OBJECTIVE: To investigate the whole-genome differential methylation profile of patients with high-altitude polycythemia (HAPC). METHODS: In this study, a total of 20 adult male patients with HAPC were included, including 10 Tibetan and 10 Han patients. The control group consisted of 20 healthy adult males, including 10 Tibetan and 10 Han patients. Peripheral blood was collected from each group for DNA extraction and quality inspection, and DNA libraries were constructed. The differential methylation regions (DMRs) between groups were detected using reduced representation bisulfite sequencing, with enriched regions compared to those of the control group. The differential enrichment regions were selected, and the intersection of the enriched regions was associated with genes. The methylation enrichment regions that differed significantly between groups were filtered based on the number of enriched samples in the enriched regions between the groups. GO, KEGG functional, and pathway analysis were performed on the differentially associated gene sets to reveal significant differences between the patients and control groups at the functional and pathway levels. RESULTS: In comparison with the control group, 17 152 sites with more than 25% difference and 15 558 sites with less than -25% difference were identified in Tibetan patients. The top 5 genes with the largest methylation differences between the two groups were MCCC2, RP3-399L15.3, ZNF621, RP11-394A14.2 and SLC39A10. The top significantly different pathways annotated in the differentially expressed genes pathway was serotonergic synapse. In comparison with the control group, 2 687 CpG sites with a greater than 25% difference and 2 602 CpG sites with a less than -25% difference were identified in Han patients. The top 5 genes with the largest methylation differences between the two groups were NAA25, CORO2B, PDC, ZNF853, and MLLT10. The top significantly different pathways annotated in the differentially expressed genes pathway were glutamatergic synapse, retrograde endocannabinoid signaling, Rap1 signaling pathway and cholinergic synapse. In comparison with the control group, 3 895 CpG sites with a greater than 25% difference and 3 969 CpG sites with a less than -25% difference were identified in HAPC patients. The maximum methylation difference between the two groups could reach 78.1%, while the minimum was -42.6%. The top 5 genes with the largest methylation differences between the two groups were MCCC2, ARSJ, CTNNA3, SLC39A10, and SWAP70. The top significantly different pathways annotated in the differentially expressed genes pathway was signaling pathways regulating pluripotency of stem cells. CONCLUSION The occurrence of HAPC may be related to abnormal changes in DNA methylation, and methylation sites may be helpful for the early diagnosis of HAPC.
Humans ; DNA Methylation ; Altitude ; Polycythemia/genetics* ; Male ; Adult ; CpG Islands

Humans ; Moxibustion ; Depression ; Acupuncture Therapy ; Gastroesophageal Reflux ; Esophagitis, Peptic

Objective: To establish an ultra-sensitive, ultra-fast, visible detection method for Vibrio parahaemolyticus (VP) . Methods: We established a new method for detecting the tdh and trh genes of VP using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 12a (CRISPR/Cas12a) combined with recombinase polymerase amplification and visual detection (CRISPR/Cas12a-VD). Results: CRISPR/Cas12a-VD accurately detected target DNA at concentrations as low as 10 ^-18 M (single molecule detection) within 30 min without cross-reactivity against other bacteria. When detecting pure cultures of VP, the consistency of results reached 100% compared with real-time PCR. The method accurately analysed pure cultures and spiked shrimp samples at concentrations as low as 10 ² CFU/g. Conclusion The novel CRISPR/Cas12a-VD method for detecting VP performed better than traditional detection methods, such as real-time PCR, and has great potential for preventing the spread of pathogens.
CRISPR-Cas Systems ; Nucleic Acid Amplification Techniques/methods* ; Recombinases/genetics* ; Vibrio parahaemolyticus/genetics*

Impaired immunomodulatory capacity and oxidative stress are the key factors limiting the effectiveness of mesenchymal stem cell transplantation therapy. The present study was aimed to investigate the effects of jujuboside A (JuA) on the protective effect and immunomodulatory capacity of human umbilical cord mesenchymal stem cells (hUC-MSCs). Hydrogen peroxide was used to establish an oxidative damage model of hUC-MSCs, while PBMCs isolated from rats were used to evaluate the effect of JuA pre-treatment on the immunomodulatory capacity of hUC-MSCs. Furthermore, Hoechst 33258 staining, lactate dehydrogenase test, measurement of malondialdehyde, Western blot, high-performance liquid chromatography; and flow cytometry were performed. Our results indicated that JuA (25 μmol·L^-1) promoted the proliferation of hUC-MSCs, but did not affect the differentiating capability of these cells. JuA pre-treatment inhibited apoptosis, prevented oxidative damage, and up-regulated the protein expression of nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase 1 in hUC-MSCs in which oxidative stress was induced with H₂O₂. In addition, JuA pre-treatment enhanced the inhibitory effect of hUC-MSCs against abnormally activated PBMCs, which was related to stimulation of the expression and activity of indoleamine 2,3-dioxygenase. In conclusion, our results demonstrate that JuA pre-treatment can enhance the survival and immunomodulatory ability through pathways related to oxidative stress, providing a new option for the improvement of hUC-MSCs in the clinical setting.
Animals ; Cell Differentiation ; Humans ; Hydrogen Peroxide/metabolism* ; Mesenchymal Stem Cells ; Oxidative Stress ; Rats ; Saponins ; Umbilical Cord/metabolism*

