,and cured by endoscopic variceal sclerosis therapy.CONCLUSION:Hepatocyte transplantation can ameliorate liver function without rejection,but it cannot relieve portal hypertension.

OBJECTIVE: To determine the types and frequency of deafness-related variants among 7875 newborns from Dongying area of Shandong Province. METHODS: One hundred loci of 18 common deafness genes were subjected to semiconductor sequencing. Variant site, frequency and distribution of the variants were analyzed. RESULTS: In total 552 deafness gene variants were detected among the 7875 newborns, which yielded a detection rate of 7.01%. Among these, common variant sites for GJB2, SLC26A4 and GJB3 genes were c.235delC, IVS7-2A>G and c.538C>T, respectively. The variant frequencies of matrilinear inheritance deafness genes MT-CO1, MT-RNR1, MT-TL1 and MT-TS1 were 0.38%, 0.25%, 0.1% and 0.01%, respectively. Four newborns were diagnosed with deafness, among which one had unilateral hearing loss. Analysis of the proportions of neonatal deafness-related variants in five counties of Dongying showed that the highest variant rate for the SLC26A4 gene compared with GJB2 was in Lijin county (51.76% vs. 40%), while the lowest was in Hekou county (30.77% vs. 56.41%). CONCLUSION The carrier rate of deafness-related variants in Dongying area is higher than other regions of China, which may be attributed to the increased types and variant sites covered by the semiconductor sequencing method compared with the chip method and time-of-flight mass spectrometry. Due to geographical and population aggregation factors, the proportion of deafness variants in the five counties of Dongying differed significantly. Above results may provide a guide for the prevention of congenital deafness in Dongying area.

In this study, the molecular mechanism of astragaloside Ⅳ(AS-Ⅳ) in the treatment of Parkinson's disease(PD) was explored based on network pharmacology, and the potential value of AS-Ⅳ in alleviating neuronal injury in PD by activating the PI3 K/AKT signaling pathway was verified through molecular docking and in vitro experiments. Such databases as SwissTargetPrediction, BTMAN-TAM, and GeneCards were used to predict the targets of AS-Ⅳ for the treatment of PD. The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) was employed to analyze protein-protein interaction(PPI) and construct a PPI network, and the Database for Annotation, Visualization and Integrated Discovery(DAVID) was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Based on the results of GO enrichment analysis and KEGG pathway analysis, the PI3 K/AKT signaling pathway was selected for further molecular docking and in vitro experiments in this study. The in vitro cell model of PD was established by MPP~+. The cell viability was measured by MTT assay and effect of AS-Ⅳ on the expression of the PI3 K/AKT signaling pathway-related genes and proteins by real-time polymerase chain reaction(RT-PCR) and Western blot. Network pharmacology revealed totally 122 targets of AS-Ⅳ for the treatment of PD, and GO enrichment analysis yielded 504 GO terms, most of which were biological processes and molecular functions. Totally 20 related signaling pathways were screened out by KEGG pathway analysis, including neuroactive ligand-receptor interaction, PI3 K/AKT signaling pathway, GABAergic synapse, and calcium signaling pathway. Molecular docking demonstrated high affinity of AS-Ⅳ to serine/threonine-protein kinases(AKT1, AKT2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3 CG), and phosphoinositide-3-kinase, catalytic, alpha polypeptide(PIK3 CA) on the PI3 K/AKT signaling pathway. In vitro experiments showed that AS-Ⅳ could effectively inhibit the decrease of the viability of PC12 induced by MPP~+ and up-regulate the mRNA expression levels of AKT1 and PI3 K as well as the phosphorylation levels of AKT and PI3 K. As an active component of Astragali Radix, AS-Ⅳ acts on PD through multiple targets and pathways. Furthermore, it inhibits neuronal apoptosis and protects neurons by activating the PI3 K/AKT signaling pathway, thereby providing reliable theoretical and experimental supports for the treatment of PD with AS-Ⅳ.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Network Pharmacology ; PC12 Cells ; Phosphatidylinositol 3-Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Rats ; Saponins ; Signal Transduction ; Triterpenes

OBJECTIVEThis study explored the correlation of longitudinal changes in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels with the incidence of metabolic syndrome (Mets) based on a dynamic health examination cohort.

METHODSA Mets-free dynamic cohort involving 4541 participants who underwent at least three health examinations from 2006 to 2011 was included in the study. Mets was defined according to the Chinese Medical Association Diabetes Branch definition that included hypertension, obesity, hyperlipidemia, and hyperglycemia. Generalized estimating equation (GEE) model was used to analyze multivariate relative risk (RR) of repeated observations of ALT and AST in quartiles for Mets or its components according to gender.

