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The early diagnosis of lung cancer has become the focus of clinical attention, with the incidence and mortality of lung cancer increasing. Aberrant DNA methylation occurs in the primary stage of lung cancer, then the methylation degree can be changed dynamically due to the progress and the treatment of lung cancer. To date, a growing number of studies have reported that special gene methylation exploits in the clinical diagnosis, curative effect monitoring, and prognosis evaluation of lung cancer. Meanwhile, clinical trials about DNA methyltransferase inhibitors for lung cancer therapy are also underway. It is worth looking forward that detecting aberrant DNA methylation helps diagnose and treat lung cancer.

Objective: To investigate the germline mutation status of related genes in breast cancer patients and high-risk individuals by next-generation sequencing. To analyze the correlations between homologous recombination repair (HR) pathway gene mutation status and clinicopathological characteristics of breast cancer patients. To supplement the database of breast cancer related gene mutations in Chinese population. Methods: This study is a cross-sectional study. From October 2020 to September 2021, whole blood samples were collected from 350 breast cancer patients and 49 high-risk individuals, admitted to Peking University People's Hospital and accepted genetic testing voluntarily. Germline mutations in 32 breast cancer related genes were detected by NGS. The clinicopathological characteristics, including age at the onset, family history, unilateral/bilateral tumor, Luminal typing (Luminal A subtype, Luminal B subtype, HER2-enriched subtype and triple negative breast cancer), tumor size and metastasis, were analyzed, and the correlations between HR pathway gene mutation status and clinicopathological characteristics were analyzed by Chi-squared test and Fisher's exact probability test. Results: Among 350 breast cancer patients, 64 (18.3%) cases carried gene pathogenic mutations (including pathogenic and likely pathogenic mutations), including 47 (13.4%) in BRCA1/2, 16 (4.6%) in non-BRCA1/2 genes, 1 (0.3%) in BRCA2 and FANCL. Among 49 high-risk individuals, 7 (14.3%) cases carried gene pathogenic mutations, including 6 (12.3%) in BRCA1/2 and 1 (2%) in ATM genes. BRCA1/2 pathogenic mutations were associated with age at the onset (18%, 8.7%, χ²=6.346, P =0.012), and the BRCA1/2 pathogenic mutation frequency was higher in patients diagnosed at age ≤45 years. HR pathway gene mutations (including pathogenic, likely pathogenic and uncertain significance mutations) were correlated with unilateral/bilateral tumor (49.5%, 68.4%, χ²=4.841, P =0.028) and Luminal typing (45.7%, 62.2%, 32%, 60%, χ²=12.004, P =0.007), and the HR mutation frequencies were higher in patients with bilateral tumor, Luminal B breast cancer and triple negative breast cancer (TNBC). Conclusion: The BRCA1/2 pathogenic mutation frequency in high-risk individuals is similar to that in breast cancer patients, and BRCA1/2 testing is helpful to guide breast cancer screening and prevention in high-risk individuals. Patients with early onset breast cancer, bilateral breast cancer, Luminal B breast cancer and TNBC have higher mutation frequencies of HR pathway genes, and HR pathway genes testing should be conducted as soon as possible to provide laboratory evidence for diagnosis, treatment, prognosis and risk evaluation of breast cancer.

