Efficacy and Safety of Keverprazan Compared With Lansoprazole in the Treatment of Duodenal Ulcer: A Phase III, Randomized, Double-Blind, Multicenter Trial.

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.

Systematic Analysis of the Clinical Significance of Hyaluronan-Mediated Motility Receptor in Colorectal Cancer.

Background: The role of hyaluronan-mediated motility receptor (HMMR) in colorectal cancer (CRC) remains unclear. The present study aimed to explore the association of HMMR with the development and prognosis of CRC using sequence datasets, clinical tissues, blood samples, and cell lines. Methods: CRC datasets were downloaded from TCGA and GEO databases. Forty CRC tissue samples, 120 CRC blood samples, and 100 healthy controls were collected. Four CRC cell lines (HCT116, HT-29, LoVo, and SW480) and one normal human colon mucosal epithelial cell line (NCM460) were cultured. RT-qPCR was used to determine the expression of HMMR in the tissues and cell lines. ELISA was used to measure HMMR levels in the blood samples. Results: The expression of HMMR was significantly increased in CRC tissues than in corresponding adjacent tissues based on TCGA and GEO datasets, and clinical CRC tissues. No associations were found between the expression of HMMR and the TNM stage or other clinical parameters. The expression of HMMR varied in different CRC cell lines. The blood levels of HMMR tended to be higher in patients with CRC than in healthy controls. TCGA and GEO datasets showed inconsistent results regarding the association of HMMR expression with the survival of patients with CRC. Conclusion: The expression of HMMR is increased in CRC tissues but not in the blood. The expression of HMMR is independent of CRC development and has no prognostic significance in patients with CRC.

Diagnostic and Predictive Value of Immune-Related Genes in Crohn's Disease.

Abnormal immune cell infiltration is associated with the pathogenesis of Crohn's disease (CD). This study aimed to determine the diagnostic and predictive value of immune-related genes in CD. Seven Gene Expression Omnibus datasets that analyzed the gene expression in CD tissues were downloaded. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate the infiltration of the immune cells in CD tissues. Immune-related genes were screened by overlapping the immune-related genes with differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was used to identify key immune-related DEGs. Diagnostic value of CD and predictive value of anti-TNFα therapy were analyzed. Immunohistochemical (IHC) assay was used to verify gene expression in CD tissues. There were significant differences among CD tissues, paired CD tissues, and normal intestinal tissues regarding the infiltration of immune cells. AQP9, CD27, and HVCN1 were identified as the key genes of the three sub-clusters in the PPI network. AQP9, CD27, and HVCN1 had mild to moderate diagnostic value in CD, and the diagnostic value of AQP9 was better than that of CD27 and HVCN1. AQP9 expression was decreased in CD after patients underwent anti-TNFα therapy, but no obvious changes were observed in non-responders. AQP9 had a moderate predictive value in patients who had undergone treatment. IHC assay confirmed that the expression of AQP9, CD27, and HVCN1 in CD tissues was higher than that in normal intestinal tissues, and AQP9, CD27 was correlated with the activity of CD. Immune-related genes, AQP9, CD27, and HVCN1 may act as auxiliary diagnostic indicators for CD, and AQP9 could serve as a promising predictive indicator in patients who underwent anti-TNF therapy.

Construction of a long noncoding RNA-based competing endogenous RNA network and prognostic signatures of left- and right-side colon cancer.

BACKGROUND: Cancers located on the right and left sides of the colon have distinct clinical and molecular characteristics. This study aimed to explore the regulatory mechanisms of location-specific long noncoding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in colon cancer and identify potential prognostic biomarkers. METHOD: Differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) between right- and left-side colon cancers were identified by comparing RNA sequencing profiles. Functional enrichment analysis was performed for the DEGs, and a ceRNA network was constructed. Associations between DELs and patient survival were examined, and a DEL-based signature was constructed to examine the prognostic value of these differences. Clinical colon cancer tissues and Gene Expression Omnibus (GEO) datasets were used to validate the results. RESULTS: We identified 376 DELs, 35 DEMs, and 805 DEGs between right- and left-side colon cancers. The functional enrichment analysis revealed the functions and pathway involvement of DEGs. A ceRNA network was constructed based on 95 DEL-DEM-DEG interactions. Three DELs (LINC01555, AC015712, and FZD10-AS1) were associated with the overall survival of patients with colon cancer, and a prognostic signature was established based on these three DELs. High risk scores for this signature indicated poor survival, suggesting that the signature has prognostic value for colon cancer. Examination of clinical colon cancer tissues and GEO dataset analysis confirmed the results. CONCLUSION: The ceRNA regulatory network suggests roles for location-specific lncRNAs in colon cancer and allowed the development of an lncRNA-based prognostic signature, which could be used to assess prognosis and determine treatment strategies in patients with colon cancer.

