Ionizing radiation (IR) is a genotoxic agent that can play an important role in the occurrence and development of various diseases by inducing epigenetic changes. Studies have shown that the basic mechanisms of IR-induced epigenetic changes include abnormal DNA methylation, increased oxidative stress levels, changes in histone modifications, and regulation by microRNAs. These can lead to health hazards such as malignant tumors, genetic effects, nervous system damage, circulatory system diseases, and radiation-induced cataracts. This article collected relevant literatures regarding epigenetic changes induced by IR from 2005 to 2024, and reviewed the basic mechanisms of IR-induced epigenetic changes and the associated disease risks, providing the reference for radiation protection in occupational exposure and radiotherapy.

BACKGROUND:Intervertebral disc degeneration is clinically considered to be the main cause of low back pain,but due to the unclear pathogenesis of intervertebral disc degeneration,there is still a lack of effective means to delay the progression of the disease.Single-cell RNA sequencing technology can amplify and sequence mRNA at the single-cell level,reveal the gene expression intensity of a single cell,discover different cell subsets in tissues according to the heterogeneity of cells,study the pathogenesis of intervertebral disc degeneration at the molecular level,and provide a new theoretical basis for its early diagnosis and treatment. OBJECTIVE:To introduce the basic principles of single-cell RNA sequencing technology and review the research progress of single-cell RNA sequencing technology in intervertebral disc degeneration in recent years. METHODS:A computer was used to search PubMed,Web of Science,CNKI and WanFang databases for the literature published from 2012 to 2022.Key words were"single-cell RNA sequencing,intervertebral disc degeneration,sequencing Technology"in Chinese and English.Duplicate,poor-quality and irrelevant articles were excluded;a total of 70 articles were eventually included. RESULTS AND CONCLUSION:(1)We identified new cell subsets such as homeostatic chondrocytes,hypertrophy chondrocyte-like nucleus pulposus cells and fibrous nucleus pulposus cells,identified the marker genes and transcription factors of these cell subsets,and described the functions,differentiation paths and cell fate of these cell subsets during the development and progression of intervertebral disc degeneration,and proposed the concept of progenitor nucleus pulposus cells.A cell subpopulation with progenitor nucleus pulposus cells properties was identified and its effectiveness in treating intervertebral disc degeneration was verified in mice.(2)Fibro chondrocyte-like annulus fibrosus cells and annulus fibrosus stem cells with both cartilage and fiber properties were identified,and a new type of composite hydrogel was prepared by combining fibrous cartilage inducers silk fibroin and hyaluronic acid in vitro.Experiments in mice demonstrated that this hydrogel could repair both annulus fibrosus tissue and cartilage matrix,and was remarkably effective in the treatment of intervertebral disc degeneration.(3)Regulatory chondrocytes were found in endplate cartilage.Two distinct fates in the progression of intervertebral disc degeneration were analyzed and the differential genes in the two fates were identified.Intercellular communication analysis indicated that regulatory chondrocytes interact with endothelial cells to promote angiogenesis.(4)Immune cells such as macrophages,T cells,myeloid progenitor cells and neutrophils were identified in the degenerated intervertebral disc tissues,demonstrating the existence of immune response during intervertebral disc degeneration.It was found that apolipoprotein induced the polarization of macrophages M1 and M2 subtypes,and this polarization process affected the activity of progenitor nucleus pulposus cells by amplifying the inflammatory response through the MIF signaling pathway.