Objective: To explore the value of radiomics model based on dynamic contrast-enhanced magnetic resonance imaging (MRI) in differentiation fat-poor angiomyolipoma (fp-AML) from alpha-fetoprotein-negative hepatocellular carcinoma (n-HCC) in the background of non-cirrhotic liver. Methods: The complete data of 121 patients from Guangdong Provincial People's Hospital, Zhongshan Hospital Affiliated to Fudan University and Sun Yat-sen University Cancer Center with hepatic fp-AML and n-HCC confirmed by pathology from October 2010 to July 2020 were retrospectively analyzed. Among them, 75 were males and 46 were females, aged from 23 to 80 (55±12) years. A total of 93 patients from Zhongshan Hospital Affiliated to Fudan University were divided into the training cohort ( n =75) and internal test cohort ( n =18) according to entry time, and the patients of other 2 hospitals were divided into external test cohort ( n =28). The radiomics features were extracted from the preoperative triple-phase contrast-enhanced images. The feature selection algorithm based on Joint Mutual Information Maximisation (JMIM) was used to extract the optimal feature subset, and support vector machine (SVM) was used to build the radiomics model. The diagnostic performance of radiomics model was evaluated using the receiver operating characteristic (ROC) curve, and was compared with that of two radiologists. Results: In the internal cohort, the area under the curve (AUC) for the differential diagnosis between fp-AML and n-HCC of the radiomics model was 0.819 (with an accuracy of 72.2%), outperforming than radiologist 1 with 10 years of diagnostic experience (AUC=0.542, P =0.029) and radiologist 2 with 2 years of diagnostic experience (AUC=0.375, P =0.004). In the external cohort, the AUC of the radiomics model was 0.772 (with and accuracy of 71.4%), which was comparable to that of radiologist 1 (AUC=0.661, P =0.442) and better than that of radiologist 2 (AUC=0.400, P =0.008). Conclusion: The radiomics model based on dynamic contrast-enhanced MRI is of high accuracy for preoperatively differentiating hepatic fp-AML from n-HCC in the noncirrhotic liver.

Objective: Mitochondrial deoxyribonucleic acid (mtDNA) 8344 A>G (m.8344A>G) mutation is the common mutation associated with mitochondrial myoclonus epilepsy with ragged-red fibers (MERRF) syndrome. Herein we report a rare case with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes/MERRF/Leigh (MELAS/MERRF/Leigh) overlap syndrome caused by m.8344A>G mutation., Methods: The clinical and imaging data of the patient were collected and an open muscle biopsy was carried out. We further employed molecular genetic analyses to detect mtDNA mutation in the proband and his mother. And then a clinical and neuroimaging follow-up was performed., Results: This patient was a 25-year-old male, who developed exercise intolerance since the age of 6. At age 10, he suffered from acute episodes of hemianopia, and cranial magnetic resonance imaging (MRI) showed occipital stroke-like lesions and cranial magnetic resonance spectroscopy (MRS) revealed a lactate peak corresponding to the lesion. After that the patient presented slowly progressive psychomotor decline. He had myoclonic seizures and cerebellar ataxia since the age of 12. At age 21, he was admitted to our hospital because of confusion and cranial MRI revealed symmetrical lesions in bilateral posterior putamen, thalami and midbrain. Then repeated MRI showed progression of original lesions and new frontal multiple stroke-like lesions. Symptomatic and rehabilitation treatment relieved his condition. Follow-up cranial MRI at age 24 showed the lesions in basal ganglia and thalami diminished, and the midbrain lesions even completely vanished. Muscle pathology indicated the presence of numerous scattered ragged-red fibers (RRF), suggestive of a mitochondrial disorder. Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) detected the m.8344A>G mutation of the MT-TK gene encoding mitochondrial transfer RNA for lysine in the patient's blood. Next generation sequencing (NGS) of the whole mitochondrial genome identified that the proportion of m.8344A>G was 90%, and no other mtDNA mutation was detected. Sanger sequencing further identified this mutation both in the proband and his mother's blood, although the mutation load was much lower in his mother's blood with approximately 10% heteroplasmy., Conclusion: The present study is the first to describe a patient with m.8344A>G mutation in association with the MELAS/MERRF/Leigh overlap syndrome, which expands the phenotypic spectrum of the m.8344A>G mutation.

Objective: To compare eradication rates and compliance of patients with Helicobacter pylori( H. pylori )infection based on clarithromycin sensitivity. Methods: From July 2015 to January 2018,patients with H. pylori infection in Peking university people's hospital were randomly assignedto a 14-day treatment with clarithromycin quadruple therapy versus tailored quadruple therapy for a prospective study. In the group of tailored therapy, medications were adjusted based on clarithromycin sensitivity. In the control group, all patients were given proton pump inhibitors (PPI), amoxicillin, clarithomycin and bismuth. Eradication status was assessed 4 weeks after treatment withurea breath test. Results: The H.pylori eradication rate were higher in the tailor therapy group than that in the control group in intention-to-treat[77.8% vs 65.3%,( P= 0.001)] and per,protocol analyses [86.4% vs 70.2%,( P< 0.001)], the differences between the two groups were statistically significant.The incidence of compliance between the two groups were also comparable. Conclusions: The tailored therapy basedon clarithromycinsensitivity has a better eradication efficacy and a higher eradication ratesin the patients with H. pylori infection.

