Objective: To investigate the mechanism of in alleviating colonic mucosal inflammation in ten-eleven translocation (TET) protein 2 gene knockout (TET2-/-) mice with ulcerative colitis (UC) by regulating DNA methyltransferase (DNMT) and DNA hydroxymethylase. Methods: Male specific pathogen-free (SPF) grade C57BL/6J wild-type (WT) mice (n = 8) and TET2-/- mice (n = 20) were used to establish UC models by freely drinking 3% dextran sulfate sodium solution for 7 d. After UC model validation through histopathological examination in two mice from each type, the remaining mice were divided into four groups (n = 6 in each group): WT model (WT + UC), TET2-/- model (TET2-/- + UC), TET2-/- mild moxibustion (TET2-/- + MM), and TET2-/- electroacupuncture (TET2-/- + EA) groups. TET2-/- + MM group received mild moxibustion on Tianshu (ST25) and Qihai (CV6) for 10 min daily for 7 d. The TET2-/- + EA group also applied electroacupuncture (1 mA, 2/100 Hz) at the same acupoints for 10 min daily for 7 d. The disease activity index (DAI) scores of each group of mice were accessed daily. The colon lengths of mice in groups were measured following intervention. The pathological changes in the colon tissues were observed with hematoxylin and eosin (HE) staining. The concentrations of interleukin (IL)-6, C-C motif chemokine 17 (CCL17), and C-X-C motif chemokine ligand 10 (CXCL10) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of DNMT proteins (DNMT1, DNMT3A, and DNMT3B) in the colon tissues was detected by immunohistochemistry. The expression of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC), histone deacetylase 2 (HDAC2), and DNA hydroxymethylase family proteins (TET 1 and TET3) was detected using immunofluorescence, which also determined the co-localization of TET1 and IL-6 protein. Results: Compared with WT + UC group, TET2-/- + UC group exhibited significantly higher DAI scores and shorter colon lengths (P < 0.01). Both mild moxibustion and electroacupuncture significantly decreased DAI scores and ameliorated colon shortening in TET2-/- mice (P < 0.001). Histopathological scores of TET2-/- + UC mice were significantly higher than those of WT + UC group (P < 0.001) and were significantly reduced after both mild moxibustion and electroacupuncture interventions (P < 0.001). Serum levels of IL-6, CCL17, and CXCL10 were significantly elevated in TET2-/- + UC group compared with WT + UC group (P < 0.001). Mild moxibustion significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.001, P < 0.001, and P < 0.01, respectively), while electroacupuncture also significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.05, P < 0.01, and P < 0.01, respectively). TET2-/- + UC mice showed increased expression levels of DNMT1, DNMT3A , DNMT3B, and 5-mC (P < 0.05, P < 0.01 and P < 0.001, respectively), with decreased expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001). Mild moxibustion significantly reduced DNMT1, DNMT3B, and 5-mC levels (P < 0.05, P < 0.01, and P < 0.001, respectively), while increasing expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001, P < 0.001, P < 0.05, and P < 0.001, respectively). Electroacupuncture significantly decreased 5-mC and DNMT3B levels (P < 0.001 and P < 0.01, respectively) and increased 5-hmC and HDAC2 levels (P < 0.05 and P < 0.001, respectively), but did not significantly affect TET1 and TET3 expression (P > 0.05). Compared with TET2-/- + MM group, TET2-/- + EA group showed significantly higher 5-mC expression (P < 0.001). TET2-/- + UC group exhibited markedly increased IL-6 expression and higher co-localization of TET1 and IL-6 in mucosal epithelium, whereas minimal IL-6 expression was observed in the other groups. Conclusion Mild moxibustion and electroacupuncture significantly ameliorate colonic inflammation exacerbated by TET2 deficiency in UC mice via epigenetic modulation. Distinct mechanisms exist between the two interventions: mild moxibustion regulates both DNMT and hydroxymethylase, whereas electroacupuncture primarily affects DNMT.

Objective To observe the effect of Shenqi Fuzheng injection combined with chemotherapy on reducing the side effects of malignant tumor chemotherapy. Methods Eighty cancer patients in Traditional Chinese Medicine Hospital of PLA General Hospital from January 2015 to March 2017 were randomly divided into treatment group and control group by using random number table method, each group contained 40 cases. The patients in the treatment group were given Shenqi Fuzheng injection combined with chemotherapy, while the control group used chemotherapy only. Results The incidence of WBC and Plt reduction in the treatment group [35.0 % (14/40), 32.5 % (13/40)] was lower than those in the control group [70.0 % (28/40), 57.5 % (23/40)], and the differences were statistically significant (χ 2= 9.825, P = 0.002;χ2=5.051, P=0.025). The incidence rates of digestive tract reaction and oral ulcers[52.5 %(21/40), 32.5 % (13/40)]were lower than those in the control group[75.0 %(30/40), 60.0 %(24/40)], and the differences were statistically significant (χ2= 4.381, P = 0.036; χ2= 6.084, P = 0.014). The quality of life in the treatment group was significantly improved compared with the control group [(51.4 ±5.1) points vs. (48.3±5.5) points], and the difference was statistically significant(t =2.595,P =0.011). Conclusions Shenqi Fuzheng injection combined with chemotherapy can reduce chemotherapy-induced side effects and improve the life quality of the patients.The injection can be used as the adjuvant therapy for chemotherapy in clinic application.

