New phorbol ester derivatives as potent anti-HIV agents.

Tigliane esters show many biological activities, including anti-HIV-1 activity. Our aim in this study was to establish structure-anti-HIV activity relationships for four series of tigliane-type diterpenoids. We synthesized and evaluated 29 new phorbol ester derivatives for anti-HIV activity and for cytotoxicity against human tumor cell lines. Among them, three derivatives, two phorbol-13-monoesters (5d and 5e) and a phorbol-12,13-diester (6a), showed significant anti-HIV activity. We found that better anti-HIV activity was often associated with a shorter acyl ester at C-13. Particularly, compounds with a phenyl ring in the ester side chain exhibited excellent anti-HIV activity and had good safety indexes. Due to its significant anti-HIV potency with a high selectivity index, phorbol-12,13-dicinnamoate (6a) was chosen as the potential candidate for further preclinical trials.

Synthesis and in vitro anticancer activities of biotinylated derivatives of glaucocalyxin A and oridonin.

Fourteen glaucocalyxin A biotinylated derivatives, one glaucocalyxin C biotinylated derivative, and two oridonin biotinylated derivatives were designed and synthesized. Their structures were confirmed from 1H NMR, 13C NMR and HRMS data. The derivatives were evaluated for cytotoxic activities against lung (A549), cervical cancer cell line HeLa derivative (KB), multidrug-resistant KB subline (KB-VIN), triple-negative breast (MDA-MB-231), and estrogen receptor-positive breast (MCF-7) cancer cell lines.[Formula: see text].

The therapeutic effects of Jaceosidin on lipopolysaccharide-induced acute lung injury in mice.

Acute lung injury (ALI) results from various factors including uncontrolled pulmonary inflammation, oxidative damage and the over-activated complement with high mortality rates. Jaceosidin was a flavonoid compound with significant anti-complement activity. We aimed to investigate the therapeutic effects of Jaceosidin on ALI induced by lipopolysaccharide (LPS). Mice were orally administrated with Jaceosidin (15, 30 and 60 mg/kg) after LPS challenge. 24 h after LPS challenge, Jaceosidin could significantly decrease the lung wet-to-dry weight (W/D) ratio and the protein concentration in bronchoalveolar lavage fluid (BALF). Jaceosidin could down-regulate the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), together with up-regulation the levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) in BALF. Jaceosidin could significantly decrease the levels of myeloperoxidase (MPO), cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB), COX-2 mRNA and NF-κB p65 mRNA together with increasing the activity of catalase (CAT). Additionally, Jaceosidin attenuated lung histopathological changes, inhibited the expressions of COX-2 and NF-κB p65 and reduced complement deposition with decreasing the levels of complement 3 (C3) and complement 3c (C3c) in serum. These data suggest that Jaceocidin may dampen the inflammatory response and decrease the levels of complement together with the antioxidant activity following LPS-induced ALI.

[Medium-chain acyl-CoA dehydrogenase deficiency: neonatal screening and follow-uP].

OBJECTIVE: To investigate the epidemiological characteristics, phenotype, genotype, and prognosis of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in the Chinese population. METHODS: A retrospective analysis was performed for the clinical data of the neonates who underwent screening with high-performance liquid chromatography-tandem mass spectrometry from January 2009 to June 2018 and were diagnosed with MCADD by gene detection. RESULTS: A total of 2 674 835 neonates underwent neonatal screening, among whom 12 were diagnosed with MCADD. Gene detection was performed for 10 neonates with MCADD and found 13 mutation types at 16 mutation sites of the ACADM gene, among which there were 7 reported mutations (p.T150Rfs*4, p.M1V, p.R206C, p.R294T, p.G310R, p.M328V, and p.G362E), 5 novel mutations (p.N194D, p.A324P, p.N366S, c.118+3A>G, and c.387+1del G), and 1 exon 11 deletion; p.T150Rfs*4 was the most common mutation (4/16). The detection rate of mutation sites in the ACADM gene was 80%. No phenotype-genotype correlation was observed. Dietary guidance and symptomatic treatment were given after confirmed diagnosis. No acute metabolic imbalance was observed within 4-82 months of follow-up. All neonates had good prognosis except one who had brain dysplasia. CONCLUSIONS: MCADD is relatively rare in southern China, and p.T150Rfs*4 is a common mutation in the Chinese population. Cases with positive screening results should be evaluated by octanoylcarnitine C8 value and gene detection.

