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The base-mediated allylic defluorinative functionalization of β-CF 2 H-1,3-enynes with nucleophiles is described, affording terminal monofluoroalkenes bearing an alkynyl group in synthetically useful yields and Z / E selectivities. Importantly, the resultant Z / E mixture could be separated by flash chromatography in all cases; thus, stereoisomerically pure monofluoroenynes were obtained. Postsynthetic modifications of the synthesized monofluoroenynes were also accomplished to access diverse molecular structures. Computational studies disclosed the origin of the diastereoselectivity.

Objective: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions., Methods: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia., Results: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed., Conclusions: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1 -/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

A base-controlled divergent cyclization between 2-mercaptobenzimidazoles and β-CF 3 -1,3-enynes providing either trifluoromethylated or fluorinated benzo[4,5]imidazo[2,1- b ][1,3]thiazines has been developed. The β-CF 3 -1,3-enyne, as a three-carbon synthon, underwent a 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU)-catalyzed tandem hydroamination/intramolecular hydrothiolation to give CF 3 -substituted 3,4-dihydro-2 H -benzo[4,5]imidazo[2,1- b ][1,3]thiazine, whereas reaction with KOH afforded fluorinated 4 H -benzo[4,5]imidazo[2,1- b ][1,3]thiazine exclusively. In addition, the synthetic utility of this methodology was showcased through a variety of downstream derivatizations.

A series of novel ferulic acid derivatives were designed and synthesized, and the twenty-one compounds were evaluated for their antiviral activities against Respiratory syncytial virus (RSV), herpes simplex virus type 1 (HSV-1), and enterovirus type 71 (EV71). These derivatives with the core structure of diphenyl acrylic acids had cis-trans isomers, which were confirmed by 1 H NMR, HPLC, and UV-vis spectra for the first time. The A5 had a selective effect against RSV but no work on herpes simplex virus type 1 and enterovirus type 71, which showed a therapeutic index (TI) of 32 and was significantly better than ferulic acid. The A5 had no scavenging effect on free radicals, but the A2 as the degradation of A5 showed an obvious scavenging effect on DPPH· and ABTS + ·. In addition, the A5 had no toxicity to endothelial cells and even showed a proliferative effect. Therefore, the A5 is worth further optimizing its structure as a lead compound and investigating the mechanism of inhibiting Respiratory syncytial virus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mao, Wang, Chen, Yan, Xun, Li, Wang and Zhao.)

A new class of Michael acceptor, tetrazolyl-trifluoromethyl alkenes, has been discovered. They readily undergo Michael-type addition instead of addition-elimination reaction with aliphatic amines and azoles to furnish β-trifluoromethyl alkylamines and CF 3 -substituted 1,2-bisazole derivatives, respectively. Additionally, some of the products are capable of engaging in microwave-assisted intramolecular denitrogenative annulation, leading to the formation of CF 3 -substituted 1,4,5,6-tetrahydro-1,2,4-triazines that are otherwise difficult to access by other methodologies.

Installing a fluoroalkyl group onto the nitrogen atom of azoles represents a potential strategy for lead optimization in medicinal chemistry. Herein, we describe a method for the N -trifluoropropylation of azoles. This process is accomplished using a combination of regioselective N -vinylation and sequential hydrogenation. The two-step sequence is applicable to a diverse set of azoles and tolerates a wide range of functionalities. In addition, we showcase its practicability and utility through the gram-scale synthesis and the late-stage modification of a complex molecule.

Although trifluoromethyl alkenes have great synthetic potential, their 1,2-difunctionalization has been a challenge. In this Letter, we disclose the first 1,2-dicarbofunctionalization of trifluoromethyl alkenes with pyridinium salts via a cascade process involving a base-promoted [3 + 2] cycloaddition followed by a visible-light-mediated Norrish-type-II fragmentation. This protocol allows for the formation of pyridines bearing a trifluoromethyl-substituted quaternary center in moderate to excellent yields under mild conditions.

Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and repair barrier function. Here, in order to reveal the interaction between UC and gut microbiota, we screened a new probiotic strain by 16S rRNA sequencing from Dextran Sulfate Sodium (DSS)-induced colitis mice, and explored the mechanism and clinical relevance. Lactobacillus johnsonii ( L. johnsonii ), as a potential anti-inflammatory bacterium was decreased colonization in colitis mice. Gavage L. johnsonii could alleviate colitis by specifically increasing the proportion of intestinal macrophages and the secretion of Il-10 with macrophages depleted model and in Il10 -/- mice. We identified this subset of immune cells activated by L. johnsonii as CD206 + macrophages IL-10 . Mechanistically, L. johnsonii supplementation enhanced the mobilization of CD206 + macrophages IL-10 through the activation of STAT3 in vivo and in vitro . In addition, we revealed that TLR1/2 was essential for the activation of STAT3 and the recognition of L. johnsonii by macrophages. Clinically, there was positive correlation between the abundance of L. johnsonii and the expression level of MRC1, IL10 and TLR1/2 in UC tissues. L. johnsonii could activate native macrophages into CD206 + macrophages and release IL-10 through TLR1/2-STAT3 pathway to relieve experimental colitis. L. johnsonii may serve as an immunomodulator and anti-inflammatory therapeutic target for UC.

