Objective To explore the differential gene expression profile and small molecule drugs for chronic atrophic gastritis(CAG)by bioinformatics technology.Methods Two gene expression samples of CAG chips(GSE27411,GSE116312)were obtained through the Gene Expression Synthesis(GEO)database,screen the differentially expressed genes(DEGs)of CAG by R language,and CAG immune-related genes were obtained for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Protein-protein interaction(PPI)network was constructed using STRING database to screen out core genes,further study on immune invasion of core genes based on GSE27411 dataset,small molecular compounds interacting with core genes were predicted,molecular docking was carried out by MOE2022,and survival analysis was carried out by GEPIA2 website.Results A total of 517 DEGs were screened out based on GEO database.GO function enrichment analysis found that it mainly involved in granulocyte chemotaxis、leukocyte chemotaxis and neutrophil chemotaxis biological processes.KEGG pathway enrichment analysis showed that it mainly involved in cytokine-cytokine receptor interaction、nuclear factor kappa B signaling pathway、interleukin-17 signaling pathway.Six key genes of NR1H4、CCK、CCL20、CXCL1、LCN2、SAA1 were obtained by PPI network,through relevant verification,NR1H4 was regarded as the core gene.Immune cell infiltration analysis showed that central memory CD8 T cell、effector memeory CD4 T cell、gamma delta T cell、natural killer T cell、neutrophil and other immune cells may be involved in the development of CAG,and the neutrophil was positively correlated with NR1H4.It was predicted that six small molecular drugs,corilagin,stigmasterol,geniposide,tangeretin,chenodeoxycholic acid and epigallocatechin 3-gallate,have good binding force with NR1H4.Conclusion The potential mechanism of CAG is preliminarily explored in this study,the key gene of NR1H4 and neutrophil may play an important role in the"inflammatory cancer transformation"process of CAG,which can provide a certain reference for the study of the"inflammatory cancer transformation"mechanism of CAG.

Clinical pathway has great similarity with DRG,and plays an important role in standardizing diagnosis and treatment behavior and controlling medical expenses.Based on the analysis of the relationship between DRG payment method reform and clinical pathway,taking a public hospital in Wuhan City,Hubei Province as an example,the clinical pathway implementation strategy of large public hospitals under the DRG payment method reform was explored from five aspects:management system,suitable disease types,doctor's order setting,information system,training and assessment.

Due to traditional professional divisions, the practice of endoscopy by gastro-intestinal surgeons in China remains controversial. However, with the evolution of treatment philo-sophies, medical technology, and equipment advancements, a trend of integration between tradi-tional surgery and endoscopy is emerging. Gastrointestinal surgeons performing endoscopy can maxi-mize patient benefits, and they naturally possess advantages in conducting endoscopic procedures. It is recommended to further establish entry thresholds for surgeons to perform endoscopy, provide standardized endoscopic training for surgeons, and coordinate efforts at the administrative depart-ment. With the support of artificial intelligence, more patients can receive minimally invasive, indivi-dualized, and precise treatments.

