The pathogenesis of pancreatic cancer is complex. While immune dysregulation and gut microbiota disturbances are considered key factors, the causal pathway between them remains unclear. This study employs a 2-step Mendelian randomization (MR) approach to empirically investigate the "immune cells - gut microbiota - pancreatic cancer" mediation pathway from a genetic perspective. Relevant data on 731 immune cell phenotypes (N = 3757), 473 gut microbiota (N=8293), and pancreatic cancer (N = 3,87,888) were extracted from large-scale genome-wide association study (GWAS) and FinnGen summary statistics. MR was employed to assess causal relationships. Inverse-variance weighted (IVW) regression served as the primary MR method, supplemented by sensitivity analyses to ensure robustness. Mediation analysis was performed to assess potential pathways from immune cells to pancreatic cancer mediated by gut microbiota. Two-step MR analyses revealed that 8 gut microbial taxa mediate the causal relationship between 14 immune cell phenotypes and pancreatic cancer. For example, Klebsiella mediated 10.2% of the protective effect of CD39+ monocytes on pancreatic cancer risk. Ruminococcus E sp003521625 accounted for 7.09% of the risk effect associated with HLA DR on B cells. Conversely, UBA7177 sp002491225 attenuated the protective effect of CD11b on CD33dim HLA DR- cells, with a mediation proportion of-10.5%. Notably, Brevibacillales exhibited the highest mediation proportion (15.5%) between Activated & resting Treg % CD4 Treg and pancreatic cancer. Our findings support a genetically predicted causal pathway linking immune cell phenotypes to pancreatic cancer via specific gut microbiota. These results underscore the mediating role of certain microbial taxa and offer novel insights for future strategies involving immune modulation or microbiota-based interventions in pancreatic cancer.

ObjectiveTo investigate the specific diagnostic value of the systemic immune–inflammation index (SII) and systemic inflammation response index (SIRI) combined with the prognostic nutritional index (PNI) and tumor markers (CA19–9 and CEA) in the stage diagnosis of pancreatic cancer.MethodsThis single-center retrospective cohort study consecutively enrolled 257 patients with pathologically confirmed pancreatic cancer. Patients with stage I–II disease were classified as the early-stage pancreatic cancer group, while those with stage III–IV disease were classified as the non-early group. Clinical and pathological characteristics, as well as pretreatment peripheral blood inflammatory, nutritional, and tumor marker data, were collected. SII, SIRI, and PNI were calculated. Differences in these parameters were compared across tumor stages and degrees of differentiation.ResultsCompared with the early-stage group, patients with non-early-stage pancreatic cancer had significantly higher levels of SII, SIRI, CA19-9, and CEA, while PNI was significantly lower (all P < 0.01). With advancing TNM stage, SII, SIRI, and tumor marker levels progressively increased, whereas PNI gradually decreased (all P < 0.05). Among individual indicators, PNI demonstrated the best diagnostic performance for early-stage pancreatic cancer (AUC = 0.78), followed by CA19-9 (AUC = 0.75), SII (AUC = 0.72), and SIRI (AUC = 0.70). The combined inflammatory and nutritional model (SII + SIRI + PNI) achieved an AUC of 0.82, which was significantly superior to that of any single marker. When inflammatory, nutritional, and tumor markers were fully combined, diagnostic performance was further improved (AUC = 0.88, sensitivity 84.6%, specificity 81.2%). In the subgroup of CA19-9–negative patients, the combined inflammatory and nutritional model still showed good diagnostic value (AUC = 0.85).ConclusionsThe combination of systemic immune–inflammation indices with nutritional parameters and tumor markers significantly enhances the specificity and accuracy of early-stage pancreatic cancer diagnosis. This multi-marker strategy provides an important complementary diagnostic approach, particularly in CA19-9–negative patients.

