Analysis of large datasets for identifying molecular targets in intestinal polyps and metabolic disorders

Background:The interrelation between intestinal polyps,metabolic syndrome(MetS),and colorectal cancer(CRC)is a critical area of study.This research focuses on pinpointing potential molecular targets to understand the link between intestinal polyp formation,metabolic irregularities,and CRC progression.Methods:We examined clinical samples from patients with intestinal polyps coexisting with MetS and compared them with samples from patients with standard intestinal polyps.Transcriptome sequencing and public database analysis were employed to identify significant pathways and genes.These targets were then validated through immunohistochemistry(IHC).Following the RNA interference of key target expression,a series of experiments,including the cell counting kit-8 assay,colony formation,wound healing,and Transwell assays,were conducted.Results:Comparative analysis revealed 75 up-regulated and 61 down-regulated differentially expressed genes(DEGs)in the MetS polyp group vs.the control.Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment suggested these DEGs were primarily associated with cell cycle and mitosis.Integration with comparative toxicogenomics database(CTD)and the cancer genome atlas(TCGA)databases highlighted 44 key CRC-related genes.Protein interaction networks indicated connections of purkinje cell protein 4(PCP4),olfactomedin 1(OLFM1),fibronectin 1(FN1),and transforming growth factor beta 3(TGF-β3)with the mitogen-activated protein kinase(MAPK)pathway.Tumor correlation studies suggested higher risk associations with FN1,PCP4,and TGF-β3,while OLFM1 was identified as a lower risk gene.Immunohistochemical analysis revealed a decrease in OLFM1 in MetS-associated intestinal polyps.Upon interference with OLFM1 in polyp epithelial cells,there was a significant enhancement in cell proliferation,colony formation,and cell migration and invasion capabilities.Conclusion:Our study highlights a significant decrease in OLFM1 expression in MetS-associated intestinal polyps.And,this reduction in OLFM1 is associated with enhanced cell proliferation,colony formation,and increased cell migration and invasion capabilities.These findings underscore the reduced OLFM1 expression in MetS-associated intestinal polyps may play a crucial role in promoting tumorigenic processes in colorectal pathology.Further research on OLFM1 may provide valuable insights into understanding and targeting MetS-associated intestinal polyps.

Ability of lactulose breath test results to accurately identify colorectal polyps through the measurement of small intestine bacterial overgrowth

BACKGROUND While colorectal polyps are not cancerous,some types of polyps,known as adenomas,can develop into colorectal cancer over time.Polyps can often be found and removed by colonoscopy;however,this is an invasive and expensive test.Thus,there is a need for new methods of screening patients at high risk of developing polyps.AIM To identify a potential association between colorectal polyps and small intestine bacteria overgrowth(SIBO)or other relevant factors in a patient cohort with lactulose breath test(LBT)results.METHODS A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology.SIBO was diagnosed by measuring LBTderived hydrogen(H)and methane(M)levels according to 2017 North American Consensus recommendations.Logistic regression was used to assess the ability of LBT to predict colorectal polyps.Intestinal barrier function damage(IBFD)was determined by blood assays.RESULTS H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group(41%vs 23%,P<0.01;71%vs 59%,P<0.05,respectively).Within 90 min of lactulose ingestion,the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group(P<0.01,and P=0.03,respectively).In 227 patients with SIBO defined by combining H and M values,the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without(15%vs 5%,P<0.05).In regression analysis with age and gender adjustment,colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO.These models had a sensitivity of≥0.67,a specificity of≥0.64,and an accuracy of≥0.66.CONCLUSION The current study made key associations among colorectal polyps,SIBO,and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps.

