When oleanolic acid (OA) was administered ig before and after sensitization on d 1 to d 5 and d 11 to d 17,it had no apparent effect on Arthus reaction.When it was administered at 48,24 and 1 h before challenge,howeve...When oleanolic acid (OA) was administered ig before and after sensitization on d 1 to d 5 and d 11 to d 17,it had no apparent effect on Arthus reaction.When it was administered at 48,24 and 1 h before challenge,however,Arthus reaction was significantly inhibited.OA showed markedly suppressive effects on reversible passive Arthus reaction and leukocyte migratory response.It could significantly stabilize erythrocyte membrane,inhibit the swelling of the rat's hind paw induced by in- jecting mycostatin,reduce the acid phosphatase content in the inflammatory exudate,suppress the syn- thesis or release of PGE,histamine,LTB4 and kinin,and the phlogistic action of PGE_2,histamine,5- HT and kinin.In addition,it could decrease the content of malonyldialdehyde (MDA) in hepatic tissue of alcohol-intoxicated mice,and increase the activity of catalase (CAT) in hepatic tissue of mice.OA had no apparent effect on the activity of super-oxide dismutase (SOD) in rat serum,on the content of immune complex in serum of rat with Arthus reaction,on the phagocytosis of monocytc-macrophage system,on the clearance of enzyme-containing immune complex by macrophage,or on the activity of total complement.展开更多
AIM: To investigate the mutation of p53 immunohistochemically in non-tumorous gastric mucosa with H pylori infection before and aEer H pylori eradication therapy. METHODS: 53 subjects (36 male, 17 female, mean age ...AIM: To investigate the mutation of p53 immunohistochemically in non-tumorous gastric mucosa with H pylori infection before and aEer H pylori eradication therapy. METHODS: 53 subjects (36 male, 17 female, mean age ± SEM, 57.1 ± 12.1) undergoing endoscopic examination were included in this study. 42 of 53 patients were H pylori-positive, and 11 were H pylorinegative. All H pylori-positive patients had successful eradication therapy. Biopsy specimens were taken from five points of the stomach, as recommended by the updated Sydney system. Immunohistochemical studies were performed by using primary antibodies against p53 (DO-7 and PAb240). RESULTS: p53 (DO-7 and PAb240) immunoreactivity was shown in the neck region of the gastric pits, however, quite a few cells were found to be immunopositive for p53 (PAb240)in the Hpylori-infected gastric mucosa. The proportion of patients immunopositive for p53 (PAb240) was significantly reduced 6 mo after eradication [28/42 (66.7%) to 6/42 (14.3%)] (P 〈 0.05), while the biopsies taken from H pylori-negative patients showed no immunoreactivity for p53 (PAb240). p53 (PAb240)-positive patients were divided into two groups by the number of positive cells detected: one with more than six positive cells per 10 gastric pits (group A, n = 12), and the other with less than five positive cells per 10 gastric pits (group B, n = 30). Atrophy scores in group A were significant higher than those in group B at the greater curvature of the antrum (group A: 2.00 ± 0.14 vs group B: 1.40 ± 0.15, P = 0.012), the lesser curvature of the corpus (group A: 2.00 ± 0.21 vs group B: 1.07 ± 0.23, P = 0.017), and the greater curvature of the corpus (group A: 1.20 ± 0.30 vs group B: 0.47 ±0.21, P = 0.031). Group A showed significant higher intestinal metaplasia scores than group B only at the lesser curvature of the antrum (group A: 2.10 ± 0.41 vs group B: 1.12 ± 0.29, P = 0.035). CONCLUSION: H pylori-associated chronic gastritis expressed the mutant-type p53, which was significantly associated with more severe atrophic and metaplastic changes. Hpylori eradication led to a significant reduction in the expression of the mutant-type p53. It is considered that H pylori-infected chronic gastritis is associated with a genetic instability that leads to gastric carcinogenesis, and H pylori eradication may prevent gastric cancer.展开更多
SARS-CoV-2(COVID-19) has been affecting the world for more than one year.The appearance of the new coronavirus variants makes the current situation full of uncertainty.In this respect,the authors discuss the connectio...SARS-CoV-2(COVID-19) has been affecting the world for more than one year.The appearance of the new coronavirus variants makes the current situation full of uncertainty.In this respect,the authors discuss the connection between virus mutation and atmospheric factors.Based on the process of nitrogen fixation and transformation of nitrate inside the human body,the authors propose that the new coronavirus variants might be related to lightning and seawater intrusion.This study provides a new perspective in terms of the possible mechanism underlying the emergence of new coronavirus variants.展开更多
Cirrhosis develops from liver fibrosis and is the severe pathological stage of all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C virus infection is especially common. Liver fibrosis and c...Cirrhosis develops from liver fibrosis and is the severe pathological stage of all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C virus infection is especially common. Liver fibrosis and cirrhosis involve excess production of extracellular matrix,which is closely related to liver sinusoidal endothelial cells(LSECs). Damaged LSECs can synthesize transforming growth factor-beta and platelet-derived growth factor,which activate hepatic stellate cells and facilitate the synthesis of extracellular matrix. Herein,we highlight the angiogenic cytokines of LSECs related to liver fibrosis and cirrhosis at different stages and focus on the formation and development of liver fibrosis and cirrhosis. Inhibition of LSEC angiogenesis and antiangiogenic therapy are described in detail. Targeting LSECs has high therapeutic potential for liver diseases. Further understanding of the mechanism of action will provide stronger evidence for the development of anti-LSEC drugs and new directions for diagnosis and treatment of liver diseases.展开更多