To facilitate scarless wound healing, developing an anti-scarring treatment that modulates dermal fibroblast activity is a promising strategy, with pirfenidone (PFD) showing potential due to its anti-fibrotic properties by targeting intracellular pathways that regulate collagen disposition. PFD, particularly when delivered via dermal fibroblast-derived exosomes, may further enhance therapeutic effectiveness and promote scarless healing. Two common isolation methods—PEG precipitation and affinity-based techniques—were compared to identify the most efficient approach for obtaining high-purity and relatively homogenous exosomes derived from human dermal fibroblasts. Characterization techniques, including transmission electron microscopy (TEM), atomic force microscopy (AFM), antibody arrays, and enzyme-linked immunosorbent assays (ELISA), confirmed the successful isolation of high-purity exosomes. The affinity-based method demonstrated superior performance, yielding well-dispersed and highly pure exosomes. We optimized the encapsulation and formulation of the antifibrotic compound PFD by exploiting exosomes as a drug delivery platform, employing an active loading method via sonication to enhance encapsulation efficiency (EE

Objectives Pancreatic ductal adenocarcinoma (PDAC) has a high recurrence rate post-curative surgery. This study aimed to evaluate the combined predictive value of preoperative carbohydrate antigen 19-9 (CA19-9) and neutrophil-to-lymphocyte ratio (NLR) for early recurrence in resected PDAC patients.Methods This was a single-centre retrospective study involving 151 patients diagnosed with PDAC. Data on patient demographics, clinical characteristics and preoperative haematological parameters were collected. Early recurrence was defined as recurrence within the first 12 months after surgery. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with early recurrence. Receiver Operating Characteristic (ROC) curves and Area Under the Curve (AUC) analyses were used to assess the diagnostic performance of CA19-9, NLR and their combination.Results Among 151 patients (median follow-up: 21 months), 32.45% (n = 49) experienced early recurrence. Multivariate logistic regression analysis revealed that preoperative CA19-9 levels and NLR were independently associated with early recurrence. ROC curve analysis demonstrated that the combination of NLR and CA19-9 had significantly better performance in predicting early recurrence compared to NLR or CA19-9 alone.Conclusion The combination of preoperative CA19-9 and NLR enhances predictive accuracy for early recurrence in PDAC, offering a useful tool for postoperative risk stratification.

Dampened antigen presentation underscores the resistance of pancreatic cancer to T cell-mediated anti-tumor immunity, rendering immunotherapy largely ineffective. By high-throughput CRISPR activation perturbation, we discovered that the transcriptional regulator MCRS1 significantly augmented the sensitivity of mouse pancreatic cancer cells to T cell immunity in vitro and in vivo. Mechanistically, MCRS1 interacted with the transcription factor and genome organizer YY1 to coordinately increase the chromatin accessibility and expression of MHC-I genes. Elevated MCRS1 subverted MHC-I suppression and activated anti-tumor T cells, which sensitized mouse pancreatic cancer to α-PD-1 therapy. Remarkably, high MCRS1 expression was associated with increased T cell infiltration and extended survival of patients with pancreatic cancer and was predictive of favorable responses to α-PD-1 therapy in patients with lung cancer. Together, our study uncovers that MCRS1 sensitizes cancer cells to T cell immunity by transcriptionally subverting MHC-I suppression, which enhances the effectiveness of α-PD-1 therapy in mice and humans, paving the way to further improve immunotherapy against solid tumors.

HS6ST2 has ability to encodes a member of the heparan sulfate (HS) sulfotransferase gene family, which catalyze the transfer of sulfate to HS and a crucial regulator of cell growth, differentiation, adhesion, and migration. Although mounting evidence supports a vital role for HS6ST2 in tumorigenesis of some cancers, no pan-cancer analysis of HS6ST2 has been reported. Therefore, we aimed to explore the prognostic value of HS6ST2 in 33 cancer types and investigate its potential immune function. Based on data from The Cancer Genome Atlas, Cancer Cell Lines Encyclopedia, Genotype Tissue Expression, and GSCA, we used a range of bioinformatics approaches to explore the potential carcinogenic role of HS6ST2, analysis of HS6ST2 and prognosis, DNA methylation, RNA methylation, microsatellite instability (MSI), tumor mutation burden (TMB), and immune cell infiltration in different tumors. The results show that HS6ST2 was highly expressed in most cancers but lower in Breast invasive carcinoma, Kidney Chromophobe, Kidney renal clear cell carcinoma, Kidney renal papillary cell carcinoma, and Uterine Corpus Endometrial Carcinoma. Moreover, HS6ST2 is positively or negatively associated with prognosis in different cancers. HS6ST2 expression was not only associated with MSI in 5 cancer types and associated with TMB in 10 cancer types, and it's significantly correlated with DNA methylation in 13 types of cancer, but it's correlated with RNA methylation related genes in most cancer. HS6ST2 expression was correlated with immune cell infiltration, immune-related genes, tumor immune microenvironment, and drug resistance in various cancers. Eventually, HS6ST2 was validated in human lung adenocarcinoma tissues. Our study reveals that HS6ST2 can function as a prognostic marker in various malignant tumors because of its role in tumorigenesis and tumor immunity.