Clinicopathological features and expression of regulatory mechanism of the Wnt signaling pathway in colorectal sessile serrated adenomas/polyps with different syndrome types

BACKGROUND Colorectal cancer(CRC)is the third most common cancer worldwide,with the fourth highest mortality among all cancers.Reportedly,in addition to adenomas,serrated polyps,which account for 15%-30%of CRCs,can also develop into CRCs through the serrated pathway.Sessile serrated adenomas/polyps(SSAs/Ps),a type of serrated polyps,are easily misdiagnosed during endoscopy.AIM To observe the difference in the Wnt signaling pathway expression in SSAs/Ps patients with different syndrome types.METHODS From January 2021 to December 2021,patients with SSAs/Ps were recruited from the Endoscopy Room of Shanghai Traditional Chinese Medicine-Integrated Hospital,affiliated with Shanghai University of Traditional Chinese Medicine.Thirty cases each of large intestine damp-heat(Da-Chang-Shi-Re,DCSR)syndrome and spleen-stomach weakness(Pi-Wei-Xu-Ruo)syndrome were reported.Baseline comparison of the general data,typical tongue coating,colonoscopy findings,and hematoxylin and eosin findings was performed in each group.The expression of the Wnt pathway-related proteins,namelyβ-catenin,adenomatous polyposis coli,and mutated in colorectal cancer,were analyzed using immunohistochemistry.RESULTS Significant differences were observed with respect to the SSAs/Ps size between the two groups of patients with different syndrome types(P=0.001).The other aspects did not differ between the two groups.The Wnt signaling pathway was activated in patients with SSAs/Ps belonging to both groups,which was manifested asβ-catenin protein translocation into the nucleus.However,SSAs/Ps patients with DCSR syndrome had more nucleation,higherβ-catenin expression,and negative regulatory factor(adenomatous polyposis coli and mutated in colorectal cancer)expression(P<0.0001)than SSA/P patients with Pi-Wei-Xu-Ruo syndrome.In addition,the SSA/P size was linearly correlated with the related protein expression.CONCLUSION Patients with DCSR syndrome had a more obvious Wnt signaling pathway activation and a higher risk of carcinogenesis.A high-quality colonoscopic diagnosis was essential.The thorough assessment of clinical diseases can be improved by combining the diseases of Western medicine with the syndromes of traditional Chinese medicine.

Comparative study of mutations in SNP loci of K-RAS, hMLH1 and h MSH2 genes in neoplastic intestinal polyps and colorectal cancer

AIM: To clarify the molecular mechanism involved in pathogenesis of colorectal cancer as well as clinical significance of genetic analysis of histological samples.

Wireless capsule endoscopy in detecting small-intestinal polyps in familial adenomatous polyposis

AIM:To detect the prevalence of small bowel polyps by wireless capsule endoscopy(WCE)in patients with familial adenomatous polyposis(FAP).METHODS:We examined prospectively 14 patients with FAP to assess the location,size and number of small-intestinal polyps.Patients'age,sex,years of observation after surgery,type of surgery,duodenal polyps and colorectal cancer at surgery were analyzed.RESULTS:During WCE,polyps were detected in 9/14(64.3%)patients.Duodenal adenomatous polyps were found in nine(64.3%)patients,and jejunal and ileal polyps in seven(50%)and eight(57.1%),respectively.The Spigelman stage of duodenal polyposis was associated with the presence of jejunal and ileal polyps.Identification of the ampulla of Vater was not achieved with WCE.Importantly,the findings of WCE had no immediate impact on the further clinical management of FAP patients.No procedure-related complications were observed in the patients.CONCLUSION:WCE is a promising noninvasive new method for the detection of small-intestinal polyps.Further investigation is required to determine which phenotype of FAP is needed for surveillance with WCE.

Therapeutic upper gastrointestinal tract endoscopy in Paediatric Gastroenterology

Since the first report of use of endoscopy in children in the 1970 s, there has seen an exponential growthin published experience and innovation in the field. In this review article we focus on modern age therapeutic endoscopy practice, explaining use of traditional as well as new and innovative techniques, for diagnosis and treatment of diseases in the paediatric upper gastrointestinal tract.

