OBJECTIVEIBS-D rat model was established to assess the effect of Shen warming Pi strengthening method (SWPSM) for intervening diarrhea-predominant irritable bowel syndrome (IBS-D) by observing rats' general state, stool properties, AWR ranking, and histopathological changes.

METHODSTotally 72 rats were randomly divided into 6 groups, i.e. the normal group, the model group, the high, middle, low dose SWPSM groups, and the control group, 12 in each group. The IBS-D rat model was successfully established referring to AL-Chaer ED's modeling method. After modeling high, middle, and low dose SWPS Recipe boil-free granules were given by gastrogavage to rats in corresponding treatment groups. Sishen Pill boil-free granule was given by gastrogavage to those in the control group. Equal volume of normal saline was given by gastrogavage to rats in the model group. The medication lasted for 2 weeks. Rats' general state, stool properties, abdominal withdrawal reflex (AWR) ranking, and histopathological changes were observed.

RESULTSAfter treatment, the general state of all rats got im- provement to various degrees. The improvement in the high and middle dose SWPS Recipe groups were superior to that in the low dose SWPS Recipe group and the control group (P < 0.05). There was no statistical difference in the growth rate between after and before treatment in each group (P > 0.05). Compared with the model group and the low dose SWPS Recipe group, the defecation amount within 4 h was less in the high and middle dose SWPS Recipe groups and the control group (P < 0.05). The Bristol ranking score, average ranking of loose stool, ratio of dry stool and wet stool were lower in the high and middle dose SWPS Recipe groups than in the control group and the low dose SWPS Recipe group (P < 0.05). The AWR ranking score was lower in the high and middle dose SWPS Recipe groups than in the control group when the volume of balloon dilation was 1.5 mL. There was no organic change of histological or morphological observation.

CONCLUSIONSHigh sensitive IBS-D model was proved to be reliable. SWPSM could reduce the quantity of stools, lower Bristol ranking score, average ranking of loose stools as well as ratios of dry stool and wet stool, contributing to reducing the high sensitivity of rats' visceral organs to some extent.

Animals ; Diarrhea ; drug therapy ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Irritable Bowel Syndrome ; drug therapy ; Male ; Phytotherapy ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the clinical efficacy of cetuximab plus chemotherapy in the treatment of metastatic colorectal carcinoma.

METHODSClinicopathological data of 128 patients with metastatic colorectal cancer admitted in the Department of Oncology, Chinese PLA General Hospital from 2008 to June 2012 were analyzed retrospectively. Among them, 91 patients received cetuximab as the first-line therapy and 37 in the second-line or more-line therapy. The chemotherapy regimens included oxaliplatin-based therapy (FOLFOX/XELOX), irinotecan-based therapy (FOLFIRI/XELIRI) and fluorouracil-based therapy (Xeloda). The efficacy was evaluated according to RECIST 1.0 criteria. The remission rate, control rate and time to disease progression were compared among patients receiving cetuximab combined with different chemotherapy regimens in different periods.

RESULTSThe disease control rate of cetuximab applied in the first-line treatment was higher than that of the second-line or more-line [85.9% (61/71) vs. 59.3% (16/27), P=0.004]. The disease control rate of the group treated with cetuximab plus oxaliplatin-based chemotherapy was much higher compared to the other two groups [91.1% (41/45) vs. 68.1% (32/47), 4/6, P=0.021]. But there were no significant differences among three regimens in the terms of overall response rate (all P>0.05). The median time to progression of groups with cetuximab plus irinotecan, oxaliplatin or capecitabine was 7.8 months, 8.5 months and 5.2 months respectively. The median time to progression of cetuximab combined with chemotherapy in the first-line treatment and the second-line or more-line was 8.2 and 7.7 months respectively. However, the differences were not statistically significant (P>0.05).

CONCLUSIONSCetuximab in combination with oxaliplatin-based chemotherapy is recommended as the first-line application in the treatment of metastatic colorectal carcinoma patients, because it is helpful to improve the rate of disease control.

Antineoplastic Combined Chemotherapy Protocols ; Camptothecin ; analogs & derivatives ; Cetuximab ; Colorectal Neoplasms ; Deoxycytidine ; analogs & derivatives ; Fluorouracil ; analogs & derivatives ; Humans ; Leucovorin ; Neoplasm Metastasis ; Organoplatinum Compounds ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo study the gastric function after esophagectomy and cardiectomy with vagus nerve preserved and reconstruction of gastric funds (VPRG)in patients with esophageal cancer (EC) and cardiac cancer (CC).