Objective To detect the level of related indexes of energy metabolism in liver tissue of alcoholic liver disease(ALD)mice,and to explore the intervention effect of Gehua Jiejiu Dizhi Decoction.Methods Forty male C57BL/6J mice were randomly divided into the normal control group,the model group,the Gehua Jiejiu Dizhi Decoction high-dose group(4.94 g/kg),the Gehua Jiejiu Dizhi Decoction low-dose group(2.47 g/kg),and the resveratrol group(0.40 g/kg),with 8 mice in each group.Except the normal control group,the mice in other groups were fed with Lieber-DeCarli control liquid diet for five days,followed by Lieber-DeCarli alcohol liquid diet for ten days,and on the 16th day,the mice were given 31.5%alcohol solution through gavage to establish the ALD model.From the second day after modeling,the rats in the intervention groups were given the corresponding drugs by gavage once a day for nine consecutive days.Hematoxylin and eosin staining and oil red O staining were used to observe the liver steatosis in liver tissue.The activities of Na+K+-ATPase and Ca2+Mg2+-ATPase,and the contents of succinate dehydrogenase(SDH)and hepatic glycogen in liver tissue were detected using spectrophotometry.The contents of ATP,ADP,AMP,the AMP/ATP value,total adenosine pool(TAN)content,and energy charge(EC)in liver tissue were detected by reversed phase high performance liquid chromatography method.The mRNA expressions of NAD dependent deacetylase Sirtuin-1(SIRT1)and AMP-activated protein kinase(AMPK)α2 in liver tissue were detected by real-time PCR.The protein expressions of SIRT1,AMPKα2,and AMPKβ1 in liver tissue were detected by Western blotting.Results Compared with the normal control group,the model group mice showed significant hepatic steatosis,significantly decreased Ca2+Mg2+-ATPase activity and SDH content in liver tissue,significantly increased hepatic glycogen content,significantly decreased EC and AMP/ATP value,significantly increased ATP,ADP,AMP,and TAN content,significantly decreased mRNA expressions of SIRT1 and AMPKα2,significantly increased protein expression of AMPKβ1(P<0.05).Compared with the model group,the Gehua Jiejiu Dizhi Decoction high-and low-dose groups significantly reduced liver tissue steatosis,and the activity of Na+K+-ATPase in liver tissue was significantly reduced,the EC and the mRNA expressions of SIRT1 and AMPKα2 were increased(P<0.05);the activity of Ca2+Mg2+-ATPase,SDH and ATP contents were increased in the Gehua Jiejiu Dizhi Decoction low-dose group(P<0.05);the AMP/ATP value was increased in the Gehua Jiejiu Dizhi Decoction high-dose group(P<0.05);and the protein expression of SIRT1 was increased in the the Gehua Jiejiu Dizhi Decoction high-and low-dose groups and the resveratrol group(P<0.05);the protein expression of AMPKα2 in the Gehua Jiejiu Dizhi Decoction low-dose group and the resveratrol group was increased(P<0.05).Compared with the Gehua Jiejiu Dizhi Decoction high-dose group,the Gehua Jiejiu Dizhi Decoction low-dose group and the resveratrol group showed a significant increase in ATP,TAN contents,and EC in liver tissue,while the AMP/ATP value decreased(P<0.05);mRNA expressionin of AMPKα2 in the Gehua Jiejiu Dizhi Decoction low-dose group was decreased(P<0.05);and the protein expressions of SIRT1 and AMPKα2 in the resveratrol group were increased(P<0.05).Compared with the Gehua Jiejiu Dizhi Decoction low-dose group,the protein expression of AMPKβ1 was decreased in the resveratrol group(P<0.05).Conclusion The changes of energy metabolism caused by chronic alcohol intake may be related to the occurrence of ALD,and the intervention of Gehua Jiejiu Dizhi Decoction can improve the abnormal energy metabolism in the liver of ALD mice.

ObjectiveTo explore the effect of Weiwei Tongtiao decoction （WTD） on chronic atrophic gastritis （CAG） rats and the underlying mechanism. MethodA total of 90 SD rats were randomized into normal control group， model group， high-dose， medium-dose， and low-dose WTD groups （18， 9， 4.5 g·kg^-1·d^-1 WTD， respectively， ig）， and weifuchun control group （0.45 g·kg^-1·d^-1 weifuchun aqueous solution， ig）， with 15 rats in each group. The N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） was employed to induced CAG in rats. After the modeling （identified by histopathological examination）， the administration began and lasted 12 weeks. Then， gastric mucosa tissues of the rats were collected and stained with hematoxylin and eosin （HE）， and the pathological changes of gastric mucosa were observed under the optical microscope. Real-time PCR， immunohistochemistry （IHC）， and Western blotting were applied to examine the mRNA and protein expression of indexes in nuclear factor kappa-B （NF-κB） signaling pathway in the gastric mucosa of rats. ResultCAG rats showed irregular arrangement and morphology of the inherent glands in gastric mucosa and the glands decreased or disappeared. In addition， inflammatory cell infiltration was observed in the lamina propria of CAG rats， and about 48.4% presented intestinal metaplasia. WTD significantly alleviated the reduction of the glands and intestinal metaplasia in a dose-dependent manner. Compared with the normal control group， the model group demonstrated increase in the mRNA expression of cyclooxygenase-2 （COX-2）， NF-κB p65， interleukin （IL）-1α， IL-1β， IL-10， IL-8α， and IL-8β， and protein expression of COX-2， NF-κB p65， and IL-10 （P<0.01）. WTD and weifuchun lowered the mRNA expression of COX-2， NF-κB p65， IL-1α， IL-1β， IL-10， IL-8α， and IL-8β， and the protein expression of COX-2， NF-κB p65， and IL-10 in gastric mucosa of CAG rats （P<0.01）. The expression of the above indexes after the intervention with high-dose WTD was close to that of the normal control group. ConclusionWTD can improve or even reverse the diseased gastric mucosa of CAG rats， and the mechanism is the likelihood that WTD down-regulates the mRNA and protein expression of the indexes in NF-κB signaling pathway in gastric mucosa of CAG rats.