Objective:To compare the clinical outcomes between pedicle screw internal fixation via the Wiltse approach and conservative treatment in young patients with thoracolumbar fracture with Thoracolumbar Injury Classification and Severity score (TLICS) ≤ 4 points.Methods:This retrospective study included 219 young patients with thoracolumbar fracture with TLICS score ≤ 4 points who had been treated from January 2014 to December 2018 at Department of Orthopaedics, The Second Hospital of Shanxi Medical University and obtained full follow-up. They were assigned into a surgery group of 126 patients subjected to pedicle screw internal fixation via the Wiltse approach and a conservative group of 93 patients subjected to conservative treatment. The surgery group included 65 males and 61 females, aged from 18 to 37 years, with a TLICS score of 1 point in 38 cases and of 2 to 4 points in 88 ones; the conservative group included 48 males and 45 females, aged from 19 to 38 years, with a TLICS score of 1 point in 29 cases and of 2 to 4 points in 64 ones. Patients in both groups underwent thoracolumbar X-ray, CT and MRI before treatment and regular thoracolumbar X-ray reexamination after treatment. Improvements in visual analog scale (VAS) for low back pain were compared between pre- and post-treatment. The 2 groups were compared in terms of VAS, anterior height of the injured vertebra and kyphosis cobb angle between pre-treatment, one month post-treatment and the last follow-up.Results:The 2 groups were comparable due to insignificant differences between them in the pre-treatment general data ( P>0.05). In the surgery group, patients were followed up for 24 to 72 months, the average VAS scores at one month post-treatment (2.5±1.2) and the last follow-up (2.3±0.8) were significantly improved compared to the pre-treatment value (6.8±2.1) ( P<0.05), and no serious surgical complications occurred. In the conservative group, patients were followed up for 30 to 65 months, the average VAS scores at one month post-treatment (3.9±1.9) and the last follow-up (3.5±0.9) were significantly improved compared to the pre-treatment value (6.2±2.0) ( P<0.05), and the rate of complications was 11.8% (11/93, including 3 cases of neural symptoms of the lower limb, 4 cases of bedsore and 4 cases of pulmonary infection). The VAS, anterior height of the injured vertebra and kyphosis cobb angle at one month post-treatment and the last follow-up in the surgery group were all significantly better than in the conservative group ( P<0.05). Conclusion:In young patients with thoracolumbar fracture with TLICS ≤ 4 points, pedicle screw internal fixation via the Wiltse approach can lead to better therapeutic outcomes than conservative treatment, especially in relief of postoperative low back pain.

Objective:To investigate the role and clinical significance of T follicular helper (Tfh) cells in the pathogenesis of eosinophilic gastroenteritis (EG) in children.Methods:A total of 17 children diagnosed with EG in the Department of Gastroenterology, Children′s Hospital of Nanjing medical University from October 2018 to January 2020 were recruited as EG group.During the same period, 15 children diagnosed with colon polyps were included as control group.Flow cytometry was used to detect Tfh cells and their functional molecules, including inducible costimulatory molecules (ICOS) and programmed cell death protein 1 (PD-1) in peripheral blood of the 2 groups.Results:The median (interquartile range) of Tfh cell frequency in peripheral blood of children with EG group was 7.3 (2.6)%, which was significantly higher than that of controls 2.8 (1.4)% ( P<0.05). There were significant differences in the median (interquartile range) of ICOS [1.5 (1.3)% vs.0.1 (0.2)%] and PD-1 expressions [1.8 (3.2)% vs.0.7 (0.6)%] on Tfh cells between children with EG group and control group (all P<0.05). The frequency of Tfh cells in the peripheral blood of children with EG was positively correlated with the expressions of ICOS ( r=0.746, P<0.05) and PD-1 ( r=0.893, P<0.05), and immunoglobulin E (IgE) level ( r=0.587, P<0.05). Conclusions:The frequency of Tfh cells in peripheral blood of children with EG significantly increases, which are proliferative and overexpressed with ICOS and PD-1.Moreover, the frequency of Tfh cells of EG patients is positively correlated with the level of IgE.The abnormal expression of Tfh cells may play a promoting role in the mechanism of EG.