OBJECTIVE: To assess the diagnostic value of copy number variation sequencing (CNV-seq) in the genetic etiology of fetuses with nasal bone dysplasia (NBD). METHODS: A total of 217 fetuses discovered with NBD from December 2017 to December 2020 were divided into the isolated NBD group and NBD combined with other anomalies group, for which copy number variations (CNVs) were analyzed. RESULTS: A total of 40 fetal abnormalities were detected in 217 cases, with an overall abnormal rate of 18.4%. These included 31 cases with aneuploidies (14.3%, 31/217) and 9 cases with genomic CNVs (4.1%, 9/217). Five cases of trisomy 21 (3.5%, 5/144) and two CNVs cases with unknown clinical significance (1.4%, 2/144) were detected in the isolated group. As for the combined NBD group, 26 aneuploidies (35.6%, 26/73), including 19 cases with trisomy 21, 6 cases with trisomy 18, 1 case with trisomy 13, 5 cases with pathogenic CNVs (6.8%, 5/73), and 2 cases with CNVs of unknown clinical significance (2.7%, 2/73) were detected. A significant difference was detected between the two groups (P < 0.01). CONCLUSION The detection rate of CNV-seq is high for chromosomal aneuploidies and pathogenic CNVs in fetuses with NBD, particularly in those combined with other ultrasonic abnormalities.
Aneuploidy ; Bone Diseases, Developmental ; Chromosome Aberrations ; DNA Copy Number Variations ; Down Syndrome/genetics* ; Female ; Fetus/abnormalities* ; Humans ; Pregnancy ; Prenatal Diagnosis ; Trisomy

Objective:To explore the long-term influence of donor central graft thickness (CGT) and donor graft size on corneal endothelial cell density (ECD) after Descemet stripping automated endothelial keratoplasty (DSAEK).Methods:An observational case series study was conducted.One hundred and forty-four eyes of 134 patients who underwent DSAEK in Peking University Third Hospital from January 2013 to December 2017 with at least 24-month follow-up were enrolled.Preoperative donor ECD was evaluated by specular microscopy, and ECD was determined by in vivo confocal microscopy at 1, 3, 6, 12, and 24 months postoperatively.Donor CGT was measured by anterior segment optical coherence tomography.According to the 3-month postoperative donor CGT, the subjects were divided into thinner graft group (45 eyes with CGT<100 μm), medium-thick graft group (66 eyes with CGT≥100-<150 μm) and thicker graft group (33 eyes with CGT≥150 μm). According to the donor trephination size, the subjects were divided into smaller graft group (31 eyes with trephination size≥7-<8 mm) and larger graft group (113 eyes with trephination size≥8-<9 mm). The changes of the donor CGT and corneal endothelial cell loss rate were compared at different time points after surgery.The relationships between 24-month postoperative ECD and donor ECD, donor graft size and donor CGT were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Peking University Third Hospital (No.IRB00006761-2008025). Written informed consent was obtained from each subject prior to any medical examination. Results:The donor CGT was 129.0 (90.8, 160.8), 115.5 (93.0, 146.0), 115.5 (89.0, 151.0), 112.5 (94.3, 146.8) and 114.0 (89.0, 144.5) μm at 1, 3, 6, 12 and 24 months after surgery, showing a statistically significant difference ( H=37.369, P<0.001). There was a statistically significant difference between 1-month and 3-month postoperative CGT ( P<0.001). There was no statistically significant difference in the endothelial cell loss rate among the three different donor CGT groups and between the two different donor graft size groups at any postoperative time points (all at P>0.05). Spearman correlation analysis showed that the 24-month postoperative ECD was strongly positively correlated with the preoperative donor ECD( rs=0.783, P<0.001), which was not associated with donor graft size and donor CGT ( rs=0.141, P=0.093; rs=-0.044, P=0.600). Conclusions:Larger postoperative ECD is correlated with larger preoperative ECD of donor graft.Lower long-term corneal endothelial cell loss rate after DSAEK is associated with thinner and larger diameter of donor graft.

OBJECTIVETo compare the validity of three currently used chronic myeloid leukemia (CML) scoring systems (Sokal CML prognostic scoring system, Hasford prognostic scoring system, and EUTOS prognostic scoring system) in chronic phase CML (CP-CML) patients.

METHODSOne hundred and thirteen CP-CML patients taking hydroxyurea, interferon or imatinib were enrolled in this study. All patients were stratified into different groups according to each scoring system and different therapies respectively. And overall survival (OS) rates were observed and compared among different groups.

RESULTSThree scoring systems were effective predictors of OS in CP-CML patients, and EUTOS scoring system may predict more validly. Hasford scoring system was well correlated with Sokal and EUTOS scores (r=0.792, P<0.01 and r=0.624, Plt;0.01). The correlation between Sokal and EUTOS scores was relatively weak (r=0.508, Plt;0.01). Despite imatinib's marked effect in prolonging survival of CML patients, it was incapable of prolonging survival in Sokal, Hasford and EUTOS high- risk patients.

CONCLUSIONEUTOS prognostic scoring system may predict better than Sokal and Hasford systems in CML patients. Classification of patients based on the three scoring systems may assist in the choice of appropriate therapy for CML.

Adolescent ; Adult ; Aged ; Child ; Female ; Follow-Up Studies ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; drug therapy ; Male ; Middle Aged ; Prognosis ; Severity of Illness Index ; Survival Rate ; Young Adult