METHODSSixty-eight patients with early or middle staged EC or CC received esophagectomy and cardiectomy with vagus nerve preserved and reconstruction of gastric funds (VPRG),while other 68 patients esophagectomy and cardiectomy with vagus nerve severed and no reconstruction of gastric funds (VSNG) as control. The symptoms,the pressure of the residual esophagus and thoracic stomach, 24-hour pH monitoring, mean basic gastric acid output, gastric emptying time of the intrathoracic stomach,fasting serum gastrin level, fibreoptic endoscopic results were compared before and after operation between the two groups.

RESULTSThe patients with VPRG had less symptoms after operation than those with VSNG such as anorexia, belch, reflux, heartburn, nausea, diarrhea, postcibal satiety (P< 0.01). In VPRG group,compared with the results before operation,there were no significant differences in 24-hour pH monitoring,the mean basic gastric acid output, the fasting serum gastrin level,the gastric emptying time of intrathoracic stomach one month and one year after operation (both P > 0.05). The pressure of the residual esophagus above the anastomosis in VPRG group was significantly higher than that in VSNG group (both P< 0.05). Fibreoptic endoscopic examination revealed higher incidences of postoperative atrophic gastritis and reflux esophagitis in VPRG group one month and one year after operation than those in VSNG group (P< 0.01).

CONCLUSIONPreservation of the vagus nerve and reconstruction of gastric funds after esophagectomy and cardiectomy for esophageal and cardiac cancer can prevent digestive disorder and improve the life quality of the patients.

Adult ; Esophageal Neoplasms ; surgery ; Esophagectomy ; methods ; Female ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Stomach ; physiopathology ; Vagus Nerve ; surgery

OBJECTIVETo study the possible association between interferon regulatory factor 5 (IRF5) gene polymorphism and allergic rhinitis (AR).

METHODSSix independent single nucleotide polymorphism (SNP, rs729302, rs4728142, rs3807306, rs2070197, rs11770589, rs2280714) were analyzed. The genotype and allele frequencies were detected in 110 AR patients and 101 healthy controls in Singapore Chinese population by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).

RESULTSRs729302 was rejected as it was not polymorphic. For others SNP, no statistically significant difference was detected in genotype between AR and healthy control group (χ(2) value were 0.21, 5.02, 0.01, 2.91, 0.37, all P > 0.05). No statistically significant difference was detected in allele frequencies between AR and healthy control group (χ(2) value were 0.00, 2.78, 0.01, 2.31, 0.00, all P > 0.05).

CONCLUSIONNo association is observed between IRF5 and AR in Singapore Chinese population.

Adolescent ; Adult ; Aged ; Case-Control Studies ; Female ; Gene Frequency ; Genotype ; Humans ; Interferon Regulatory Factors ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Rhinitis, Allergic ; Rhinitis, Allergic, Perennial ; genetics ; Singapore ; Young Adult

OBJECTIVETo identify clinical and laboratory abnormalities and genetic defect of Fechtner syndrome in a Chinese family.

METHODSThe characteristic morphological features of platelets and leukocytes were examined on blood smears with Wright's-Giemsa staining and ultrastructure of platelet and leukocyte were investigated under electron microscope. Genomic DNA was isolated from peripheral blood of the proband and 9 members of his family. All the exons and exon-intron boundaries of the MYH9 gene were amplified by PCR followed by direct sequencing.

RESULTSPatients presented the characteristic clinical features including macrothrombocytopenia, leukocyte inclusions and/or hereditary nephritis. A heterozygous C to T mutation was found in the proband and three members of his family at nucleotide 5981 in exon 40 of MYH9 gene, resulting in a nonsense mutation which encoded truncated protein due to premature termination at the Arg 1933 codon.

CONCLUSIONIt is the first report of a Chinese family with Fechtner syndrome. The Arg (CGA) 1933--> stop (TGA) nonsense mutation in MYH9 gene is a causative genetic defect.

