Xiaojianzhong decoction prevents gastric precancerous lesions in rats by inhibiting autophagy and glycolysis in gastric mucosal cells

BACKGROUND Gastric precancerous lesions(GPL)precede the development of gastric cancer(GC).They are characterized by gastric mucosal intestinal metaplasia and dysplasia caused by various factors such as inflammation,bacterial infection,and injury.Abnormalities in autophagy and glycolysis affect GPL progression,and their effective regulation can aid in GPL treatment and GC prevention.Xiaojianzhong decoction(XJZ)is a classic compound for the treatment of digestive system diseases in ancient China which can inhibit the progression of GPL.However,its specific mechanism of action is still unclear.AIM To investigate the therapeutic effects of XJZ decoction on a rat GPL model and the mechanisms underlying its effects on autophagy and glycolysis regulation in GPLs.METHODS Wistar rats were randomly divided into six groups of five rats each and all groups except the control group were subjected to GPL model construction for 18 wk.The rats’body weight was monitored every 2 wk starting from the beginning of modeling.Gastric histopathology was examined using hematoxylin-eosin staining and Alcian blue-periodic acid-Schiff staining.Autophagy was observed using transmission electron microscopy.The expressions of autophagy,hypoxia,and glycolysis related proteins in gastric mucosa were detected using immunohistochemistry and immunofluorescence.The expressions of the following proteins in gastric tissues:B cell lymphoma/Leukemia-2 and adenovirus E1B19000 interacting protein 3(Bnip-3),microtubule associated protein 1 light chain 3(LC-3),moesin-like BCL2-interacting protein 1(Beclin-1),phosphatidylinositol 3-kimase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR),p53,AMP-activated protein kinase(AMPK),and Unc-51 like kinase 1(ULK1)were detected using western blot.The relative expressions of autophagy,hypoxia,and glycolysis related mRNA in gastric tissues was detected using reverse transcription-polymerase chain reaction.RESULTS Treatment with XJZ increased the rats’body weight and improved GPL-related histopathological manifestations.It also decreased autophagosome and autolysosome formation in gastric tissues and reduced Bnip-3,Beclin-1,and LC-3II expressions,resulting in inhibition of autophagy.Moreover,XJZ down-regulated glycolysis-related monocarboxylate transporter(MCT1),MCT4,and CD147 expressions.XJZ prevented the increase of autophagy level by decreasing gastric mucosal hypoxia,activating the PI3K/AKT/mTOR pathway,inhibiting the p53/AMPK pathway activation and ULK1 Ser-317 and Ser-555 phosphorylation.In addition,XJZ improved abnormal gastric mucosal glucose metabolism by ameliorating gastric mucosal hypoxia and inhibiting ULK1 expression.CONCLUSION This study demonstrates that XJZ may inhibit autophagy and glycolysis in GPL gastric mucosal cells by improving gastric mucosal hypoxia and regulating PI3K/AKT/mTOR and p53/AMPK/ULK1 signaling pathways,providing a feasible strategy for the GPL treatment.

Reduced gastric acid production in burn shock period and its significance in the prevention and treatment of acute gastric mucosal lesions

AIM To investigate the changes of gastric acidproduction and its mechanism in shock period ofsevere burn in rats.METHODS A rat model with 30% TBSA full-thickness burn injury was employed and thegastric acid production,together with gastricmucosal blood flow(GMBF)and energy charge(EC)were measured serially within 48hpostburn.RESULTS The gastric acid production in theacute shock period was markedly inhibited aftersevere burn injury.At the 3rd h postburn,thegastric juice volume,total acidity and acidoutput were already significantly decreased(P【0.01),and reached the lowest point,0.63mL/L±0.20mL/L,10.81mmol/L±2.58mmol/L and 2.23mmol/h±0.73mmol/hrespectively,at the 12th h postburn.Althoughrestored to some degree 24 h after thermalinjury,the variables above were stillstatistically lower,compared with those ofcontrol animals at the 48th h postburn.TheGMBF and EC were also significantly reducedafter severe burns,consistent with the trend ofgastric acid production changes.CONCLUSION Gastric acid production,as wellas GMBF and EC was predominantly decreased in the early postburn stage,suggesting that gastricmucosal ischemia and hypoxia with resultantdisturbance in energy metabolism,but notgastric acid proper,might be the decisive factorin the pathogenesis of AGML after thermalinjury,and that the preventive use of anti-aciddrugs during burn shock period wasunreasonable in some respects.Therefore,taking effective measures to improve gastricmucosal blood perfusion as early as possiblepostburn might be more preferable for the AGMLprevention and treatment.

