Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ² analysis, and a paired χ² test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ²=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ²=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ²=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ²=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ²=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.

This study analyzed the changes in macrophage phagocytosis after Echinococcus multilocularis protoscoleces(PSC)infection.The distribution of macrophages in hepatic alveolar echinococcosis patients was analyzed by immunohisto-chemistry.PD-1 blockade,PSCs and macrophages were co-cultured to analyze macrophage phagocytosis and the expression lev-els of CD47 and PD-1.Macrophages labeled by CD68 aggregated in close live tissue from the lession of alveolar echinococcosis patients.PSC infection resulted in lower intensity of Escherichia coli and higher expression of CD47 and PD-1 than observed in the control group(P＜0.001).The intensity of Escherichia coli increasedin the PD-1 blockade group after PSC infection(q=40.63,P＜0.05).PD-1 blockade restored macrophage phagocytosis after PSC infection.

Genome-wide association studies (GWASs) are the most widely used method to identify genetic risk loci associated with orofacial clefts (OFC). However, despite the increasing size of cohort, GWASs are still insufficient to detect all the heritability, suggesting there are more associations under the current stringent statistical threshold. In this study, we obtained an integrated epigenomic dataset based on the chromatin conformation of a human oral epithelial cell line (HIOEC) using RNA-seq, ATAC-seq, H3K27ac ChIP-seq, and DLO Hi-C. Presumably, this epigenomic dataset could reveal the missing functional variants located in the oral epithelial cell active enhancers/promoters along with their risk target genes, despite relatively less-stringent statistical association with OFC. Taken a non-syndromic cleft palate only (NSCPO) GWAS data of the Chinese Han population as an example, 3664 SNPs that cannot reach the strict significance threshold were subjected to this functional identification pipeline. In total, 254 potential risk SNPs residing in active cis-regulatory elements interacting with 1 718 promoters of oral epithelium-expressed genes were screened. Gapped k-mer machine learning based on enhancers interacting with epithelium-expressed genes along with in vivo and in vitro reporter assays were employed as functional validation. Among all the potential SNPs, we chose and confirmed that the risk alleles of rs560789 and rs174570 reduced the epithelial-specific enhancer activity by preventing the binding of transcription factors related to epithelial development. In summary, we established chromatin conformation datasets of human oral epithelial cells and provided a framework for testing and understanding how regulatory variants impart risk for clefts.
Chromatin ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Epithelium ; Genome-Wide Association Study ; Humans

OBJECTIVE: To summarize and compare the clinical baseline characteristics of patients with monoclonal gammopathy of undetermined significance (MGUS), primary light chain amyloidosis (pAL), multiple myeloma (MM), or MM with concurrent amyloidosis, especially the differences in cytogenetic abnormalities. METHODS: The clinical data of 15 cases of MGUS, 34 cases of pAL, 842 cases of MM and 23 cases of MM with concurrent amyloidosis were analyzed and compared retrospectively. RESULTS: Cytogenetic statistics showed that the incidence of t (11; 14) in the four groups (MGUS vs pAL vs MM vs MM with concurrent amyloidosis) was 0%, 33.3%, 16.4%, and 15.8%, respectively (P=0.037); that of 13q deletion was 20.0%, 14.7%, 45.8% and 56.5%, respectively (P<0.001); gain of 1q21 was 50.0%, 12.5%, 47.4% and 40.9%, respectively (P=0.001). Proportion of pAL patients with 0, 1 and≥2 cytogenetic abnormalities (including 13q deletion, 17p deletion, 1q21 amplification and IgH translocation) accounted for 41.9%, 41.9% and 16.1%, respectively; while the proportion of the same category in MM was 17.6%, 27.3%, and 55.2% respectively; this ratio of MM with concurrent amyloidosis was more similar to MM. Subgroup analysis showed that genetic abnormalities (including 13q deletion, 17p deletion and 1q21 amplification) were comparable within t (11; 14) negative and positive groups. Compared with positive cases, t(11; 14) negative patients with MM or MGUS were more likely to have 13q deletions and multiple genetic abnormalities. CONCLUSION Clinical characteristics of pAL, especially cytogenetic abnormalities, are significantly different from MM with concurrent amyloidosis. It suggests that although the onset characteristics are similar, actually the two diseases belong to different disease subtypes which should be carefully predicted and identified.
Amyloidosis ; Humans ; In Situ Hybridization, Fluorescence ; Monoclonal Gammopathy of Undetermined Significance/complications* ; Multiple Myeloma ; Retrospective Studies

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Objective:To investigate MAML2 gene rearrangement, gene fusion patterns, and the clinicopathological characteristics of primary pulmonary mucoepidermoid carcinoma (PMEC).Methods:Forty-six cases of primary PMEC from Fudan University Zhongshan Hospital and Fudan University Shanghai Cancer Center between 2017 and 2020 were collected. MAML2 gene rearrangement in all cases was detected by fluorescence in situ hybridization (FISH). In 20 cases, MAML2 fusion patterns were detected by targeted RNA sequencing (RNAseq). The relationship between MAML2 gene rearrangement, fusion patterns, clinicopathological characteristics, and prognosis was analyzed.Results:The average age of PMEC patients was 41 years (range 15-71 years); the ratio of male to female was about 1.1 ∶ 1.0. Most PMECs were low grade in histopathology with an early clinical stage (stageⅠ-Ⅱ).The overall positive rate of MAML2 gene rearrangement detected by FISH was about 80.4% (37/46), and the rate was higher in low-grade PMEC (91.7%, 33/36). Of the 20 cases detected by RNAseq, all the 19 FISH positive cases showed gene fusion, mainly CRTC1-MAML2 fusion (16/19), the other three cases showed CRTC3-MAML2 fusion (3/19), the break point of all the fusion patterns was CRTC1/3 (exon 1)-MAML2 (exon 2); No gene fusion was detected in the single FISH negative case; Compared with the MAML2 FISH negative patients, the PMECs carrying CRTC1-MAML2 fusion were more commonly found in patients age ≤ 40 years, maximum tumor diameter ≤ 2 cm, low histopathological grade and early clinical stage (all P<0.05); The three PMECs carrying CRTC3-MAML2 fusion gene were all female with early clinical stage; Univariate analysis showed that MAML2 gene rearrangement/fusion, onset age ≤ 40 years old, smaller tumor size, low histopathological grade, early clinical stage, no metastasis at diagnosis and surgical treatment were significantly correlated with overall survival ( P<0.05), but Cox regression analysis suggested that none of the above indicators were the independent prognostic factors for the survival of PMEC. Conclusions:The high incidence of MAML2 gene rearrangement in PMEC suggests that it is an important molecular diagnostic marker of PMEC. RNAseq confirms that CRTC1/3-MAML2 is the main fusion pattern in PMEC, suggesting that MAML2 fusion transcription may be an important driving factor of PMEC. MAML2 rearrangement/fusion and related clinicopathological characteristics are associated with good prognosis.

Electrocardiography ; Heart Ventricles ; Humans ; Myocardial Infarction