Association between cigarette smoking and impaired clinical symptoms in systemic sclerosis: A review.

It has been established that smoking has a profound impact on susceptibility and severity in some rheumatic diseases (e.g., rheumatoid arthritis), a mild impact in others (e.g., systemic lupus erythematosus) through epidemiological studies. And smoking is known to affect many inflammatory and autoimmune diseases through various mechanisms, including immunomodulation and chemical exposure. Although similar studies investigating the role of cigarette exposure in susceptibility to SSc have been rarely reported and specific mechanisms have never been established, the relationship between smoking and some SSc-related symptoms have been demonstrated during the last decade. However, due to the diversity of study designs, control populations, patient populations and the methodology used to determine smoking history, these results are contradictory in some respects. This paper will review current evidence on the association between smoking and SSc and summarize potential mechanisms.

Nitrogen-doped porous carbon nanosheets as low-cost, high-performance anode material for sodium-ion batteries.

Between the sheets: Sodium-ion batteries are an attractive, low-cost alternative to lithium-ion batteries. Nitrogen-doped porous carbon sheets are prepared by chemical activation of polypyrrole-functionalized graphene sheets. When using the sheets as anode material in sodium-ion batteries, their unique compositional and structural features result in high reversible capacity, good cycling stability, and high rate capability.

[Clinical value of wireless capsule endoscopy in diagnosis of small bowel disease in children].

OBJECTIVE: The pathological change of small bowel is difficult to examine because it is anatomically unique. The development of wireless capsule endoscopy provides an unique opportunity to visualize the entire small bowel in a minimally invasive manner. The aim of this study was to assess the safety and clinical value of wireless capsule endoscopy in children. METHODS: During the last 4 years (June, 2004-June, 2008), 46 times of wireless capsule endoscopy were performed in 43 patients with suspected small bowel disease, including obscure gastrointestinal bleeding (n = 11), recurrent abdominal pain (n = 20), chronic diarrhea (n = 9), protein losing enteropathy (n = 2), recurrent vomiting (n = 1). Of the 43 cases, 28 were male and 15 were female, the age ranged from 6 to 18 years, 8 of these cases were < 10 years old. The weight of the patients ranged between 15 kg and 60 kg. The average time of capsule passing through the stomach and the small intestine, the tolerance to and complication of wireless capsule endoscopy in patients, the image quality of capsule endoscopy, and the cleanliness of small intestine after fasting for 8 hours were observed and recorded. RESULT: All the patients could easily swallow the capsule and had good tolerance. The overall success rate was 94% (43/46). The median time of capsule passing through the stomach and small intestine was 73 min (range, 3 - 600 min) and 246 min (range, 73 - 413 min), respectively. The diagnostic yield of pathological change in small intestine was 90% (37/41), and the diagnostic accordance rate was 84% (31/37). Based on the wireless capsule endoscopy, diagnostic findings included Crohn's diseases (15), lymph follicular hyperplasia (4), nonspecific enteritis (4), vascular malformations (3), small bowel tumour (2), primary intestinal lymphangiectasia (2), gastrointestinal motility disorders (2), Meckel's diverticulum (1), angioma (1), small intestinal worm disease (1), duodenal ulcer (1), and polyposis syndromes (1). The capsule of 1 patient remained in the stomach. The cleanliness of small intestine after 8 hours fasting was good. And the capsule endoscopy can show high quality small intestine image. CONCLUSION: Wireless capsule endoscopy is a noninvasive, safe and useful tool for the investigation of the small intestine in children, especially for obscure gastrointestinal bleeding and Crohn's disease.

[Rapid detection of clarithromycin resistant Helicobacter pylori from children's gastric biopsy specimens by polymerase chain reaction-restriction fragment length polymorphism].