Differential diagnosis of gastric submucosal masses and external pressure lesions

Lesions of the left triangular ligament of the liver are rare,and there are even fewer cases of vascular tumors misdiagnosed as gastrointestinal stromal tumors.We comment on the two cases reported in the article.The article did not include pictures of laparoscopic surgery,making it unconvincing.For gastric submucosal lesions,enhanced computed tomography venous phase imaging may be beneficial for differential diagnosis.Although endoscopic ultrasound is an effective tool for diagnosing submucosal lesions of the stomach,due to various factors,it cannot achieve an accurate diagnosis.During endoscopic examination,a more accurate diagnosis can be made depending on the personal experience of the operators.

Role of the nucleus tractus solitarii in the protection of pre-moxibustion on gastric mucosal lesions

Previous studies have shown that somatic sensation by acupuncture and visceral nociceptive stimulation can converge in the nucleus tractus solitarii where neurons integrate signals impact- ing on the function of organs. To explore the role of the nucleus tractus solitarii in the protective mechanism of pre-moxibustion on gastric mucosa, nucleus tractus solitarii were damaged in rats and pre-moxibustion treatment at the Zusanli （ST36） point followed. The gastric mucosa was then damaged by the anhydrous ethanol lavage method. Morphological observations, enzyme linked immunosorbent assays, and western immunoblot analyses showed that gastric mucosa surface lesion and the infiltration of inflammatory cells were significantly ameliorated after pre-moxibustion treatment. Furthermore, the gastric mucosal damage index and somatostatin level were reduced, and epidermal growth factor content in the gastric mucosa and heat-shock protein-70 expression were increased. These results were reversed by damage to the nucleus tractus solitarii. These findings suggest that moxibustion pretreatment at the Zusanli point is protective against acute gastric mucosa injury, and nucleus tractus solitarii damage inhibits these responses. Therefore, the nucleus tractus solitarii may be an important area for regulating the signal transduction of the protective effect of pre-moxibustion on gastric mucosa.

Efficacy and safety of endoscopic submucosal dissection for early gastric cancer and precancerous lesions in elderly patients

BACKGROUND With advancements in the development of endoscopic technologies,the endo-scopic submucosal dissection(ESD)has been one of the gold-standard therapies for early gastric cancer.AIM To investigate the efficacy and safety ESD in the treatment of early gastric cancer and precancerous lesions in the elderly patients.METHODS Seventy-eight elderly patients with early gastric cancer and precancerous lesions admitted to the Third Affiliated Hospital of Qiqihar Medical University were se-lected and classified into two groups according to the different surgical therapies they received between January 2021 and June 2022.Among them,39 patients treated with ESD were included in an experimental group,and 39 patients treated with endoscopic mucosal resection(EMR)were included in a control group.We compared the basic intraoperative conditions,postoperative short-term recovery,long-term recovery effects and functional status of gastric mucosa between the two groups;the basic intraoperative conditions included lesion resection,intra-operative bleeding and operation time;the postoperative short-term recovery assessment indexes were length of hospital stay and incidence of surgical complic-ations;and the long-term recovery assessment indexes were the recurrence rate at 1 year postoperatively and the survival situation at 1 year and 3 years postoper-atively;and we compared the preoperative and predischarge serum pepsinogen I(PG I)and PG II levels and PG I/PG II ratio in the two groups before surgery and discharge.RESULTS The curative resection rate and the rate of en bloc resection were higher in the experimental group than in the control group.The intraoperative bleeding volume was higher in the experimental group than in the control group.The operation time was longer in the experimental group than that in the control group,and the rate for base residual focus was lower in the experimental group than that of the control group,and the differences were all statistically significant(all P<0.05).The length of hospital stay was longer in the experi-mental group than in the control group,and the incidence of surgical complications,1-year postoperative recu-rrence rate and 3-year postoperative survival rate were lower in the experimental group than in the control group,and the differences were statistically significant(all P<0.05).However,the difference in the 1-year postoperative survival rate was not statistically significant between the two groups(P>0.05).Before discharge,PG I and PG I/PG II ratio were elevated in both groups compared with the preoperative period,and the above indexes were higher in the experimental group than those in the control group,and the differences were statistically significant(both P<0.05).Moreover,before discharge,PG II level was lower in both groups compared with the preoperative period,and the level was lower in the experimental group than in the control group,and the differences were all statistically significant(all P<0.05).CONCLUSION Compared with EMR,ESD surgery is more thorough.It reduces the rate of base residual focus,recurrence rate,surgical complications,and promotes the recovery of gastric cells and glandular function.It is safe and suitable for clinical application.