An interesting β-isoquinidine catalyzed divergent reaction was developed to produce either spirocyclopentene oxindoles, spirocyclopentadiene oxindoles or bisoxindoles in a high enantioselective fashion. The utility of this protocol was demonstrated by the versatile transformations of the products. This work not only represents the first highly stereoselective intermolecular catalytic asymmetric allylic alkylation reaction between two isatin-derived MBH carbonate molecules but also constitutes a rare example of isatin-derived MBH carbonate-based enantioselective and α-regioselective [3+2] cycloaddition reactions., (© 2021 Wiley-VCH GmbH.)

The development of catalytic enantioselective isocyanide-based reactions is currently of great interest because the resulting products are valuable in organic synthesis, pharmacological chemistry, and materials science. This review assembles and comprehensively summarizes the recent achievements in this rapidly growing area according to the reaction types. Special attention is paid to the advantages, limitations, possible mechanisms, and synthetic applications of each reaction. In addition, a personal outlook on the opportunities for further exploration is given at the end., (© 2020 Wiley-VCH GmbH.)

A one-pot synthesis of 1,3-diyne-tethered trifluoromethylcyclopropanes starting from 2-CF 3 -3,5-diyne-1-enes and sulfur ylides via a sulfur ylide mediated cyclopropanation and a DBU-mediated epimerization sequence is described in this work. This process is highly diastereoselective with broad substrate scope. Moreover, a series of synthetic transformations based on the diyne moieties were conducted smoothly, affording cyclopropanes featuring trifluoromethyl-substituted all-carbon quaternary centers.

An expedient and economic approach for constructing O,O,N-spiro compounds consisting of both a 1,3-oxazine and a furan ring through a catalyst-free formal [4+1]/[4+2] cycloaddition cascade sequence of isocyanides with two molecules of acylketene formed in situ through thermal-induced Wolff rearrangement of 2-diazo-1,3-diketones was developed. The reaction displayed good functional group tolerance and was compatible with different isocyanides and 2-diazo-1,3-diketones. Furthermore, preliminary asymmetric attempts of this reaction are made by utilizing optically pure isocyanides as inputs, and moderate diastereomeric induction was observed., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2019 Science China Press. Published by Elsevier B.V. All rights reserved.)

Tandem reactions of Pd-catalyzed cross-coupling of 3-(2-isocyanoethyl)indoles with diazoacetates and subsequent spirocyclization/Mannich-type reaction have been developed to assemble polycyclic spiroindoline skeletons. Formation of spiroindolenines has been proven as the crucial step for the following Mannich-type cyclization reaction. Accordingly, a novel approach on chiral phosphoric acid catalyzed Mannich-type cyclization toward the formation of diastereomerically and enantiomerically enriched pentacyclic spiroindolines has been established. Moreover, the products of the reaction are versatile building blocks in synthetic chemistry, as demonstrated by the synthesis of the key framework of aspidosperma and kopsia alkaloids., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background and Aims: Hydrotalcite plays an important role in the therapy of gastric ulcer induced by nonsteroidal anti-inflammatory drugs (NSAIDs), but little is known about the mechanism. We designed two experiments to study the preventive and curative effects of hydrotalcite on NSAIDs-related gastric injury in rats and to investigate the relationship between the protective and curative mechanism of hydrotalcite and the secretion of epidermal growth factor (EGF)/prostaglandin E2 (PGE2)., Methods: Two experiments were separately designed to evaluate the preventive and curative effects of hydrotalcite. A total of 25 male rats and 25 female rats were randomly divided into five groups (vehicle group, model group, omeprazole group, hydrotalcite group, and ranitidine group) in each experiment. Rats were treated with indomethacin by gavage to build the model of acute gastric mucosal injury. The concentrations of EGF and PGE2 in blood specimens and mucosal injury indexes by gross inspection were measured and an immunohistochemical technique was also employed to test the levels of EGF, cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2) in gastric mucosa., Results: Comparing with model group in both preventive and curative experiments, hydrotalcite decreased the gastric injury in the mucosa of stomach significantly (7±4.5 vs. 16±11.25, 1.5±2 vs. 2.5±6; P <0.01 , P <0.05). The levels of EGF and PGE2 in blood serum were markedly higher in hydrotalcite group than that in model group and ranitidine group in preventive experiment (574.39±34.28 vs. 486.22±41.73, 488.07±24.44; P <0.01, P <0.01). The expression levels of COX-2 in gastric mucosa were also higher in hydrotalcite group than that in model group in both preventive and therapeutic experiments (12±4 vs. 9±6, 14±7 vs. 9±4; P <0.01 , P <0.05)., Conclusions: Hydrotalcite promotes gastric protection and healing via several mechanisms, including increased levels of PGE2 in blood serum, activation of EGF, and antagonising the inhibition of cyclooxygenase (COX) caused by NSAIDs.