OBJECTIVE: Infection with clarithromycin-resistant Helicobacter pylori (Hp) is often predictive of treatment failure. Susceptibility testing for Hp could guide therapy of Hp infections. However, agar dilution approved by the Clinical and Laboratory Standards Institute (CLSI) to test for antimicrobial susceptibility of Hp is time consuming (results are often not available in a week or more). So a more expeditious method is necessary. The purpose of this study was to evaluate polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) test performed directly on gastric biopsy specimen from children to detect 23S rRNA mutations (A2143G and A2144G) indicating clarithromycin resistance. METHODS: All biopsy specimens were derived from patients presenting with upper gastrointestinal symptoms, submitted to endoscopy in the Affiliated Children's Hospital, Zhejiang University School of Medicine from September 2006 to February 2007. No patients had undergone eradication therapy. Thirty-nine samples randomly selected from positive specimens by rapid urease test, were homogenized in 500 microl brucella broth with 30% glycerol. The 200 microl homogenized fluid was used to purify genomic DNA with the kit according to the instructions provided by manufacturer, and the rest was used to isolate Hp strains by culturing. All the Hp isolates were tested for clarithromycin susceptibility with the agar dilution and classified as resistant if the minimum inhibitory concentrations (MIC) exceeded 1 microg/ml. Simultaneously, PCR-RFLP analysis was performed in order to identify 23S rRNA mutations (A2143G and A2144G). Finally, the two methods were compared by statistics. The agar dilution was used as a standard to determine the sensitivity and specificity of the PCR-RFLP assay. RESULTS: Of the 39 samples, agar dilution and PCR-RFLP method respectively detected 13 (33.3%) and 14 (35.9%) clarithromycin-resistant gastric specimens. The sensitivity and specificity of PCR-RFLP for the detection of Hp in biopsy specimens were both 92%. The positive and negative predictive value was 85.7% and 96% respectively. No statistically significant difference was found between the two methods (chi2=0.06, P>0.05). The rate of Hp resistance to clarithromycin significantly increased compared with a previous report from the authors' hospital in 2004 (chi2=6.20, P<0.05). CONCLUSIONS: Rising clarithromycin resistance rates were observed in children who visited the authors' hospital. PCR-RFLP test is reliable and rapid for detection of clarithromycin resistance directly on gastric biopsy specimen from children and may help choose appropriate antibiotic in Hp eradication therapy.

[Preliminary study on in-vitro induction of antibiotic resistance in Helicobacter pylori strains isolated from children].

OBJECTIVE: Many clinical studies indicated that Helicobacter pylori (Hp) strains rarely acquired resistance to amoxicillin but easily to clarithromycin and metronidazole. However, it was unclear whether the antibiotic resistance of Hp strains was induced or passively selected during long-term or frequent treatment with metronidazole, clarithromycin and amoxicillin. To compare the propensity of acquired resistance to antibiotics, Hp strains were exposed to amoxicillin, clarithromycin and metronidazole in vitro in this study. METHODS: All Hp strains were clinical isolates, derived from biopsy specimens of patients taken during endoscopy in the Affiliated Children's Hospital, Zhejiang University School of Medicine from December 2004 to July 2005. To seek susceptible strains, the minimum inhibitory concentrations (MICs) of the three antibiotics were determined by using Epsilometer test (E-test) method. In vitro induction was carried out on serially doubling concentrations of antibiotics incorporated into agar. Isolates were also transferred at least three times on antimicrobial agent-free medium, followed by a redetermination of the final MICs to assess the stability of the selected resistance. RESULTS: 7 strains were exposed to antibiotics in vitro. After 6 - 17 passages on antibiotic plates, 7 and 3 strains respectively acquired resistance to metronidazole and clarithromycin, while none of the strains were resistant to amoxicillin. The inductive folds were different among three groups: 8 - 128 folds in metronidazole group; 1 - 256 folds in clarithromycin group; 2 - 16 folds in amoxicillin group. After three transfers on antimicrobial agent-free medium, the MICs decreased significantly in amoxicillin group (P < 0.05) but had no change in metronidazole group and clarithromycin group (P > 0.05). CONCLUSIONS: The metronidazole resistance in Hp was easily selected. Strains resistant to clarithromycin could be selected, but the amoxicillin resistance could not be selected after in vitro induction for Hp isolated from children. The correlation between in vitro and in vivo outcomes suggests that acquired resistance was the main cause for the resistance in Hp strains. The laboratory results of in vitro antibiotic induction could help predict the actual rate of resistance and select appropriate antibiotics for treatment.