Association of Helicobacter pylori infection with colorectal polyps and malignancy in China

BACKGROUND Gastric Helicobacter pylori(H.pylori)infection is related to chronic gastritis,gastroduodenal ulcer,and gastric malignancies;whether this infection is related to colorectal polyps and colorectal cancer(CRC),remains debatable.AIM To investigate the relationship between gastric H.pylori infection and the risk of colorectal polyps and CRC.METHODS We retrospectively analyzed 3872 patients with colorectal polyps who underwent colonoscopy and pathological diagnosis.We also analyzed 304 patients with primary CRC.The characteristics of these patients were compared with those of the control group,which included 2362 patients with the normal intestinal mucosa.All subjects completed a 14C-urea breath test,bidirectional gastrointestinal endoscopy,and a biopsy on the same day.Data on the number,size,location,and pathology of the polyps,the location,and pathology of the CRC,the detection of H.pylori,and the incidence of H.pylori-associated atrophic gastritis or intestinal metaplasia were obtained.A logistic regression model was used to analyze the relationship between gastric infection due to H.pylori,and the incidence of colorectal polyps and CRC.RESULTS The prevalence of H.pylori infection was higher in the multiple polyps group than in the solitary polyp group and the control group[95%confidence interval(CI)=1.02-1.31,P=0.03;95%CI:2.12-2.74,P<0.001].The patients with adenomatous polyps had a higher incidence of H.pylori infection than patients with non-adenomatous polyps[59.95%vs 51.75%,adjusted odds ratio(OR)=1.41,95%CI:1.24-1.60,P<0.01].Patients with H.pylori-associated atrophic gastritis or intestinal metaplasia were at high risk of CRC(adjusted OR=3.46,95%CI:2.63-4.55,P<0.01;adjusted OR=4.86,95%CI:3.22-7.34,P<0.01,respectively).The size and location of the polyps,the histopathological characteristics and the location of CRC were not related to H.pylori infection.CONCLUSION Our study demonstrates that the incidence of gastric H.pylori infection and H.pylori-associated atrophic gastritis or intestinal metaplasia elevates the risk of colorectal polyps and CRC.

Ultrasound virtual endoscopy: Polyp detection and reliability of measurement in an in vitro study with pig intestine specimens

AIM: To present our initial experience regarding the feasibility of ultrasound virtual endoscopy(USVE) and its measurement reliability for polyp detection in an in vitro study using pig intestine specimens.METHODS: Six porcine intestine specimens containing 30 synthetic polyps underwent USVE, computed tomography colonography(CTC) and optical colonoscopy(OC) for polyp detection. The polyp measurement defined as the maximum polyp diameter on twodimensional(2D) multiplanar reformatted(MPR) planes was obtained by USVE, and the absolute measurement error was analyzed using the direct measurement as the reference standard.RESULTS: USVE detected 29(96.7%) of 30 polyps, remaining a 7-mm one missed. There was one falsepositive finding. Twenty-six(89.7%) of 29 reconstructedimages were clearly depicted, while 29(96.7%) of 30 polyps were displayed on CTC with one false-negative finding. In OC, all the polyps were detected. The intraclass correlation coefficient was 0.876(95%CI: 0.745-0.940) for measurements obtained with USVE. The pooled absolute measurement errors ± the standard deviations of the depicted polyps with actual sizes ≤ 5 mm, 6-9 mm, and ≥ 10 mm were 1.9 ± 0.8 mm, 0.9 ± 1.2 mm, and 1.0 ± 1.4 mm, respectively.CONCLUSION: USVE is reliable for polyp detection and measurement in in vitro study.

Th17 Cells Influence Intestinal Muscle Contraction during Trichinella spiralis Infection

Trichinella spiralis infection in rodents is a well-known model of intestinal inflammation associated with hypermotility. The aim of the study was to use this experimental model to elucidate if Thl 7 cells are involved in the development of gastrointestinal hypermotility. Colonic smooth muscle contractility was investigated in response to acetylcholine. The levels of IL-17, IL-23 and TGF-β1 in colon were measured by Western blotting. Flow cytometric detection of intracellular IFN-7/IL-4/ IL- 17 cytokine production was used to analyze the proportions of CD4＋ T cells subsets in colon. Our results showed that colonic muscle contractility was increased 2 weeks post infection （PI） and stayed high 12 weeks PI when no discernible inflammation was present in the gut. The proportion of Th17 cells and the expression of IL-17 were up-regulated in colon 2 weeks PI and returned to normal 8 weeks PI. The content of IL-17 was correlated with the colonic smooth muscle hypercontracility 2 weeks PI. Meanwhile, TGF-β1 was increased 2 weeks PI, while IL-23 was normal. Our results suggest that Th17 cells affect the colonic muscle contractility in mice infected with Trichinella spiralis at intestine stage but not at muscle stage and the effect of Th17 cells on muscle contractility might be induced by TGF-β1. Other cytokines might be involved in the hypercontracility of colonic smooth muscle at muscle stage.