AIM: To compare the sequencing of PCR products, pyro- sequencing, and real-time PCR for detection of Tyrosine- methionine-aspartate-aspartate (YMDD) mutants in patients with chronic hepatitis B. METHODS: Mixtures of p...AIM: To compare the sequencing of PCR products, pyro- sequencing, and real-time PCR for detection of Tyrosine- methionine-aspartate-aspartate (YMDD) mutants in patients with chronic hepatitis B. METHODS: Mixtures of plasmids and serum samples from 69 chronic hepatitis B patients treated with lamivu- dine were tested for YMDD mutations by sequencing of PCR products, pyrosequencing, and real-time PCR, re- spectively. Time required and reagent costs of the three assays were evaluated. RESULTS: Real-time PCR detected 100%, 50%, 10%, 1% and 0.1% of YVDD plasmid in mixtures with 106 copies/mL of YMDD plasmid, whereas sequencing and pyrosequencing only detected 100% and 50% of YVDD plasmid in aliquots of the corresponding mixtures. Com- pletely concordant results were obtained from 60 (87%) out of the 69 clinical serum samples by the three assays. Mutants were detected by real-time PCR in less than 20% of the total virus population, but no mutant was de- tected by sequencing and pyrosequencing. In addition, real-time PCR required less time and was more cost-ef- fective than the other two assays. However, throughput of pyrosequencing was the highest. CONCLUSION: Among the three assays compared, real-time PCR is the most sensitive, cost-effective, and time saving for monitoring YMDD mutants in patients with chronic hepatitis B on lamivudine therapy.展开更多
ABM: This study aims at exploring the distribution of TCM syndromes in CHB patients with HBV pre-core mutation (1896) and the relationship between pre-core mutation and T lymphocytes subgroup, through which to provide...ABM: This study aims at exploring the distribution of TCM syndromes in CHB patients with HBV pre-core mutation (1896) and the relationship between pre-core mutation and T lymphocytes subgroup, through which to provide objective data on clinical syndrome differentiation of TCM, and further to suggest the therapeutic principle and guide clinical treatment. METHODS: One hundred and forty CHB patients were evenly divided into two study groups, HBV pre-core mutant group and HBV pre-core wild-type group. Besides, 30 healthy blood donors were selected as a healthy control group. HBV-labeled compound, T lymphocytes subgroup, and HBV-DNA pre-core mutant were tested in the study groups. T lymphocytes subgroup were also tested in the control group. All the patients were both diagnosed by syndrome differentiation of TCM and western medicine. RESULTS: The most common syndrome in mutant group was damp-heat combined with blood stasis, and the most common syndrome in the wild-type group was damp-heat stasis in the middle-jiao. There were more cases of medium and severe hepatitis in mutant group than that in wild-type group. The content of CD4+ lymphocytes and CD4+/CD8+ ratio were decreased gradually (healthy control group>wild-type group>mutant group). In the wild-type group, severe and medium CHB patients had considerably lower level of them than mild CHB patients. However, in the mutant group, the opposite result appeared. Meanwhile, the content of HBV-DNA in mutant group was higher than that in wild-type group. CONCLUSION: Damp, heat, toxin and blood stasis were the basic pathogens of CHB, whether pre-core mutant or not. CHB with precore mutant may lead to more severe hepatitis. The decreased content of CD4+ lymphocytes and ratio of CD4+/CD8+ may be taken as one of the indices in confirming the deficiency syndrome of CHB patients with pre-core mutation.展开更多
We report a case of fatal liver failure due to reactivation of lamivudine-resistant HBV. A 53-year-old man was followed since 1998 for HBV-related chronic hepatitis. Serum HBV-DNA was 150 MEq/mL (branched DNA signal a...We report a case of fatal liver failure due to reactivation of lamivudine-resistant HBV. A 53-year-old man was followed since 1998 for HBV-related chronic hepatitis. Serum HBV-DNA was 150 MEq/mL (branched DNA signal amplification assay) and ALT levels fluctuated between 50-200 IU/L with no clinical signs of liver cirrhosis. Lamivudine (100 mg/d) was started in May 2001 and serum HBV-DNA subsequently decreased below undetectable levels. In May 2002, serum HBV-DNA had increased to 410 MEq/mL, along with ALT flare (226 IU/L). The YMDD motif in the DNA polymerase gene had been replaced by YIDD. Lamivudine was continued and ALT spontaneously decreased to the former levels. On Oct 3 the patient presenting with general fatigue, nausea and jaundice was admitted to our hospital. The laboratory data revealed HBV reactivation and liver failure (ALT: 1828 IU/L, total bilirubin: 10 mg/dL, and prothrombin INR: 3.24). For religious reasons, the patient and his family refused blood transfusion, plasma exchange and liver transplantation. The patient died 10 d after admission. The autopsy revealed remarkable liver atrophy.展开更多