[Diagnosis and treatment of Crohn's disease in children: 10 years' clinical experience].

OBJECTIVE: To enhance our understanding of pediatric Crohn's disease and improve diagnostic accuracy and therapeutic efficacy by characterizing the clinical picture and reviewing 10 years' clinical experience in diagnosis and treatment. METHODS: Nine cases with active Crohn's disease diagnosed between 1996 and 2005, including 8 males and 1 female, aged 6 - 13 years, were reviewed. Clinical, radiologic, endoscopic and histological data as well as therapeutic results were analized. RESULTS: The mean interval from the onset of symptoms to the diagnosis was 10 months. The sites of involvement were both the small intestine and colon in 6, small intestine only in 3. Abdominal pain and diarrhea were the two most common gastrointestinal symptoms. The main extraintestinal manifestations were weight loss in 7, hypoalbuminemia in 5, mild anemia in 5, fever in 4 and hypocalcemia in 2. All the patients had undergone colonoscopy, and the findings included ulcerations, segmental lesions, cobblestone appearance, pseudopolyps and perianal abnormalities. Capsule endoscopic examination in one patient demonstrated the segmental distribution with typical longitudinal cleft-like ulcers and cobblestone appearance. Gastrointestinal barium meal X-ray examination was performed in 7 patients, the main findings were segmental strictures and abnormal mucosa. Histological examination of biopsy specimens mainly showed nonspecific chronic inflammation. Non-caseating granulomas were identifiable in 2 cases. Although there were many macroscopic and microscopic features supporting the diagnosis of Crohn's disease, no epithelioid granuloma could be found in surgical specimens of two patients. Treatment was given up by parents of 2 patients after the diagnosis was established. All the other 7 patients were treated with 5-acetylsalicylic acid, antibiotics and nutritional support during the acute phase. Corticosteroids were used in two patients. Long-term remission was achieved and maintained in 3 children, and in one of them medication could be discontinued and had no signs of disease activity at the end of the follow-up. CONCLUSIONS: Children and adolescents presenting with Crohn's disease commonly have weight loss and nutritional impairment, which may provide clues to the diagnosis. Appropriate formulation and higher dosage of 5-acetylsalicylic acid [30-50 mg/(kg x d)] may be effective in inducing and maintaining remission in pediatric Crohn's disease.

[Clinical manifestations and endoscopic features of abdominal type Henoch purpura in children].

OBJECTIVE: To investigate the clinical manifestations and endoscopic features of abdominal type Henoch purpura in children and improve the diagnostic level. METHODS: Retrospective review was made on the clinical, endoscopic and histopathological features of 57 cases of children with Henoch purpura abdominal type who had been hospitalized from Jan. 2002 to May 2007. Upper gastrointestinal endoscopy was performed in all cases. All the cases had various digestive system symptoms without cutaneous purpura before endoscopy. Mucosal specimens were taken from sinus ventriculi and duodenum for histopathological analysis. Helicobacter pylori (H.pylori) infection was identified by rapid urease test and histology, and diagnosis of H.pylori infection was made when both were positive. RESULTS: The common gastrointestinal symptoms of Henoch purpura were abdominal pain (46 cases), vomiting (32 cases), hematochezia (11 cases), diarrhea (4 cases) and abdominal distention (1 case). Three cases had arthralgia and joint swelling. The main laboratory findings were increased peripheral white blood cells (33 cases, 57.9%), 1/5 of cases had elevated C reactive protein (CRP), low serum albumin and seroperitoneum. Endoscopy demonstrated the damages to the mucosa, which varied from congestion, edema, petechia and ecchymosis (37 cases, 64.9%) to erosive and multiple ulcers (14 cases, 24.6%), granulation of mucosa in descendent duodenum (4 cases, 7.0%), and diffuse hemorrhage of mucosa (2 cases, 3.5%). The upper gastrointestinal endoscopy showed that the commonest and most serious position involved was the descendent duodenum (55 cases, 96.5%), followed by duodenal bulb (32 cases, 56.1%) and stomach (18 cases, 36.1%), esophagus was less involved (1 case, 1.8%). Histological manifestations showed swollen vascular endothelial cells of capillary vessels and small blood vessels, fibrotic necrosis of small vessels and bleeding, diffuse perivascular lymphocytic and neutrophilic infiltration and nuclear debris in mucosa and submucosa. Three cases (5.3%) were found infected with H. pylori. In 49 cases (86.0%) cutaneous purpura appeared 1 - 7 days after endoscopy. Eight cases had no cutaneous purpura until they left hospital. Two cases were lost to follow up and 6 cases (10.5%) remained free from cutaneous purpura were followed up until now (1 - 5 years). CONCLUSION: Descending duodenum is the commonest and most serious position of upper gastrointestinal tract involved in Henoch purpura. Upper gastrointestinal endoscopy with the mucosal biopsy are useful for the early diagnosis of Henoch purpura.