Effects of pre-moxibustion at Zusanli (ST36) on heat shock protein 70 expression in rats with gastric mucosal lesions after neurotomy

Studies have shown that pre-moxibustion protects the gastric mucosa by up-regulating the expression of heat shock protein 70. However, the signaling pathway underlying this effect remains unclear. Rats were intragastrically administered absolute alcohol, causing obvious lesion of the gastric mucosa. Following pre-moxibustion at Zusanfi （ST36） for 8 days, the ulcer index decreased to different degrees. The results of an enzyme linked immunosorbent assay and western blotting showed significant upregulation of heat shock protein 70 expression in the gastric mucosa and serum. None out of transection of the spinal cord, damage to the nucleus of the solitary tract, neurotomy of the vagal nerve and neurotomy of the common peroneal nerve affected the decrease in ulcer index or the increase in heat shock protein 70 expression in serum after pre-moxibustion at Zusanfi, and heat shock protein 70 expression was obviously decreased in the gastric mucosa. These findings suggest that pre-moxibustion at Zusanfi can protect the gastric mucosa against lesioning, and that the mechanism underlying this effect involves its induction of heat shock protein 70 expression. Neural pathways participate in the regulatory effects of moxibustion on heat shock protein 70 expression in the gastric mucosa.

Protective effect of Irsogladine on monochloramineinduced gastric mucosallesions in rats:a comparative study with rebamipide

AIM To examine the effect of irsogladine, a novel antiulcer drug, on the mucosal ulcerogenic response to monochloramine (NH 2Cl) in rat stomach, in comparison with rebamipide, another antiulcer drug with cytoprotective activity. METHODS AND RESULTS Oral administration of NH 2Cl (120*!mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs. Both irsogladine ( 1*!mg/*!kg - 10*!mg/*!kg , po ) and rebamipide ( 30*!mg/*!kg - 100*!mg/*!kg , po ) dose dependently prevented the development of these lesions in response to NH 2Cl, the effect of irsogladine was significant at 3*!mg/*!kg or greater, and that of rebamipide only at 100*!mg/*!kg . The protective effect of irsogladine on NH 2Cl induced gastric lesions was significantly reduced by N G nitro L arginine methyl ester (L NAME) but not by indomethacin, while that of rebamipide was significantly mitigated by indomethacin but not by L NAME. Topical application of NH 2Cl (20*!mM) caused a marked reduction of potential difference (PD) in ex vivo stomachs. This PD reduction was not affected by mucosal application of irsogladine, but significantly prevented by rebamipide. The mucosal exposure to NH 4OH (120*!mM) also caused a marked PD reduction in the ischemic stomach (bleeding from the carotid artery), resulting in gastric lesions. These ulcerogenic and PD responses caused by NH 4OH plus ischemia were also significantly mitigated by rebamipide, in an indomethacin sensitive manner, while irsogladine potently prevented such lesions without affecting the PD response, in a L NAME sensitive manner. CONCLUSION These results suggest that ① NH 2Cl generated either exogenously or endogenously damages the gastric mucosa, ② both irsogladine and rebamipide protect the stomach against injury caused by NH 2Cl, and ③ the mechanism underlying the protective action of irsogladine is partly mediated by endogenous nitric oxide, while that of rebamipide is in part mediated by endogenous prostaglandins.