For decades, tumor-bearing murine models established using tumor cell lines have been the most commonly used models to study human cancers. Even though there are several studies reported that implant sites caused disparities in tumor behaviors, few of them illuminated the positional effect on immunotherapy. Herein, we describe surgical techniques for a novel orthotopic implantation of syngeneic pancreatic ductal adenocarcinoma (PDAC) tissue slices. This method has a high success modeling rate and stable growth kinetics, which makes it useful for testing novel therapeutics. Pathological examination indicated that the orthotopic tumor displayed poor vascularization, desmoplastic stromal reaction, and a highly immunosuppressive tumor microenvironment. This unique microenvironment resulted in limited response to PD1/CTLA4 blockade therapy and anti-MUC1 (αMUC1) CAR-T transfer treatment. To reverse the suppressive tumor microenvironment, we developed gene modified T-cells bearing a chimeric receptor in which activating receptor NKG2D fused to intracellular domains of 4-1BB and CD3ζ (NKG2D CAR). The NKG2D CAR-T cells target myeloid-derived suppressor cells (MDSCs), which overexpress Rae1 (NKG2D ligands) within the TME. Results indicated that NKG2D CAR-T cells eliminated MDSCs and improved antitumor activity of subsequently infused CAR-T cells. Moreover, we generated a bicistronic CAR-T, including αMUC1 CAR and NKG2D CAR separated by a P2A element. Treatment with the dual targeted bicistronic CAR-T cells also resulted in prolonged survival of orthotopic model mice. In summary, this study describes construction of a novel orthotopic PDAC model through implantation of tissue slices and discusses resistance to immunotherapy from the perspective of a PDAC microenvironment. Based on the obtained results, it is evident that elimination MDSCs by NKG2D CAR could rescue the impaired CAR-T cell activity.

Background To explore the impact of distant metastases on cancer-specific survival in patients with intraductal papillary mucinous neoplasm (IPMN) with associated invasive carcinoma and identify the risk factor of distant metastases in IPMN with associated invasive carcinoma. Methods Patients with IPMN with associated invasive carcinoma between 2010 and 2015 were retrospectively selected from the Surveillance, Epidemiology, and End Results (SEER) database. The survival analyses were assessed by Kaplan-Meier analyses and log-rank test. The impact of distant metastases was evaluated by Cox regression model and the risk factors of distant metastases were identified by logistic regression analyses, respectively. Results The median cancer-specific survival time of patients with no metastases, isolated liver, isolated lung, and multiple site metastases were 19 months, 4 months, 7 months, and 3 months, respectively. In patients with isolated liver metastases, multivariate analysis after adjustment indicated that chemotherapy (Hazard Ratio [HR]=0.351, 95% confidence interval [CI]=0.256-0.481, P<0.001) was a protective prognostic factor for cancer-specific survival (CSS) in patients with isolated liver metastases. In isolated lung metastases subgroup, old age (HR=1.715, 95% CI=1.037-2.838, P=0.036) and chemotherapy (HR=0.242, 95% CI=0.134-0.435, P<0.001) were related to CSS in multivariable Cox regression analysis(P<0.05). Tumor located in the pancreatic body/tail (HR=2.239, 95% CI=1.140-4.400, P=0.019) and chemotherapy (HR=0.191, 95% CI=0.108-0.340, P<0.001) were independent prognostic factors for CSS in patients with multiple metastases. Finally, a nomogram was constructed for cancer-specific survival and the predicted C-index was 0.780 (95% CI=0.762-0.798). Conclusion The liver is the most common site of distant metastases in IPMN with associated invasive carcinoma. Tumor located in the pancreatic body/tail and chemotherapy are independent prognostic factors for CSS in patients with multiple metastases. Further, tumor located in body/tail is identified as a risk factor of distant metastases.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor and is insensitive to radiotherapy and chemotherapy, as it is highly correlated with its complex tumor microenvironment (TME). A comprehensive description of PDAC’s immune microenvironment at the pathological level has not been reported, thus limiting its treatment. Previous studies have shown that large-section histopathology (LSH) can reveal the complete structure and margin of the tumor on a single slice and effectively reflect intratumoral heterogeneity. LSH, as opposed to classic small-section histopathology (SSH), can also be used to explore the infiltration state of immune cells in different regions. In the current study, EnVision immunohistochemical staining was used to explore the panoramic distribution of CD4-, CD8-, CD15-, CD20-, and CD56 (surface markers of helper T cells, cytotoxic T cells, neutrophils, B cells, and NK cells, respectively)-positive cells in 102 pairs of paraffin wax-embedded PDAC samples (LSH vs SSH) for the first time. These indicators were then analyzed, and correlations of clinicopathological characteristics with clinical prognoses were analyzed. The findings of this study show that LSH can effectively indicate more immune cells than SSH. Upregulated CD4, CD8, CD20, and CD56 or downregulated CD15 was correlated with a good prognosis in PDAC patients. However, analysis of SSH showed that only upregulated CD4 and CD8 can be used as indicators of a good prognosis. Multivariate Cox regression analysis showed that 7 variables, namely, pTNM stage ( P =0.002), PDL1 expression ( P =0.001), CDX2 expression ( P =0.008), DPC4 expression ( P =0.004), CD4 expression in LSH ( P <0.001), CD8 expression in LSH ( P =0.010) and CD15 expression in LSH ( P =0.031), were significantly correlated with the prognosis of PDAC patients. The findings of this study indicate that LSH is an effective tool for a panoramic assessment of the immune microenvironment in pancreatic cancer patients.