Hypertrophied anal papillae and fibrous anal polyps,should they be removed during anal fissure surgery?

AIM:Hypertrophied anal papillae and fibrous anal polyps are not given due importance in the proctology practice. They are mostly ignored being considered as normal structures.The present study was aimed to demonstrate that hypertrophied anal papillae and fibrous anal polyps could cause symptoms to the patients and that they should be removed in treatment of patients with chronic fissure in anus. METHODS:Two groups of patients were studied.A hundred patients were studied in group A in which the associated fibrous polyp or papillae were removed by radio frequency surgical device after a lateral subcutaneous sphincterotomy for relieving the sphincter spasm.Another group of a hundred patients who also had papillae or fibrous polyps,were treated by lateral sphincterotomy alone.They were followed up for one year. RESULTS:Eighty-nine percent patients from group A expressed their satisfaction with the treatment in comparison to only 64% from group B who underwent sphincterotomy alone with the papillae or anal polyps left untreated.Group A patients showed a marked reduction with regard to pain and irritation during defecation (P=0.0011), pricking or foreign body sensation in the anus (P=0.0006) and pruritus or wetness around the anal verge (P=0.0008). CONCLUSION:Hypertrophied anal papillae and fibrous anal polyps should be removed during treatment of chronic anal fissure.This would add to effectiveness and completeness of the procedure.

Azathioprine does not reduce adenoma formation in a mouse model of sporadic intestinal tumorigenesis

AIM: To investigate if azathioprine could reduce adenoma formation in ApcMin/+, a mouse model of sporadic intestinal tumorigenesis.

Mechanism of Th17/Treg immune axis regulating the intestinal microflora of ulcerative colitis

Ulcerative colitis(UC)is a type of chronic inflammatory recurrent disease.At present,the etiology and pathogenesis are still unclear,and immune factors are usually considered to be the final link in the pathogenesis of UC.Due to the increasing incidence of this disease,longer course of disease,and difficult to heal,related research has gradually deepened,and related researches on intestinal flora,immunity,genetics,etc.have become hotspots.A large amount of evidence indicates that regulatory T cells(Treg),helper T cell 17(Th17),Th17/Treg immune axis and intestinal microbiota in UC patients play an important role in regulating the occurrence and development of diseases.In recent years,the intestine has been gradually discovered There is also a certain correlation between the tract microbiota and the Th17/Treg immune axis.Therefore,this article examines a large number of relevant Chinese and English materials at home and abroad in recent years to analyze the Th17/Treg cells,intestinal microbiota and the relationship between the two in UC patients.The existing relevance and other issues are briefly discussed and summarized in order to provide more practical basis for clinical targeted therapy.

Effects of nutritional support and intervention on intestinal flora, Th cellular immune response and inflammatory response in patients with severe ulcerative colitis

Objective: To explore the effects of nutritional support and intervention on intestinal flora, Th cellular immune response and inflammatory response in patients with severe ulcerative colitis. Methods: A total of 90 UC patients who were diagnosed and treated in the hospital between August 2014 and January 2017 were divided into the control group (n=45) and the nutritional intervention group (n=45) by random number table. Control group received clinical routine therapy for UC, and nutritional intervention group received routine therapy as well as nutritional support and intervention. The differences in the intestinal flora distribution, Th1/Th2 cytokine contents and inflammatory mediator contents were compared between the two groups. Results: Before intervention, there was no statistically significant difference in the intestinal flora distribution, Th1/Th2 cytokine contents and inflammatory mediator contents between the two groups. After intervention, the number of enterobacter and enterococcus in nutritional intervention group were lower than those in control group whereas the number of lactobacilli, Bifidobacterium and clostridium butyricum were higher than those in control group;serum IL-2 and IFN-γ contents were lower than those of control group whereas IL-4 and IL-10 contents were higher than those of control group;serum MCP-1, MIP-1a and HMGB-1 contents were lower than those of control group. Conclusion: Nutritional support and intervention can further balance the intestinal flora distribution and Th1/Th2 immune response and suppress the systemic inflammatory response in patients with severe ulcerative colitis.

