Exploring the diagnostic potential of immunoglobulin A-microbiota interplay in liver cirrhosis and spontaneous bacterial peritonitis.

The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA-coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child-Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro-inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver-related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes.

Therapeutic potential of gene therapy for gastrointestinal diseases: Advancements and future perspectives.

Advancements in understanding the pathogenesis mechanisms underlying gastrointestinal diseases, encompassing inflammatory bowel disease, gastrointestinal cancer, and gastroesophageal reflux disease, have led to the identification of numerous novel therapeutic targets. These discoveries have opened up exciting possibilities for developing gene therapy strategies to treat gastrointestinal diseases. These strategies include gene replacement, gene enhancement, gene overexpression, gene function blocking, and transgenic somatic cell transplantation. In this review, we introduce the important gene therapy targets and targeted delivery systems within the field of gastroenterology. Furthermore, we provide a comprehensive overview of recent progress in gene therapy related to gastrointestinal disorders and shed light on the application of innovative gene-editing technologies in treating these conditions. These developments are fueling a revolution in the management of gastrointestinal diseases. Ultimately, we discuss the current challenges (particularly regarding safety, oral efficacy, and cost) and explore potential future directions for implementing gene therapy in the clinical settings for gastrointestinal diseases.

Application of Nanoparticles in the Diagnosis of Gastrointestinal Diseases: A Complete Future Perspective.

The diagnosis of gastrointestinal (GI) diseases currently relies primarily on invasive procedures like digestive endoscopy. However, these procedures can cause discomfort, respiratory issues, and bacterial infections in patients, both during and after the examination. In recent years, nanomedicine has emerged as a promising field, providing significant advancements in diagnostic techniques. Nanoprobes, in particular, offer distinct advantages, such as high specificity and sensitivity in detecting GI diseases. Integration of nanoprobes with advanced imaging techniques, such as nuclear magnetic resonance, optical fluorescence imaging, tomography, and optical correlation tomography, has significantly enhanced the detection capabilities for GI tumors and inflammatory bowel disease (IBD). This synergy enables early diagnosis and precise staging of GI disorders. Among the nanoparticles investigated for clinical applications, superparamagnetic iron oxide, quantum dots, single carbon nanotubes, and nanocages have emerged as extensively studied and utilized agents. This review aimed to provide insights into the potential applications of nanoparticles in modern imaging techniques, with a specific focus on their role in facilitating early and specific diagnosis of a range of GI disorders, including IBD and colorectal cancer (CRC). Additionally, we discussed the challenges associated with the implementation of nanotechnology-based GI diagnostics and explored future prospects for translation in this promising field.

Plant-derived exosomal nanoparticles: potential therapeutic for inflammatory bowel disease.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic autoimmune disorder characterized by inflammation. However, currently available disease-modifying anti-IBD drugs exhibit limited efficacy in IBD therapy. Furthermore, existing therapeutic approaches provide only partial relief from IBD symptoms and are associated with certain side effects. In recent years, a novel category of nanoscale membrane vesicles, known as plant-derived exosome-like nanoparticles (PDENs), has been identified in edible plants. These PDENs are abundant in bioactive lipids, proteins, microRNAs, and other pharmacologically active compounds. Notably, PDENs possess immunomodulatory, antitumor, regenerative, and anti-inflammatory properties, making them particularly promising for the treatment of intestinal diseases. Moreover, PDENs can be engineered as targeted delivery systems for the efficient transport of chemical or nucleic acid drugs to the site of intestinal inflammation. In the present study, we provided an overview of PDENs, including their biogenesis, extraction, purification, and construction strategies, and elucidated their physiological functions and therapeutic effects on IBD. Additionally, we summarized the applications and potential of PDENs in IBD treatment while highlighting the future directions and challenges in the field of emerging nanotherapeutics for IBD therapy.

Fecal microbiota transplantation ameliorates active ulcerative colitis.

Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.

Diagnostic Performance of Intestinal Fusobacterium nucleatum in Colorectal Cancer: A Meta-Analysis.