Gastric mucosal precancerous lesions in Helicobacter pyloriinfected pediatric patients in central China:A single-center,retrospective investigation

BACKGROUND Helicobacter pylori(H.pylori)infects about 50%of the world population and is the major cause of chronic gastritis,peptic ulcers,and gastric cancer.Chronic H.pylori infection induces gastric mucosal precancerous lesions mostly in adulthood,and it is debatable whether these pathological conditions can occur in childhood and adolescents as well.Since this is a critical issue to determine if intervention should be offered for this population group,we investigated the gastric mucosal precancerous lesions in pediatric patients in an area in central China with a high prevalence of H.pylori and gastric cancer.AIM To investigate the relationship of H.pylori infection and gastric mucosal precancerous lesions in children and adolescents in central China.METHODS We screened 4258 ward-admitted children and adolescent patients with upper gastrointestinal symptoms,and finally enrolled 1015 pediatric patients with H.pylori infection and endoscopic and histological data.H.pylori infection status was determined by rapid urease test and histopathological examination.Both clinical and pathological data were collected and analyzed retrospectively.Occurrence of gastric mucosal precancerous lesions,inflammatory activity and degree of inflammatory cell infiltration between H.pylori-positive and-negative groups were compared.RESULTS Among the 1015 eligible children and adolescents,the overall H.pylori infection rate was 84.14%(854/1015).The infection rate increased with age.The incidence of gastric mucosal precancerous lesions in H.pylori-infected children was 4.33%(37/854),which included atrophic gastritis(17 cases),intestinal metaplasia(11 cases)and dysplasia(9 cases).In H.pylori-negative patients,only 1 atrophic gastritis case[0.62%,(1/161)]was found(P<0.05).Active inflammation in H.pyloriinfected patients was significantly higher than that in non-infected patients,and the H.pyloriinfected group showed more severe lymphocyte and neutrophil granulocyte infiltration(P<0.001).In addition,endoscopy revealed that the most common findings in H.pylori-positive patients were antral nodularity,but in H.pylori-negative patients only superficial gastritis was observed.CONCLUSION In children and adolescents,gastric mucosal precancerous lesions occurred in 4.33%of H.pyloriinfected patients in central China.These cases included atrophic gastritis,intestinal metaplasia,and dysplasia.The data revealed an obvious critical issue requiring future investigation and intervention for this population group.

Experimental study on model establishment, mechanism of production, and reverse therapy of gastric mucosal precancerous lesions in rats

This study was designed to establish an animal model of gastric mucosal precancerous lesions in Wistar rats and on this model, the mechanism to produce the precancerous lesions and their reverse therapy were studied. Ranitidine (R) 0.03% in the diet, N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)50 μg/ml in drinking water, or both of them were administered to Wistar rats for 20 weeks. The iats were maintained without the drugs for additional 23 weeks. A control group of rats without any treatment of drugs were kept for 43 weeks Intestinal metaplasia (IM) was found in 86.5% of the rats in MNNG group, 22.5% in R groupand 100% in MNNG+R while only 7.5% in the control. The incidence of IM was significantly different between MNNG+R group and R group or MNNG group. The number of metaplastic glands was also the highest in the MNNG+R group. The therapeutic effects of retinoic acid (RA) and sodium butyrate (SB) on the iNduced precancerousous lesions of the glandular gastric mucosa were observed. It was found that the incidence of IM, moderate and severe dysplasia, and gastric cancer and the number of metaplastic glands in the pylorus and fundus were significantly lower in RA treated group (72.0%, 24.0%, 0%, 130.2±93.9 and 51.5±39.1) and SB treated gioup (60.0%,20.0%, 0%, 70.3±46.8, and 39.8±29.6) than in the RA untreated group (100%, 52.2%, 16.0%, 442.4±230.0 and 247.4±112.07) and the SB untreated group (88.0%, 48.0%. 16.0%, 241.4±113.9 and 146.4±66.3)(P<0.01 to 0.05). A mucosal flap with vascular pedicle from the gastric wall of the Wistar rats was transplanted to the duodenum, jejunum and colon respectively and the rats were killed in the 3td, 6th, 9th and 12th month after operation. IM was found in all the gastric grafts to the intestines with optical and electron microscopy. It is concluded on the basis of the findings that the concomitant administration of MNNG and R is a reliable method to induce IM of gastric mucosa in rats; RA and SB are efficient agents for the reverse thevapy of the precancerous lesions of gastric glandular mucosa in rats; and the formation of IM of gastric mucosa might be a pH-related process. The possible mechanism of the development of IM was discussed.