Background: Long non-coding RNAs (LncRNAs) exert their functions mainly by binding to their corresponding proteins. Runt-related transcription factor 3 (Runx3) is an important transcription factor that functions as a tumor suppressor in gastric cancer. Whether there is an interplay between LncRNAs and Runx3 remains unclear., Methods: RPISeq was applied to screen the LncRNAs that potentially bind to Runx3. The interaction between LncRNA HOX antisense intergenic RNA (HOTAIR) and Runx3 was validated by RNA Immunoprecipitation and RNA pull-down assays. The role of Mex3b in the ubiquitination of Runx3 induced by HOTAIR was assessed by immunoprecipitation. Pearson's correlation between HOTAIR mRNA expression and Runx3 protein expression was analyzed. Cell migration and invasion were explored by transwell assays., Results: We found that HOTAIR was bound to Runx3 protein and identified the fragment of HOTAIR spanning 1951-2100 bp as the specific binding site. In addition, mex-3 RNA binding family member B (Mex3b) was an E3 ligase involved in HOTAIR-induced ubiquitous degradation of Runx3. Silencing the expression of HOTAIR or Mex3b attenuated the degradation of Runx3. In human gastric cancer tissues, HOTAIR was negatively associated with the expression level of Runx3 protein (Pearson coefficient - 0.501, p = 0.025). Inhibition of HOTAIR significantly suppressed gastric cancer cell migration and invasion through upregulating claudin1, which could be reversed by co-deficiency of Runx3., Conclusions: These results uncovered the novel interaction between HOTAIR and Runx3, and provided potential therapeutic targets on the metastasis of gastric cancer.

Multispectral imaging system is of wide application in relevant fields for its capability in acquiring spectral information of scenes. Its limitation is that, due to the large number of spectral channels, the imaging process can be quite time-consuming when capturing high-resolution (HR) multispectral images. To resolve this limitation, this paper proposes a fast multispectral imaging framework based on the image sensor pixel-binning and spectral unmixing techniques. The framework comprises a fast imaging stage and a computational reconstruction stage. In the imaging stage, only a few spectral images are acquired in HR, while most spectral images are acquired in low resolution (LR). The LR images are captured by applying pixel binning on the image sensor, such that the exposure time can be greatly reduced. In the reconstruction stage, an optimal number of basis spectra are computed and the signal-dependent noise statistics are estimated. Then the unknown HR images are efficiently reconstructed by solving a closed-form cost function that models the spatial and spectral degradations. The effectiveness of the proposed framework is evaluated using real-scene multispectral images. Experimental results validate that, in general, the method outperforms the state of the arts in terms of reconstruction accuracy, with additional 20× or more improvement in computational efficiency.

We present a rare case of invasive liver abscess syndrome due to Klebsiella pneumoniae (K. pneumoniae) with metastatic meningitis and septic shock. A previously healthy, 55-year-old female patient developed fever, liver abscess, septic shock, purulent meningitis and metastatic hydrocephalus. Upon admission, the clinical manifestations, laboratory and imaging examinations were compatible with a diagnosis of K. pneumoniae primary liver abscess. Her distal metastasis infection involved meningitis and hydrocephalus, which could flare abruptly and be life threatening. Even with early adequate drainage and antibiotic therapy, the patient's condition deteriorated and she ultimately died. To the best of our knowledge, this is the first case of K. pneumoniae invasive liver abscess syndrome with septic meningitis reported in mainland China. Our findings reflect the need for a better understanding of the epidemiology, risk factors, complications, comorbid medical conditions and treatment of this disease.

Objective: To investigate the accuracy of the cytological Ki-67 index in distinguishing intermediate and high-grade (G2 + G3) from low-grade (G1) pancreatic neuroendocrine tumors (PNETs)., Methods: Two investigators independently searched databases to identify eligible studies using the following term: ('Ki-67') AND ('pancreatic endocrine tumor' OR 'pancreatic neuroendocrine tumor' OR 'pancreatic endocrine tumour' OR 'pancreatic neuroendocrine tumour' OR 'pancreatic endocrine tumors' OR 'pancreatic neuroendocrine tumors' OR 'pancreatic endocrine tumours' OR 'pancreatic neuroendocrine tumours'), and meta-analysis was performed to calculate the pooled sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), and diagnostic odds ratio (DOR)., Results: A total of 263 lesions from 13 studies were included in the study. The pooled sensitivity and specificity of Ki-67 (cut-off value: 2%) in the differential diagnosis of G2 + G3 from G1 PNETs were 64% and 87%, respectively. The pooled PLR, NLR and DOR were 3.96, 0.42 and 11.21, respectively. The area under the summary receiver operating characteristic curve (AUROC) was 0.8397. While the cut-off value of Ki-67 index was set as 5%, the sensitivity and specificity were increased up to 69% and 93%, respectively, and the AUROC was increased to 0.955., Conclusion: The cytological Ki-67 index is very useful in distinguishing intermediate and high-grade from low-grade PNETs, and a cut-off value of 5% had a better predictive value compared with that of 2%., (© 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Out-of-focus blur occurs frequently in multispectral imaging systems when the camera is well focused at a specific (reference) imaging channel. As the effective focal lengths of the lens are wavelength dependent, the blurriness levels of the images at individual channels are different. This paper proposes a multispectral image deblurring framework to restore out-of-focus spectral images based on the characteristic of interchannel correlation (ICC). The ICC is investigated based on the fact that a high-dimensional color spectrum can be linearly approximated using rather a few number of intrinsic spectra. In the method, the spectral images are classified into an out-of-focus set and a well-focused set via blurriness computation. For each out-of-focus image, a guiding image is derived from the well-focused spectral images and is used as the image prior in the deblurring framework. The out-of-focus blur is modeled as a Gaussian point spread function, which is further employed as the blur kernel prior. The regularization parameters in the image deblurring framework are determined using generalized cross validation, and thus the proposed method does not need any parameter tuning. The experimental results validate that the method performs well on multispectral image deblurring and outperforms the state of the arts.

