Objective To identify the enhancer profile marked by histone H3K27ac modification in high-grade intraepithelial neoplasia(HGIN)in order to reveal the novel regulatory mechanism of HGIN pathogensis.Methods Gastric tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA between June 2022 and June 2023,including 14 normal gastric tissues(Nor group),31 HGIN tissues(HGIN group)and 17 gastric cancer tissues(GC group).Cleavage under targets and tagmentation(CUT&Tag)technique was employed to capture enhancer regions modified by histone H3K27ac.Multi-omics analysis was performed to identify HGIN-specific active enhancers and their potentially regulated genes.Immunohistochemical profiling was performed to assess differential expression of the gene of interest across clinically stratified specimens,combined with CRISPR-dCas9-mediated ablation of active enhancers to monitor the gene of interest transcriptional dynamics and validate enhancer-mediated regulatory mechanisms.Results Epigenomic sequencing obtained the data with excellent quality,and indicated that obvious remodeling was observed in H3K27ac enhancers in HGIN and GC groups(P<0.05),though no significant difference in the genome-wide distribution of H3K27ac modification among the 3 groups.Combining transcriptome data revealed that enhancer remodeling may up-regulate the expression of the proliferation-related target gene,CD24,in the HGIN tissue;while,inhibiting enhancer activity can notably reduce CD24 expression level(P<0.05).Immunohistochemical assay displayed a positive correlation between the expression levels of CD24 and Ki-67(P<0.001).Conclusion The remodeling of H3K27ac enhancer represents a significant epigenetic feature of the transformation from normal condition to HGIN.Remodeling of H3K27ac enhancer up-regulates CD24,which may facilitate the abnormal proliferation of gastric epithelial cells.

Objective To analyze clinical characteristics of mesenchymal-subtype gastric cancer(Mes-GC)by integrating multi-omics data and explore the characteristics of tumor cells and microenvironment associated with the risk for recurrence.Methods Gastric tumor tissue samples were collected from the patients who visited Department of Gastroenterology of Army Medical Center of PLA from January 2022 to December 2023.Transcriptome and genome sequencing were applied for these tissue samples,including 19 cases of diffuse-type gastric cancer,22 cases of intestinal-type gastric cancer,and 23 cases of mixed-type gastric cancer patients.Bioinformatics analysis was employed to investigate the differences in clinical characteristics and tumor microenvironment between Mes-GC and non-mesenchymal-subtype gastric cancer(non-Mes-GC)by integrating data resources including The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),and National Genomics Data Center(NGDC).Results Compared to non-Mes-GC patients,Mes-GC ones were characterized by later clinical stages,deeper tumor infiltration,and higher rates of lymph node metastasis.Kaplan-Meier survival analysis confirmed that Mes-GC patients were associated with shorter survival time,poor prognosis as well as increased risk of cancer recurrence(P<0.05).Single-cell RNA sequencing data revealed that tumor cells in Mes-GC showed higher expression levels of the genes related to stemness,metastasis(P<0.05),and epithelial-mesenchymal transition(EMT).And in the tumor microenvironment,there were significant more myeloid cells,smooth muscle cells,endothelial cells and fibroblasts,with the most pronounced elevation in the proportion of fibroblasts(P<0.05).Moreover,the patients with larger proportion of fibroblasts were associated with poorer prognosis.Conclusion Mes-GC tumor cells exhibit higher stemness and EMT characteristics,and stromal cells such as myeloid cells,endothelial cells,and fibroblasts are enriched in the tumor microenvironment.These features may be key factors contributing to poor prognosis and high recurrence rate of Mes-GC.