Gastric ''inflammation-cancer'' transformation stars from inflammation and ends as gastric cancer （GC）， and the pathogenesis is still unclear. In China， GC features high morbidity and mortality and poor prognosis， influencing the quality of life and physical and mental health of patients. Therefore， it is of great significance to construct the prevention and treatment system for GC. Chronic atrophic gastritis （CAG） plays a key role in the occurrence， development， and outcome of gastric ''inflammation-cancer'' transformation. Modern therapies for CAG generally aim at eliminating causes and alleviating clinical symptoms， which show satisfactory short-term efficacy， but the reverse and recurrence are common. Based on the holistic view， syndrome differentiation-based treatment， and the ''inflammation-cancer'' transformation in modern medicine， traditional Chinese medicine emphasizes both prevention and treatment， with individualized therapies for CAG and GC to control the transformation. According to the pathogenesis of CAG-asthenia in origin and sthenia in superficiality and deficiency-excess in complexity， this study proposed the theory of spleen deficiency and pathogen stagnation in CAG， and believed spleen deficiency， pathogen， and stagnation are respectively the root cause of， the main factor of， and the key to ''inflammation-cancer'' transformation， respectively. Spleen deficiency and pathogen stagnation are closely related to the process of the transformation. For the treatment， the spleen-invigorating and pathogen-eliminating method should be used for invigorating the spleen to consolidate original Qi， improve the blood supply in stomach， and regulate immunity， and eliminating the pathogen to relieve stagnation， reduce the occurrence of non-controllable inflammation， and improve inflammatory micro-environment. As a result， the gastric inflammation is controlled at the early stage and the gastric ''inflammation-cancer'' transformation is blocked. The gastric mucosal lesions are blocked， delayed， or even reversed. This study provides a new idea in clinical diagnosis and treatment of CAG and in the prevention of GC.

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

Objective:To analyze the interim clinical efficacy of laparoscopic and open distal gastrectomy for gastric cancer in elderly patients.Methods:The prospective randomized controlled study was conducted. The clinicopathological data of 102 patients aged ≥65 years who underwent distal gastrectomy for gastric cancer in the Nanfang Hospital of Southern Medical University from September 2014 to May 2018 were collected. After excluding 6 patients, 96 patients were finally included. Based on random number table, patients were allocated into two groups. Patients undergoing laparoscopic distal gastrectomy were allocated into laparoscopic group, and patients undergoing open distal gastrectomy were allocated into open group, respectively. Obser-vation indicators: (1) grouping situations of the enrolled patients; (2) intraoperative situations; (3) postoperative situations; (4) follow-up. Follow-up using outpatient examination and telephone interview was conducted to detect complications in the postoperative 30 days up to July 2018. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M( P25, P75) or M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter Mann-Whitney U test. Results:(1) Grouping situations of the enrolled patients: a total of 96 patients were selected for eligibility. There were 66 males and 30 females, aged from 65 to 85 years, with a median age of 69 years. There were 49 of 96 patients in the laparoscopic group and 47 patients in the open group. (2) Intraoperative situations: patients in the two groups underwent distal gastrectomy successfully with D 2 lymphadenectomy, without intra-operative conversion to laparotomy. The volume of intraoperative blood loss and surgical incision length were 50 mL(50 mL,100 mL) and (7.1±1.7)cm for the laparoscopic group, respectively, versus 100 mL(100 mL,200 mL) and (19.1±1.7)cm for the open group, showing significant differences between the two groups ( Z=?3.779, t=?34.880, P<0.05) . (3) Postoperative situations: the number of lymph node dissected, time to postoperative initial out-of-bed activities, time to postoperative first flatus, time to postoperative first liquid food intake, time to postoperative first semi-liquid food intake, time to drainage tube removal, duration of postoperative hospital stay were 49(35,62), 1.9 days(1.3 days,2.9 days), 2.6 days(2.2 days,2.9 days), 3.4 days(2.7days,4.0 days), 5.9 days(4.7 days,7.7 days), 4.9 days(3.5 days,6.8 days), 7.7 days(6.7 days,8.9 days) for the laparoscopic group, respectively, versus 40(27,51), 2.5 days (1.8 days,3.3 days), 2.6 days(2.2 days,2.9 days), 3.9 days(2.9 days,5.7 days), 4.9 days(3.9 days, 5.9 days), 6.3 days(4.7 days,8.9 days), 8.7 days(6.9 days,11.7 days), showing significant differences between the two groups ( Z=?2.354, ?2.210, ?2.743, ?2.474, ?2.906, ?2.503, ?2.359, P<0.05). (4) Follow-up: patients in the two groups received 30 days of follow-up. During the follow-up, 8 patients in the laparoscopic group had postoperative complications, including 1 case with Clavien-Dindo grade Ⅰ complications, 7 cases with Clavien-Dindo grade Ⅱ complications, and no patient with Clavien-Dindo grade Ⅲ complications. Thirteen patients in the open group had postoperative complications, including 2 cases with Clavien-Dindo grade Ⅰ complications, 10 cases with Clavien-Dindo grade Ⅱ complications, and 1 case with Clavien-Dindo grade Ⅲ complications. There was no significant difference in the above indicators between the two groups ( χ2=1.135, 1.973, 1.054, P>0.05). The overall complication rate was 16.3%(8/49) and 27.7%(13/47) for the laparoscopic group and open group, respectively, showing no significant difference between the two groups ( χ2=1.803, 99.7% confidence interval as ?∞ to 2.4%, P>0.05). The upper limit of 99.7% confidence interval was less than non-inferiority level of 15%, interim analysis of which showed that the complication rate of the laparoscopic group was non-inferior to the open group. Conclusion:For elderly patients undergoing laparoscopic or open distal gastrectomy for gastric cancer, laparoscopic surgery does not increase intraoperative or postoperative complications, and has advantages of minimally invasiveness, fine operation, quicker recovery, and shorter hospital stay. Registry: this study was registered at clinicaltrials.gov in United States, with the registry number of NCT02246153.