Background: The effectiveness of endoscopic submucosal dissection (ESD) has been increasingly reported. However, studies addressing the safety and application value of ESD in elderly patients with early gastric cancer (EGC) were still lacking. This meta-analysis was intended to evaluate the feasibility and safety of ESD in elderly patients with EGC., Methods: A systematic search was conducted in PubMed, EBSCO, Cochrane Library, EMBASE, and Web of Science. Studies were screened out if data of elderly and non-elderly gastric cancer patients were reported separately. The qualities of included studies were assessed using Newcastle-Ottawa Quality Assessment Scale. The pooled odd ratios (ORs) with 95 % confidence intervals (CIs) were calculated. Statistical analysis was conducted using the Review Manager 5.2 (Cochrane Collaboration, Oxford, UK)., Results: Nine studies (eight in Japan, one in China), including a total of 30,100 lesions, met the inclusion criteria. The "en bloc" and histological complete resection rates of the elderly and non-elderly groups were similar [OR, 0.98, 95 % CI, 0.56 to 1.71; P = 0.93 and OR, 0.79, 95 % CI, 0.58 to 1.07; P = 0.13, respectively]. As for procedure-related complications, similar perforation rates [OR, 1.19, 95 % CI, 0.94 to 1.51; P = 0.15], and bleeding rates [OR, 1.13, 95 % CI, 0.83 to 1.56); P = 0.43] between the elderly and non-elderly groups were observed. Whereas, the elderly patients had a higher procedure-related pneumonia rate compared with non-elderly ones [OR, 2.18, 95 % CI, 1.55 to 3.08; P < 0.01]., Conclusions: The ESD procedure appears to be a safe technique in elderly patients with EGC while appropriate approach should be taken to avoid procedure-related pneumonia.

A highly regioselective protocol for the direct synthesis of γ,δ-unsaturated ketones from β-ketoacids and allylic alcohols was proposed and accomplished relying on the combination of [Ir(cod)Cl]2 and 10-camphorsulfonic acid via decarboxylative allylation.

Cytomegalovirus, regarded as a trigger of several autoimmune diseases, is an opportunistic pathogen. Patients with ulcerative colitis (UC) undergoing steroid treatment are susceptible to this infection. In the presence of cytomegalovirus, inflammation becomes more complex. Patients with active UC who are infected with cytomegalovirus are usually non-responders to steroid, while antiviral drugs could induce remission. Cytomegalovirus should be suggested as a probable cause of steroid-refractory UC based on the clinical data in the literatures., (© 2013 The Authors. Journal of Digestive Diseases © 2013 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

The potential anti-senescence gene Klotho (KL) has been recently found to participate in the progression of several different human cancers including breast, lung, and cervical cancer. In this current study, we identified KL as a candidate tumor suppressor gene silenced through promoter hypermethylation in colorectal cancer (CRC). KL gene expression is found to be absent or reduced in colon cancer cell lines (5/6, 83.3%), which can be reversed by treatment with demethylation agent 5-aza-2'-deoxycytidine (Aza), but not HDAC inhibitor trichostatin A. In addition, KL expression is markedly downregulated in colorectal carcinoma tissues when compared to the adjacent nontumor tissues (n=25, p<0.001). The methylation of the KL gene promoter was frequently detected in primary tumor tissues (34/40, 85%) when compared with adjacent nontumor colon tissues. Furthermore, ectopic expression of KL led to the cell proliferation inhibition of colon cancer cell lines via the induction of cell apoptosis and S-phase cell cycle arrest. Taken together, our results suggest that KL is inactivated through promoter hypermethylation and potentially functions as a tumor suppressor gene in CRC.

Objective: To determine DNA methylation status of ZIC1 and KLOTHO gene in colorectal carcinomas and its relationship with clinicopathological features of patients., Methods: The mRNA expression of ZIC1 and KLOTHO genes in colorectal carcinomas was detected by real-time quantitative RT-PCR, and the promoter methylation status was detected by methylation specific PCR (MSP). The relationship of ZIC1 and KLOTHO methylation status with clinicopathological features of colorectal carcinoma was analyzed., Result: The mRNA expression levels of ZIC1 and KLOTHO genes were significantly down-regulated in tumor tissues when compared to adjacent nontumor tissues (P<0.001). ZIC1 and KLOTHO methylation was detected in 80.0%(20/25) and 76.0%(19/25) of colorectal tumor tissues, respectively, and the both positive rate was 64.0%(16/25)., Conclusion: The down-regulated expression of ZIC1 and KLOTHO in colorectal carcinoma may relate to promoter methylation. The detection of methylation of ZIC1 and KLOTHO gene potentially provides biomarkers for diagnosis of colorectal carcinoma.

We investigated the underlying mechanisms of penehyclidine hydrochloride (PHC), a novel selective anticholinergic drug on isolated rat uterus. The method of radio-immunity assay was further employed to determine cyclic adenosine mono phosphate (cAMP) levels in isolated rat uterus for comparing with selective effect on muscarinic receptor subtypes. In the assay, PHC could decrease the content of cAMP in isolated rat uterus, but the difference was not statistically significant at dose of 10 mumol/L. In conclusion, our results suggested that PHC has no or poor effect on M(2) receptor subtypes in isolated rat uterus.