Objective: To investigate the characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza. Methods: This was a single-center cross-sectional study in influenza patients admitted to Peking Union Medical College Hospital from August 2017 to April 2018. Peripheral blood lymphocyte subsets were detected by flow cytometry in both patients and 108 healthy controls. Influenza patients were divided into mild group and severe group. Severe patients were further classified into alive and fatal subgroups. Results: A total of 42 influenza patients were recruited in this study, including 24 severe cases (6 deaths). The remaining 18 cases were mild. The peripheral blood lymphocyte counts and lymphocyte subset counts (B, NK, CD4⁺T, CD8⁺T) in either mild patients[795 (571,1 007), 43 (23,144), 70 (47,135), 330 (256,457), 226 (148,366) cells/μl respectively] or severe patients[661 (474,1 151),92 (52,139), 54 (34,134), 373 (235,555), 180 (105,310) cells/μl respectively] were both significantly lower than those of healthy controls [1 963 (1 603,2 394),179 (119,239), 356 (231,496), 663 (531,824), 481 (341,693) cells/μl respectively]. Meanwhile, the T cells and CD8⁺T counts in fatal patients [370 (260,537) cells/μl and 87 (74,105) cells/μl] were significantly lower than those in severe and alive patients [722 (390,990) cells/μl and 222 (154,404) cells/μl]. CD8⁺HLA-DR/CD8⁺and CD8⁺CD38⁺/CD8⁺T cell activating subgroups in mild cases[(53.7±19.2)% and 74.8% (64.1%,83.7%) respectively] were significantly higher than those in severe cases[(38.5±21.7)% and 53.3% (45.3%,67.2%) respectively].Moreover,CD8⁺HLA-DR/CD8⁺count in severe and alive group was higher than that in fatal group [(46.1±19.1)% vs. (18.2±14.6)%, P<0.01]. Logistic regression analysis showed that CD8⁺T cell count (OR=0.952, 95%CI 0.910-0.997, P=0.035) and CD8⁺HLA-DR/CD8⁺T (OR=0.916, 95%CI 0.850-0.987, P=0.022) were both negatively correlated with mortality.Peripheral blood lymphocyte counts in mild cases rapidly decreased within 1 day after diagnosis, and returned to the basic level one week later. Conclusions All peripheral blood lymphocyte subsets (T,B,NK) in patients with influenza are significantly reduced. These findings are consistent with the immunological characteristics of respiratory viral infections, in which peripheral lymphocytes (especially T cells) migrate to respiratory tract in the early stage and circulate to the peripheral blood after recovery. The activated CD8⁺T cell counts in peripheral blood are negatively correlated with the severity of disease, which could be considered as a prognostic indicator of severe influenza.

To explore the mechanism for changes in brain microstructure in long-term abstinent from methamphetamine-dependence by using the diffusion tensor imaging (DTI).
 Methods: A total of 26 patients with long-term abstinent methamphetamine-dependence, whose abstinence time more than 14 months, and 26 normal controls all underwent cognitive executive function tests and DTI scans. We used voxel-based analysis to compare the fractional anisotropy (FA) and mean diffusivity (MD) to obtain the abnormal brain regions of DTI parameters between the two groups. Spearman correlation analysis was used to explore the correlation between FA, MD of the brain regions with abnormal parameters and cognitive executive function tests.
 Results: There were no statistical differences in the cognitive executive function tests between the two groups (P>0.05). Compared with the normal control group, the long-term abstinent from methamphetamine-dependence group showed the decreased FA in the right precuneus, right superior frontal gyrus, right calcarine, left inferior temporal gyrus and the increased MD in the right triangular part of inferior frontal gyrus, right precuneus, right posterior cingulate, right middle temporal gyrus, bilateral middle occipital gyrus, left superior parietal lobule, and lobule VIII of cerebellar hemisphere. The MD values of the right middle temporal gyrus in the long-term abstinent group were negatively correlated with the number of completions within 60 seconds (r=-0.504) and within 120 seconds (r=-0.464) .
 Conclusion: The DTI parameters in multiple brain regions from the methamphetamine-dependence patients are still abnormal after a long-term abstinence. DTI can provide imaging evidence for brain microstructural abnormalities in long-term abstinent from methamphetamine-dependence.
Amphetamine-Related Disorders ; Anisotropy ; Brain ; Diffusion Tensor Imaging ; Humans ; Methamphetamine