Objective: To describe the distribution characteristics of coronary heart disease in adult twins recruited from Chinese Twin Registry (CNTR), and provide clues and evidence for the effect of genetic and environmental influences on coronary heart disease. Methods: By using the data of CNTR during 2010-2018, a total of 34 583 twin pairs aged ≥18 years who completed questionnaire survey and had related information were included in the current study to analyze the population and area distribution characteristics of coronary heart disease. Random effect models were used to compare the differences between groups. The concordane rate of coronary heart disease were calculated respectively in monozygotic (MZ) twin pairs and dizygotic (DZ) twin pairs to estimate the heritability. Results: The twin pairs included in this analysis were aged (34.2±12.4) years. The overall prevalence rate of coronary heart disease in twin pairs was 0.7%. Twin pairs who were women, older, obese and lived in northern China had higher prevalence of coronary heart disease (P<0.05). Intra-pair analysis in the same-sex twin pairs found that the concordane rate of coronary heart disease was higher in MZ twin pairs (25.3%) than in DZ twins (7.4%), and the difference was statistically significant (P<0.001). The overall heritability of coronary heart disease was 19.3% (95%CI: 11.8%-26.8%). Stratified by gender, age and area, the concordane rate was still higher in MZ twin pairs than in DZ pairs. Participants who were women, aged 18-30 years or ≥60 years and lived in northern China had a higher heritability of coronary heart disease. Conclusion: The distribution of coronary heart disease in twin pairs differed in populations and areas. The prevalence of coronary heart disease was affected by genetic factors, but the effect varied with age, gender and area.
Adolescent ; Adult ; China/epidemiology* ; Coronary Disease/genetics* ; Diseases in Twins/genetics* ; Female ; Humans ; Male ; Twins, Dizygotic ; Twins, Monozygotic/genetics*

ObjectiveTo investigate the biological effect of circ_0036176 on myocardial fibrosis. MethodsLevels of circ_0036176 and its host gene Myo9a were determined by real-time quantitative polymerase chain reaction （RT-qPCR） assay in human myocardial tissue， including 22 healthy organ donors and 26 patients with heart failure （HF）. A cell model of angiotensin Ⅱ （Ang-Ⅱ）-induced fibrosis in human atrial fibroblasts （HAFs） was achieved. To test the typical ring structure of circ_0036176， actinomycin D treatment and RNase R exonuclease digestion were performed. The expression of fibrosis-related gene in HAFs with overexpression of circ_0036176 was detected at mRNA and protein level. To select miRNAs that can effectively bind to circ_0036176， dual luciferase reporter gene assay and RNA antisense purification assay （RAP） were conducted， respectively. The neonatal mouse cardiac fibroblasts （mCFs） were used to study whether mir-218-5p mediates the effect of circ_0036176 on myocardial fibrosis phenotype. ResultsThe expression of circ_0036176 was up-regulated in the myocardium of HF patients （P＜0.001）， and the expression of circ_0036176 and the host gene Myo9a was down-regulated in Ang-Ⅱ-induced HAFs （P＜0.01）. In response to actinomycin D treatment and RNase R exonuclease digestion， circ_0036176 was more stable than Myo9a mRNA. The expression of COL1A1， COL3A1， TGF-β1 and ACTA2 was down-regulated in HAFs with overexpression of circ_0036176 （P＜0.05）. Results of dual luciferase reporter gene assay and RAP assay confirmed the interaction between miR-218-5p and circ_0036176. Overexpression of miR-218-5p could promote the expression of fibrosis-related genes， and attenuate the inhibitory effect of circ_0036176 on cardiac fibrosis. ConclusionsCirc_0036176 is up-regulated in the myocardium of HF patients， and circ_0036176 inhibits the expression of fibrosis-related gene through sponging miR-218-5p in CFs.