Percentage of Natural Killer (NK) Cells in Peripheral Blood Is Associated with Prognosis in Patients with Gastric Cancer: A Retrospective Study from a Single Center.

BACKGROUND Natural killer (NK) cells are important for the prognosis of multiple cancers, but their prognostic value remains to be evaluated in patients with gastric cancer. Thus, this retrospective study was conducted at a single center to investigate the association between percentage of NK cells in the peripheral blood and prognosis in patients with gastric cancer. MATERIAL AND METHODS The data of 180 gastric cancer patients were collected. Univariate and multivariate Cox regression models were applied to screen candidate prognostic factors. A time-dependent receiver operating characteristic curve was employed to evaluate the ability of NK cells as a prognostic marker. Furthermore, we determined the correlation between the NK cells percentage and other parameters and their clinical significance. RESULTS Patients with a higher percentage of NK cells survived longer than those with a lower percentage of NK cells. Cox analysis revealed that NK cells could be used as an independent indicator for patients with gastric cancer. The percentage of NK cells was positively correlated with lymphocyte count and albumin, but was negatively correlated with CA125 and neutrophil-lymphocyte ratio. The area under the curve for NK cells in predicting the 5-year survival rate for gastric cancer was 0.792. This increased to 0.830 upon combining NK cells with neutrophil-lymphocyte ratio. Patients at early T, N, and clinical stages possessed a significantly higher percentage of NK cells compared to those at advanced T, N, and clinical stages of gastric cancer. CONCLUSIONS Our results suggest that a higher percentage of NK cells predicts is associated with longer survival of gastric cancer patients and could serve as an independent prognostic biomarker.

Diagnostic and prognostic value of plasma heat shock protein 90alpha in gastric cancer.

BACKGROUND: The role of plasma heat shock protein 90alpha (Hsp90α) in gastric cancers remains unclear. This study aimed to clarify the diagnostic and prognostic value of plasma Hsp90α in gastric cancer. METHODS: Data regarding 976 gastric cancer, 50 gastric inflammatory diseases, and 100 healthy controls were collected. Plasma Hsp90α levels in gastric cancer were compared to those in controls. Its correlation with tumor biomarkers and immune cells was examined. The association of plasma Hsp90α with clinical features and the diagnostic and prognostic value in gastric cancer were also determined. RESULTS: Plasma Hsp90α levels were remarkably increased in gastric cancer, compared to those in gastric inflammatory diseases and healthy controls. Moreover, plasma Hsp90α was correlated with CEA, CA125, CA153, CA199, T cells, Th/Ts ratio, and B cells. Plasma Hsp90α was also associated with the metastasis stage. Multivariate logistic regression analysis revealed that Hsp90α, B cells, and T cells were significantly associated with gastric cancer. Plasma Hsp90α has a moderate diagnostic value, which increased when combined with B cell, T cells. Finally, plasma Hsp90α was not associated with the survival of gastric cancer patients. CONCLUSION: Plasma Hsp90α was elevated in gastric cancer and correlated with tumor biomarkers and immune cells. Plasma Hsp90α was associated with the metastasis stage and had moderate diagnostic performance but little prognostic value in gastric cancer.

Epigastric pain syndrome: What can traditional Chinese medicine do? A randomized controlled trial of Biling Weitong Granules.