Background: The extensive involvement of microRNAs (miRNAs) in the pathogenesis of psoriasis is well documented. However, little is known about the contribution of specific miRNAs to the prevalence of this disease., Objectives: To explore the role of miR-145-5p in psoriasis., Methods: miRNA microarray analysis was performed in four patients with psoriasis and four controls. Quantitative reverse-transcriptase polymerase chain reaction and fluorescence in situ hybridization were used to identify the dysregulated miRNAs. Luciferase assays were performed to determine whether miR-145-5p targets mixed-lineage kinase (MLK)3. CCK-8 assay and Magnetic Luminex Assay were performed to measure cell proliferation and chemokine secretion. Western blot analysis was used to investigate the protein levels of MLK3 and its downstream effectors. Mouse models of psoriasis were established for in vivo experiments., Results: miR-145-5p was downregulated in psoriatic lesional skin. Luciferase assays showed that MLK3 is a direct target of miR-145-5p. Overexpression of miR-145-5p in normal human epidermal keratinocytes (NHEKs) suppressed cell proliferation and secretion of chemokines. In contrast, silencing miR-145-5p promoted NHEK proliferation and increased chemokine secretion. Silencing MLK3 abrogated miR-145-5p inhibitor-induced promotion of cell proliferation and chemokine expression. miR-145-5p regulates nuclear factor-κB and signal transducer and activator of transcription 3 by targeting MLK3. Delivery of agomiR-145-5p into the skin decreased epidermal hyperplasia and ameliorated psoriasis-like dermatitis. Delivery of antagomiR-145-5p led to the opposite effects., Conclusions: Our findings indicate that miR-145-5p negatively regulates proliferation and chemokine secretion of NHEKs by targeting MLK3, and downregulation of miR-145-5p contributes to skin inflammation in psoriasis lesions., (© 2018 British Association of Dermatologists.)

Objective: To explore the computed tomography(CT) features of inflammatory myofibroblastic tumor(IMT) in different pathological types, and improve the diagnostic level of this disease. Methods: The CT features of 29 cases pathologically confirmed IMTs were retrospectively reviewed along with a literature review to analyze the CT features and pathological correlations, and three kinds of pathological classification of IMT in patients with gender , shape, boundary and location were respectively analyzed by Chi - Square test. Results: The age ranges from 2 to 78 years.There were 7 cases of mucinous blood vessel type and 13 cases of spindle cell type and 9 cases of fiber type.Immunohistochemically, Vimentin (22/29) and SMA (28/29) were positive in all the cases, ALK (4/29) and CD-67(6/29) were partly positive expression, other markers such as S-100 were negative expression.The Chi - Square test showed that there were statistically differences in the gender of the patients. Conclusion: The CT and clinical features differ according to pathological types of IMT. Its final diagnosis still needs to be combined with pathology and immunohistochemistry result. In all, CT has a role in assessing the extension of IMT and especially about the relationship with adjacent organs which can effectively direct the establishment of clinical treating scheme.