Objective To identify the enhancer landscape marked by histone H3K27ac modifications in diffuse-type gastric cancer(DGC)tissues,and to elucidate the epigenetic remodeling mechanisms by which active enhancers regulate cachexia-related genes.Methods Gastric mucosal tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA during January 2022 to March 2023,including 10 normal gastric mucosa tissues(Normal group),10 DGC tissues diagnosed with cachexia(DGC group),and 10 organoids derived from DGC tissues(Organoid group).Using H3K27ac chromatin targeting cleavage and tagmentation(CUT&Tag)technology,genomic modification regions were captured to screen specific active enhancers and their potential target genes in DGC tissues.CRISPR-dCas9 gene editing technology was used to intervene with the enhancers,and the expression of target genes was detected with Western blotting and qRT-PCR.Sixteen female SPF-grade BALB/c Nude mice(6～8 weeks old,weighing 18～21 g)were utilized to establish an orthotopic xenograft tumor model using the human diffuse-type gastric cancer cell line MKN45.Cachexia-related phenotypes were evaluated in 3 groups:normal group(n=4),silencing group(n=6),and control group(n=6).Results Significant differential enhancer regions were identified between DGC and normal gastric mucosa tissues.DGC tissues exhibited a marked increase in enhancer abundance(P<0.05)and signal intensity when compared with the normal counterparts.Integrated analysis of transcriptome data revealed that some of these active enhancers up-regulated the expression of GDF15,a cachexia-associated target gene in DGC.Targeted silencing of the active enhancer of GDF15 using CRISPR/dCas9-KRAB plasmid technology resulted in a significant reduction in GDF15 expression at both mRNA levels(P<0.05)and protein.Results from orthotopic transplantation experiments of DGC demonstrated that silencing of active enhancers alleviated the cachexia phenotype in nude mice(P<0.05).Conclusion DGC exhibits enhancer remodeling,which regulates the expression of the cachexia-associated gene GDF15,and thereby contributes to the pathogenesis and progression of cancer cachexia.

Objective To explore and establish a medical complaint prevention system in stomatological hospitals,eval-uate its effect on improving the quality of medical services,in order to provide practical experience for the high-quality develop-ment of peer hospitals.Methods The sample hospitals were problem-oriented,based on the concept of PDCA cycle manage-ment,and integrated multidisciplinary knowledge.Successfully established a medical complaint prevention system for dental hos-pitals.This system mainly includes the planning phase:collecting and analyzing complaint characteristics,formulating plans and expected goals;Implementation stage:Adhere to problem oriented approach and actively implement measures that have been for-mulated;Check stage:Regularly evaluate the effectiveness of measures and conduct targeted surveys of patient opinions;Action stage:Summarizing relevant experiences and developing a recycling and rectification plan,and it has played an important role in improving the quality of medical services in sample hospitals,achieving significant results.Results Compared with 2022,the total number of outpatient and emergency patients in the sample hospitals increased by 14.4％in 2023,the total number of medi-cal complaints decreased by 7.6％,the total number of praise letters from patients and their families to medical staff increased fourfold,and the total number of suggestions for hospital improvement and enhancement decreased by 71.4％.Conclusion The medical complaint prevention system in dental hospitals has improved the quality of medical services in sample hospitals to a cer-tain extent,and the relevant experience is worth promoting.

Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.

Objective:To study combined adjuvant transcatheter arterial chemoembolization (TACE) with anti-tumor drug treatment on early hepatocellular carcinoma (HCC) recurrence in patients with microvascular invasion (MVI) after partial hepatectomy with curative intent.Methods:The clinical and pathological data of 169 patients with HCC who underwent partial hepatectomy with curative intent from January 2015 to December 2018 at the Affiliated Hospital of Qingdao University were retrospectively analyzed. MVI was diagnosed by postoperative histopathology. There were 147 males and 22 females, with the median age 56 years(ranged 32-79 years). The patients were divided into surgery group ( n=62, patients who did not receive adjuvant therapy), TACE group ( n=42, patients who only received TACE) and combined group ( n=65, patients who received TACE with anti-tumor drug) according to the therapies after resection. Patients in each group were further divided into grade M1 (mild) and grade M2 (severe) subgroups according to the severity of MVI. All patients were followed-up for observing tumor recurrence. The relapse-free survival in the three groups were compared using the Kaplan-Meier method and the log-rank test was used to compare the tumor-free survival rates. Results:The tumor-free survival rates of 169 patients at 1 and 2 years after operation were 59.2% and 40.8%. The tumor-free survival rates at 1 and 2 years after operation were 45.2% and 25.8% in surgery group, 61.9% and 40.5% in TACE group, 70.8% and 52.3% in combined group respectively. The differences among the three groups were significant: TACE group was better than surgery group, and combined group was better than TACE group, combined group was better than surgery group (all P<0.05). In TACE group and combined group, tumor-free survival rates of M1patients better than M2 patients, and the difference was significant ( P<0.05). Among M1 patients and M2 patients, tumor-free survival rates of combined group patients were better than surgery group and TACE group, the difference was significant (all P<0.05). The cumulative tumor-free survival rate was not significantly affected by different antineoplastic agents. Conclusion:Adjuvant TACE reduced the early recurrence rate of HCC patients with MVI. Adjuvant TACE combined with anti-tumor drug further reduced early tumor recurrence.