AIM: To compare the ligase detection reaction (LDR) and real-time PCR for detection of low abundant YMDD mutants in patients with chronic hepatitis B infection.METHODS: Mixtures of plasmids and serum samples from 52 c...AIM: To compare the ligase detection reaction (LDR) and real-time PCR for detection of low abundant YMDD mutants in patients with chronic hepatitis B infection.METHODS: Mixtures of plasmids and serum samples from 52 chronic hepatitis B patients with low abundant lamivudine-resistant mutations were tested with LDR and real-time PCR. Time required and reagent cost for both assays were evaluated.RESULTS: Real-time PCR detected 100, 50, 10, 1 and 0.1% of YIDD plasmid, whereas LDR detected 100, 50, 10, 1, 0.1, and 0.01% of YIDD plasmid, in mixtures with YMDD plasmid of 106 copies/mL. Among the 52 clinical serum samples, completely concordant results were obtained for all samples by both assays, and 39 YIDD, 9 YVDD, and 4 YIDD/YVDD were detected. Cost and time required for LDR and real-time PCR are 60/80 CNY (8/10.7 US dollars) and 4.5/2.5 h, respectively.CONCLUSION: LDR and real-time PCR are both sensitive and inexpensive methods for monitoring low abundant YMDD mutants during lamivudine therapy in patients with chronic hepatitis B. LDR is more sensitive and less expensive, while real-time PCR is more rapid.展开更多
Objective: To study the clinical features of chronic hepatitis B (CHB) patients with tyrosine-methionine-aspartateaspartate (YMDD) mutation after lamivudine therapy. Methods: This investigation was a retrospective stu...Objective: To study the clinical features of chronic hepatitis B (CHB) patients with tyrosine-methionine-aspartateaspartate (YMDD) mutation after lamivudine therapy. Methods: This investigation was a retrospective study of 63 CHB patients with YMDD mutation during lamivudine therapy. Clinical data, including period and types of YMDD mutation; hepatitis B virus (HBV) DNA levels and alanine aminotransferase (ALT) levels before and after YMDD mutation were measured. YMDD mutation in the HBV DNA polymerase gene was determined using polymerase chain reaction (PCR) and direct sequencing. HBV DNA quantification was determined using real-time PCR. Relevant serum markers of HBV were measured. The follow-up period was 12 months after YMDD mutation. Results: YMDD mutation occurred 7~44 months (median, 21.5 months) after the start of lamivudine therapy. The majority of the cases (42/63, 66.6%) had YMDD mutants detected between 12 and 24 months. Four types of YMDD mutation were observed in this study, rtL180M/M204V mutation was the predominant type (26/63, 41.3%). A proportion of patients (16/63, 25.4%; 12/63, 19.1%) had higher HBV DNA levels and ALT levels (after mutation vs before mutation),respectively. Conclusion: The majority of patients with YMDD mutants had similar or lower HBV DNA levels and ALT levels compared with baseline values. This subset of patients might have benefited from the continued lamivudine therapy. The patients with increased ALT and HBV DNA levels (breakthrough hepatitis) should benefit from the addition of a newer nucleotide analogue (e.g. adefovir).展开更多
AIM: To investigate the usefulness of a new rendezvous technique for placing stents using the Kumpe (KMP) catheter in angulated or twisted biliary strictures. METHODS: The rendezvous technique was performed in pat...AIM: To investigate the usefulness of a new rendezvous technique for placing stents using the Kumpe (KMP) catheter in angulated or twisted biliary strictures. METHODS: The rendezvous technique was performed in patients with a biliary stricture after living donor liver transplantation (LDLT) who required the exchange of percutaneous transhepatic biliary drainage catheters for inside stents. The rendezvous technique was performed using a guidewire in 19 patients (guidewire group) and using a KMP catheter in another 19 (KMP catheter group). We compared the two groups retrospectively. RESULTS: The baseline characteristics did not differ between the groups. The success rate for placing insidestents was 100% in both groups. A KMP catheter was easier to manipulate than a guidewire. The mean pro- cedure time in the KMP catheter group (1012 s, range: 301-2006 s) was shorter than that in the guidewire group (2037 s, range: 251-6758 s, P = 0.022). The cu- mulative probabilities corresponding to the procedure time of the two groups were significantly different (P = 0.008). The factors related to procedure time were the rendezvous technique method, the number of inside stents, the operator, and balloon dilation of the stric- ture (P 〈 0.05). In a multivariate analysis, the rendez- vous technique method was the only significant factor related to procedure time (P = 0.010). The procedural complications observed included one case of mild acute pancreatitis and one case of acute cholangitis in the guidewire group, and two cases of mild acute pancre- atitis in the KMP catheter group. CONCLUSION: The rendezvous technique involving use of the KIVlp catheter was a fast and safe method for placing inside stents in patients with LDLT biliary stric- ture that represents a viable alternative to the guide- wire rendezvous technique,展开更多
AIM:To characterize the increasing incidence and geographic variation of acute diverticulitis.METHODS:Using the nationwide inpatient sample (NIS) we identified a cohort who had been admitted with diverticulitis betwee...AIM:To characterize the increasing incidence and geographic variation of acute diverticulitis.METHODS:Using the nationwide inpatient sample (NIS) we identified a cohort who had been admitted with diverticulitis between 1998 and 2005.We calculated age-,sex-,and region-specific rates of hospitalizations for diverticulitis over time.RESULTS:The age-adjusted hospitalization rate for diverticulitis increased from 61.8 per 100000 to 75.5 per 100 000 between 1998 and 2005,and increased similarly in both sexes.Diverticulitis-associated admissions were male-predominant in those younger than age 45 years but were female-predominant thereafter.Admission rates increased the most among those<45 years,while remaining unchanged for those≥65 years.By 2005,the majority of hospitalized patients were<65 years.Age-adjusted rates of diverticulitis-associated hospitalizations were lower in the West(50.4/100000) compared to the Northeast(77.7/100000),South (73.9/100000),and Midwest(71.0/100000).CONCLUSION:Diverticulitis-associated hospitalizations have steeply risen,especially in young adults.These epidemiological trends vary by geographic region and warrant further investigation into potential dietary and environmental etiologies.展开更多