BACKGROUND: Increasing evidence has supported the link of intestinal Fusobacterium nucleatum infection to colorectal cancer (CRC). However, the value of F. nucleatum as a biomarker in CRC detection has not been fully defined. In order to reduce the random error and bias of individual research, this meta-analysis aimed to evaluate the diagnostic performance of intestinal F. nucleatum in CRC patients and provide evidence-based data to clinical practice. METHODS: An article search was performed from PubMed, Embase, Cochrane Library, and Web of Science databases up to December 2017, using the following key words: "Fusobacterium nucleatum", "Fusobacterium spp.", "Fn", "colorectal cancer(s)", "colorectal carcinoma(s)", "colorectal neoplasm(s)", and "colorectal tumor(s)". Articles on relationships between F. nucleatum and CRC were selected according to the preestablished inclusion and exclusion criteria. This meta-analysis was performed using STATA 12.0 software, which included mapping of forest plots, heterogeneity tests, meta-regression, subgroup analysis, sensitivity analysis, and publication bias. The sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and their corresponding 95% confidence interval (CI) of each eligible study were summarized. RESULTS: Finally, data for 1198 participants (629 CRC and 569 healthy controls) in 10 controlled studies from seven articles were included. The summary receiver operator characteristic curve was mapped. The diagnostic performance of intestinal F. nucleatum infection on CRC was as follows: the area under the curve: 0.86 (95% CI: 0.83-0.89), the pooled sensitivity: 0.81 (95% CI: 0.64-0.91), specificity: 0.77 (95% CI: 0.59-0.89), and DOR: 14.00 (95% CI: 9.00-22.00). CONCLUSION: Intestinal F. nucleatum is a valuable marker for CRC diagnosis.

NIMA-related kinase 2 regulates hepatocellular carcinoma cell growth and proliferation.

NIMA-related kinase 2 (Nek2) is often upregulated in human cancer and is important in regulating the cell cycle and gene expression, and maintaining centrosomal structure and function. The present study aimed to investigate the expression pattern, clinical significance, and biological function of Nek2 in hepatocellular carcinoma (HCC). mRNA and protein levels of Nek2 were examined in HCC and corresponding normal liver tissues. The MTT and soft agar colony formation assays, and flow cytometry were employed to assess the roles of Nek2 in cell proliferation and growth. In addition, western blot analysis was performed to assess the expression of cell cycle- and proliferation-related proteins. The results revealed that Nek2 was upregulated in HCC tissues and cell lines. The clinical significance of Nek2 expression was also analyzed. Inhibiting Nek2 expression by siRNA suppressed cell proliferation, growth, and colony formation in hepatocellular carcinoma cell line HepG2 cells, induced cell cycle arrest in the G2/M phase by retarding the S-phase, and promoted apoptosis. Furthermore, Nek2 depletion downregulated ß-catenin expression in HepG2 cells and diminished expression of Myc proto-oncogene protein (c-Myc), cyclins D1, B1, and E and cyclin-dependent kinase 1, whilst increasing protein levels of p27. This demonstrates that overexpression of Nek2 is associated with the malignant evolution of HCC. Targeting Nek2 may inhibit HCC cell growth and proliferation through the regulation of ß-catenin by the Wnt/ß-catenin pathway and therefore may be developed as a novel therapeutic strategy to treat HCC.

Association of Fusobacterium nucleatum infection with colorectal cancer in Chinese patients.

AIM: To investigate Fusobacterium nucleatum (F. nucleatum) abundance in colorectal cancer (CRC) tissues and its association with CRC invasiveness in Chinese patients. METHODS: The resected cancer and adjacent normal tissues (10 cm beyond cancer margins) from 101 consecutive patients with CRC were collected. Fluorescent quantitative polymerase chain reaction (FQ-PCR) was applied to detect F. nucleatum in CRC and normal tissues. The difference of F. nucleatum abundance between cancer and normal tissues and the relationship of F. nucleatum abundance with clinical variables were evaluated. Fluorescence in situ hybridization (FISH) analysis was performed on 22 CRC tissues with the highest F. nucleatum abundance by FQ-PCR testing to confirm FQ-PCR results. RESULTS: The median abundance of F. nucleatum in CRC tissues [0.242 (0.178-0.276)] was significantly higher than that in normal controls [0.050 (0.023-0.067)] (P < 0.001). F. nucleatum was over-represented in 88/101 (87.1%) CRC samples. The abundance of F. nucleatum determined by 2(-ΔCT) was significantly greater in tumor samples [0.242 (0.178, 0.276)] than in normal controls [0.050 (0.023, 0.067)] (P < 0.001). The frequency of patients with lymph node metastases was higher in the over-abundance group [52/88 (59.1%)] than in the under-abundance group [0/13 (0%)] (P < 0.005). No significant association of F. nucleatum with other clinico-pathological variables was observed (P > 0.05). FISH analysis also found more F. nucleatum in CRC than in normal tissues (median number 6, 25(th) 3, 75(th) 10 vs 2, 25(th) 1, 75(th) 5) (P < 0.01). CONCLUSION: F. nucleatum was enriched in CRC tissues and associated with CRC development and metastasis.