BACKGROUND: Recent research suggests that although prokinetic agents, acid suppressors, and radical treatment for Helicobacter pylori infection may be effective in patients with functional dyspepsia (FD), a large proportion of patients still fail to respond to these treatments or may suffer from severe adverse reactions. Many traditional Chinese medicinal herbs can regulate the status of the entire body and have special advantages in the treatment of functional diseases. The present study was designed to verify the efficacy of Biling Weitong Granules (BLWTG), a traditional Chinese medicinal herbal compound formula, in alleviating epigastric pain syndrome (EPS) in FD patients, in an attempt to provide an effective prescription for the clinical treatment of this disease. AIM: To evaluate the clinical efficacy and safety of BLWTG in treating EPS in patients with FD. METHODS: In this multicenter, stratified, randomized, double-blind, placebo-controlled, parallel group clinical trial, eligible patients were randomized into the BLWTG and placebo groups who were treated for 6 wk. Efficacy indicators including the severity and frequency of EPS and the time to pain resolution and safety indicators including adverse events were observed and compared. RESULTS: The baseline demographic data and clinical characteristics, such as epigastric pain symptoms, pain intensity, and frequency of attacks, were matched between the two groups before randomization. After 6 wk of treatment and after the center effect was eliminated, the epigastric pain was significantly improved in 28.33% and 85.59% of the patients in the placebo and BLWTG groups, respectively (P < 0.05). At 6 wk, the resolution rate of epigastric pain was 15% and 69.49% in the placebo and BLWTG groups, respectively (P < 0.05). The differences of total FD clinical score between these two groups were significant (P < 0.05) at 2, 4, and 6 wk (P < 0.05). The scores of each item and the total score in the Functional Digestive Disorders Quality of Life Questionnaire showed significant differences between the two groups at 6 wk after both the center and interaction effects were eliminated (P < 0.05). There was no significant difference in the incidence of adverse events between the two groups, and no serious adverse event was noted during the observation. CONCLUSION: Compared with placebo, BLWTG markedly improved EPS in FD patients without causing serious adverse reactions.

Clinical Significance and Prognostic Value of miR-28-5p in Colon Cancer.

BACKGROUND: The association of miR-28-5p with colon cancer remains to be elucidated. This study aimed to determine the clinical significance and prognostic value of miR-28-5p in colon cancer. METHODS: We retrospectively analyzed the data of miR-28-5p in colon adenocarcinoma data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and the data was divided into cancer group and normal group, respectively. Forty colon cancer tissues and adjacent normal tissues were collected and tested by qRT-PCR methods. The difference of the miR-28-5p expression between colon cancer and normal tissues was compared. The clinical significance of miR-28-5p in colon cancer and the association with the survival were determined. The predictive value of miR-28-5p in clinical features was determined using receiver operating characteristic curve. The target genes of miR-28-5p were identified, and the functional of target genes was performed using bioinformatics analysis. RESULTS: : The expression of miR-28-5p was increased in colon cancer tissues compared with normal controls (p = 0.037). The expression of miR-28-5p was significantly increased in tissues with distant metastases compared with that without distant metastases (p = 0.026). Patients with high expression of miR-28-5p have a shorter survival time than those with low expression (p = 0.004). Cox analysis showed that miR-28-5p was an independent predictor for the survival of patients (p = 0.014). Combination of miR-28-5p with TNM stage and clinical stage can improve the prognostic value for the patients (p < 0.05). miR-28-5p has a moderate predictive value in predicting the TNM stage and clinical stage (T stage: AUC = 0.515; N stage: AUC = 0.523, M stage: AUC = 0.572; clinical stage: AUC = 0.539). 711 potential target genes of miR-28-5p were screened; their function and pathways were identified. CONCLUSIONS: : This study demonstrated that miR-28-5p was increased in colon cancer and can be an independent indicator for the overall survival in patients with colon cancer.

Global transcriptomic study of circRNAs expression profile in sorafenib resistant hepatocellular carcinoma cells.