[Enhancement of antioxidant capability of cancer patients during chemotherapy by reduced glutathione].

BACKGROUND & OBJECTIVE: It is unknown how administration of reduced glutathione (GSH) affects chemotherapy of cancer patients. This study was designed to investigate the effect of GSH on lipid peroxidation, and activities of antioxidant enzyme among cancer patients with chemotherapy. METHODS: Sixty-two cancer patients with chemotherapy were enrolled randomly into AB or BA group in cross-over pattern. In AB group, combination of chemotherapy and GSH was administrated first, then following chemotherapy alone was given 21 or 28 days later. In group BA, chemotherapy alone was administrated first, then the combination therapy was given. Duration of chemotherapy was 2-5 days, 21-28 days for a cycle, depended on chemotherapy strategies. GSH was given as a 15 minute intravenous infusion at the dose of 1 500 mgx(m(2)xd)(-1) for 7 days from day 1. Serum samples were collected from the patients on the day just before the chemotherapy, the 7(th) day, and the 21(st) (if 21 days per cycle of the chemotherapy) or 28(th) day of treatment. Concentration of malondialdehyde (MDA), activity of glutathione peroxidase (GSH-Px), and total superoxide dismutase (T-SOD) of serum samples were analyzed biochemically. RESULTS: (1)Administration of chemotherapy significantly increased serum MDA level on the 7(th) day compared with that before chemotherapy (mean+/-SD,6.12+/-1.94 micromol/L versus 4.63+/-1.87 micromol/L,P< 0.01). The increased serum MDA level was restored partially (5.05+/-2.07)micromol/L on the 21(th) or 28(th) day, but still higher than that before chemotherapy (P< 0.05). (2)Serum activity of T-SOD and GSH-Px decreased on the 7(th) day (P< 0.01) and restored partially on the 21(th) or 28th day, but still lower than that before chemotherapy (T-SOD, P< 0.05;GSH-Px,P< 0.01).(3)Co-treatment of GSH prevents lipid peroxidation and depletion of antioxidant enzymes by chemotherapy partially but significantly (P< 0.01). (4)Similar results were obtained in both AB group and BA group. CONCLUSION: Chemotherapy depletes antioxidant capability of cancer patients and co- treatment of GSH might prevent such depletion.

[Prevalence and mechanism of Helicobacter pylori resistance to clarithromycin in children].