Adult ; Codon, Nonsense ; DNA Mutational Analysis ; Exons ; genetics ; Humans ; Inclusion Bodies ; genetics ; Male ; Molecular Motor Proteins ; genetics ; Myosin Heavy Chains ; genetics ; Nephritis, Hereditary ; genetics ; Pedigree ; Syndrome ; Thrombocytopenia ; genetics

To identify up-regulated genes in adult rat cardiac fibroblasts (CF) induced by angiotensin II (Ang II), suppression subtractive hybridization (SSH) was performed between the CF stimulated by Ang II (tester) and unstimulated CF (driver) to generate subtractive cDNA library. The library was screened with dot blots hybridization to further verify the differentially expressed cDNA clones. Partial positive clones (19 up-regulated genes) were sequenced and BLAST analyzed. Twelve up-regulated genes related to extracellular matrix, cell cycle, intracellular signal transduction, cell cytoskeleton, cell metabolism and 7 new expressed sequence tags (EST) were acquired (GenBank accession number: CN382808, CN382809, CN382810, CN382811, CN382812, CN382813, CN382814). Our data reveal that SSH is a powerful technique of high sensitivity for the detection and cloning of up-regulated genes expressed in CF induced by Ang II, which may be helpful to clarify the mechanism of cardiac remodeling.
Angiotensin II ; pharmacology ; Animals ; Cells, Cultured ; DNA, Complementary ; genetics ; Expressed Sequence Tags ; Fibroblasts ; cytology ; Gene Expression Regulation ; Male ; Myocardium ; cytology ; Rats ; Rats, Sprague-Dawley ; Up-Regulation ; Ventricular Remodeling ; genetics

OBJECTIVETo identify gene mutations involved in five cases of inherited factor V (FV) deficiency.

METHODSActivity of FV was determined by one-stage clotting assay using FV-deficiency plasma, and FV antigen by an ELISA assay. All the exons and exon-intron boundaries of FV gene were amplified by PCR and then DNA sequencing. Restriction enzyme analysis was used to analyze the probands, their family members and healthy volunteers.

RESULTSBoth activity and antigen of FV in the 5 patients were extremely lower compared with that of normal mixed plasma. Six mutations were identified in these 5 patients, G69969T (G2079V), C45533T (R712Ter), C46796T (R1133Ter), G45366A (C656Y), C46253T (R952C) and G16088C (D68H), the latter three were novel mutations reported for the first time and the C46253T (R952C) was the first missense mutation reported in B domain. The result of sequencing or restriction enzyme analysis showed that the three novel missense mutations were not caused by single nucleotide polymorphisms.

CONCLUSIONGene mutations in 5 type I inherited FV deficiency of patients including 2 nonsense mutations and 4 missense mutations identified which led to the instability of FV protein and the reducing of FV: Ag in the plasma.

Adolescent ; Adult ; Child ; DNA Mutational Analysis ; Exons ; genetics ; Factor V ; genetics ; metabolism ; Factor V Deficiency ; blood ; genetics ; Female ; Humans ; Male ; Mutation ; Pedigree ; Phenotype ; Young Adult

Objective To evaluate the efficacy of peripheral blood combined with cord blood model for haplo-hematopoietic stem cell transplantation and the occurrence,survival of complications in patients of different ages.Methods From January 2014 to December 31,2017,there were 50 patients undergoing haploid allogeneic hematopoietic stem cell transplantation in our department.There were 39 males and 11 females.The median age was 35 (9-67) years.The stratification was divided into 3 groups.In group A,17 patients were younger than 30 years old;in group B,19 patients were between 30 and 49 years old,and in group C,14 patients were not less than 50 years.No remission was assessed before transplantation in this group.On the morning of the reinfusion,the selection of a third-party umbilical cord blood for transfusion reduced the occurrence of GVHD.Peripheral blood was infusion in the afternoor.All patients were treated with ATG + CSA + shortterm MTX to prevent GVHD.Results Two patients died of infection prior to graft,4 (8.0％) patients were graft failure.The median time of ANC≥0.5 × 109/L (range) and platelet ≥20 × 109/L (range) in the other patients were 14d(10-22 d) and 20(11-186) d,individually.The median time of full donor chimerism(range)was 28d(14-42 d).Graft failure was occurred in one case (5.9％),two cases (10.5％) and one case (7.1％) in each group,with no statistically significant difference (x2 =0.282,P =0.868).With a median follow-up of 7.2 months (0.4-27.2 months),12 (24％) had aGVHD of Ⅱ-Ⅳ degrees,among them,6 cases (35.3％) in group A,5 cases (26.3％) in group B,1 case (7.1％) in group C had aGVHD of Ⅱ-Ⅳ degrees.There was no significant in the incidence of aGVHD in three groups (x2 =3.624,P =0.180).Twenty-nine (58％) patients had viral infections after transplantation.One patient in both group A and B relapsed,and there was no recurrence in group C.21 (42％) patients died and 29 (58％) patients survived.The predicted 2-year overall survival (OS) was 60.2％.In group C,the 2-year overall survival (OS) was 77.1％.Conclusion The haploidentical hematopoietic cell transplantation model of peripheral blood combined with third-party umbilical cord blood transfusion has a good outcome and prolonged survival time in high-risk elder patients.The use of suitable conditioning regimens did not increase the incidence of aGVHD and virus infection.