AgNOR and rasp21 expression in gastric mucosal lesions with Helicobacter pylori infection

IM To study the number of AgNOR and rasp21 expression in different gastric mucosal lesions with Helicobacter pylori (Hp) infection to evaluate their biological behaviour and possible mechanism of Hp. METHODS Hp (using CLO test combined with WathinStarry staining), AgNOR (silver colloid technique) and rasp21 (monoclonal antibody and immunohistochemical staining—ABC method) were detected in 278 patients with endoscopically and pathologically confirmed gastric mucosal lesions, including chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia (Dys), and gastric cancer (GC). Among them, 146 cases were Hp positive, and 132 cases Hp negative. RESULTS The mean number of AgNOR in Hp positive group was significantly higher than that in Hp negative group in the gastric mucosal lesions except for CSG (P<005 or P<001). The positive rate of rasp21 expression in Hp positive group was also significantly higher than that in Hp negative group in gastric mucosal lesions except for CSG and CAG (P<005).CONCLUSION Hp+ gastric mucosal lesions have more biological behaviour of tumors. Hp may act as a promoter to activate ras gene and to stimulate cell over proliferation.

Streptococcus anginosus in the development and treatment of precancerous lesions of gastric cancer

The microbiota is strongly association with cancer.Studies have shown significant differences in the gastric microbiota between patients with gastric cancer(GC)patients and noncancer patients,suggesting that the microbiota may play a role in the development of GC.Although Helicobacter pylori(H.pylori)infection is widely recognized as a primary risk factor for GC,recent studies based on microbiota sequencing technology have revealed that non-H.pylori microbes also have a significant impact on GC.A recent study discovered that Streptococcus anginosus(S.anginosus)is more prevalent in the gastric mucosa of patients with GC than in that of those without GC.S.anginosus infection can spontaneously induce chronic gastritis,mural cell atrophy,mucoid chemotaxis,and heterotrophic hyperplasia,which promote the development of precancerous lesions of GC(PLGC).S.anginosus also disrupts the gastric barrier function,promotes the proliferation of GC cells,and inhibits apoptosis.However,S.anginosus is underrepresented in the literature.Recent reports suggest that it may cause precancerous lesions,indicating its emerging pathogenicity.Modern novel molecular diagnostic techniques,such as polymerase chain reaction,genetic testing,and Ultrasensitive Chromosomal Aneuploidy Detection,can be used to gastric precancerous lesions via microbial markers.Therefore,we present a concise summary of the relationship between S.anginosus and PLGC.Our aim was to further investigate new methods of preventing and treating PLGC by exploring the pathogenicity of S.anginosus on PLGC.

Prospects in the application of ultrasensitive chromosomal aneuploidy detection in precancerous lesions of gastric cancer

Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents,the prognosis for GC remains poor.New targeted therapies and immunotherapies are currently under invest-igation,but no significant breakthroughs have been achieved.Studies have indicated that GC is a heterogeneous disease,encompassing multiple subtypes with distinct biological characteristics and roles.Consequently,personalized treatment based on clinical features,pathologic typing,and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer(PLGC).Current research has categorized GC into four subtypes:Epstein-Barr virus-positive,microsatellite instability,genome stability,and chromosome instability(CIN).Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas.Among these,ultrasensitive chromosomal aneuploidy detection(UCAD)can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology,in conjunction with bioinformatics analysis,to achieve qualitative and quantitative detection of chromosomal stability.This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.

Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer:A critical review

Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to GC remains a challenge.Traditional Chinese medicine(TCM)has been used to treat gastric disease for millennia.A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL.This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC,especially focusing on antiinflammatory,anti-angiogenesis,proliferation,and apoptosis.This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.

Clinical features of acute esophageal mucosal lesions and reflux esophagitis Los Angeles classification grade D: A retrospective study

BACKGROUND Acute esophageal mucosal lesions(AEMLs)are an underrecognized and largely unexplored disease.Endoscopic findings are similar,and a higher percentage of AEML could be misdiagnosed as reflux esophagitis Los Angeles classification grade D(RE-D).These diseases could have different pathologies and require different treatments.AIM To compare AEML and RE-D to confirm that the two diseases are different from each other and to clarify the clinical features of AEML.METHODS We selected emergency endoscopic cases of upper gastrointestinal bleeding with circumferential esophageal mucosal injury and classified them into AEML and RE-D groups according to the mucosal injury’s shape on the oral side.We examined patient background,blood sampling data,comorbidities at onset,endoscopic characteristics,and outcomes in each group.RESULTS Among the emergency cases,the AEML and RE-D groups had 105(3.1%)and 48(1.4%)cases,respectively.Multiple variables exhibited significantly different results,indicating that these two diseases are distinct.The clinical features of AEML consisted of more comorbidities[risk ratio(RR):3.10;95%confidence interval(CI):1.68–5.71;P<0.001]and less endoscopic hemostasis compared with RE-D(RR:0.25;95%CI:0.10–0.63;P<0.001).Mortality during hospitalization was higher in the AEML group(RR:3.43;95%CI:0.82–14.40;P=0.094),and stenosis developed only in the AEML group.CONCLUSION AEML and RE-D were clearly distinct diseases with different clinical features.AEML may be more common than assumed,and the potential for its presence should be taken into account in cases of upper gastrointestinal bleeding with comorbidities.