To elucidate the role of proton pump inhibitors (PPIs) in collagenous disease, direct effect of PPI on colonocytes was examined.METHODSCollagenous colitis is a common cause of non-bloody, watery diarrhea. Recently, th...To elucidate the role of proton pump inhibitors (PPIs) in collagenous disease, direct effect of PPI on colonocytes was examined.METHODSCollagenous colitis is a common cause of non-bloody, watery diarrhea. Recently, there has been increasing focus on the use of proton PPIs as a risk factor for developing collagenous colitis. Mouse CT26 colonic cells were treated with PPI and/or PPI-induced alkaline media. Expression of fibrosis-associated genes was examined by RT-PCR. In human materials, collagen expression was examined by immunohistochemistry.RESULTSCT26 cells expressed a Na<sup>+</sup>-H<sup>+</sup> exchanger gene (solute carrier family 9, member A2). Treatment with PPI and/or PPI-induced alkaline media caused growth inhibition and oxidative stress in CT26 cells. The treatment increased expression of fibrosis inducing factors, transforming growth factor β and fibroblast growth factor 2. The treatment also decreased expression of a negative regulator of collagen production, replication factor C1, resulting in increased expression of collagen types III and IV in association with lipid peroxide. In biopsy specimens from patients with collagenous colitis, type III and IV collagen were increased. Increase of type III collagen was more pronounced in PPI-associated collagenous colitis than in non-PPI-associated disease.CONCLUSIONFrom these findings, the reaction of colonocytes to PPI might participate in pathogenesis of collagenous colitis.展开更多
Subclinical gut inflammation has been described in up to twothirds of patients with spondyloarthropathies(SpA).Arthritis represents an extraintestinal manifestation of several gastrointestinal diseases, including infl...Subclinical gut inflammation has been described in up to twothirds of patients with spondyloarthropathies(SpA).Arthritis represents an extraintestinal manifestation of several gastrointestinal diseases, including inflammatory bowel disease(IBD), Whipple's disease, Behcet's disease, celiac disease, intestinal bypass surgery, parasitic infections of the gut and pseudomembranous colitis.Moreover about two thirds of nonsteroidal antiinflammatory drug users demonstrate intestinal inflammation.Arthritis may manifest as a peripheral or axial arthritis.The spondyloarthropathy family consists of the following entities:ankylosing spondylitis, undifferentiated spondyloarthritis, reactive arthritis, psoriatic arthritis, spondyloarthritis associated with IBD, juvenile onset spondyloarthritis.This topic reviews the major gastrointestinal manifestations that can occur in patients with SpA and in nonsteroidal anti inflammatory drugs users.展开更多
AIM: To confirm the presence of recombination, fulllength hepatitis B virus (HBV) from chronic patients was sequenced and analyzed. METHODS: Full-length HBV genomes from 12 patients were amplified and sequenced in...AIM: To confirm the presence of recombination, fulllength hepatitis B virus (HBV) from chronic patients was sequenced and analyzed. METHODS: Full-length HBV genomes from 12 patients were amplified and sequenced in an automated sequencer. Phylogenetic analysis was carried out on full-length, Core and preS2/Surface regions using MEGA software. SimPIot Boot Scanning and amino acid sequence analysis were performed for confirmation of recombination. RESULTS: Eight patients were infected with genotype D strain; one patient with genotype A and three patients had genotype A and D recombination; two of them had cirrhosis and one had hepatocellular carcinoma. Phylogenetic analysis of core and preS2/surface regions separately showed evidence of genotype A and D recombination. The breakpoints of recombination were found to be at the start of preS2 and at the endof surface coding regions. CONCLUSION: We identified and characterized recombinant A and D genotype HBV in hepatitis B surface antigen (HBsAg)-positive patients.展开更多
The hepatitis B virus (HBV) particle consists of an envelope containing three related surface proteins and probably lipid and an icosahedral nucleocapsid of approximately 30 nm diameter enclosing the viral DNA genom...The hepatitis B virus (HBV) particle consists of an envelope containing three related surface proteins and probably lipid and an icosahedral nucleocapsid of approximately 30 nm diameter enclosing the viral DNA genome and DNA polymerase. The capsid is formed in the cytosol of the infected cell during packaging of an RNA pregenome replication complex by multiple copies of a 21-kDa C protein. The capsid gains the ability to bud during synthesis of the viral DNA genome by reverse transcription of the pregenome in the lumen of the particle. The three envelope proteins S, t4, and L shape a complex transmembrane fold at the endoplasmic reticulum, and form disulfide-linked homoand heterodimers. The transmembrane topology of a fraction of the large envelope protein L changes posttranslationally, therefore, the N terminal domain of L (preS) finally appears on both sides of the membrane. During budding at an intracellular membrane, a short linear domain in the cytosolic preS region interacts with binding sites on the capsid surface. The virions are subsequently secreted into the blood. In addition, the surface proteins can bud in the absence of capsids and form subviral lipoprotein particles of 20 nm diameter which are also secreted.展开更多