Overexpression of activated leukocute cell adhesion molecule in gastric cancer is associated with advanced stages and poor prognosis and miR-9 deregulation.

Activated leukocyte cell adhesion molecule (ALCAM) has been identified as a novel potential molecular marker of human tumors. The present study aimed to assess ALCAM as a prognostic marker for gastric cancer (GC), and to explore the mRNA deregulation underlying the abnormal expression of ALCAM. The mRNA and protein expression of ALCAM in GC and adjacent non­tumor tissues from 66 patients with GC were analyzed. The association between miR­9 and ALCAM mRNA expression was determined by quantitative polymerase chain reaction. Serum soluble ALCAM (sALCAM) was analyzed by ELISA in 72 patients with GC, 82 patients with gastric precancerous lesions and 73 controls. ALCAM and sALCAM levels were associated with certain clinicopathological variables, including overall survival. Compared with the non­tumor tissues, the expression of ALCAM mRNA in the GC tissues was significantly upregulated (P=0.013). The expression of miR­9 was reduced and inversely correlated with ALCAM mRNA levels in GC tissues and cell lines. The ALCAM mRNA level was reduced following ectopic overexpression of miR­9 in SGC­7901 human gastric cancer cells. The rates of membranous and cytoplasmic expression of ALCAM in GC tissues were 59.1 and 48.48%, respectively, and the serum sALCAM levels were significantly elevated in patients with GC. Elevated ALCAM mRNA, membranous ALCAM expression in GC tissues and high sALCAM levels are associated with advanced tumor stage, lymphatic invasion and shorter overall survival duration. The results of the current study indicated that membranous ALCAM expression and high serum sALCAM levels are independent prognostic markers of poor survival for patients with GC, and that the overexpression of ALCAM may be due to the downregulation of miR­9.

Gastric cancer stem cells in gastric carcinogenesis, progression, prevention and treatment.

In recent decades, the study of the mechanism of tumorigenesis has brought much progress to cancer treatment. However, cancer stem cell (CSC) theory has changed previous views of tumors, and has provided a new method for treatment of cancer. The discovery of CSCs and their characteristics have contributed to understanding the molecular mechanism of tumor genesis and development, resulting in a new effective strategy for cancer treatment. Gastric CSCs (GCSCs) are the basis for the onset of gastric cancer. They may be derived from gastric stem cells in gastric tissues, or bone marrow mesenchymal stem cells. As with other stem cells, GCSCs highly express drug-resistance genes such as aldehyde dehydrogenase and multidrug resistance, which are resistant to chemotherapy and thus form the basis of drug resistance. Many specific molecular markers such as CD44 and CD133 have been used for identification and isolation of GCSCs, diagnosis and grading of gastric cancer, and research on GCSC-targeted therapy for gastric cancer. Therefore, discussion of the recent development and advancements in GCSCs will be helpful for providing novel insight into gastric cancer treatment.

Association of CD14/-260 polymorphism with gastric cancer risk in Highland Tibetans.