Objectives: The aim was to characterize the effect of penehyclidine hydrochloride, which mediates the relaxation of guinea-pig isolated gastrointestinal smooth muscle, on muscarinic receptor subtypes., Methods: Radioimmune assay was used to determine cAMP levels in isolated guinea-pig gastrointestinal smooth muscle to compare the selective effects of penehyclidine hydrochloride on muscarinic receptor subtypes., Key Findings: The results indicated that the relaxing effect of penehyclidine hydrochloride on isolated gastrointestinal smooth muscle contraction induced by acetylcholine was stronger than that of atropine (based on PA2 values). In the radioimmune assay, penehyclidine hydrochloride increased the cAMP content in isolated guinea-pig stomach smooth muscle and decreased the cAMP content in isolated guinea-pig intestinal smooth muscle, but the difference was not statistically significant at a dose of 10 mumol/l., Conclusions: The results suggest that penehyclidine hydrochloride has little or no effect on M2 receptor subtypes in guinea-pig gastrointestinal smooth muscle.

Objective: To detect whether muscovite exerts its protective role in the progression of atrophic gastritis (AG) and evaluate the possible mechanism., Methods: AG rats were established and then randomly divided into groups administrated with different doses of muscovite for 8 weeks. Histological changes in gastric antrum and the number of parietal cells, chief cells, and G/D cells were observed. Serum gastrin and prostaglandin E2 (PGE2) were evaluated by enzyme-linked immunosorbent assay (ELISA). The expression of proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR), C-erbB-2, p21, p53, p16 and bcl-2 in gastric tissue were detected by immunohistochemistry. The concentrations of TNF-alpha and IL-1beta secreted by THP-1 cells were detected when incubated with different doses of muscovite., Results: The grade of inflammation in muscovite groups was lower (p < 0.05), while the thickness and number of gastric glands were significantly elevated in muscovite groups (p < 0.01). The expression height of PCNA in the muscovite group was higher than in the AG group (p < 0.01). Immunohistochemistry results showed a positive expression rate of EGFR; p16 in muscovite-treated AG rats was increased (p < 0.05), while C-erbB-2 and p21 were decreased (p < 0.05). Serum gastrin and PGE2 were significantly elevated in the high-dose muscovite-treated rats (p < 0.05). In vitro studies showed that muscovite had a dose-dependent adsorption of TNF-alpha and IL-1beta., Conclusion: Muscovite could reverse gastric gland atrophy and intestinal metaplasia by promoting cell proliferation and revitalization in gastric mucosa in AG rats., (Copyright 2009 S. Karger AG, Basel.)

Aim: To investigate the relationship between H pylori infection, blood ammonia concentration and hepatic encephalopathy (HE), and the effect of H pylori eradication in cirrhotic patients., Methods: From July 2003 to January 2005, 457 cirrhotic patients in five regions of Zhejiang Province were enrolled. Patients were evaluated for demographics, number connection test, H pylori infection, liver impairment, blood ammonia concentration and HE. Patients with H pylori infection were given 1 wk therapy with omeprazole plus clarithromycin and tinidazole. (14)C urea breath test was performed and mental symptoms and blood ammonia level were reassessed after bacterium eradication., Results: Overall H pylori infection rate was 60.6%, and HE occurred in 47.5% of cirrhotic patients. Subclinical HE (SHE) was detected in 55 of 117 cirrhotic patients. Blood ammonia concentration in H pylori negative (n = 180) and positive (n = 277) cirrhotic patients was 53.8 +/- 51.4 and 78.4 +/- 63.6 mumol/L, respectively (P < 0.01), which was significantly reduced to 53.5 +/- 37.7 mumol/L after bacterium eradication (n = 126) (P < 0.01). Blood ammonia was 97.5 +/- 81.0 mumol/L in H pylori-positive cirrhotic patients, and this did not significantly change in those with persistent infection after H pylori eradication (n = 11). HE was more frequently observed in patients with H pylori infection than in those without (58.5% vs 30.6%, P < 0.01). HE rate significantly dropped to 34.1% after H pylori eradiation (P < 0.01). H pylori prevalence significantly differed among cirrhotic patients with HE (74.4%), SHE (69.1%), and those without HE (53.2%) (P < 0.05). Blood ammonia level was significantly different among cirrhotic patients with HE (94.5 +/- 75.6 mumol/L), SHE (59.9 +/- 49.2 mumol/L), and without HE (47.3 +/- 33.5 mumol/L) (P < 0.05). Logistic regression analysis showed that blood ammonia concentration, Child-Pugh stage, upper gastrointestinal bleeding, electrolyte disturbance, and urea nitrogen were risk factors for HE., Conclusion: H pylori infection is an important factor for inducing high blood ammonia concentration and HE in cirrhotic patients. H pylori eradication may be helpful for treatment and prevention of HE.