AIM: To find out whether there is a significant difference in the prevalence of the precore stop codon mutation between HBeAg positive and anti-HBe positive children. METHODS: We investigated a large pediatric popul...AIM: To find out whether there is a significant difference in the prevalence of the precore stop codon mutation between HBeAg positive and anti-HBe positive children. METHODS: We investigated a large pediatric population of 155 European children (mean age 10.9 years) with chronic hepatitis B by PCR and direct sequencing. Ninety were HBeAg positive and 65 had seroconversion to anti-HBe. Additionally genotyping was performed. RESULTS: Seventy-four (48%) of the sequenced HBV strains were attributed to genotype D and 81 (52%) to genotype A. In the group of 90 HBeAg positive patients, 2 (2.2%) 1896-G-to-A transitions leading to precore stop codon mutation were found, and in the group of 65 anti-HBe positive children, 5 (7.7%) were identified harbouring HBeAg-minus mutants. The difference was not statistically significant (P= 0.13). CONCLUSIONS: HBeAg minus variants as predominant viral HB strains play a minor role in the course of chronic hepatitis B in European children.展开更多
文摘When oleanolic acid (OA) was administered ig before and after sensitization on d 1 to d 5 and d 11 to d 17,it had no apparent effect on Arthus reaction.When it was administered at 48,24 and 1 h before challenge,however,Arthus reaction was significantly inhibited.OA showed markedly suppressive effects on reversible passive Arthus reaction and leukocyte migratory response.It could significantly stabilize erythrocyte membrane,inhibit the swelling of the rat's hind paw induced by in- jecting mycostatin,reduce the acid phosphatase content in the inflammatory exudate,suppress the syn- thesis or release of PGE,histamine,LTB4 and kinin,and the phlogistic action of PGE_2,histamine,5- HT and kinin.In addition,it could decrease the content of malonyldialdehyde (MDA) in hepatic tissue of alcohol-intoxicated mice,and increase the activity of catalase (CAT) in hepatic tissue of mice.OA had no apparent effect on the activity of super-oxide dismutase (SOD) in rat serum,on the content of immune complex in serum of rat with Arthus reaction,on the phagocytosis of monocytc-macrophage system,on the clearance of enzyme-containing immune complex by macrophage,or on the activity of total complement.
基金Supported by Grants-in-Aid (C-14) from the Ministry of Health,Labor and Welfare,Japan
文摘AIM: To investigate the mutation of p53 immunohistochemically in non-tumorous gastric mucosa with H pylori infection before and aEer H pylori eradication therapy. METHODS: 53 subjects (36 male, 17 female, mean age ± SEM, 57.1 ± 12.1) undergoing endoscopic examination were included in this study. 42 of 53 patients were H pylori-positive, and 11 were H pylorinegative. All H pylori-positive patients had successful eradication therapy. Biopsy specimens were taken from five points of the stomach, as recommended by the updated Sydney system. Immunohistochemical studies were performed by using primary antibodies against p53 (DO-7 and PAb240). RESULTS: p53 (DO-7 and PAb240) immunoreactivity was shown in the neck region of the gastric pits, however, quite a few cells were found to be immunopositive for p53 (PAb240)in the Hpylori-infected gastric mucosa. The proportion of patients immunopositive for p53 (PAb240) was significantly reduced 6 mo after eradication [28/42 (66.7%) to 6/42 (14.3%)] (P 〈 0.05), while the biopsies taken from H pylori-negative patients showed no immunoreactivity for p53 (PAb240). p53 (PAb240)-positive patients were divided into two groups by the number of positive cells detected: one with more than six positive cells per 10 gastric pits (group A, n = 12), and the other with less than five positive cells per 10 gastric pits (group B, n = 30). Atrophy scores in group A were significant higher than those in group B at the greater curvature of the antrum (group A: 2.00 ± 0.14 vs group B: 1.40 ± 0.15, P = 0.012), the lesser curvature of the corpus (group A: 2.00 ± 0.21 vs group B: 1.07 ± 0.23, P = 0.017), and the greater curvature of the corpus (group A: 1.20 ± 0.30 vs group B: 0.47 ±0.21, P = 0.031). Group A showed significant higher intestinal metaplasia scores than group B only at the lesser curvature of the antrum (group A: 2.10 ± 0.41 vs group B: 1.12 ± 0.29, P = 0.035). CONCLUSION: H pylori-associated chronic gastritis expressed the mutant-type p53, which was significantly associated with more severe atrophic and metaplastic changes. Hpylori eradication led to a significant reduction in the expression of the mutant-type p53. It is considered that H pylori-infected chronic gastritis is associated with a genetic instability that leads to gastric carcinogenesis, and H pylori eradication may prevent gastric cancer.
文摘SARS-CoV-2(COVID-19) has been affecting the world for more than one year.The appearance of the new coronavirus variants makes the current situation full of uncertainty.In this respect,the authors discuss the connection between virus mutation and atmospheric factors.Based on the process of nitrogen fixation and transformation of nitrate inside the human body,the authors propose that the new coronavirus variants might be related to lightning and seawater intrusion.This study provides a new perspective in terms of the possible mechanism underlying the emergence of new coronavirus variants.