The anti-angiogenic drugs represented by sorafenib over the years have always been the first-line treatment of hepatocellular carcinoma (HCC), but the drug resistance has always been a "bottleneck" in curative effect. Recently, aberrant expression of circular RNA (circRNA) is considered to play a crucial role in many types of cancers. However, the genome-wide expression pattern of circRNAs in sorafenib-resistant HCC cells remains unknown. Herein, we identified 1717 differentially expressed circRNAs with 559 up-regulated and 1158 down-regulated (fold change > 2, P < 0.05) in sorafenib-resistant (HUH7-S) HCC cells along with 582 differentially expressed circRNAs with 272 up-regulated and 310 down-regulated (fold change > 2, P < 0.05) in sorafenib-resistant (HepG2-S) HCC cells, compared to parental sorafenib-sensitive (HUH7, HepG2) HCC cells by high-throughput sequencing. In addition, GO (Gene Ontology) term enrichment analysis results revealed an enrichment for binding and catalytic activity and for biological regulation of metabolic processes in both the Huh7-S and HepG2-S cell lines compared to parental cell lines. Moreover, KEGG (Kyoto Encyclopedia of Genes and Genomes) Pathway analysis of the differentially expressed genes were significantly related to pathways in cancer. Among them, hsa_circ_0006294 and hsa_circ_0035944 expression were consistently down-regulated in resistant HCC cells. Taken together, our data demonstrate, using a global transcriptomic network, that the circRNA expression profile is significantly altered in sorafenib-resistant HCC cells and that the differentially expressed circRNAs may play important functions in HCC sorafenib resistance and HCC progression.

Prognostic value of peripheral blood natural killer cells in colorectal cancer.

BACKGROUND: The association between natural killer (NK) cells and survival in colorectal cancer (CRC) patients remains controversial. This study aimed to clarify the prognostic value of peripheral blood NK cells in CRC patients. METHODS: A total of 447 CRC patients who underwent radical surgery and chemotherapy were retrospectively analyzed. Cox regression analyses were used to identify independent prognostic indicators. Correlation between NK cell percentage and other clinicopathological features (gender, age, histological grade, tumor stage, immune cells, and inflammatory indicators) was analyzed. The prognostic values of the combinations of NK cell percentage and other clinicopathological features were also determined. RESULTS: Multivariate Cox regression analysis revealed that NK cell percentage in the peripheral blood was an independent prognostic indicator in CRC patients. A higher percentage of NK cells indicated a longer survival time than a lower percentage. NK cell percentage was positively correlated to the T and B lymphocyte counts and negatively correlated to the patients' age and albumin levels. With an area of 0.741 under a receiver operating characteristic curve, NK cells have a moderate predictive value for 3rd-year survival in CRC. This area increased to 0.851 by combining NK cell percentage with the B lymphocyte count. Elderly patients and those at an advanced clinical stage presented a lower percentage of NK cells than younger patients and those at an early clinical stage. CONCLUSIONS: This study demonstrated that NK cells in the blood were an independent predictor of survival in CRC patients, and the combined count of NK cells and B lymphocytes could increase the prognostic value.

Hypermethylation of N-Acetyltransferase 1 Is a Prognostic Biomarker in Colon Adenocarcinoma.

Background: The N-acetyltransferase 1 (NAT1) gene is downregulated in several cancers and associated with patient survival. In this study, we sought to examine the prognostic value and clinical significance of NAT1 methylation in colon adenocarcinoma (COAD). Methods: Data relating to NAT1 mRNA expression and methylation and clinicopathological features of COAD were extracted from the database of The Cancer Genome Atlas. We compared the mRNA expression and methylation of NAT1 between COAD and normal tissues and performed correlation analysis to assess the association between NAT1 mRNA expression and methylation. Furthermore, we assessed patient survival based on CpG sites in the promoter region of NAT1 and analyzed the association between the NAT1 mRNA expression and CpG site methylation and clinicopathological features. An independent Gene Expression Omnibus (GEO) dataset was used to validate the results. Results: We found that the expression of NAT1 mRNA was reduced in COAD compared with normal tissues and that mean methylation of the eight CpG sites in the promoter region of NAT1 was higher in COAD tissues than in normal tissues. Furthermore, five CpG sites were demonstrated to be significantly negatively correlated with NAT1 mRNA expression in COAD. Survival analysis indicated that NAT1 mRNA expression and the cg15797286 and cg18509990 sites were associated with the overall survival of COAD patients. Combined survival analysis revealed that combinations of NAT1 mRNA expression with five CpG sites were significantly associated with the overall survival of COAD patients. Both NAT1 mRNA and cg15797286 were associated with the T, N, and clinical stages of COAD. The GEO data indicated that cg15797286 was hypermethylated in recurrent colorectal adenomas. Conclusions: Methylation of NAT1 is associated with the development of COAD, and may serve as prognostic and treatment biomarkers for COAD.