OBJECTIVE: To investigate the prevalence of Helicobacter pylori (H. pylori) resistance to clarithromycin (CLM) in children and to demonstrate the correlation of 23S rRNA gene mutation to clarithromycin resistance of Helicobacter pylori isolates. METHODS: Totally 108 clinical strains of H. pylori were isolated from gastric biopsy specimens obtained from children who underwent endoscopy during the period from October 2002 to January 2004 in Children's Hospital Affiliated to Medical College of Zhejiang University. H. pylori was identified by morphology and biochemical tests after culture. Clarithromycin susceptibility of H. pylori isolates was determined by both E-test and two-fold agar dilution method. A strain was considered resistant when the MIC was defined as >or= 1 microg/ml. Genome DNAs of the 108 isolates were extracted and prepared for PCR to detect the corresponding gene in the V domain of the 23S rRNA. The amplified fragments were recognized and analyzed by restriction fragment length polymorphism (RFLP) when an additional restriction site is created by the mutation. The PCR products of all sensitive and resistant strains were digested with restriction enzyme BbsI and BsaI and were analyzed on a 1.5% agarose gel to discriminate different kinds of mutant genotype. RESULTS: Sixteen of 108 isolates of H. pylori were resistant to clarithromycin by the agar dilution method and E-test method in clinical isolates from children, and the CLM resistance rate was 14.8% (16/108) with MICs ranging from 1 microg/ml to 128 microg/ml. Comparison of results of the two methods showed that these two methods were quite consistent in determination of susceptibility and resistance. The target fragment 425 bp in length containing 23S rRNA corresponding gene was successfully amplified. An A2144G mutation digested with BsaI was detected in 13 resistant isolates, but an A2143G mutation digested with BbsI in only 3 among all 16 clarithromycin resistant strains. None of the sensitive isolates was cleaved by either BsaI or BbsI enzyme, indicating that there was no mutation on them. It was also found that all the fragments from the resistant strains were not completely digested, and 425 bp uncut fragments were also visible and showed three bands indicating that they were heterozygotic strains with a mixture of wild-types and A-->G genotypes. In addition, in this study, no statistically significant difference between mutations at positions 2143 and 2144 with respect to the MIC was observed (r = 0.035, P > 0.05). CONCLUSION: A high prevalence of clarithromycin-resistant H. pylori strains were detected among strains isolated from Chinese children studied. The 23S rRNA gene mutation at positions A2143G and A2144G plays an important role in clarithromycin resistance of H. pylori and A2144G mutation is the predominant finding among the resistant strains.

[Levels and mRNA expression of interleukin-8 in gastric and duodenal mucosa of children Infected with Helicobacter pylori].

OBJECTIVE: To determine the changes of IL-8 and IL-8 mRNA in gastric and duodenal mucosa of children with Hp infection, to study the effect of Helicobacter pylori (Hp) infection on the expression of IL-8 and IL-8 mRNA, and to evaluate its possible roles in the pathogenesis of gastric and duodenal mucosal inflammation in Hp related gastroduodenal diseases. METHODS: Biopsy specimens were taken from the antral and duodenal mucosa on endoscopy in patients with or without Hp infection, which was diagnosed by urease test and Warshing-Starry staining. The expression of IL-8 in gastric and duodenal mucosa was determined by ELISA, the expression of IL-8 mRNA was determined by using RT-PCR. RESULTS: Inflammation of gastric antral mucosa was more severe in Hp-positive group than in Hp-negative group. Active inflammation often existed on the basis of chronic inflammation in Hp-positive mucosa, and duodenal mucosa had mild chronic inflammation in Hp-positive group. Of 17 children who were not infected with Hp, 4 had pathologically normal gastric mucosa and had mild chronic gastritis, one child had an active chronic gastritis. Nineteen children were infected with Hp and all had chronic gastritis with signs of active inflammation. Gastric and duodenal mucosal IL-8 and IL-8 mRNA were higher in HP infected than in non infected children (IL-8: in gastric mucosa 24.66 - 177.77 pg/mg, 2.94 - 12.98 pg/mg, t = 12.34, P < 0.01; in duodenal mucosa: 4.28 - 47.76 pg/mg, 2.04 - 9.52 pg/mg, t = 7.18, P < 0.01. IL-8 mRNA: in gastric mucosa 2.37 - 4.99, 0.05 - 0.44, t = 29.29, P < 0.01; in duodenal mucosa 1.22 - 1.87, 0.01 - 0.23, t = 37.20, P < 0.01). Children with active chronic gastritis had higher interleukin-8 levels and IL-8 mRNA expression than those with inactive gastritis (IL-8 in gastric mucosa: 12.98 - 177.77 pg/mg, 2.04 - 10.43 pg/mg, t = 10.66, P < 0.01; in duodenal mucosa: 5.28 - 47.76 pg/mg, 3.19 - 8.14 pg/mg, t = 6.52, P < 0.01. IL-8 mRNA in gastric mucosa: 0.51 - 4.99, 0.01 - 0.44, t = 18.62, P < 0.01; in duodenal mucosa: 0.23 - 1.87, 0.01 - 0.20, t = 19.10, P < 0.01). CONCLUSION: Higher expression of IL-8 and IL-8 mRNA was seen in Hp-positive gastric and duodenal mucosa and in active gastritis. IL-8 may play an important role in the local gastric and duodenal mucosal inflammatory infiltration with a large number of neutrophils when there is Hp infection.