Objective: To retrospectively investigate the clinical characteristics, risk factors of Cytomegalovirus (CMV) infection in patients with underlying rheumatic diseases. Methods: Clinical records of 263 rheumatic patients with or without CMV infection, hospitalized from March 2011 to June 2014 in Peking University People's Hospital, were analyzed.Clinical characteristics were summarized and compared in CMV positive and negative groups, to investigate the risk factors for CMV infection.Statistical analyses were conducted with SPSS 20.0 software. Results: A total of 62 rheumatic patients were found to have CMV infection, with 48 regarded as CMV viremia, 7 diagnosed as CMV pneumonia, while the remaining 7 suffered both CMV viremia and pneumonia.Eleven of 62 patients (17.7%) had a fatal outcome.Systemic lupus erythematosus (SLE) was the most commonly underlying disease (41.9%), followed by Sjögren syndrome (16.1%) and systemic vasculitis (12.9%). Lymphopenia and the reduction of CD4 + T lymphocytes, corticosteroids, cyclophosphamide (CTX) or mycophenolate mofetil (MMF), combined use of more than 2 immunosuppressants and other severe underlying infections as risk factors for CMV infection in rheumatic patients.Meanwhile, the total dose of CTX wasn't different significantly between CMV positive and negative groups.Multivariate analysis revealed that large or pulsed dose of corticosteroids, combined use of immunosuppressants, and severe underlying infections remained independent risk factors for CMV infection. Conclusions: Lymphocytes, particularly the CD4 + T subsets, might play a vital role in the regulation and control of CMV infection.Other underlying infections, undergoing large dose corticosteroids therapy or combined use of immunosuppressants could be the risk factors for CMV infection in rheumatic patients.

This paper reports a microfluidic system that enables the characterization of tumor cell electrical properties where cells were aspirated through a constriction channel (cross-section area smaller than that of biological cells) with cellular impedance profiles measured and translated to specific membrane capacitance (Cspecific membrane) and cytoplasm conductivity (σcytoplasm). Two batches of H1299 cells were quantified by the microfluidic platform with different constriction channel cross-section areas, recording no differences with statistical significance (p<0.001) in both Cspecific membrane (1.63±0.52 vs. 1.65±0.43 μF/cm(2)) and σcytoplasm (0.90±0.19 vs. 0.92±0.15S/m), and thus confirming the reliability of the microfluidic platform. For paired high- and low-metastatic carcinoma strains 95D (ncell=537) and 95C cells (ncell=486), significant differences in both Cspecific membrane (2.00±0.43 vs. 1.62±0.39 μF/cm(2)) and σcytoplasm (0.88±0.46 vs. 1.25±0.35S/m) were observed. Statistically significant difference only in Cspecific membrane (2.00±0.43 vs. 1.58±0.30 μF/cm(2)) was observed for 95D cells (ncell=537) and 95D CCNY-KD cells with single oncogene CCNY down regulation (ncell=479, CCNY is a membrane-associated protein). In addition, statistically significant difference only in σcytoplasm (0.73±0.17 vs. 1.01±0.17S/m) was observed for A549 cells (ncell=487) and A549 CypA-KD cells with single oncogene CypA down regulation (ncell=597, CypA is a cytosolic protein). These results validated the developed microfluidic platform for Cspecific membrane and σcytoplasm quantification and confirmed the feasibility of using Cspecific membrane and σcytoplasm for tumor cell classification., (Copyright © 2014 Elsevier B.V. All rights reserved.)

This study aimed to investigate the effects of single-nucleotide polymorphisms (SNPs) XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPG His104Asp, and XPG His46His in genes involved in the DNA-repair pathway on the outcomes of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). The study period was from January 2005 to January 2006, and 378 NSCLC patients were enrolled within 1 month after being diagnosed with NSCLC. Genomic DNA was extracted using the Qiagen Blood Kit. Polymerase chain reaction combined with a restriction fragment length polymorphism assay was used for genotyping. Individuals with the XRCC1 399A/A genotype had a higher probability of responding well to platinum-based chemotherapy, indicated by an odds ratio (OR) of 2.27 [95% confidence interval (CI)=1.64-6.97]. Similarly, the XPG T/T genotype was significantly associated with improved responses to chemotherapy, indicated by an OR of 1.90 (95%CI=1.10-3.28). The XRCC1 399A/A genotype was significantly associated with longer disease-free survival and overall survival, indicated by hazard ratios (HRs) of 0.48 (95%CI=0.25-0.88) and 0.51 (95%CI=0.26- 0.98), respectively. Moreover, the XPG 46T/T genotype increased the likelihood of longer disease-free survival and overall survival of NSCLC patients treated with platinum-based chemotherapy (HR=0.47; 95%CI=0.22-0.82 and HR=0.52; 95%CI=0.31- 0.96, respectively). These results indicate that XRCC1 Arg399Gln and XPG His46His might significantly affect the clinical outcomes of platinum-based chemotherapy, highlighting the need for larger studies to confirm the role of these two SNPs in outcomes of NSCLC treatments.

Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In this work, we report on a comprehensive characterization of gene expression profiles of hepatitis B virus-positive HCC through the generation of a large set of 5'-read expressed sequence tag (EST) clusters (11,065 in total) from HCC and noncancerous liver samples, which then were applied to a cDNA microarray system containing 12,393 genes/ESTs and to comparison with a public database. The commercial cDNA microarray, which contains 1,176 known genes related to oncogenesis, was used also for profiling gene expression. Integrated data from the above approaches identified 2,253 genes/ESTs as candidates with differential expression. A number of genes related to oncogenesis and hepatic function/differentiation were selected for further semiquantitative reverse transcriptase-PCR analysis in 29 paired HCC/noncancerous liver samples. Many genes involved in cell cycle regulation such as cyclins, cyclin-dependent kinases, and cell cycle negative regulators were deregulated in most patients with HCC. Aberrant expression of the Wnt-beta-catenin pathway and enzymes for DNA replication also could contribute to the pathogenesis of HCC. The alteration of transcription levels was noted in a large number of genes implicated in metabolism, whereas a profile change of others might represent a status of dedifferentiation of the malignant hepatocytes, both considered as potential markers of diagnostic value. Notably, the altered transcriptome profiles in HCC could be correlated to a number of chromosome regions with amplification or loss of heterozygosity, providing one of the underlying causes of the transcription anomaly of HCC.

Using a combination of hybridization of PAC to a cDNA library and RACE technique, we isolated a novel cDNA, designated as C17orf25 (Chromosome 17 open reading frame 25, previously named it HC71A), from the deletion region on chromosome 17p13.3. The cDNA encodes a protein of 313 amino acids with a calculated molecular mass of 34.8 kDa. C17orf25 is divided into 10 exons and 9 introns, spanning 23 kb of genomic DNA. Northern blot analysis showed that the mRNA expression of C17orf25 was decreased in hepatocellular carcinoma samples as compared to adjacent noncancerous liver tissues from the same patients. The transfection of C17orf25 into the hepatocellular carcinoma cell SMMC7721 and overexpression could inhibit the cell growth. The above results indicate that C17orf25 is a novel human gene, and the cloning and preliminary characterization of C17orf25 is a prerequisite for further functional analysis of this novel gene in human hepatocellular carcinoma.

Slowing of transit through the proximal small intestine by fat in the distal gut is termed the ileal brake. Intravenous naloxone, an opioid receptor antagonist, abolished the fat-induced ileal brake, suggesting that an endogenous opioid pathway may be involved in this response. To test the hypothesis that slowing of intestinal transit by fat in the distal half of the gut depends on an opioid pathway located on the efferent limb of this response, we compared intestinal transit in dogs equipped with duodenal and midgut fistulas while naloxone was either compartmentalized with oleate to the distal half of the gut or with buffer to the proximal half of the gut. We found that intestinal transit depended on the perfusion conditions (P<0.00001). Specifically, compared with ileal brake (marker recovery of 35.7+/-7.4%), intestinal transit was accelerated when naloxone was delivered into the proximal half of the gut (76.2+/-5.2%) (P<0.005) but not the distal half of the gut (29.4+/-5.4%). We conclude that slowing of intestinal transit by fat in the distal half of the gut depends on an opioid pathway located on the efferent limb of the ileal brake.

Fat in small intestine decreases meal-stimulated gastric acid secretion and slows gastric emptying. CCK is a mediator of this inhibitory effect (an enterogastrone). Because intravenously administered peptide YY (PYY) inhibits acid secretion, endogenous PYY released by fat may also be an enterogastrone. Four dogs were equipped with gastric, duodenal, and midgut fistulas. PYY antibody (anti-PYY) at a dose of 0.5 mg/kg or CCK-A receptor antagonist (devazepide) at a dose of 0.1 mg/kg was administered alone or in combination 10 min before the proximal half of the gut was perfused with 60 mM oleate or buffer. Acid secretion and gastric emptying were measured. We found that 1) peptone-induced gastric acid secretion was inhibited by intestinal fat (P < 0.0001), 2) inhibition of acid secretion by intestinal fat was reversed by CCK-A receptor antagonist (P < 0.0001) but not by anti-PYY, and 3) slowing of gastric emptying by fat was reversed by CCK-A antagonist (P < 0. 05) but not by anti-PYY. We concluded that inhibition of peptone meal-induced gastric acid secretion and slowing of gastric emptying by intestinal fat depended on CCK but not on circulating PYY.

