Epigenetic modification genes are defined as genes whose products modify the epigenome directly through DNA methylation, histone modification or chromatin remodeling.More and more studies have shown that mutations in epigenetic modification genes are an important etiology of rare diseases with abnormal cardiac development.And these diseases usually affect multiple organs including heart due to the change of epigenetic components.Moreover, children′s lives and health are often threatened by a lack of effective drugs and complex cardiovascular malformations.This article reviews advances in molecule genetics of Tatton-Brown-Rahman syndrome, Kabuki syndrome, Rubinstein-Taybi syndrome, CHARGE syndrome and Sifrim-Hitz-Weiss syndrome, and mainly elaborates the mechanism of cardiovascular malformations caused by mutations in corresponding epigenetic modification genes, providing more comprehensive reference for clinical diagnosis and management.

Objective:To explore the therapeutic effects of lamb′s tripe extract and vitamin B12 (hereinafter referred to as lamb′s tripe) capsule on precancerous lesions of gastric mucosa in rats.Methods:Thirty-two rats of the 42 Wistar rats (model group) were selected for modelling, and in model group six rats died due to gavage, 10 rats were sacrificed for observing the results of modeling, and the left 16 rats were divided into administration group (eight rats) and non-administration group (eight rats). After modeling, five of the 10 rats without modelling treatment were selected as the normal control of the model group, the other five (negative control group) rats were included in drug intervention experiment. The drug intervention program was as follows: in administration group, rats were gavaged with lamb′s tripe 0.2 g/kg once per day for three months; in non-administration group and negative control group, rats were gavaged with 0.9% sodium chloride solution 0.2 g/kg once per day for three months. One rat died in each for the administration group and non-administration group due to gavage. Body weight gain, pH value of gastric juice and pathological changes of gastric mucosa of the three groups were evaluated. The number of nodules on gastric mucosal surface and the incidence and scores of precancerous lesions (intraepithelial neoplasia) in gastric mucosal were analyzed. The therapeutic effects of lamb′s tripe capsule on gastric mucosal precancerous lesions in rats were evaluated. Independent sample t test , Mann Whitney U test and chi-square test were used for statistical analysis. Results:The body weight gain of rats at the 6th week in the administration group was higher than that of rats in the non-administration group ((508.26±33.96) g vs. (495.50±23.01) g), and the pH value of gastric juice of rats in the administration group was lower than that of rats in the non-administration group (3.07±0.55 vs. 4.45±0.72), and the differences were statistically significant (both P<0.05). The number of proliferative nodules on the gastric mucosal surface of the rats in the administration group was less than that of rats in the non-administration group (the ratio of gastric fundus: 6.00(3.00, 7.00) vs. 11.00(7.00, 13.00); the ratio of gastric antrum: 0.00(0.00, 1.00) vs. 3.00(2.00, 4.00); the ratio of whole stomach: 7.00(3.00, 10.00) vs. 15.00(13.00, 17.00)), and the differences were statistically significant ( U=43.50, 49.00, 49.00, all P<0.05). The score of gastric mucosal precancerous lesions in the administration group was lower than that in the non-administration group(1.00±0.00 vs.1.14±0.38), and the incidence of precancerous lesions in the administration group was lower than that in the non-administration group (1/7 vs. 5/7), and the differences were statistically significant ( t=2.45, χ2=4.67, both P=0.031). Conclusions:Lamb′s tripe capsule can significantly inhibit the progression of precancerous lesions of gastric mucosa in rats, so as to play a role in preventing the occurrence of gastric cancer.

Objective:To compare the efficacy and safety of unilateral biportal endoscopy (UBE) and microendoscopic discectomy (MED) in the treatment of lumbar spinal stenosis by Meta-analysis.Methods:PubMed, Web of Science, CNKI and Wanfang Data were searched from their establishment to January 2021 for all the studies on UBE and MED in the treatment of lumbar spinal stenosis. The data extracted were authors, year of publication, study design, subject characteristics, sample size, surgical protocol, age, sex ratio, duration of surgery, length of hospital stay, complications, visual analogue scale (VAS), and Oswestry Disability Index (ODI). The Meta-analysis was conducted with software Revman 5.3 to analyze the operation time, hospital stay, complication rate, waist and lower extremity VAS scores and ODI scores at preoperation, early postoperation and the last follow-up. The quality of the case-control studies included was evaluated using the Newcastle Ottawa Scale (NOS) while the methodological quality and risk of bias of the randomized controlled studies (RCT) included were evaluated using the Cochrane Bias Risk Assessment Tool.Results:Finally, 7 studies were included, 6 in English and one in Chinese. There were 2 RCTs and 5 case-control studies. There were 251 patients in the UBE group and 224 patients in the MED group. Compared with the MED group, the UBE group had a significantly shorter hospital stay ( MD=-2.28, 95% CI: -3.42 to -1.14, P<0.001), and a significantly lower VAS score for early postoperative low back pain ( MD=-0.80, 95% CI:-1.44 to -0.16, P=0.01). There were no significant differences between the 2 groups in operation time, complication rate, waist VAS scores at preoperation or the last follow-up, lower extremity VAS or ODI scores at preoperation, early postoperation or the last follow-up, or dural dilatation area ( P>0.05). Conclusions:In the treatment of lumbar spinal stenosis, compared with MED, UBE is superior in early relief of low back pain and hospital stay after operation, but shows no significant difference in long-term efficacy or safety.

Objective:To investigate the radiologic, pathologic, and molecular features of simple bone cysts (SBC), and their differential diagnoses.Methods:Fourteen cases of SBC were collected at the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from 2017 to 2022, and fluorescence in situ hybridization (FISH) was performed for retrospective analysis.Results:There were 14 patients, including 7 females and 7 males, with age range of 7 to 45 (median 29) years. The most common complaint was pain, including 4 cases with pathological fracture and 5 with history of previous trauma. The tumor size ranged from 3.4 to 13.5 (median 5.6) cm. The lesion involved the femur ( n=4), humerus ( n=5) and iliac bone ( n=5). Radiologic diagnoses included SBC, aneurysmal bone cyst, and giant cell tumor of the bone or its combination with aneurysmal bone cyst-like region and fibrous dysplasia. Histologically, the cyst walls of the lesions were composed of fibrous tissue, fibrin-like collagen deposits, bone-like matrix and occasional woven bone. The lesional cells were spindled to ovoid, with scattered osteoclast-like giant cells, foamy histiocytes, hemosiderin deposits and cholesterol clefts. In 6 cases there were nodular fasciitis-like areas. Immunohistochemically, the spindled to ovoid cells were positive for SMA, EMA and SATB2 in varying degrees. FISH detection was performed in all 14 cases and EWSR1/FUS rearrangement were found in 9 cases. One case of FUS::NFATC2 fusion was detected by next-generation sequencing. Nine cases of SBC with the rearrangement were more cellular, and there were more mitotic figures in the recurrent FUS::NFATC2 fusion tumor. Clinical follow-up was obtained in all 14 cases with the time ranging from 5 to 105 (mean 46) months. Amongst them, the tumor with FUS::NFATC2 rearrangement had local recurrence twice after the first local excision, but had no more recurrence or metastasis 34 months after the subsequent segmental resection. The other 13 cases had no recurrence. Conclusions:EWSR1 or FUS rearrangement is most commonly identified in SBC, suggesting that SBC might be a neoplastic disease. In cases where the radiologic appearance and histomorphology are difficult to differentiate from aneurysmal bone cyst, FISH detection can aid in the definitive diagnosis.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.