The Protective Effect of a Puerariae flos Extract (Thomsonide) against Ethanol-Induced Gastric Lesions in Rats

Objectives: Puerariae flos has popularly been used to treat alcoholic disorders. However, the effect of Puerariae flos on alcoholic disorders in the gastrointestinal system has not been identified. We investigated the protective effect of an extract of Puerariae flos against the murine gastric mucosa. Methods: Thomsonide, the extracts containing large amounts of isoflavonoid and triterpenoid saponin, was obtained fr om Puerriae flos via Diaion HP-20 column chromatography using water and 99.5% ethanol. It was investigated whether thomsonide, as well as geranylgeranylacetone (teprenone), a popular anti-ulcer agent developed in Japan, had a cytoprotective effect that might be related to endogenous prostaglandins, which played an important role in preventing gastric mucosal lesions. Results: Thomsonide and teprenone inhibited ethanol-induced gastric lesions. Furthermore, thomsonide increased the production of PGE2 and 6-ketoPGF1α, a stable metabolite of PGI2, in the gastric mucosa, and protective effects of thomsonide, as well as teprenone, against ethanol-induced gastric lesions were attenuated by pretreatment with indomethacin. Conclusions: These findings suggest that thomsonide, as well as teprenone, has the gastro protective effect which may be related to the cytoprotective activity of endogenous prostaglandins. The results of this study also suggest that the gastro protective effect of thomsonide may partially mitigate alcoholic disorders in the gastrointestinal tract, and support our pharmacological belief that Puerariae flos is useful for treatment of alcoholic disorders.

Research of Helicobacter pylori infection in precancerous gastric lesions

INTRODUCTION Helicobacter pylori(Hp)infection has beenconsidered to play significant roles in pathogenesisof peptic ulcer.Additionally Hp is associated withthe development of gastric epithelial hyperplasiaand lymphoid malignancies.The InternationalAgency for Research on Cancer has classified lip asa class Ⅰ carcinogen and a definite cause of gastriccancer in humans.Hp infection first causes chronicactive gastritis and may slowly lead to infection ofwhole stomach.In the late stages of infection,mucosal atrophy and intestinal metaplasia(IM),

Factors affecting occurrence of gastric varioliform lesions: A case-control study

AIM: To investigate the factors influencing the occurrence of gastric varioliform lesions(GVLs) and their possible link with gastric cancer.METHODS: A 1:1 matched case-control study was performed to retrospectively analyze data from 1638 chronic gastritis patients who had undergone gastroscopy at one of two Chinese hospitals between 2009 and 2014. Patients with GVLs(cases) were compared to those without such lesions(controls). Endoscopic and pathological findings were recorded, along with interview information on Helicobacter pylori(H. pylori) infection, medical, drug and family histories, lifestyle and eating habits. The association between each factor and the occurrence of GVLs was estimated, and then multivariate conditional logistic regression was used to evaluate the independent factors.RESULTS: The frequency and severity of glandular atrophy, intestinal metaplasia(IM) and low-grade intraepithelial neoplasia were significantly increased in the GVL group(P < 0.01). Overall analysis showed that H. pylori infection [3.051(2.157, 4.317), P <0.001], allergic respiratory diseases [3.636(2.183, 6.055), P < 0.001], work-related stress [2.019(1.568, 2.600), P < 0.001], irregular meals [2.300(1.462, 3.619), P < 0.001], high intake of spicy food [1.754(1.227, 2.507), P = 0.002] and high intake of fresh fruit [0.231(0.101, 0.529), P = 0.001] were significantly correlated with the occurrence of GVLs(positively, except for the latter). Stratified analyses indicated that pickled food consumption in patients over 50 years old [7.224(2.360, 22.115), P = 0.001] and excessive smoking in men [2.013(1.282, 3.163), P = 0.002] were also positively correlated, and that, for antral GVLs, vegetable consumption [0.491(0.311, 0.776), P = 0.002] was negatively correlated. CONCLUSION: Seven risk factors and two protective factors are determined for GVLs, which were found to be associated with premalignant abnormalities.