Reduction of the incidence and mortality of rectal cancer bypolypectomy:a prospective cohort study in Haining County

AIM: To reduce the incidence and mortality of rectal cancer and address the hypothesis that colorectal cancer often arise from precursor lesion(s), either adenomas or non-adenomatous polyps, by conducting a population-based mass screening for colorectal cancer in Haining County, Zhejiang, PRC. METHODS: From 1977 to 1980, physicians screened the population of Haining County using 15 cm rigid endoscopy. Of over 240000 participants, 4076 of them were diagnosed with precursor lesions, either adenomas or non-adenomatous polyps, which were then removed surgically. All individuals with precursor lesions were followed up and reexamined by endoscopy every two to five years up to 1998. RESULTS: After the initial screening, 953 metachronous adenomas and 417 non-adenomatous polyps were detected and removed from the members of this cohort. Further, 27 cases of colorectal cancer were detected and treated. Log-rank tests showed that the survival time among those cancer patients who under went mass screening increased significantly compared to that of other colorectal cancer patients (P【0.0001). According to the population-based cancer registry in Haining County, age-adjusted incidence and mortality of rectal cancer decreased by 41% and 29% from 1977-1981 to 1992-1996, respectively. Observed cumulative 20-year rectal cancer incidence was 31% lower than the expected in the screened group; the mortality due to rectal cancer was 18% lower than the expected in the screened group. CONCLUSION:Mass screening for rectal cancer and precursor lesions with protocoscopy in the general population and periodical following-up with routine endoscopy for high-risk patients may decrease both the incidence and mortality of rectal cancer.

Obstructive ileus due to a giant fibroepithelial polyp of the anus

Fibroepithelial polyps or hypertrophied anal papillae are essentially skin tags that project up from the dentate line and the junction between the skin and the epithelial lining of the anus. They are usually small in size, but sometimes they become enlarged, causing unexpected medical conditions. An extremely rare case of a giant hypertrophied anal papilla complicated by obstructive ileus is reported. Fibroepithelial anal polyp, despite its size, should be included in the differential diagnosis of a smooth mass located near the anal verge, especially in a patient with a history of chronic anal irritation or infection.

Colo-colonic intussusception with post-polypectomy electrocoagulation syndrome:A case report

BACKGROUND Post-polypectomy electrocoagulation syndrome(PPES)can occur after colonoscopic polypectomy and is usually treated conservatively with a positive prognosis.Nevertheless,there can be cases with complications developing.CASE SUMMARY A 58-year-old woman,who had no previous medical history,visited the Emergency Department of another hospital with symptoms of abdominal pain and fever,1 d after multiple colonoscopic polypectomies.An abdominopelvic computed tomography(CT)scan demonstrated colo-colonic intussusception,and she was transferred to our hospital to consider an operation.CT showed colocolonic intussusception with PPES and no evidence of obstruction.The physical examination showed localized mild tenderness on the right sided abdomen.The patient fasted and was admitted for treatment with intravenous antibiotics(piperacillin/tazobactam 4.5 g each 8 h,ornidazole 500 mg each 12 h).After admission,the symptoms got better and a follow-up CT scan demonstrated resolution of the PPES and intussusception.The patient was discharged on hospital day 9.CONCLUSION Colo-colic intussusception can occur with PPES,and it can be properly treated conservatively.

Network Biological Modeling:A Novel Approach to Interpret the Traditional Chinese Medicine Theory of Exterior-Interior Correlation Between the Lung and Large Intestine