基金Supported by the Young Elite Scientists Sponsorship Program by CAST,No.2016QNRC001Beijing Natural Science Foundation,No.7172187
文摘Cirrhosis develops from liver fibrosis and is the severe pathological stage of all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C virus infection is especially common. Liver fibrosis and cirrhosis involve excess production of extracellular matrix,which is closely related to liver sinusoidal endothelial cells(LSECs). Damaged LSECs can synthesize transforming growth factor-beta and platelet-derived growth factor,which activate hepatic stellate cells and facilitate the synthesis of extracellular matrix. Herein,we highlight the angiogenic cytokines of LSECs related to liver fibrosis and cirrhosis at different stages and focus on the formation and development of liver fibrosis and cirrhosis. Inhibition of LSEC angiogenesis and antiangiogenic therapy are described in detail. Targeting LSECs has high therapeutic potential for liver diseases. Further understanding of the mechanism of action will provide stronger evidence for the development of anti-LSEC drugs and new directions for diagnosis and treatment of liver diseases.
文摘AIM: To compare the sequencing of PCR products, pyro- sequencing, and real-time PCR for detection of Tyrosine- methionine-aspartate-aspartate (YMDD) mutants in patients with chronic hepatitis B. METHODS: Mixtures of plasmids and serum samples from 69 chronic hepatitis B patients treated with lamivu- dine were tested for YMDD mutations by sequencing of PCR products, pyrosequencing, and real-time PCR, re- spectively. Time required and reagent costs of the three assays were evaluated. RESULTS: Real-time PCR detected 100%, 50%, 10%, 1% and 0.1% of YVDD plasmid in mixtures with 106 copies/mL of YMDD plasmid, whereas sequencing and pyrosequencing only detected 100% and 50% of YVDD plasmid in aliquots of the corresponding mixtures. Com- pletely concordant results were obtained from 60 (87%) out of the 69 clinical serum samples by the three assays. Mutants were detected by real-time PCR in less than 20% of the total virus population, but no mutant was de- tected by sequencing and pyrosequencing. In addition, real-time PCR required less time and was more cost-ef- fective than the other two assays. However, throughput of pyrosequencing was the highest. CONCLUSION: Among the three assays compared, real-time PCR is the most sensitive, cost-effective, and time saving for monitoring YMDD mutants in patients with chronic hepatitis B on lamivudine therapy.
基金Supported by the Foundation of TCM Administration Bureau, Guangdong Province, No. 100115
文摘ABM: This study aims at exploring the distribution of TCM syndromes in CHB patients with HBV pre-core mutation (1896) and the relationship between pre-core mutation and T lymphocytes subgroup, through which to provide objective data on clinical syndrome differentiation of TCM, and further to suggest the therapeutic principle and guide clinical treatment. METHODS: One hundred and forty CHB patients were evenly divided into two study groups, HBV pre-core mutant group and HBV pre-core wild-type group. Besides, 30 healthy blood donors were selected as a healthy control group. HBV-labeled compound, T lymphocytes subgroup, and HBV-DNA pre-core mutant were tested in the study groups. T lymphocytes subgroup were also tested in the control group. All the patients were both diagnosed by syndrome differentiation of TCM and western medicine. RESULTS: The most common syndrome in mutant group was damp-heat combined with blood stasis, and the most common syndrome in the wild-type group was damp-heat stasis in the middle-jiao. There were more cases of medium and severe hepatitis in mutant group than that in wild-type group. The content of CD4+ lymphocytes and CD4+/CD8+ ratio were decreased gradually (healthy control group>wild-type group>mutant group). In the wild-type group, severe and medium CHB patients had considerably lower level of them than mild CHB patients. However, in the mutant group, the opposite result appeared. Meanwhile, the content of HBV-DNA in mutant group was higher than that in wild-type group. CONCLUSION: Damp, heat, toxin and blood stasis were the basic pathogens of CHB, whether pre-core mutant or not. CHB with precore mutant may lead to more severe hepatitis. The decreased content of CD4+ lymphocytes and ratio of CD4+/CD8+ may be taken as one of the indices in confirming the deficiency syndrome of CHB patients with pre-core mutation.
文摘We report a case of fatal liver failure due to reactivation of lamivudine-resistant HBV. A 53-year-old man was followed since 1998 for HBV-related chronic hepatitis. Serum HBV-DNA was 150 MEq/mL (branched DNA signal amplification assay) and ALT levels fluctuated between 50-200 IU/L with no clinical signs of liver cirrhosis. Lamivudine (100 mg/d) was started in May 2001 and serum HBV-DNA subsequently decreased below undetectable levels. In May 2002, serum HBV-DNA had increased to 410 MEq/mL, along with ALT flare (226 IU/L). The YMDD motif in the DNA polymerase gene had been replaced by YIDD. Lamivudine was continued and ALT spontaneously decreased to the former levels. On Oct 3 the patient presenting with general fatigue, nausea and jaundice was admitted to our hospital. The laboratory data revealed HBV reactivation and liver failure (ALT: 1828 IU/L, total bilirubin: 10 mg/dL, and prothrombin INR: 3.24). For religious reasons, the patient and his family refused blood transfusion, plasma exchange and liver transplantation. The patient died 10 d after admission. The autopsy revealed remarkable liver atrophy.