Objective:To explore the characteristics of brain structure in patients with long-term withdrawal of methamphetamine-dependence.Methods:A total of 44 patients with withdrawal of methamphetamine-dependent for more than 14 months were recruited,who met the diagnostic criteria for substance dependence in the fifth edition of the American Mental Disorders Diagnostic and Statistical Manual (DSM-Ⅴ),and 40 healthy subjects were used as the control.In addition to the general scale of drug-relevant survey,the subjects received the 3.0T magnetic resonance high-resolution scan.The voxel-based morphometric measurements for the subject's brain gray volume were conducted.Results:There was no significant difference in age,education,smoking and alcohol consumption between the methamphetamine-dependent withdrawal group and the control group (P＞0.05).The volumes for the bilateral cerebellum,the left side of temporal gyrus and the right side of the lingual gyrus in the methamphetamine-dependent withdrawal group were increased than those in the control group.The volumes for the bilateral lingual gyrus and bilateral cuneus in the methamphetamine-dependent withdrawal group were decreased than those in the control group.The volumes of left of cuneus and cerebellum were positively correlated with the duration of abstinence.Conclusion:After long-term abstinence,although the patients still show abnormal brain structure,their behavior and cognitive function is improved.The cerebral nerve structural is recovered from long-term abstinence.

Objective To analyze the consistency between constipated symptoms and the parameters of gastrointestinal transit time (GITT),anorectal manometry (ARM) in elderly patients with functional constipation.Methods Total 111 patients (54 males and 57 females) with an average age of (70.2±6.5) years,who met Rome Ⅲ criteria of functional constipation were enrolled from June 2010 to October 2012.After enrollment,patients took two-week diary,recording the spontaneous bowel movements per week,stool type of Bristol Stool Form,the frequency and severity of defecation straining,sensation of anorectal obstruction,manual maneuvers and sensation of incomplete evacuation.The GITT and ARM tests were performed,and the consistency between symptoms and test results were analyzed.Results Patients with symptoms of slow transit,defecation disorder and mixed symptoms were 19.8％ (22/111),16.2％ (18/ 111) and 59.5％ (66/111) respectively;and 4.5％ (5/111) patients had scattered symptoms.Based on results of GITT,slow transit subtype,defecation disorder subtype and mixed subtype were 54.1％ (59/109),1.8％ (2/ 109) and 29.4％ (32/109) respectively;and 14.7％ (16/109) patients were with normal transit time.ARM results showed that 38.0％ (41/109) of patients had dyssynergic defecation.The percentage of slow transit in GITT test showed no significant difference between patients with slow transit symptoms and mixed symptoms [50.0％ (11/22)vs.57.9％(33/57),x2=0.401,P=0.527].The consistency of predominant symptom with GITI subtype was low (κ=-0.013).The percentage of dyssynergic defecation detected with ARM showed no significant difference between patients with defecation disorder-predominant symptom and with mixed symptom [23.1％ (6/24)vs.38.2％ (21/55),x2=1.813,P=0.178].The consistency of defecation disorderpredominant symptom with dyssynergic defecation in ARM was low (κ=-0.019).Conclusion The mixed subtype symptoms are the most common presentations of elderly patients with functional constipation,and the consistency of predominant constipated symptoms with GITI,ARM test results is poor.