[Objective]To investigate the effect of KIF23 gene expression on the proliferation,migration and invasion of human hepatocellular carcinoma HepG2 cells in vitro,and to explore the possible mechanism.[Methods]The KIF23 siRNA was transfected into HepG2 cells by lipofectamine 3000.The expression of KIF23 mRNA and protein in HepG2 cells was de-tected by qRT-PCR and Western blot.The effect of silencing KIF23 on the proliferation of HepG2 cells was studied by CCK-8 assay and plate clone formation assay.The tumor cell abilities of migration and invasion after transfection were measured by scratch assay and Transwell assay.The expression of protein kinase B(PKB/Akt)and phosphorylated Akt(p-Akt)protein in HepG2 cells transfected with KIF23-siRNA2 was detected by Western blot.[Results]KIF23-siRNA could effectively si-lence the expression of KIF23 mRNA and protein in HepG2 cells(P<0.01).The results of CCK-8 assay,plate clone forma-tion assay,scratch assay and Transwell assay demonstrated that the cell proliferation,migration and invasion ability of the KIF23-siRNA2 interference group were significantly inhibited,compared to the negative control group and the blank control group(P<0.05).The expression level of total Akt protein in HepG2 cells was not changed,but the expression level of phos-phorylated Akt protein was down-regulated(P<0.05).[Conclusions]KIF23 may promote the proliferation,migration and in-vasion of human hepatocellular carcinoma cells by activating Akt signal transduction pathway.KIF23 is expected to be a new target for gene therapy of hepatocellular carcinoma.

OBJECTIVETo investigate the potential association between factor VIII inhibitor development and polymorphisms of tumor necrosis factor-α (TNF-α)-308 and cytotoxic T-lymphocyte associated protein-4 gene in Chinese Han patients with hemophilia A (HA).

METHODSThe single base change polymorphism in TNF-α and CTLA-4 gene was analyzed in 140 Chinese Han patients with hemophilia A who have been treated with plasma-derived FVIII concentrates and 108 normal controls by using PCR-restrictive fragment length polymorphism (RFLP). All of the HA patients' plasma samples were measured by modified-Nijmegen assay simultaneously.

RESULTSIn HA patients, G/G genotype, G/A genotype and A/A genotype were detected in 118 (84.3%), 18 (12.8%) and 4 cases (2.9%) respectively; C/C genotype, C/T genotype and T/T genotype were detected in 108 (77.2%), 30 (21.4%) and 2 cases (1.4%) respectively. The difference in the genotype frequencies between HA patients and controls was nonsignificant (P > 0.05). Patients who were carriers of homozygotes for A allele had a higher risk of inhibitor development compared with those who were not (OR = 7.519, 95% CI = 3.168 - 17.844). Severe HA patients who were carriers of homozygotes for A allele had a higher risk of inhibitor development compared with those who were not (OR = 8.163, 95% CI = 2.521 - 26.434). There was no statistical difference in the risk of inhibitor development between the patients who were carriers or not (OR = 1.586, 95% CI = 0.729 - 3.450).

CONCLUSIONTNF-α-308 gene polymorphism is significantly associated with inhibitor development in Chinese Han patients with severe hemophilia A. TNF-α gene may be a useful marker and potential modulator of the immune response to replacement therapy for hemophilia A patients.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; CTLA-4 Antigen ; genetics ; Child ; Child, Preschool ; Genotype ; Hemophilia A ; genetics ; Humans ; Infant ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Tumor Necrosis Factor-alpha ; genetics ; Young Adult