3115 Background: Tislelizumab, an anti-PD-1 monoclonal antibody, has demonstrated clinical benefit as a single agent and in combination with chemotherapy for patients (pts) with gastroesophageal adenocarcinoma (GEA), including gastric, gastroesophageal junction (G/GEJ), and esophageal adenocarcinoma (EAC). Immune- and tumor-transcriptomic features of response and resistance to tislelizumab were assessed from data collected in two monotherapy studies (NCT02407990, CTR20160872) and one tislelizumab plus chemotherapy study (NCT03469557). Methods: Gene expression profiling (GEP), using the 1392-gene HTG EdgeSeq panel, was performed on baseline tumor samples from 103 pts with GEA receiving monotherapy and 13 receiving combination therapy. Signature scores were calculated using the Gene Set Variation Analysis package with publicly available gene signatures (GS). Differential gene signature (DEG) analysis was performed between responders and nonresponders (NRs) using Wilcoxon rank-sum test; GS associated with survival were evaluated using Cox proportional hazards model. Results: Of the 76 pts with available GEP data, 64 (n=51 G/GEJ; n=13 EAC) had evaluable responses. Across these pts with GEA, tislelizumab demonstrated antitumor activity (Table). In pts treated with monotherapy, DEG showed IFNγ GS ( IFNG, CXCL9, CXCL10, HLA-DRA, IDO1, STAT1) scores were positively correlated with response ( P=0.03) as well as progression-free (HR=0.5, 95% CI: 0.27–0.93) and overall survival (HR=0.44, 95% CI: 0.21–0.89). Monotherapy NRs could be clustered into distinct GEP subgroups. Compared with responders, two NR subgroups had lower IFNγ GS ( P=0.002, 0.047) along with either higher epithelial-mesenchymal transition (EMT; P=0.027), and angiogenesis ( P=0.002) or cell cycle (CC; P=0.097) GS expression. A third NR subgroup showed higher CC GS scores compared with responders ( P=0.015), despite high IFNγ GS levels. Unlike tislelizumab monotherapy, responders to combination therapy showed higher CC GS expression versus NRs ( P=0.089). Conclusions: While higher IFNγ GS was associated with clinical benefit with monotherapy, elevated EMT/angiogenesis and CC GS levels may indicate resistance. The effects of these signatures in pts treated with combination therapy may vary. Both immune- and tumor-intrinsic factors may be considered for validation in a phase 3 study (NCT03777657). [Table: see text]