Expression and significance of Musashi-1 in gastric cancer and precancerous lesions

AIM:To investigate expression of stem cell marker Musashi-1(Msi-1)in relationship to tumorigenesis and progression of intestinal-type gastric cancer(GC).METHODS:Endoscopic biopsy specimens and surgical specimens were obtained,including 54 cases of intestinal-type GC,41 high-grade intraepithelial neoplasia,57low-grade intraepithelial neoplasia,31 intestinal metaplasia,and 36 normal gastric mucosa.Specimens were fixed in 10%paraformaldehyde,conventionally dehydrated,embedded in paraffin,and sliced in 4-μm-thick serial sections.Two-step immunohistochemical staining was used to detect Msi-1 and proliferating cell nuclear antigen(PCNA)expression.Correlation analysis was conducted between Msi-1 and PCNA expression.The relationship between Msi-1 expression and clinicopathological parameters of GC was analyzed statistically.RESULTS:There were significant differences in Msi-1and PCNA expression in different pathological tissues(χ2=15.37,P<0.01;χ2=115.36,P<0.01).Msi-1and PCNA-positive cells were restricted to the isthmus of normal gastric glands.Expression levels of Msi-1and PCNA in intestinal metaplasia were significantly higher than in normal mucosa(U=392.0,P<0.05;U=40.50,P<0.01),whereas there was no significant difference compared to low or high-grade intraepithelial neoplasia.Msi-1 and PCNA expression in intestinaltype GC was higher than in high-grade intraepithelial neoplasia(U=798.0,P<0.05;U=688.0,P<0.01).There was a significantly positive correlation between Msi-1 and PCNA expression(rs=0.20,P<0.01).Msi-1expression in GC tissues was correlated with their lymph node metastasis and tumor node metastasis stage(χ2=12.62,P<0.01;χ2=11.24,P<0.05),but not with depth of invasion and the presence of distant metastasis.CONCLUSION:Msi-1-positive cells may play a key role in the early events of gastric carcinogenesis and may be involved in invasion and metastasis of GC.

Significance and relationship between Cripto-1 and p-STAT3 expression in gastric cancer and precancerous lesions

AIM:To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis.METHODS: The PV9000 immunohistochemical method was used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal meta-plasia (IM) and 25 dysplasia (DYS). RESULTS: The positive rates of CR-1 and p-STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3% and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p-STAT3 (78.3% and 66.7%) were signifi cantly higher in GC with lymphnode metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1 expression was also related to histological and Lauren's types of GC (P < 0.001). Furthermore, there was positive relation-ship between CR-1 and p-STAT3 expressions in GC (rk = 0.189, P = 0.002).CONCLUSION: The up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the relevant molecular mechanism requires further investigations.

Ligustrazine alleviates gastric mucosal injury in a rat model of acute necrotizing pancreatitis

BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inflammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP. METHODS: Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group Q; ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood flow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score; meanwhile, the levels of serum interleukin-1 beta (IL-1 beta) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils. RESULTS: Blood flow in group P was significantly lower than that in group C (P < 0.01). Pathological changes were significantly aggravated in group P. The gastric MPO activity in group P was significantly higher than that in group C (P < 0.01). The level of serum IL-1 beta in group P increased more significantly than that in group C (P < 0.01). Blood flow of the stomach in group T was significantly higher than that in group P after 2 hours (P < 0.01). The pathological changes were significantly alleviated in group T. The MPO activity of group T was significantly lower than that of group P (P < 0.01). Although serum IL-1 beta level of group T, was higher than of group C (P < 0.01), it was lower than that of group P (P < 0.01). There was a negative correlation between gastric blood flow and MPO activity (r=-0.983, P < 0.01), and between gastric blood flow and pathological score (r=-0.917, P < 0.05). CONCLUSIONS: Decreased gastric blood flow and increased inflammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.