OBJECTIVE: This study aims to use Arginine-gingipain A gene vaccine (pVAX1-rgpA) to immunize adult Beagle dogs and to evaluate its effect during peri-implantitis progression and development. METHODS: Plasmid pVAX1-rgpA was constructed. The second and third bilateral mandible premolars of 15 adult Beagle dogs were extracted, and the implants were placed immediately. After 3 months, the animals were randomly divided into groups A, B, and C. Afterward, the animals were immunized thrice with plasmid pVAX1-rgpA, with heat-killed Porphyromonas gingivalis, or pVAX1, respectively. IgG in the serum and secretory IgA (sIgA) in saliva were quantitatively analyzed by enzyme-linked immunosorbent assay before and after 2 weeks of immunization. Peri-implantitis was induced with cotton ligatures fixed around the neck of implants. Probing depth (PD) and bleeding on probing were recorded. All animals were sacrificed after ligaturation for 6 weeks. Decalcified sections with thickness of 50 μm were prepared and dyed with methylene blue to observe the bone phenotype around implants. RESULTS: Levels of serum IgG and sIgA in saliva were higher in groups A and B after immunization than before the process (P<0.05) and higher than those in group C (P<0.05). However, no difference was observed between groups A and B (P>0.05). At 4 and 6 weeks after ligaturation, PD of the ligatured side in group C was higher than that in groups A and B (P<0.05). On the other hand, no difference was identified between groups A and B (P>0.05). Bone loss in group A was significantly lower than that of the other groups (P<0.05). Abundant inflammatory cells and bacteria were present in the bone loss area around the implants in the three groups, as identified through hard tissue section observation. However, group C presented the most number of inflammatory cells and bacteria in the bone loss area around the implants. CONCLUSIONS IgG and sIgA can be generated by immunity with rgpA DNA vaccine, which can significantly slow down bone loss during experimental peri-implantitis in dogs.
Adhesins, Bacterial ; therapeutic use ; Alveolar Bone Loss ; Animals ; Arginine ; Cysteine Endopeptidases ; therapeutic use ; Dental Implants ; Dogs ; Peri-Implantitis ; prevention & control ; Porphyromonas gingivalis ; chemistry ; Vaccines ; therapeutic use

Objective To evaluate the efficacy and safety of testa triticum tricum purif for the treatment of functional constipatiofi(FC) in the late middle-aged and elderly patients.Methods This study was designed as a multicenter randomized controlled trial.Patients who met Rome Ⅲ diagnostic criteria of FC were enrolled,with age between 55-85 years old.Those with organic diseases were excluded.The patients were randomly allocated to receive testa triticum tricum purif (3.5 g bid) or polyethylene glycol 4000 powder (PEG4000,10g bid) for 8 weeks,followed by single dose of maintenance therapy for 4 weeks.Follow-up visits were at 4 and 12 weeks after treatment discontinuation.The independent investigators in each center evaluated the constipation symptoms scores.The primary endpoints included rates of significant improvement,improvement and overall improvement at the end of 2,4 and 8 weeks of therapy,which were calculated by the reduction of symptom scores ≥ 75 ％,50％-74％,≥ 25 ％ respectively.Results A total of 127 FC subjects were enrolled from 3 centers,and 122 cases valid for final analysis.The mean age was (69.4 ± 6.9) years old,including 62 cases in testa triticum tricum purif group and 60 cases in PEG4000 group.The demographic data,constipated symptoms scores and proportion of FC subtypes at baseline were comparable.The rates of significant improvement,improvement and overall improvement in testa triticum tricum purif and PEG4000 groups at the end of 2,4 and 8 weeks were 37.70％ (23/61) vs 59.32％(35/59) (P=0.018),57.38％ (35/61)vs74.14％ (43/58) (P=0.054),and64.41％ (38/59)vs 79.31％ (46/58) (P =0.073) respectively.Testa triticum tricum purif therapy significantly improved the proportion of spontaneous bowel movement (SBM) ≥ 3 times/week from 43.55％ (27/62) to 80.33％ (49/61),83.61％ (51/61) and 93.22％ (55/59) at 2,4,and 8 weeks respectively (all P＜0.01),which were comparable with PEG4000 group (all P ＞ 0.05).The proportion of normalized stool forms in study group was significant higher than that of control group at the end of 8 weeks [86.44％ (51/59) vs 67.24％ (39/58),P =0.014].Only one patient complained mild abdominal distension during testa triticum tricum purif therapy.Conclusions The efficacy of testa triticum tricum purif for the treatment of FC in late middle-aged and older patients is comparable with osmotic laxatives PEG4000,which has significant effect on normalization of fecal forms and reliable safety.