RESULTSIn all, 826 Mets cases were reported. Adjustment of relevant parameters indicated that time-varying changes in ALT and AST levels were positively associated with the incidence of Mets in a dose-response manner. Positive association between high ALT levels and fatty liver was much stronger than that between high AST levels and fatty liver, particularly in male participants. These associations were consistently observed in the following subgroups: participants with ALT and AST levels of <40 U/L, participants with of <25 kg/m2, and participants with non-fatty liver. Furthermore, participants with 2 Mets components at baseline showed lower multivariate adjusted RRs of ALT and AST for Mets than participants with 0-1 Mets component.

CONCLUSIONThese results suggested that elevated serum ALT and AST levels were early biomarkers of Mets or its components.

Adult ; Aged ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Biomarkers ; blood ; China ; epidemiology ; Cohort Studies ; Female ; Hepatitis ; complications ; epidemiology ; etiology ; Humans ; Incidence ; Liver ; enzymology ; physiopathology ; Male ; Metabolic Syndrome ; complications ; diagnosis ; enzymology ; epidemiology ; Middle Aged ; Young Adult

ObjectiveTo study the metabolism of chemical components from Citri Reticulatae Pericarpium（CRP）in different parts of rats by sequential metabolism and ultra performance liquid chromatography-high resolution mass spectrometry（UPLC-HRMS）. MethodSD male rats were employed as experimental subjects， and blood samples of intestinal metabolism and hepatic metabolism were prepared after administration of CRP ethanol extract by in situ intestinal perfusion， and comprehensive metabolic samples were collected after intragastric administration. UPLC-HRMS was used to analyze the samples with acetonitrile（A）-0.1% formic acid aqueous solution（B）as the mobile phase for gradient elution（0-10 min， 10%-30%A； 10-30 min， 30%-95%A； 30-31 min， 95%-10%A； 31-35 min， 10%A）at a flow rate of 0.35 mL·min^-1， using a heated electrospray ionization with positive and negative ion mode scanning in the range of m/z 100-1 500. Under these conditions， the differences in the profiles of CRP ethanol extract， blank plasma and drug-containing plasma under different treatment groups were compared， and the chemical components of each sample were analyzed and identified based on the retention time， accurate relative molecular mass， primary and secondary ion fragments， and the information of reference substances. ResultA total of 44 chemical components were identified in the CRP ethanol extract， including flavone-O-glycosides， flavone-C-glycosides and polymethoxyflavonoids， etc. The results of sequential metabolism showed that 22 chemical components in CRP were detected in the intestinal metabolic sample， 18 chemical components were detected in the hepatic metabolic sample， and 9 identical chemical components（narirutin， hesperidin， meranzin， 5，7，8，3ʹ，4ʹ，5ʹ-hexamethoxy-flavone， isosinensetin， sinensetin， 3，5，6，7，8，3ʹ，4ʹ-heptamethoxyflavone， nobiletin and tangeretin）could be detected in all three metabolic samples， with a total of 22 compounds entering the blood in prototype form. ConclusionThe identified 21 components with well-defined structures entering the blood as prototypes may be potential active components of CRP， and differences in the components at different metabolic parts can provide an experimental basis for elucidating the in vivo biotransformation process of the metabolic components of CRP.

ObjectiveBased on sequential metabolism and ultra-high performance liquid chromatography-high resolution mass spectrometry （UPLC-HRMS）， to identify the prototype components and metabolites of Tongfengding capsules in rat plasma. MethodAn ACQUITY UPLC BEH Shield RP18 column （2.1 mm×100 mm， 1.7 µm） was used for gradient elution with 0.1% formic acid aqueous solution （A）-acetonitrile （B） as the mobile phase （0-1 min， 5%B； 1-2.4 min， 5%-10%B； 2.4-13.5 min， 10%-32%B； 13.5-18.5 min， 32%-90%B； 18.5-19 min， 90%-5%B； 19-21 min， 5%B） at a flow rate of 0.3 mL·min^-1， injection volume of 2 μL and column temperature at 35 ℃. The heated electrospray ionization （HESI） was applied under positive and negative ion modes， and the scanning range was m/z 100-1 500. By comparing the differences between the administered plasma and the blank plasma， the prototype components and metabolites in intestinal metabolism sample and liver metabolism sample prepared by intestinal perfusion with parallel blood collection， and comprehensive metabolism sample prepared by intragastric administration method were identified. ResultA total of 76， 53， 74 chemical components were detected in the intestinal metabolism sample， the liver metabolism sample and the comprehensive metabolism sample. A total of 100 components were identified from these different plasma samples， including 64 prototype components （34 alkaloids， 12 terpenoids， 9 organic acids， 6 flavonoids and 3 other components） and 36 metabolites. The main metabolic reactions involved in the formation of metabolites were glucuronidation， deglucosylation， dehydrogenation and hydroxylation. ConclusionThe chemical components of Tongfengding capsules can undergo a series of metabolic reactions in the intestine and liver， and a large number of metabolites are generated， among which alkaloids may be the leading component group for efficacy， which can lay the foundation for systematic elucidating the material basis of Tongfengding capsules in vivo.