Identification and Expression Patterns of Anoplophora chinensis (Forster) Chemosensory Receptor Genes from the Antennal Transcriptome.

The citrus long-horned beetle (CLB), Anoplophora chinensis (Forster) is a destructive native pest in China. Chemosensory receptors including odorant receptors (ORs), gustatory receptors (GRs), and ionotropic receptors (IRs) function to interface the insect with its chemical environment. In the current study, we assembled the antennal transcriptome of A. chinensis by next-generation sequencing. We assembled 44,938 unigenes from 64,787,784 clean reads and annotated their putative gene functions based on gene ontology (GO) and Clusters of Orthologous Groups of proteins (COG). Overall, 74 putative receptor genes from chemosensory receptor gene families, including 53 ORs, 17 GRs, and 4 IRs were identified. Expression patterns of these receptors on the antennae, maxillary and labial palps, and remaining body segments of both male and female A. chinensis were performed using quantitative real time-PCR (RT-qPCR). The results revealed that 23 ORs, 6 GRs, and 1 IR showed male-biased expression profiles, suggesting that they may play a significant role in sensing female-produced sex pheromones; whereas 8 ORs, 5 GRs, and 1 IR showed female-biased expression profiles, indicating that these receptors may be involved in some female-specific behaviors such as oviposition site seeking. These results lay a solid foundation for deeply understanding CLB olfactory processing mechanisms. Moreover, by comparing our results with those from chemosensory receptor studies in other cerambycid species, several highly probable pheromone receptor candidates were highlighted, which may facilitate the identification of additional pheromone and/or host attractants in CLB.

Endoscopic therapy for patients with pancreaticobiliary maljunction: a follow-up study.

BACKGROUND: Data on the experience of endoscopic retrograde cholangiopancreatography (ERCP) in the management of pancreaticobiliary maljunction (PBM) is limited. METHODS: A retrospective review of patients with PBM who underwent therapeutic ERCP at our endoscopy center between January 2008 and January 2016 was performed. Demographic, clinical, radiological and endoscopic data was documented. Patients who underwent sphincterotomy were divided into dilated group and undilated group based on their common channel diameter. RESULTS: Sixty-three PBM patients underwent 74 ERCP procedures. The technical success rate was 97.3%. ERCP therapy significantly decreased the levels of elevated liver enzymes and bilirubin. After an average of 27 months follow-up, 7 patients (11.1%) were lost. The overall effective rate of ERCP therapy was 60.7% (34/56). Decline in severity and frequency of abdominal pain was significant. Procedure-related complications were observed in 5 (6.8%) cases. Between the dilated group and undilated group, no significant difference was observed in effective rate, adverse events and follow-up results. CONCLUSIONS: ERCP can serve as a transitional step to stabilize PBM patients before definitive surgery. PBM patients with undilated common channel could benefit from sphincterotomy as well as those with dilated common channel.

Associations between serum HBX quasispecies and their integration in hepatocellular carcinoma.

HBV quasispecies are closely related to the course and outcome of liver disease. However, whether the complexity and diversity of HBX quasispecies affects its integration in the liver cell and thereby enhances the resultant carcinogenesis is still not clear. 15 HCC patients were recruited; genomic DNA and HBV DNA were extracted from liver cancer tissue and serum respectively. The integrated HBX fragment in liver cancer tissue was amplified by Alu repeat sequence-polymerase chain reaction (Alu-PCR) and sequenced. The serum HBX gene was amplified by nested PCR and sequenced. Quasispecies complexity and diversity, phylogenetic characteristics, lymphocyte count and survival time between HBX-integrated and HBX-unintegrated patients were evaluated. Results showed that the integrated HBX fragment was detected in the tumor tissue of nine patients, and the integration rate was 60.00% (9/15). Compared with the HBX-unintegrated patients, the HBX-integrated patients had a higher quasispecies complexity (P=0.028 and 0.004, at the nucleotide and amino acid levels, respectively). The HBX-integrated patients had a tendency of higher quasispecies diversity, lower lymphocyte count and the survival time. A total of 12 mutation sites were revealed in the HBX-integrated fragment after alignment with the reference sequence. In these, the HBX-integrated groups had significantly higher mutation frequencies at C1497T, A1630G, G1721A, A1762T/G1764A and A1774G. This study revealed influence factors of HBX integration both in virus and the host. The increased complexity and diversity of HBX quasispecies might destroy the host immune balance, and lead to HBX integration ultimately.