Aim: To investigate the effect of geranylgeranylacetone (GGA) on the progression of atrophic gastritis in rats and its potential mechanism., Methods: Atrophic gastritis was induced in Sprague-Dawley rats with 0.1% ammonia solution, 60% ethanol, and 20 mmol/L deoxycholic acid for 24 weeks. Accompanied by the induction of atrophic gastritis, 200 mg/kg GGA was administered by oral gavage for 8 weeks (weeks 17-24). The histological changes in gastric mucosa were quantitated by the index of inflammation, the gastric mucosal thickness, and the amount of glands of 1 mm horizontal length in antrum. Endogenous heat shock protein (HSP)70 levels and distribution were determined by immunoblotting and immunohistochemistry in gastric mucosa., Results: GGA alleviated the pathological progression of atrophic gastritis with inflammation relief (inflammation index: 1.40 in the GGA group and 1.65 in the atrophic gastritis group) and glandular restoration (mucosal thickness and quantity of glands: 194.3 microm and 38.7 mm in the GGA group; 123.3 microm and 32.7 mm in the atrophic gastritis group; P<0.05). GGA significantly induced HSP70 synthesis (P<0.05). Moreover, quercetin, an inhibitor of HSP70 expression, aggravated the infiltration of inflammatory cells and glandular loss in the antrum., Conclusion: GGA prevented the progression of atrophic gastritis in rats via the induction of HSP70 expression.

Objective: To explore the mucosal protective effect on the quality of gastric ulcer healing., Methods: Gastric ulcers were induced in male rats by serosal application of acetic acid. Rats were gavaged for 14 days with saline, omeprazole (OME), teprenone (TEP) and TEP plus OME starting 3 days after ulcer induction. Then the tissues and blood samples were obtained and measured., Result: The lower ulcer index (UI) and increased ulcer inhibition rate were observed in OME and OME+TEP groups. In TEP and OME+TEP groups, restored mucosa thickness increased, cystically dilated glands decreased, microvessels in connective tissue increased, the secretion of mucus, hexosamine, PGE(2), bFGF were enhanced, the expression of EGFR was increased., Conclusion: TEP can improve the quality of gastric ulcer healing, when combined with OME,the effect is more marked.

Objective: To evaluate the efficacy and safety of live combined Bifidobacterium, Lactobacillus and Enterococcus capsules in treatment of irritable bowel syndrome., Methods: Eighty-five patients [male 32, female 53; age (45.31+/-11.72) years] were given live combined Bifidobacterium, Lactobacillus and Enterococcus capsules 1260 mg/d t.i.d.x4 weeks. Syndrome scales were used to evaluate the efficacy in gastrointestinal syndrome. Fecal flora was also measured before and after the treatment. Six bacteria were cultured and the colony forming units were counted in stool. SPSS was used for data analysis., Results: Seventy-four patients finished the follow-up. No side-effect was found. For treatment of irritable bowel syndrome, the effective rate of live combined Bifidobacterium, Lactobacillus and Enterococcus capsules was 56.8% in the second week, 74.3% in the fourth week and 73.0% in the sixth week. Single symptom was improved, especially in abdominal pain and stool character. The probiotica containing live combined Bifidobacterium, Lactobacillus and Enterococcus could increase bifidobacterium count (P<0.01) and lactobacillus count (P<0.05); decrease bacteroides count (P<0.05) and enterococci count (P<0.01); No obvious changes were observed in clostridium difficile colonitis and enterobacteriaceae (P>0.05)., Conclusion: The result of the study indicated that the administration of live combined Bifidobacterium, Lactobacillus and Enterococcus improved the symptom of irritable bowel syndrome and that there was a gradual increase of this effect. Thereafter conditions remained stable for 2 weeks. That improvement may be associated with alterations in gastrointestinal flora.

Objective: To study the pathologic change and molecular regulation in cell proliferation and apoptosis of gastric mucosa in rats with chronic atrophic gastritis (CAG), and evaluate the possible mechanisms., Methods: Rats were administered with 60% alcohol or 2% salicylate sodium, 20 mmol/L deoxycholate sodium and 0.1% ammonia water to establish chronic atrophic gastritis (CAG) models. The gastric specimens were prepared for microscopic view with hematoxylin and eosin (H-E) and alcian blue (A-B) stain. The number of infiltrated inflammatory cells, the thickness of the mucosa gland layer (microm) and the number of gastric glands were calculated. The damage of barrier in mucosa with erosion or ulceration, and the thickness of mucin were examined by scanned electron microscope (SEM). The levels of PGE(2), EGF (epiderminal growth factor) and gastrin in the serum were measured with radioimmunoassay or ELISA method. The immunohistochemistry method was used to observe the number of G cells, the expression of protein of EGFR (EGF receptor), C-erbB-2, p53, p16 and bcl-2 in gastric tissue., Results: Under SEM observation, the gastric mucosa was diffused erosion or ulceration and the thickness of mucin was decreased. Compared with normal rats, the grade of inflammatory cell infiltration in CAG rats was elevated, whereas the thickness and number of gastric gland were significantly lower (P<0.05). Compared with normal level of (0.61+/-0.28) microg/L, EGF in CAG (2.24+/-0.83) microg/L was significantly higher (P<0.05). The levels of PGE(2) and gastrin in serum were significantly lower in CAG rats than that in normal rats (P<0.05). Immunohistochemistry detection showed that the number of G cell in antrum was lower in CAG group (P<0.05). Immuno-stain showed EGFR protein expression in the basal and bilateral membrane, and the cytoplasma in atrophic gastric gland, while negative expression was observed in normal gastric epithelial cells. Positive staining of p53 and p16 protein was localized in the nucleus of epithelial cells. The former was higher positively expressed in atrophic gland, while the later was higher positively stained in normal gastric tissue. bcl-2 protein was positively stained in the cytoplasma in atrophic gastric gland, while very weakly stained in normal gastric tissue., Conclusion: The pathological findings in gastric gland accorded with the Houston diagnostic criteria of antrum-predominant CAG. CAG in rats was related with the damage of barrier in gastric mucosa and the misbalance of cell proliferation and apoptosis. There was high protein expression of oncogene, while inhibitor of suppressor gene in CAG rats indicated high trend of carcinogenesis.