Objective:To study the independent risk factors of tumor recurrence after radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC), and to establish a preoperative prediction score.Methods:A retrospective study was conducted on 168 HCC patients treated with RFA at Zhongshan Hospital affiliated to Sun Yat-sen University from June 2016 to September 2019. The X-tile software was used to determine the optimal cut-off value of preoperative circulating tumor cells (CTC) which was then used to analyze the relationship between different CTCs values with various clinical factors. The Cox regression model was used to analyze independent risk factors of recurrence after RFA, and each independent risk factor was assigned a score of 1 to compose the prediction score. The patients were divided into the low-risk group (0-2 scores), intermediate-risk group (3 scores) and high-risk group (4-5 scores). The Kaplan-Meier method was used to draw cumulative recurrence curves in calculating the cumulative recurrence rates of the 3 different groups.Results:Of 168 patients, there were 151 males and 17 females. Their age (Mean±SD) was 58.33±9.53 years. CTC≥1/3.2 ml was detected in 131 patients (77.98%) (range 0-20/3.2 ml). The X-tile software determined the preoperative CTC cut-off value of HCC patients to be 2/3.2ml which separated a CTC-negative group with 93 patients, and a positive group of 75 patients. On analyses, the relationship between preoperative CTC and various preoperative clinical parameters were related to number of tumor nodules, tumor maximum diameter and alpha-fetoprotein (AFP) levels ( P<0.05). Multivariate analysis showed that CTC positivity[ HR(95% CI): 1.990(1.332-2.974)], AFP>20 ng/ml[ HR(95% CI): 1.659(1.111-2.477)], PIVKA-II>40 mAU/ml[ HR(95% CI): 1.580 (1.022-2.443)], number of tumor nodules ≥2[ HR(95% CI): 1.568 (1.057-2.326)], and tumor diameter>30 mm[ HR (95% CI): 1.544 (1.007-2.369)] were independent risk factors of recurrence ( P<0.05) after RFA in HCC patients. The cumulative recurrence rates of patients at 6 months, 12 months, and 18 months were 14.9%, 35.6%, and 56.4% in the low-risk group, 38.9%, 70.5%, and 85.0% in the intermediate-risk group, and 64.5%, 84.5% and 100% in the high-risk group. The differences were significant ( P<0.05). Conclusion:Preoperative CTC positivity, AFP>20 ng/ml, PIVKA-II>40 mAU/ml, tumor nodules ≥2, and tumor diameter>30 mm were independent risk factors of recurrence after RFA in HCC patients. This preoperative predictive score could be used to guide clinical treatment strategies.

Objective:To analyze the risk factors of hepatocellular carcinoma microvascular invasion (MVI) and to construct a preoperative prediction clinical scoring system.Methods:A retrospective analysis was made on 113 patients with hepatocellular carcinoma undergoing hepatectomy at Zhongshan Hospital from March 2018 to Jun 2019.Postoperative pathology confirmed 35 cases with microvascular invasion.Results:The multivariate logistic regression model showed that the maximum tumor diameter( OR: 1.028, 95% CI: 1.001-1.005), the smoothness of the capsule edge( OR: 0.208, 95% CI: 0.062-0.699), the positive circulating tumor cells (CTC)( OR: 3.728, 95% CI: 1.029-13.501) and abnormal prothrombin(PIVKA-Ⅱ)( OR: 1.001, 95% CI: 1.000-1.002) were risk factors for MVI. The area, sensitivity and specificity of the clinical score constructed by assigning 1 point to each risk factor were 0.906, 74.29% and 92.31%, respectively. Clinical scores of 0, 1, 2, 3, and 4 predict MVI positive rates of 0 (0/26), 9.09% (3/33), 28.57% (6/21), 77.78% (14/ 18), 85.71% (12/14). Conclusions:Tumor maximum diameter>62 mm, PIVKA-Ⅱ>115 mAU/ml, unsmooth tumor capsule and CTC in peripheral blood are independent high risk factors in patients with MVI.