Interference of TRPV1 function altered the susceptibility of PTZ-induced seizures.

Transient receptor potential vanilloid 1 (TRPV1) is widely distributed in the central nervous system (CNS) including hippocampus, and regulates the balance of excitation and inhibition in CNS, which imply its important role in epilepsy. We used both pharmacological manipulations and transgenic mice to disturb the function of TRPV1 and then studied the effects of these alterations on the susceptibility of pentylenetetrazol (PTZ)-induced seizures. Our results showed that systemic administration of TRPV1 agonist capsaicin (CAP, 40 mg/kg) directly induced tonic-clonic seizures (TCS) without PTZ induction. The severity of seizure was increased in lower doses of CAP groups (5 and 10 mg/kg), although the latency to TCS was delayed. On the other hand, systemic administration of TRPV1 antagonist capsazepine (CPZ, 0.05 and 0.5 mg/kg) and TRPV1 knockout mice exhibited delayed latency to TCS and reduced mortality. Furthermore, hippocampal administration of CPZ (10 and 33 nmol/µL/side) was firstly reported to increase the latency to TCS, decrease the maximal grade of seizure and mortality. It is worth noting that decreased susceptibility of PTZ-induced seizures was observed in hippocampal TRPV1 overexpression mice and hippocampal CAP administration (33 nmol/µL/side), which is opposite from results of systemic agonist CAP. Our findings suggest that the systemic administration of TRPV1 antagonist may be a novel therapeutic target for epilepsy, and alteration of hippocampal TRPV1 function exerts a critical role in seizure susceptibility.

[Shen warming Pi strengthening method intervened IBS-D rats: an efficacy assessment].

OBJECTIVE: IBS-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. METHODS: Totally 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. RESULTS: After 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. CONCLUSIONS: High 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.

[Effect of pungent dispersion bitter purgation method on the esophageal mucosal intercellular space of reflux esophagitis model rats].

OBJECTIVE: To observe the effect of pungent dispersion bitter purgation method (PDBPM) on the esophageal mucosal intercellular space of reflux esophagitis (RE) model rats. METHODS: Totally 100 Wistar rats were randomly divided into the control group, the model group, the Western medicine group (WM), the Chinese medicine group (CM), 25 rats in each group. Rats in the control group only received switch operation. Rats in the rest three groups received modified partial cardia muscle incision combined pylorus ligation of external parts to prepare the RE rat model. Starting from the 3rd day after operation, WM mixture (Motilium 3. 2 mg/kg + Omeprazole Capsule 4.3 mg/kg + Hydrotalcite Tablet 161.4 mg/kg) was administered by gastrogavage to rats in the WM group. Rats in the CM group was administered by gastrogavage with Modified Banxia Xiexin Decoction (5.7 g/kg), 2.5 mL each time, twice daily for 14 consecutive days. Equal volume of normal saline was administered by gastrogavage to rats in the control group and the model group. On day 7 and 14, the lower esophagus pH value, general specimen of mucosa and histopathologic changes were observed. Intercellular spaces of esophageal epithelium were measured for a control study. RESULTS: Compared with the same group at day 7, the lower esophagus pH value increased at day 14 (P < 0.01); the naked eye integral of esophageal mucosa and intercellular spaces of esophageal epithelium also decreased at day 14 in the CM group and the WM group (P < 0.05). Compared with the control group at the same time point, the lower esophagus pH value decreased in the model group (P < 0.01). The naked eye integral of esophageal mucosa, and intercellular spaces of esophageal epithelium increased in the model group with increased intercellular spaces (P < 0.01). Compared with the model group at the same time point, the lower esophagus pH value increased and the naked eye integral of esophageal mucosa decreased in the CM group and the WM group at day 7 and 14 (P < 0.01). Intercellular spaces of esophageal epithelium of RE model rats at day 14 was lower in the CM group and the WM group than in the model group (P < 0.01). Compared with the WM group, the lower esophagus pH value decreased at day 7 in the CM group (P < 0.05); the naked eye integral of esophageal mucosa and intercellular spaces of esophageal epithelium decreased at day 14 in the CM group (P < 0.05). CONCLUSIONS: PDBPM had favorable treatment effect on RE model rats. The therapeutic effect was more obvious along with the therapeutic course went by. Its mechanism might be achieved through good repair effect on damaged mucosa, increasing the pressure of esophageal sphincter, and inhibiting gastric acid.