文摘AIM: To compare the ligase detection reaction (LDR) and real-time PCR for detection of low abundant YMDD mutants in patients with chronic hepatitis B infection.METHODS: Mixtures of plasmids and serum samples from 52 chronic hepatitis B patients with low abundant lamivudine-resistant mutations were tested with LDR and real-time PCR. Time required and reagent cost for both assays were evaluated.RESULTS: Real-time PCR detected 100, 50, 10, 1 and 0.1% of YIDD plasmid, whereas LDR detected 100, 50, 10, 1, 0.1, and 0.01% of YIDD plasmid, in mixtures with YMDD plasmid of 106 copies/mL. Among the 52 clinical serum samples, completely concordant results were obtained for all samples by both assays, and 39 YIDD, 9 YVDD, and 4 YIDD/YVDD were detected. Cost and time required for LDR and real-time PCR are 60/80 CNY (8/10.7 US dollars) and 4.5/2.5 h, respectively.CONCLUSION: LDR and real-time PCR are both sensitive and inexpensive methods for monitoring low abundant YMDD mutants during lamivudine therapy in patients with chronic hepatitis B. LDR is more sensitive and less expensive, while real-time PCR is more rapid.
文摘Objective: To study the clinical features of chronic hepatitis B (CHB) patients with tyrosine-methionine-aspartateaspartate (YMDD) mutation after lamivudine therapy. Methods: This investigation was a retrospective study of 63 CHB patients with YMDD mutation during lamivudine therapy. Clinical data, including period and types of YMDD mutation; hepatitis B virus (HBV) DNA levels and alanine aminotransferase (ALT) levels before and after YMDD mutation were measured. YMDD mutation in the HBV DNA polymerase gene was determined using polymerase chain reaction (PCR) and direct sequencing. HBV DNA quantification was determined using real-time PCR. Relevant serum markers of HBV were measured. The follow-up period was 12 months after YMDD mutation. Results: YMDD mutation occurred 7~44 months (median, 21.5 months) after the start of lamivudine therapy. The majority of the cases (42/63, 66.6%) had YMDD mutants detected between 12 and 24 months. Four types of YMDD mutation were observed in this study, rtL180M/M204V mutation was the predominant type (26/63, 41.3%). A proportion of patients (16/63, 25.4%; 12/63, 19.1%) had higher HBV DNA levels and ALT levels (after mutation vs before mutation),respectively. Conclusion: The majority of patients with YMDD mutants had similar or lower HBV DNA levels and ALT levels compared with baseline values. This subset of patients might have benefited from the continued lamivudine therapy. The patients with increased ALT and HBV DNA levels (breakthrough hepatitis) should benefit from the addition of a newer nucleotide analogue (e.g. adefovir).
文摘AIM: To investigate the usefulness of a new rendezvous technique for placing stents using the Kumpe (KMP) catheter in angulated or twisted biliary strictures. METHODS: The rendezvous technique was performed in patients with a biliary stricture after living donor liver transplantation (LDLT) who required the exchange of percutaneous transhepatic biliary drainage catheters for inside stents. The rendezvous technique was performed using a guidewire in 19 patients (guidewire group) and using a KMP catheter in another 19 (KMP catheter group). We compared the two groups retrospectively. RESULTS: The baseline characteristics did not differ between the groups. The success rate for placing insidestents was 100% in both groups. A KMP catheter was easier to manipulate than a guidewire. The mean pro- cedure time in the KMP catheter group (1012 s, range: 301-2006 s) was shorter than that in the guidewire group (2037 s, range: 251-6758 s, P = 0.022). The cu- mulative probabilities corresponding to the procedure time of the two groups were significantly different (P = 0.008). The factors related to procedure time were the rendezvous technique method, the number of inside stents, the operator, and balloon dilation of the stric- ture (P 〈 0.05). In a multivariate analysis, the rendez- vous technique method was the only significant factor related to procedure time (P = 0.010). The procedural complications observed included one case of mild acute pancreatitis and one case of acute cholangitis in the guidewire group, and two cases of mild acute pancre- atitis in the KMP catheter group. CONCLUSION: The rendezvous technique involving use of the KIVlp catheter was a fast and safe method for placing inside stents in patients with LDLT biliary stric- ture that represents a viable alternative to the guide- wire rendezvous technique,
基金Supported by An AGA Research Scholar Award to Nguyen GC
文摘AIM:To characterize the increasing incidence and geographic variation of acute diverticulitis.METHODS:Using the nationwide inpatient sample (NIS) we identified a cohort who had been admitted with diverticulitis between 1998 and 2005.We calculated age-,sex-,and region-specific rates of hospitalizations for diverticulitis over time.RESULTS:The age-adjusted hospitalization rate for diverticulitis increased from 61.8 per 100000 to 75.5 per 100 000 between 1998 and 2005,and increased similarly in both sexes.Diverticulitis-associated admissions were male-predominant in those younger than age 45 years but were female-predominant thereafter.Admission rates increased the most among those<45 years,while remaining unchanged for those≥65 years.By 2005,the majority of hospitalized patients were<65 years.Age-adjusted rates of diverticulitis-associated hospitalizations were lower in the West(50.4/100000) compared to the Northeast(77.7/100000),South (73.9/100000),and Midwest(71.0/100000).CONCLUSION:Diverticulitis-associated hospitalizations have steeply risen,especially in young adults.These epidemiological trends vary by geographic region and warrant further investigation into potential dietary and environmental etiologies.