AIM: To investigate the relationship between CD14-260 and -651 polymorphisms and the risk of developing gastric cancer. METHODS: DNA was extracted from peripheral blood samples obtained from 225 Tibetans with gastric cancer and 237 healthy Tibetans, and analyzed using the polymerase chain reaction/ligase detection (PCR/LDR) method to determine the genotypes at -260 and -651 loci of the CD14 promoter. The allele frequencies, genotype frequencies, and haplotypes were analyzed for their association with gastric cancer risk using online SHEsis software. The luciferase reporter assay and point mutation analysis were used to construct in vitro plasmids expressing a C/T homozygote at the -260 locus of the CD14 promoter. RESULTS: The frequencies of CC, CT and TT genotypes in the CD14-260 C/T locus in gastric cancer patients were 19.1%, 38.7% and 42.2%, respectively, whereas they were 33.3%, 32.5% and 34.2%, respectively, in healthy control subjects. CT genotype carriers were more frequently found among gastric cancer patients than healthy controls (OR = 2.076; 95%CI: 1.282-3.360). Also, TT genotype carriers were more frequently found among gastric cancer patients (OR = 2.155; 95%CI: 1.340-3.466). Compared to the C allele of CD14/-260, the T allele was associated with an increased risk for gastric cancer (OR = 1.574; 95%CI: 1.121-2.045). Furthermore, the frequencies of CC, CT and TT in the CD14-651 C/T locus in gastric cancer patients were 64.4%, 29.3% and 6.2%, respectively, while they were 56.5%, 35.0% and 8.4%, respectively, in the healthy control subjects (P > 0.05). Data obtained using the luciferase reporter assay showed that the p260T homozygote was associated with greater CD14 promoter activity (P < 0.01). CONCLUSION: CD14/-260 polymorphism is associated with gastric cancer risk in Highland Tibetans and affects CD14 promoter activity, thereby regulating CD14 expression.

Expression of survivin and its four splice variants in colorectal cancer and its clinical significances.

The aim of this study was to investigate the clinical significances of the mRNA expression of survivin gene and its four splice variants in the pathogenesis of colorectal cancer (CRC). CRC samples, matched adjacent tissues, and normal tissues were collected from surgical resections of 39 patients with histologically confirmed diagnosis. The mRNA expression of survivin and its four splice variants, that is, survivin-△Ex3, survivin-2B, survivin-3B, and survivin-2α, was detected using semiquantitative PCR and RT-PCR. Carcinoembryonic antigen (CEA) CAM5 was determined as control. The mRNA expression rates of survivin, survivin-△Ex3, survivin-2B, survivin-3B, surviving-2α, and CEA CAM5 in CRC samples were significantly higher than those in adjacent tissues (P < 0.01) and those in normal tissues (P < 0.01). The mRNA levels of the above variants in CRC samples were also significantly higher than those in adjacent tissues (P < 0.01) and those in normal tissues (P < 0.01). The mRNA levels of survivin, survivin-2B, and survivin-2α were not associated with any clinical variable of patients, while the levels of survivin-△Ex3 and survivin-3B were associated with lymphoid metastasis and Dukes grade (P < 0.05), and survivin-△Ex3 was associated with invasiveness. We concluded that mRNA expression rates and levels of survivin and its four splice variants elevated in CRC tissues, and expression levels of survivin-△Ex3 and survivin-3B were positively associated with tumor aggression.

Nur-related receptor 1 gene polymorphisms and alcohol dependence in Mexican Americans.