Because an increase in flow rate accelerates intestinal transit, a reduction in the flow rate of formula delivery is recommended frequently for treatment of diarrhea that develops during enteral feeding. Because intestinal transit is slowed by nutrient-triggered inhibitory feedback, the rate of intestinal transit during enteral feeding may depend on a balance between the accelerating effect of flow and the inhibiting effect of the nutrient load. The addition of fiber to a formula may alter this balance. By delaying absorption of nutrients, fiber may extend the length of small intestine exposed to nutrients and thereby trigger more intense inhibitory feedback. To determine whether the addition of fiber favors nutrient-triggered inhibition over flow-driven acceleration, we studied intestinal transit after perfusion of a low-residue enteral formula compared with a fiber-supplemented formula at two perfusion rates (50 or 100 mL/h for 2 h) into the duodenum of dogs each with both a duodenal and midgut fistula. With the low-residue formula, intestinal transit accelerated when the flow rate increased from 50 to 100 mL/h (P < 0.05). With the fiber-supplemented formula, however, intestinal transit was inhibited regardless of the flow rate. To determine whether the fiber-supplemented formula inhibited intestinal transit by displacing nutrients distally, we compared intestinal transit when the two formulas, delivered at 100 mL/h, were diverted completely at the midgut fistula. Intestinal transit of the fiber-supplemented formula increased by 400%, eliminating the difference in intestinal transit speed between the two formulas. We concluded that the fiber-supplemented formula slowed intestinal transit by intensifying inhibitory feedback from the distal gut.

Ileal perfusion of protein slows intestinal transit. Because optimal absorption of nutrients requires adequate time in contact with the mucosa, slowed intestinal transit may increase protein absorption by increasing the residence time of nutrients in the small intestine. Although protein supplements are routinely added to enteral feeding to correct protein malnutrition, little information is available on the effect of increasing the load of protein on intestinal transit and the efficiency of protein absorption. In six dogs equipped with duodenal and midintestinal fistulas, intestinal transit and the efficiency of protein absorption (percentage protein absorbed as estimated from the output of midintestinal fistula) were compared during intestinal perfusion with 0-, 50-, 100-, and 200-g/L solutions of a whey-based protein supplement. We found that intestinal transit slowed in a load-dependent fashion (P < 0.05); the amount of protein absorbed within the proximal one-half of the small intestine increased in a load-dependent fashion (P < 0.05) as intestinal transit slowed, and the percentage protein absorbed (reflecting the efficiency of protein absorption) was maintained at a high and nearly constant value of 66.5-72.5% across protein loads of 9-36 g. We conclude that enhanced protein absorption is associated with a load-dependent inhibition of intestinal transit.

Occlusion of feeding tubes is a common and costly complication of enteral feeding. Although the composition of feeding formulas, the size, design, and material of the feeding tube, and the rate of delivery have been considered as factors that determine the rate of tube occlusion, little information is available on the effect of the luminal content of the gut on tube occlusion. Enteral feeding tubes are placed either in the stomach or postpylorically, in the small intestine. The chemical composition of these regions including acidity and bile salt concentration may vary. Since acidity has been shown to promote tube occlusion and bile salts have detergent-like properties, these chemical differences in the luminal environment may be important to tube occlusion. To test the idea that bile salt inhibits acid-promoted occlusion of feeding tubes, in an in vitro study, we compared the time-to-complete occlusion of four groups of formula-filled feeding tubes (six tubes in each group) immersed in an acidic solution (pH 3.0) containing 0 (control), 10, 20, or 40 mM of taurocholate. We found that although 33% of the feeding tubes were occluded within 12 hours in the absence of exposure to bile salt, none were occluded when 20 or 40 mM of taurocholate was added to the acidic solution. After 24 hours, 40 mM of taurocholate inhibited acid-promoted occlusion of 67% of the feeding tubes. Thus 0 to 40 mM of taurocholate still inhibited acid-promoted tube occlusion in a dose-dependent fashion (p < .05). Acidity and the concentration of bile salt may work together, but in opposite directions, as luminal factors that determine the rate of occlusion of feeding tubes.