Objective To study the common pathogenesis of pneumonia and colitis using modern biological network analysis tools,and to explore the theory that the lung and large intestine are exteriorly and interiorly related.Methods The relevant target genes(hereinafter,“targets”)of pneumonia and colitis were separately queried on the GeneCards database.The main targets of the two diseases were then screened out according to their correlation scores and intersected to obtain those common to the two diseases.Metascape was used to analyze the main and common targets identified,and the Database for Annotation,Visualization and Integrated Discovery(DAVID)was used to enrich and analyze the common targets.Cytoscape 3.7.2 software was used to build the network diagram.Results In total,54 targets,such as TNF,IL-10,IL-6,IL-2,IL-4,TLR4,TLR2,CXCL8,IL-17A and IFNG,etc.,are common to pneumonia and colitis,which are mainly enriched in these processes such as cytokine–cytokine receptor interaction,the Tcell receptor signaling pathway,the Toll-like receptor signaling pathway and the Jak-STAT signaling pathway.The Metascape modular analysis identified 11 modules for pneumonia,six modules for colitis,and two modules for the common targets.Conclusions Pneumonia and colitis have the same pathogenic targets and mechanisms of action and finally interact with each other through inflammatory reactions and immune responses.This provides a probable molecular mechanism that explains the theory that the lung and large intestine are exteriorly and interiorly related.

Cumulative incidence and risk factors for pouch adenomas associated with familial adenomatous polyposis following restorative proctocolectomy

BACKGROUND The emergence of restorative total proctocolectomy has significantly reduced the lifetime colorectal cancer risk associated with familial adenomatous polyposis(FAP).However,adenomas may develop in the ileal pouch over time and may even progress to carcinoma.We evaluated the cumulative incidence,time to development,and risk factors associated with ileal pouch adenoma.AIM To evaluate the cumulative incidence,time to development,and risk factors associated with pouch adenoma.METHODS In this retrospective,observational study conducted at a tertiary center,95 patients with FAP who underwent restorative proctocolectomy at our center between 1989 and 2018 were consecutively included.The mean follow-up period was 88 mo.RESULTS Pouch adenomas were found in 24(25.3%)patients,with a median time of 52 mo to their first formation.Tubular adenomas were detected in most patients(95.9%).There were no high-grade dysplasia or malignancies.Of the 24 patients with pouch adenomas,13 had all detected adenomas removed.Among the 13 patients who underwent complete adenoma removal,four(38.5%)developed recurrence.Among 11(45.8%)patients with numerous polyps within the pouch,seven(63.6%)exhibited progression of pouch adenoma.The cumulative risks of pouch adenoma development at 5,10,and 15 years after pouch surgery were 15.2%,29.6%,and 44.1%,respectively.Severe colorectal polyposis(with more than 1000 polyps)was a significant risk factor for pouch adenoma development(hazard ratio,2.49;95% confidence interval:1.04-5.96;P=0.041).CONCLUSION Pouch adenomas occur at a fairly high rate in association with FAP after restorative proctocolectomy,and a high colorectal polyp count is associated with pouch adenoma development.

An Inflammatory Fibroid Polyp (Vanek’s Tumor) of the Ileum that Presented as Intussusception

Ileoileal intussusceptions caused by inflammatory fibroid polyps are uncommon. Inflammatory fibroid polyps (Vanek’s tumor) are rare benign lesions that originate in the submucosa of the gastrointestinal tract. Here, we report the case of a 54-year-old woman who was admitted with an acute onset of abdominal pain and signs of intestinal obstruction. The ileal segment was resected, and single-layer end-to-end anastomosis was performed. A submucosal polypoid mass measuring approximately 4.5 × 4.0 cm was found. The histopathological analysis revealed an ulcerated mucosal lesion with variable cellularity that was formed by spindle cells with slight mitosis and abundant inflammatory infiltrate that was mainly composed of eosinophils. Immunohistochemistry confirmed the diagnosis of ileal inflammatory fibroid polyps. Cross-sectional imaging (multidetector computed tomography) plays a significant role in diagnosing this condition and guiding its management.

基于因子分析193例大肠腺瘤性息肉患者中医证候特点研究

目的 研究大肠腺瘤性息肉患者的中医证候特点,为此病的中医证候标准化提供可靠依据。方法 根据制定的中医证候信息调查表,选择符合大肠腺瘤性息肉诊断标准的病例200例,采用因子分析等统计学方法进行中医证候特点研究。结果 剔除7例患者,最终纳入193例患者,因子分析得出脾虚湿阻证、大肠湿热证、肝郁气滞证、脾虚气滞证4类证型。结论 大肠腺瘤性息肉患者的病机为本虚标实,脾虚为本,湿热为标。病性证素为湿、热、气滞、气虚,病位证素为大肠、脾、肝。