AIM: To investigate the association of polymorphisms of nur-related receptor 1 (Nurr1) and development of alcohol dependence in Mexican Americans. METHODS: Peripheral blood samples were collected from 374 alcoholic and 346 nonalcoholic Mexican Americans; these two groups were sex- and age-matched. Sample DNA was extracted and genomic DNA was amplified by polymerase chain reaction. The -2922(C) 2-3 polymerase chain reaction products were digested with Sau96I, alleles of 1345(G/C), and -1198(C/G) in the regulatory region as well as Ex+132 (G/T/A/C) and Ex+715(T/-) in exon 3 were studied by sequencing. RESULTS: The C2/C2, C2/C3, C3/C3 genotype distribution of -2922(C) 2-3 was 34.4%, 38.2% and 27.5% in the nonalcoholic group compared to 23.3%, 51.2% and 25.4% in the alcoholic group (P = 0.001). The C/C, C/G, G/G genotype distribution of -1198(C/G) was 23.5%, 46.1% and 30.3% in the nonalcoholic group compared to 13.9%, 50.9% and 35.3% in the alcoholic group (P = 0.007). However, the -1345 (G/C), Ex3+132(G/T/A/C) and Ex3+715(T/-) alleles were not polymorphic in Mexican Americans, and all those studied had G/G, G/G and T/T genotype for these three alleles, respectively. The -2922(C) 2-3 did not show allele level difference between alcoholic and nonalcoholic individuals, but -1198 (C/G) showed a significant allele frequency difference between alcoholic (39.3%) and nonalcoholic (46.6%) populations (P = 0.005). Excluding obese individuals, significant differences were found at both genotypic and allelic levels for the -2922(C) 2-3 polymorphism (P = 0.000 and P = 0.049) and the -1198 (C/G) polymorphism (P = 0.008 and P = 0.032) between nonobese alcoholics and nonobese controls. Excluding smokers, a significant difference was found only at the genotypic level for the -2922(C) 2-3 polymorphism (P = 0.037) between nonsmoking alcoholics and nonsmoking controls, but only at the allelic level for the -1198(C/G) polymorphism (P = 0.034). CONCLUSION: Polymorphisms in the regulatory region of Nurr1 are implicated in pathogenesis of alcohol dependence and the Nurr1/dopamine signaling pathway might be important for this dependence development in Mexican Americans.

Expression and clinical significance of hedgehog signaling pathway related components in colorectal cancer.

AIM: To investigate the expression of three components of the Hedgehog (Hh) signaling pathway (SHH, SMO and GLI1) in human colorectal cancer (CRC) tissues and evaluate their association with clinicopathologic characteristics of the patients. METHODS: Fresh tumor tissues and matched tissues adjacent to the tumor were collected from 43 CRC patients undergoing surgery. Normal colorectal tissues from 20 non-CRC cases were also sampled as normal controls. The expression of SHH, SMO, GLI1 mRNAs was assessed by RT-PCR and proteins were detected by immunohistochemical staining. Associations with clinicopathological characteristics of patients were analyzed. RESULTS: SHH mRNA was expressed more frequently in tumor tissues than in normal tissues, but the difference did not reach significance in comparison to that in the adjacent tissues. SMO and GLI1 mRNAs were expressed more frequently in tumor tissues than in both adjacent andnormal tissues. The expression intensities of SHH, SMO, GLI1 mRNA in tumor tissues were significantly higher than those in adjacent tissues and normal tissues. Proteins were also detected more frequently in tumors than other tissues. No significant links were apparent with gender, age, location, degree of infiltration or Dukes stage. CONCLUSION: Positive rates and intensities of mRNA and protein expression of Hh signaling pathway related genes SHH, SMO, GLI1 were found to be significantly increased in CRC tissues. However, over-expression did not appear to be associated with particular clinicopathological characteristics.

[In vitro anti-tumor effect of cytotoxic T lymphocyte activated by antigen- loaded dendritic cells from peripheral blood mononuclear cells treated with calcium ionophore A23187 and GM-CSF].