基金Supportedby MEXT KAKENHI,No.14478268 and No.16675788
文摘To elucidate the role of proton pump inhibitors (PPIs) in collagenous disease, direct effect of PPI on colonocytes was examined.METHODSCollagenous colitis is a common cause of non-bloody, watery diarrhea. Recently, there has been increasing focus on the use of proton PPIs as a risk factor for developing collagenous colitis. Mouse CT26 colonic cells were treated with PPI and/or PPI-induced alkaline media. Expression of fibrosis-associated genes was examined by RT-PCR. In human materials, collagen expression was examined by immunohistochemistry.RESULTSCT26 cells expressed a Na<sup>+</sup>-H<sup>+</sup> exchanger gene (solute carrier family 9, member A2). Treatment with PPI and/or PPI-induced alkaline media caused growth inhibition and oxidative stress in CT26 cells. The treatment increased expression of fibrosis inducing factors, transforming growth factor β and fibroblast growth factor 2. The treatment also decreased expression of a negative regulator of collagen production, replication factor C1, resulting in increased expression of collagen types III and IV in association with lipid peroxide. In biopsy specimens from patients with collagenous colitis, type III and IV collagen were increased. Increase of type III collagen was more pronounced in PPI-associated collagenous colitis than in non-PPI-associated disease.CONCLUSIONFrom these findings, the reaction of colonocytes to PPI might participate in pathogenesis of collagenous colitis.
文摘Subclinical gut inflammation has been described in up to twothirds of patients with spondyloarthropathies(SpA).Arthritis represents an extraintestinal manifestation of several gastrointestinal diseases, including inflammatory bowel disease(IBD), Whipple's disease, Behcet's disease, celiac disease, intestinal bypass surgery, parasitic infections of the gut and pseudomembranous colitis.Moreover about two thirds of nonsteroidal antiinflammatory drug users demonstrate intestinal inflammation.Arthritis may manifest as a peripheral or axial arthritis.The spondyloarthropathy family consists of the following entities:ankylosing spondylitis, undifferentiated spondyloarthritis, reactive arthritis, psoriatic arthritis, spondyloarthritis associated with IBD, juvenile onset spondyloarthritis.This topic reviews the major gastrointestinal manifestations that can occur in patients with SpA and in nonsteroidal anti inflammatory drugs users.
基金Indian Council of Medical Research-Advanced Center for Liver Diseases Project (ICMR-ACLD)
文摘AIM: To confirm the presence of recombination, fulllength hepatitis B virus (HBV) from chronic patients was sequenced and analyzed. METHODS: Full-length HBV genomes from 12 patients were amplified and sequenced in an automated sequencer. Phylogenetic analysis was carried out on full-length, Core and preS2/Surface regions using MEGA software. SimPIot Boot Scanning and amino acid sequence analysis were performed for confirmation of recombination. RESULTS: Eight patients were infected with genotype D strain; one patient with genotype A and three patients had genotype A and D recombination; two of them had cirrhosis and one had hepatocellular carcinoma. Phylogenetic analysis of core and preS2/surface regions separately showed evidence of genotype A and D recombination. The breakpoints of recombination were found to be at the start of preS2 and at the endof surface coding regions. CONCLUSION: We identified and characterized recombinant A and D genotype HBV in hepatitis B surface antigen (HBsAg)-positive patients.
文摘The hepatitis B virus (HBV) particle consists of an envelope containing three related surface proteins and probably lipid and an icosahedral nucleocapsid of approximately 30 nm diameter enclosing the viral DNA genome and DNA polymerase. The capsid is formed in the cytosol of the infected cell during packaging of an RNA pregenome replication complex by multiple copies of a 21-kDa C protein. The capsid gains the ability to bud during synthesis of the viral DNA genome by reverse transcription of the pregenome in the lumen of the particle. The three envelope proteins S, t4, and L shape a complex transmembrane fold at the endoplasmic reticulum, and form disulfide-linked homoand heterodimers. The transmembrane topology of a fraction of the large envelope protein L changes posttranslationally, therefore, the N terminal domain of L (preS) finally appears on both sides of the membrane. During budding at an intracellular membrane, a short linear domain in the cytosolic preS region interacts with binding sites on the capsid surface. The virions are subsequently secreted into the blood. In addition, the surface proteins can bud in the absence of capsids and form subviral lipoprotein particles of 20 nm diameter which are also secreted.
文摘AIM: To find out whether there is a significant difference in the prevalence of the precore stop codon mutation between HBeAg positive and anti-HBe positive children. METHODS: We investigated a large pediatric population of 155 European children (mean age 10.9 years) with chronic hepatitis B by PCR and direct sequencing. Ninety were HBeAg positive and 65 had seroconversion to anti-HBe. Additionally genotyping was performed. RESULTS: Seventy-four (48%) of the sequenced HBV strains were attributed to genotype D and 81 (52%) to genotype A. In the group of 90 HBeAg positive patients, 2 (2.2%) 1896-G-to-A transitions leading to precore stop codon mutation were found, and in the group of 65 anti-HBe positive children, 5 (7.7%) were identified harbouring HBeAg-minus mutants. The difference was not statistically significant (P= 0.13). CONCLUSIONS: HBeAg minus variants as predominant viral HB strains play a minor role in the course of chronic hepatitis B in European children.