[Association of CFTR gene polymorphism with congenital bilateral absence of vas deferens in ethnic Han Chinese patients].

OBJECTIVE: To assess the association between a 5T polymorphism in intron 8 of cystic fibrosis transmembrane conductance regulator (CFTR) gene and congenital bilateral absence of vas deferens (CBAVD) in Han Chinese males. METHODS: Genomic DNA from 33 individuals with CBAVD and 99 azoospermic males with CBAVD were recruited. The 5T polymorphism was detected with PCR, TA cloned and sequenced. RESULTS: CFTR gene mutations were identified in 17 (51.5%) of patients with CBAVD. In 3 patients (17.6%), the mutations were identified on both alleles. Nine CFTR gene mutations (9.1%) were detected in 99 azoospermic patients, for whom none had mutations on both alleles. CONCLUSION: This study has confirmed molecular heterogeneity of CFTR mutations in CBAVD. For CBAVD patients without 5T mutations, other changes may be found in the same gene.

Clinical assessment and genomic landscape of a consanguineous family with three Kallmann syndrome descendants.

Although some genes that cause Kallmann syndrome (KS) have been identified by traditional linkage analysis and candidate gene techniques, the syndrome's molecular etiology in the majority of patients remains poorly understood. In this paper, we present the clinical assessments of a consanguineous Han Chinese family with three KS descendants. To understand the molecular etiology of KS from a genome-wide perspective, we investigated the genome-wide profile of structural variation in this family using the Affymetrix Genome-Wide Human SNP Array 6.0 platform. The results revealed that the three affected individuals had common copy number variants (microdeletions) on chromosomes 1p21.1, 2q32.2, 8q21.13, 14q21.2 and Xp22.31. Moreover, the copy number variants on Xp22.31 were located in the intron of KAL1, which causes X-linked KS. Two PCR assays were performed on these regions to validate the results obtained using the chips. In addition, genomic microdeletions in this region were verified in one of 29 Han Chinese sporadic KS cases and one of four other family cases, but not in 26 Han Chinese sporadic normosmic idiopathic hypogonadotropic hypogonadism cases and 100 unrelated Han Chinese normal controls. Our results provide a novel insight into the relative contributions of certain copy number variants to KS's molecular etiology and generate a list of interesting candidate regions for further studies.

Therapeutic DNA vaccination as a repair strategy following spinal cord injury.

Myelin-derived proteins, such as tenascin-R (TN-R), myelin associate glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp), and Nogo-A, inhibit the central nervous system regeneration. In this study, the DNA vaccine encoding for oligodendrocyte and myelin-related antigens was employed to attenuate the axonal growth inhibitory properties of myelin in the setting of spinal cord injury. Using a rat spinal cord dorsal hemisection model, the vaccine directed against the inhibitory epitopes of Nogo-A, MAG, OMgp, and TN-R was administered intramuscularly once a week following spinal cord injury, supplemented with local application of specific anti-sera against the four antigens. Anterograde labeling of dorsal column fibers showed active axonal regeneration through the lesion site at the eighth week following the treatment in experimental group but not in control groups. Light microscopic and ultrastructural analysis revealed that vaccination with these myelin-related antigens did not lead to demyelinating disease. OMgp and TN-R levels were down-regulated at the lesion site together with a parallel increase in growth-associated protein 43 levels in the treatment groups. This study reveals the effective approach of a DNA vaccine strategy by attaining the special antibody to direct neutralization of the myelin inhibitors during spinal cord injury.