Background & Aims: Fat in the distal gut inhibits transit through the proximal small intestine as the ileal brake. Although the mediator of this response is not established, peptide YY (PYY) has been considered the most likely peptide candidate because inhibition of intestinal motility by fat in the distal gut correlated with the release of PYY but not other distal gut peptides such as enteroglucagon or neurotensin. Although intravenous administration of PYY inhibits intestinal transit, the role of this peptide remains to be confirmed because systemic PYY may not exert its effect by the same regulatory pathway as fat-induced ileal brake. The aim of this study was to definitively test the hypothesis that PYY mediates fat-induced ileal brake using the technique of peptide immunoneutralization., Methods: In a fistulated dog model, intestinal transit during perfusion of the distal gut with 60 mmol/L oleate (ileal brake) was examined after intravenous administration of 0.5 mg/kg of PYY antibody (anti-PYY), nonspecific immunoglobulin G (control), or 0.15 mol/L NaCl. Intestinal transit result (cumulative percent recovery of 99mTc) was normalized within each animal against the transit result of the 0.15 mol/L NaCl experiment., Results: Intestinal transit accelerated with PYY immunoneutralization, increasing cumulative percent recovery from 25.9 +/- 6.2 (control) to 81.2 +/- 6.3 (anti-PYY)., Conclusions: Fat-induced ileal brake depends on PYY.

Optimal absorption of fat requires adequate time of contact with the absorptive sites of the small intestine. In order to prevent steatorrhea, intestinal transit must be slowed in response to the fat that has emptied into the small intestine. Intestinal transit is known to be inhibited by fat in the ileum via the ileal brake. This response has suggested that the regulation of intestinal transit is a function of the distal small intestine. However, clinical observations suggest that the ileal brake is not the only control mechanism for intestinal transit. In short bowel patients with resection of the ileum, the proportion of fecal fat recovery remained constant even after the fat intake was increased threefold. In these patients, optimal fat absorption based on the slowing of intestinal transit must have been triggered by an inhibitory mechanism located outside of the distal small intestine. To test the hypothesis that fat in the proximal small intestine inhibited intestinal transit, we compared intestinal transit during perfusion of the proximal half of the small intestine with 0 (buffer only), 15, 30, or 60 mM oleate in dogs equipped with duodenal and mid-intestinal fistula. Intestinal transit across a 150-cm test segment (between fistulas) was measured by counting for the recovery of a radioactive marker in the output of the mid-intestinal fistula during the last 30 min of a 90-min perfusion. We found that oleate inhibited intestinal transit in a load-dependent fashion (P < 0.005). Specifically, while the mean cumulative recovery of the transit marker was 95.5% during buffer perfusion, the recovery decreased when 15 mM (64.3%), 30 mM o(54.7%), or 60 mM oleate (38.7%) was perfused into the proximal half of the small intestine. We conclude that fat in the proximal small intestine inhibits intestinal transit as the jejunal brake.

The concentration of total protein and 17 different proteins in gallbladder bile of patients with gallstones and normal controls were analyzed. The result showed that the amount of total protein and 11 of 17 proteins was much higher in patients with cholesterol gallstones than that of normal controls. These proteins may be involved in the nucleation of cholesterol crystal in gallbladder bile of patients with cholesterol gallstones. The nucleation activity titre (NAT) of gallbladder bile of patients with gallstones and controls was determined. The NAT of gallbladder bile of patients with gallstones was 1/25-1/100 and that of controls was 1/100-1/6400. There was a statistically significant difference of NAT between patients with cholesterol gallstones and normal controls.