Nutrition literacy is one of essential components of health literacy. A relatively mature health literacy evaluation system has been established in China so far. However, the studies on nutrition literacy evaluation are still limited, especially for specific population, such as children, adolescents, older people, and maternal. The present study introduces the concept of nutrition literacy, and summarizes the evaluation tools of nutrition literacy for both general population and special population (i.e., children, adolescents, older people, and maternal) in China and foreign countries, and their dimension, reliability, validity and applicable scope. This study aim to provide evidence for the development of nutrition literacy evaluation tools for different population according to the current problem of nutrition in China.

Nutrition literacy is one of essential components of health literacy. A relatively mature health literacy evaluation system has been established in China so far. However, the studies on nutrition literacy evaluation are still limited, especially for specific population, such as children, adolescents, older people, and maternal. The present study introduces the concept of nutrition literacy, and summarizes the evaluation tools of nutrition literacy for both general population and special population (i.e., children, adolescents, older people, and maternal) in China and foreign countries, and their dimension, reliability, validity and applicable scope. This study aim to provide evidence for the development of nutrition literacy evaluation tools for different population according to the current problem of nutrition in China.

Liver can be regenerated after chemical injury or localized resection of the surgery by dynamic interactions between hepatocytes and non-parenchymal cells. Liver sinusoidal endothelial cells (LSECs) are the most abundant cells in liver non-parenchymal cells and participate in liver development, injury and regeneration. Currently more and more studies have shown that LSECs are essential for hepatocyte regeneration. In this paper, we summarized the research progress of LSECs and liver regeneration in recent years, aiming to provide new ideas for promoting liver regeneration by targeting LSECs.

Objective: To study the learning curve of laparoscopic pacreaticoduodenectomy (LPD) with a view to find an appropriate way to develop LPD step by step. Methods: 112 consecutive patients who completely underwent LPD in a single surgery center at the First People’s Hospital of Changzhou from December 2015 to February 2018 were retrospectively reviewed. By using both the cumulative sum (CUSUM) and the risk-adjusted CUSUM (RA-CUSUM) methods to analyze the perioperative data of these patients, the learning curve of LPD was studied in a more scientific way. Results: The learning curve could be divided into three phases: Phase 1, the initial period (the initial 45 patients); Phase 2, the enhancement period (the subsequent 31 patients); Phase 3, the maturation period (the remaining patients). For these 3 phases, the corresponding operative times were (448.4±75.0), (381.3±74.3), and (336.2±52.1) min, respectively (P<0.05). The intraoperative blood losses were (373.3±250.1), (332.3±211.6), and (265.3±253.2) ml, respectively (P<0.05). The times to oral intake were 6.0(5.0, 8.0), 5.0(3.0, 6.0), and 3.0(3.0, 5.0) days, respectively (P<0.05). The number of lymph nodes harvested were (10.0±7.0), (8.8±4.3), and (13.3±6.2), respectively (P<0.05). All these showed significant improvement through the 3 phases. On the other hand, the postoperative stays, the postoperative pancreatic fistula rates were also decreased. But these failed to reach statistical significance. Vascular reconstruction was carried out in the 48th patient in phase 2 of the study. Conclusions The initial phase of LPD passed after LPD for 46 patients, but the maturation phase occurred after LPD on 76 patients. Vascular reconstruction should be considered as passing through the learning phase rather than reaching the maturity phase. Adjustments made in the enhancement phase helped to get through the maturation phase earlier.