OBJECTIVE: To evaluate the effect of calcium ionophore (CI) A23187 and human recombinant granulocyte/macrophage colony stimulating factor (rhGM-CSF) on the cultivation of dendritic cell (DC) from healthy human peripheral blood mononuclear cell (PBMC) and to evaluate the in vitro effect of DC stimulated by K562 cell lysate on inducing specific cytotoxic T lymphocyte (CTL) against K562 cell. METHODS: Human PBMCs isolated from healthy subjects were separated into two groups. In Group A, the cells were cultured with additional rhGM-CSF, recombinant human interleukin 4 and recombinant human tumor necrosis factor-α only as control group. In Group B, the cells were cultured in the presence of rhGM-CSF and CI A23187. The cells in both groups were pre-incubated with K562 cell lysate at 37°C for 30 min. The cells were harvested after a 4-day cultivation. Morphology of DC was continuously observed under inverted microscope. The surface antigens of induced cells were analyzed by flow cytometry (FCM). Then the proliferation of allogeneic T cell and the specific cytotoxicity of T cell primed with DC were examined by colorimetry. Also, the nonspecific inhibition of DC loaded K562 cell lysate against K562 cell was detected. RESULTS: Typical morphological features of DC could be observed in both groups. The expressions of CD83, CD1a, CD86 and CD40 were stronger in Group B than those in control group (45.2% ± 1.8%, 31.5% ± 3.9%, 40.1% ± 7.8%, 36.4% ± 6.3% vs 16.9% ± 1.3%, 20.4% ± 3.4%, 26.5% ± 2.2%, 22.3% ± 3.0%) (all P < 0.05). The expression of CD14 was weaker in Group B than that in control group (5.7% ± 0.8% vs 19.0% ± 1.6%) (P < 0.05). As compared with the control group, DC in Group B loaded with K562 lysate could evidently stimulate the proliferation of allogeneic T cell (P < 0.05, exclusion of effector-to-target ratio of 1:40) and inhibit the growth of K562 cell (P < 0.05). In addition, both groups of DC-stimulated CTL had specific cytotoxicity against K562 cell. At the effector-to-target ratios of 10:1 and 40:1, the DC-stimulated CTL of Group B had stronger cytotoxicity against K562 cell (both P < 0.05). CONCLUSION: In combination with rhGM-CSF, CI A23187 induces PBMC into DC in a more effective way. DC loaded with K562 lysate can stimulate CTL and maintain high immunocompetence with specific cytotoxicity against K562 cell.

Influence of polygenetic polymorphisms on the susceptibility to non-alcoholic fatty liver disease of Chinese people.

BACKGROUND AND AIM: The aim of this study was to investigate the influence of polygenetic polymorphisms, which play a role in the pathogenesis of metabolic syndrome, on the susceptibility to non-alcoholic fatty liver disease (NAFLD) of Chinese people. METHODS: The subjects were selected from an epidemiological survey in the Guangdong province of southern China. In each polymorphism study, 50-117 subjects who met the diagnostic criteria of NAFLD and had typical clinical and ultrasonographic findings were placed into the case group. Using a nested case-control design, the same numbers of matched people without NAFLD were included as controls. Single nucleotide polymorphisms (SNP) at nine positions in seven candidate genes were tested. These SNP were found to be associated with the pathogenesis of metabolic syndrome. Genetic analyses were performed using genomic DNA extracted from peripheral blood leukocytes. Polymerase chain reaction-restriction fragment length polymorphism was applied to detect SNP. RESULTS: Most candidate genes' SNP were associated with susceptibility to NAFLD. Some showed positive relationships (increased risk): tumor necrosis factor-alpha-238, adiponectin-45, leptin-2548, peroxisome proliferator-activated receptors-161 and phosphatidyletha-nolamine N-methyltransferase-175. Other SNP demonstrated a negative association (decreased risk): adiponectin-276 and hepatic lipase-514. Only two were not associated: tumor necrosis factor-alpha-380 and peroxisome proliferator-activated receptors-gamma co-activator-1alpha-482. CONCLUSION: Most candidate genes' SNP examined in metabolic syndrome patients were associated with susceptibility to NAFLD.

Experimental ablation of the pancreas with high intensity focused ultrasound (HIFU) in a porcine model.

The aim of this study was to determine the feasibility and safety of high intensity focused ultrasound's (HIFU) in pancreatic diseases. Twelve pigs were divided into three groups. The pancreases of pigs in Group A were ablated directly with HIFU, but those in Group B and C ablated by extracorporeal HIFU. The pigs in Group C were sacrificed at day 7 after HIFU. Serological parameters were determined pre-operation and post-operation. The entire pancreas was removed for histological examination. Each animal tolerate the HIFU ablation well. The complete necrosis was observed in targeted regions. The margins of the necrotic regions were clearly delineated from the surrounding normal tissues. Infiltration of inflammatory cells and phorocytosis on the boundary were found in group C. Blood and urine amylase levels were relatively steady after HIFU. No acute pancreatitis or severe complications occurred. In conclusion, HIFU ablation on the pancreas was safe and effective in experimental pigs.

[Expression of NK cells receptor NKG2D from peripheral blood in patients with primary hepatic carcinoma and its clinical significance].