Objective: To examine the efficacy of Muscovite on acetic acid-induced ulcerative colitis in rats, and to research the mechanisms of intestinal mucosal protection., Method: Ulcerative colitis was induced in rats by intracolonic injection of 2 mL of 7% acetic acid. Rats were treated with three different doses of the Muscovite and SASP at random by intracolonic injecion, the normal saline was considered as control group. The rats were sacrificed and the colons were excised and opened longitudinally. Under a dissecting microscope, gross findings were observed and scored. MPO activity was assayed by spectrophotometry in colonic mucosa., Result: Gross finding showed that multiple ulcer with diameter more than 1 cm, surrounded with erosion, erythematous and edema in the proximal colon in ulcerative coltis. The colon from Muscovite treatment group were histopatholgically normal, with slight erosion, erythematous and edema. The colon in SASP group had small ulceration and severe erosion and edema. The score of gloss change were significant lower in Muscovite groups than that in normal saline group (P < 0.01). There were necrosis and exfoliation of mucosa, multiple cystic dilation of mucosa gland, and large number of and inflammation attenuated in Muscovite groups. There nerutrophils and vessel infiltration in ulcerative colitis. The ulceration disappeared were erosion in mucosa and inflammatory cell infiltrating into submucosa in SASP group. Compared with normal saline group, the pathological scale were significant decreased in Muscovite and SASP groups (P < 0.05). The MPO activity was significant increased in colitis tissue compared with normal group (P < 0.001). After administrating with Muscovite or SASP, the level of MPO were significant decreased (P < 0.01)., Conclusion: Muscovite has the effect of mucosal protection by attenuating the inflammation of colonic mucosa and decreasing the activity of MPO.

Objective: To explore the mechanisms of muscovite gastric mucosal protective effect., Method: Rat model of chronic gastritis were used. After gastric mucosal injury was induced, the rats were divided into 6 groups and were treated with different drugs. 2 weeks later, the tissue and blood samples were obtained and measured., Result: The general conditions, the observations under macroscopy, microscope and electron microscope of the middle and high dose of muscovite groups resembled those of the normal group. Their PH levels were higher than those of the model group, and the rates of intestinal metaplasia were lower, but the PGE2 level of the middle dose of muscovite group was the highest., Conclusion: Muscovite can be adsorbed on the surface of the gastric mucosa. It has gastric mucosal protective effect by improving excretion of mucus and synthesis of PGE2 in gastric mucosa, restraining gastric acid, reversing of intestinal metaplasia and decreasing inflammation cells.

Aim: It has been noticed that gastroenteritis or dysentery plays a role in pathogenesis of irritable bowel syndrome (IBS), and antibiotics can increase functional abdominal symptoms, both of which may be partly due to intestinal flora disorders. This study was to determine the change of gut flora of IBS, a cluster of abdominal symptoms. Because of the chronic course and frequent occurrence of the disease, IBS patients suffered much from it. So the quality of life (Qol) of IBS patients was also evaluated in this study., Methods: Twenty-five Rome II criteria-positive IBS patients were recruited, and 25 age and gender-matched healthy volunteers were accepted as control. The fecal flora, including Lactobacillus, Bifidobacterium, Bacteroides, C. perfringens Enterobacteriacea and Enterococus, were analyzed quantitatively and qualitatively. We also calculated the ratio of Bifidobacterium to Enterobacteriaceae (B/E ratio) in both IBS patients and controls. In both groups, the data were further analyzed based on age difference, and comparisons were made between the younger and elder subgroups. We also evaluated the quality of life (QoL) of IBS patients and the control group using the Chinese version of SF-36 health questionnaire., Results: In IBS patients, the number of fecal Bifidobacterium was significantly decreased and that of Enterobacteriaceae was significantly increased compared with that in healthy controls (both P<0.05). The mean microbial colonization resistance (CR) of the bowel in IBS patients was smaller than 1, making a significant difference compared with that in control which was more than 1 (P<0.01). There was no significant difference in gut flora between two subgroups. While in control, the elder subgroup presented more Enterobacteriacea than the younger one (P<0.05). Compared with the control group, IBS patients had significantly lower scores on all SF-36 scales, with the exception of physical functioning. However, there was no significant correlation between quality of life and enteric symptoms in IBS patients., Conclusion: There are intestinal flora disorders in IBS patients, which may be involved in triggering the IBS-like symptoms. IBS patients experience significant impairment in QoL, however, the impairment is not caused directly by enteric symptoms.