OBJECTIVE:To assess the value of detecting multiple rearrangements of MLL gene in children with acute mononuclear leukemia (AML).METHODS:Eighty six children with AML were analyzed by fluorescence in situ hybridization (FISH), chromosomal karyotyping and multiplex reverse transcription-PCR (RT-PCR).RESULTS:Cross signals were detected by FISH in 26 cases, and 30.2% were detected with MLL gene rearrangements. R-band karyotyping analysis revealed 14 translocations with breakages involving 11q23 and 5 other aberrations, which yielded an overall detection rate of 22.1%. Multiple RT-PCR has detected 12 fusion genes produced by the MLL translocation, which yielded a detection rate of 14.0%. A significant difference was found in the detection rate of the three methods (P< 0.05).CONCLUSION:Combined use of FISH, chromosomal karyotyping and multiplex RT-PCR can improve the detection of MLL gene rearrangements and provide important clues for clinical diagnosis, treatment and prognosis of AML.

Purpose: We aimed to evaluate the performance of International Index (IPI) and an enhanced NCCN-IPI in prognostic prediction for diffuse large-B-cell lymphom, (DLBCL) and compare these two clinically derived indices. Materials and Methods: Totally 80 patients who were diagnosed as DLBCL from Jan. 2009 to Dec. 2013 were enrolled in this retrospective study and divided into RCHOP group and Non-RCHOP group based on their treatment strategy. Clinical information of these patients was obtained, based on which prognosis of survival was predicted by IPI and NCCN-IPI, respectively. Statistical analyses were performed to evaluate the differences of the potentially influencing factors between RCHOP group and Non-RCHOP group, associated factors of DLBCL prognosis, and prognostic capacity of IPI and NCCN-IPI. Results: Among the included patients, 26 ones received standard RCHOP or RCHOP-like chemotherapy and 54 ones received Non-RCHOP chemotherapy. No significant difference was observed in gender, age, tumor stage, lactate dehydrogenase (LDH) ratio, Eastern Cooperative Oncology Group performance status (ECOG PS), IPI or NCCN-IPI categories (P>0.05) between RCHOP group and Non-RCHOP group. Risk stratifications by IPI and NCCN-IPI were significant different (chi(2) = 16.018, P = 0.001). Compared with original IPI, NCCN-IPI showed more distinctive clinical outcome of overall survival, event-free survival and progression-free survival by Kaplan-Meier curves. Conclusions: The enhanced NCCN-IPI is superior over the traditional IPI for prognostication of the selected cohort of DLBCL patients.

In this study, we investigated the roles of miR-132 in tumor growth of osteosarcoma. We found that overexpression of miR-132 significantly suppressed in vitro cell proliferation and in vivo tumor growth. In addition, miR-132 overexpression induced G1/S cell cycle arrest of osteosarcoma cells. Further study showed that miR-132 could interact with the 3′-untranslated region of cyclin E1 (CCNE1) gene and repress its expression. Re-expression of CCNE1 (without the 3′UTR) could partially abrogate the miR-132-induced cell proliferation inhibition. Of significance, contrary to CCNE1, expression level of miR-132 was significantly lower in osteosarcoma tissues than in the adjacent normal tissues. Taken together, these results indicate that miR-132 functions as a tumor suppressor in osteosarcoma and that its suppressive effects are mediated chiefly by repressing CCNE1 expression.

Background/Aims: Mounting evidence has shown that aberrant expression of miRNAs correlates with human cancers, and that miRNAs can function as tumor suppressors or oncogenes. Here, we investigated the role and mechanism of miR-142-3p in human osteosarcoma. Methods: We used quantitative real-time RT-PCR to measure the expression of miR-142-3p in human osteosarcoma cell lines and tissues. The roles of miR-142-3p in osteosarcoma development were studied using cultured HOS, MG63 and Saos-2 cells and tumor xenograft analyses in nude mice; their target genes were also investigated. Results: We found that miR-142-3p was significantly downregulated in osteosarcoma cell lines and clinical specimens. Overexpression of miR-142-3p suppressed osteosarcoma cell proliferation, migration and invasion, whereas miR-142-3p knockdown increased these parameters. The xenograft mouse model also revealed the suppressive effect of miR-142-3p on tumor growth. High mobility group AT-hook 1 (HMGA1) was identified as a target of miR-142-3p. Downregulation of HMGA1 induced effects on osteosarcoma cell lines similar to those induced by miR-142-3p. In contrast, restoration of HMGA1 abrogated the effects induced by miR-142-3p up-regulation. Conclusion: These results indicated that miR-142-3p may function as a tumor suppressor by targeting HMGA1 in osteosarcoma. Copyright (C) 2014 S. Karger AG, Basel