OBJECTIVE: To investigate the expression of NK cells receptor NKG2D from peripheral blood in patients with primary hepatic carcinoma and the relationship between NKG2D expression and cytotoxicity of NK cells. METHODS: Flow cytometry was used to determine the number of NK cells and the expression of NK cells receptor NKG2D from peripheral blood in patients with primary hepatic carcinoma (20 cases), hepatitis B cirrhosis (23 cases), hepatitis B (20 cases) and healthy control (20 cases). The microplate reader was used to detect cytotoxicity of NK cells in all cases. RESULTS: Among killing rate of NK cell for K562 cell, the expression rate of NKG2D in NK cells, the number of NKG2D(+)NK cells, NKG2D expression level of NK cells and the number of NK cells, the liver cancer group [(25 +/- 7)%, 6%, 0.7 x 10(7)/L, 15, (1.1 +/- 0.6) x 10(8)/L] decreased significantly as compared with the healthy group [(63 +/- 7)%, 36%, 8.3 x 10(7)/L, 116, (2.7 +/- 1.1) x 10(8)/L] and the hepatitis B group [(41 +/- 8)%, 16%, 2.8 x 10(7)/L, 49, (1.9 +/- 1.1) x 10(8)/L] (P < 0.05); and there was a slight decrease as compared with the hepatitis B cirrhosis group [(29 +/- 10)%, 7%, 0.6 x 10(7)/L, 29, (1.5 +/- 1.2) x 10(8)/L] (all P > 0.05 except NKG2D expression level of NK cells P < 0.05). The activity of NK cells showed a obvious positive correlation with the number of NK cell and the positive rate of NKG2D in NK cells, the number of NKG2D(+)NK cells and NKG2D expression level of NK cells (r = 0.657, 0.770, 0.927, 0.734, all P < 0.01). CONCLUSION: The cytotoxicity and the NKG2D expression of NK cells decreased significantly from peripheral blood in patients with primary hepatic carcinoma. The activity of NK cells was closely related to the NKG2D expression level of NK cells. Enhancing the NKG2D expression level of NK cell may provide a new idea for adoptive immunotherapy of primary hepatic carcinoma.

[Treatment of congenital hypertrophic pyloric stenosis with endoscopic pyloromyotomy].

OBJECTIVE: To evaluate the effect of the treatment of congenital hypertrophic pyloric stenosis (CHPS) with endoscopic pyloromyotomy. METHOD: Nine consecutive infants (7 boys, 2 girls; age range 26 - 70 days; weight range 2.65 - 6.10 kg), with a diagnosis of CHPS according to typical clinical manifestations, transabdominal ultrasound (US), gastroenterography and gastroscope. All the cases had accompanying malnutrition, anaemia, metabolic alkalosis, and some were complicated with congenital heart disease. In gastroscope operating room, all the patients were given pentobarbital and midazolam intravenously. A gastroscope with an outer diameter of 5.9 mm was passed through mouth, stomach, pylorus to the descending segment of duodenum. Under gastroscopy, two incisions were made along the anterior and posterior wall of pylorus from the duodenal bulb to the antrum by using endoscopic electrosurgical needle knife and an arch sphincter sarcosome. Incisions were deepened by 2 to 3 procedures until the longitudinal muscle was exposed, about 2 to 4 mm according to transabdominal US performed before operation. The incision depth was 2 - 3 mm if pylorus wall was 4 - 6 mm in thickness; or 3 - 4 mm when the wall was thicker than 6 mm. RESULT: The endoscope was easily passed through the pylorus to the duodenum post-operation. The transabdominal US and gastroenterography showed that liquid easily flew through pylorus. All patients were able to have regular feeding about 2 to 10 hours after the operation. Vomiting in all patients was significantly decreased in frequency and amount, and in 8 infants vomiting stopped within 1 week, in one case it did not stop until 1 month after the treatment. Some cases showed slight adverse reaction, no perforation or massive haemorrhage in stomach or intestines occurred in any of the patients during and post-operation. Eight infants were doing well at follow-up (range 2 to 9 months). One girl had recurred vomiting at normal feeding after a period of 1 month postoperation without vomiting. This case was cured by second endoscopic pyloromyotomy. CONCLUSIONS: Endoscopic pyloromyotomy is effective, safe, simple, and offers several advantages: no need for open-abdomen surgery, feeding can be initiated rapidly.