Aim: To investigate the pattern of symptoms, predominant bowel habits and quality of life (QOL) by the Chinese version of the SF-36 in irritable bowel syndrome (IBS) consulters in Zhejiang province., Methods: From January 2001 to January 2002, 662 Roma II criteria-positive IBS patients were enrolled by gastroenterologists in 10 hospitals from Digestive Disease Center of Zhejiang (DDCZ). Patients were classified into constipation predominant IBS (IBS-C), diarrhea predominant IBS (IBS-D) and alternating constipation and diarrhea IBS (IBS-A) according to the predominant bowel habits. All patients were evaluated for the demographic checklists, IBS bowel symptoms, extra-colonic symptoms, and QOL by Chinese version of the SF-36 questionnaire., Results: (1) Besides abdominal pain, the predominant colonic symptoms were in order of altered stool form, abnormalities of stool passage, abdominal distension and passage of mucus in IBS patients. Also, IBS subjects reported generalized body discomfort and psychosocial problems including dyspeptic symptoms, poor appetite, heartburn, headache, back pain, difficulty with urination, fatigue, anxiety and depression. (2) IBS-C and IBS-A are more common among female patients, whereas male patients experienced more cases of IBS-D. In regards to the IBS symptoms, there were significant differences among IBS subgroups. Abdominal pain (frequency > or =2 days per week and duration > or =1 hour per day) was frequent in IBS-A patients (P=0.010 and 0.027, respectively), IBS-D patients more frequently experienced the passage of mucus, dyspeptic symptoms and anxiety (P=0.000, 0.014 and 0.015, respectively). (3) IBS patients experienced significant impairment in QOL, decrements in QOL were most pronounced in vitality, general health, mental health, and bodily pain. Compared with the general population (adjusted for gender and age), IBS patients scored significantly lower on all SF-scales (P<0.001), except for physical function scale (P=0.149). (4) QOL was impaired in all subgroups, particularly in scales of vitality, general health and mental health. Compared with IBS-D, QOL in IBS-C scored significantly lower on physical function, role physical, general health, role emotional, and mental health scales (P=0.037, 0.040, 0.039, 0.005 and 0.026, respectively)., Conclusion: Besides colonic symptoms, IBS could cause generalized body discomfort and psychosocial problems. The IBS subgroups based on predominant bowel habits are helpful to identify clinical distinction of the IBS. QOL is significantly impaired in IBS patients. The Chinese version of the SF-36 health survey scales may be a useful measurement of IBS patients.

Objective: To evaluate clinical, Quality of Life (QoL) and medical cost outcomes in patients with symptomatic reflux esophagitis (RE) receiving different "triple combination therapy"., Methods: A multicenter medical effectiveness trial conducted in 10 hospitals of 5 regions in Zhejiang Province. 248 patient-volunteers were assigned to 8 weeks of "triple combination therapy" with Lansoprazole plus Cisapride and Sucralfate or Ranitidine plus Cisapride and Sucralfate. Main outcomes assessment included symptoms scale scores, RE severity, QoL at baseline and 8 weeks. Medical cost data were collected with cost analysis questionnaire., Results: (1) More Lansoprazole group patients noted RE symptoms resolution than Ranitidine group (92.3% vs 78.4%, P<0.01). There was no striking difference between two groups in RE healing rate (90.8% vs 82.9%, P>0.05). (2) RE significantly impaired QoL of patients (P<0.001). Compared with Ranitidine group, QoL in Lansoprazole group had significant improvement (rate of "good" QoL 64.5% vs 45.6%, P<0.01). (3) There was close correlation between symptomic effectiveness and QoL rating scale in both the Lansoprazole and Ranitidine group (P<0.01, r=0.235 and 0.353 respectively). There were no statistical difference of medical cost between the two groups (P>0.05)., Conclusion: RE significantly impaired QoL of patients. "Triple combination therapies" can significantly improve RE symptoms and QoL. Lansoprazole combination therapy was more cost-effective than Ranitidine combination group.

Objective: To evaluate the prevalence and quality of life (QOL)on irritable bowel syndrome (IBS) patients in Zhejiang province, and to evaluate the applying of Chinese version of the SF-36 questionnaire on IBS., Methods: From Jan 2001 through Jan 2002, IBS patients from city, island, countryside and suburban in 10 hospitals in Zhejiang province were recruited to the study. 662 Roma II criteria-positive IBS patients completed the demographic checklists, symptoms questionnaire and QOL by Chinese version of the SF-36. We compared the demographic characteristics of IBS with the general population in Zhejiang province. The previously reported SF-36 (Chinese vision) data in general population were considered normative QOL., Results: (1) Male to female was 0.89:1. Compared with general population, IBS was more common in female (P < 0.05), adults in 25 - 50 years old (P < 0.001), and among high educated and cadres samples (P < 0.001). (2) The dominant symptoms in IBS included the change of stool formation (79.1%), abnormal of processing of stool (67.9%), abdominal pain (67.7%), abdominal distention (63.2%) and mucous stool (49.8%). Besides colonic symptoms, IBS can cause generalized body discomfort and psychosocial problems. (3) IBS patients experienced significant impairment in QOL. Decrements are most pronounced in vitality, general health, mental health and bodily pain scales. (4) Compared with the general population in Hangzhou city (adjusted to gender and age), IBS patients scored significantly lower on all SF-36 scales (P < 0.001), with the exception of physical function scale. There was a significant correlation between symptom scores and all 8 SF-36 scales., Conclusions: The prevalence of IBS had a close correlation with sex, age, education and profession. IBS patients experience significant impairment in QOL. The Chinese version of the SF-36 Health Survey Scales may be a useful measurement of IBS patients. These data offer further insight into epidemiology and the impact of IBS on patient functional status and well-being of Chinese.