目的:探讨中高危以上弥漫大B细胞型非霍奇金淋巴瘤(diffuse large B cell lymphoma, DLBCL)的临床特征、治疗措施与预后.方法:对42例中高危以上的弥漫大B细胞型非霍奇金淋巴瘤患者进行国际标准化预后指数(IPI)评分、Ann Arbor分期,将采用联合化疗为主和造血干细胞移植为主的两组患者的治疗疗效进行回顾性临床分析.结果:按国际预后指数(IPI)评分,中高危25例(59.52%),高危17例(40.48%);按Ann Arbor分期,Ⅱ期2例(4.76%),Ⅲ期29例(69.05%),Ⅳ期11例(26.19%);10例(23.81%)伴骨髓受侵,其中5例诊断为淋巴肉瘤细胞白血病;38例(90.48%)LDH值升高,其中最高达10000U/L以上;伴B症状共35例(83.33%).治疗总有效率达71.43%,其中完全缓解25例(59.52%),部分缓解5例(11.90%),病情稳定1例(2.38%),死亡11例(26.19%),4年总生存率为73.81%;采取造血干细胞移植治疗的患者完全缓解率为72.73%,高于化疗组54.84%(P<0.05),中位生存期35.38个月,较化疗组(29.25个月)延长.综合分析显示IPI评分、临床分期、治疗策略的选择、造血干细胞移植术是影响预后的重要因素.结论:规范及强力化疗方案是治疗中高危以上弥漫大B细胞淋巴瘤的主要措施:造血干细胞移植是治疗弥漫大B细胞淋巴瘤的最佳治疗策略.

Objective: To investigate telomerase activity and telomerase expression in the human gastric carcinoma cell line SGC7901 and its multi-drug resistant subcultured cell line SGC7901/VCR, and to search for a new target within the drug-resistance mechanism of the gastric carcinoma cell line. Methods: Silver staining TRAP(telomeric repeat amplification protocol) assay was used to detect telomerase activity. Semi-quantitative reverse transcriptase PCR was employed to detect hTERT, Mad1 and c-Myc mRNA expression. Plasmid (pGL3B-TRTP) was transfected into SGC7901/VCR and SGC7901. Expression of the reporter gene in the cell lysates was assayed by a dual luciferase reporter assay system. Results: Both telomerase activity and telomerase hTERT mRNA expression in SGC7901/VCR cells were higher than those in SGC7901 cells. hTERT promoter activity was significantly higher in SGC7901/VCR than in SGC7901. c-Myc mRNA expression was detected in SGC7901/VCR, but Mad1 mRNA was not. In SGC7901, both c-Myc and Mad1 mRNA expression could be detected and c-Myc mRNA expression was higher than that in SGC7901/VCR. Conclusion: Telomerase activity in SGC7901/VCR was higher than that in SGC7901, and the high level of telomerase hTERT gene transcription and expression in SGC7901/VCR was correlated with drug-resistance. Mad1 and c-Myc expression may contribute to hTERT transcription and telomerase activity.

AIM:Inducing mesenchymal stem cells (MSCs) differentiate to myoblasts with 5-azacytidine(5-Aza-CR), investigating the expression of Myf5 and the role of the signal transduction case of p38 in all the course of differentiation.METHODS:Separating and purifying bone marrow-derived MSCs, inducing MSCs differentiation to myoblasts with 10 micromol/L 5-Aza-CR, assaying the gene expression time of Myf5 with RT-PCR method, the antigen expression of myosin with immunohistochemistry method and observing the changes of the activity of phosphorylation p38 before and after inhibited by SB203580 with Western-blot method.RESULTS:MSCs begin to express Myf5 delayed to the 9th day after inhibited by SB203580. Some of MSCs express myosin at the 7th day after induced; The phosphorylation p38 activity of MSCs enhanced after induced by 5-Aza-CR but obviously decreased after inhibited by SB203580.CONCLUSION:MSCs can express myogenic regulator factors and orientation differentiate to myoblasts after induced by 5-Aza-CR, p38 really have a positive signal transduction affection in this course.