BACKGROUND: The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM. METHODS: We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated. RESULTS: In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in "disturbances of pigmentation" and "neurological and psychogenic dermatoses". The duration of T2DM also significantly associated with the prevalence of "disturbances of pigmentation" and "neurological and psychogenic dermatoses". Subsequently, the prevalence of "disturbances of pigmentation" was higher in males than females in NGT (P < 0.01) and T2DM (P < 0.01) groups. In addition, the difference in the prevalence of "disturbances of pigmentation" was also significant in NGT and T2DM groups (P < 0.01). CONCLUSIONS There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented.
Aged ; Aged, 80 and over ; Blood Glucose ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/epidemiology* ; Female ; Glucose Intolerance/epidemiology* ; Glucose Tolerance Test ; Humans ; Male ; Middle Aged ; Skin Diseases/epidemiology*

Objective: To confirm the impact of obstructive sleep apnea hypopnea syndrome (OSAHS) on perioperative and long-term outcome in patients with Stanford type A aortic dissection. Methods: From June 2010 to July 2017, the clinical data of 91 patients with Stanford type A aortic dissection were analyzed. Among them, 51 patients with OSAHS were included in the study group and 40 patients without OSAHS were included in the control group. After 36 months follow-up, all-cause death was regarded as the end event. The clinical baseline data, perioperative period and 36 months survival rate of the two groups were compared. Kanplan-Meier method was used to describe the 36 month survival curve of the two groups. Cox proportional risk model was used to evaluate the risk ratio (HR) and 95%CI of 36 month survival rate. Results: The mortality rate during hospitalization was 5.9% (3 cases) in the study group and 5.0% (2 cases) in the control group, and the difference was not statistically significant (χ~2=0.03, P>0.05). The actual follow-up was (36.2±1.5) months, 88 cases were followed up and 3 cases were lost. The all cause mortality rate of 36 months was 27.5% (14/51)in the study group and 10.0%(4/40) in the control group, the difference was statistically significant (χ~2=4.30, P<0.05).By Cox proportional risk model analysis, 36 months after operation, the study group was compared with the control group after adjusting for age, male, bicuspid of aortic valve, chronic obstructive pulmonary disease, anemia, preoperative pericardial tamponade, postoperative organ dysfunction, preoperative LVEF, emergency operation, Sun's operation, coronary artery bypass grafting, hypertension, cardiac arrhythmia, and advanced avulsion of distal aortic dissection The survival rate was lower, the difference was statistically significant (P<0.05).In addition to OSAHS, coronary artery bypass grafting and preoperative pericardial tamponade were also risk factors for the increase of 36 month mortality rate (HR=11.28,95%CI: 1.98-46.25, P=0.009; HR=9.08, 95%CI: 2.22-41.3, P=0.032). Conclusions: There was no significant difference in mortality during hospitalization in patients with Stanford A aortic dissection combined with OSAHS. The survival rate of 36 months after operation was lower than that of the control group.
Aneurysm, Dissecting/surgery* ; Humans ; Hypertension ; Male ; Postoperative Period ; Risk Factors ; Sleep Apnea, Obstructive

Aviation ; Humans ; Physical Fitness ; Resistance Training ; Schools ; Students

Objective: To analyze the epidemiological characteristics of coronavirus disease 2019 ( COVID-19 ) clusters in Lishui, so as to provide basis for the prevention and control of COVID-19 clusters. Methods: The data of COVID-19 clusters in Lishui from January 23 to March 29, 2020 were collected through China Disease Control and Prevention Information System-Public Health Emergency Information System, and analyzed time, space, scale, source of infection, exposure and transmission route by descriptive epidemiological method. Results: There were 31 cases in 8 clusters ( about 4 cases per cluster ), with no death. The report time was bimodal, peaked first from January 20 to February 10 with 4 clusters imported from domestic and peaked second from March 1 to 29 with 4 clusters imported from overseas. Qingtian County reported 4 clusters, Liandu District, Yunhe County, Qingyuan County and Jingning County each reported 1 cluster. Thirteen cases were restaurant employees, accounting for 41.94%. The cases were mainly occurred in the condition that exposed in the same family ( 6 clusters ), in the same dinner and car ( 1 clusters ), and in the same party ( 1 clusters ). The exposure modes that caused more cases infected were through the same family (9 cases) and through the same dinner and car ( 6 cases ). There were 3 clusters with first-generation cases, 3 clusters with second-generation cases and 2 clusters with third-generation cases. The recurrence rate of the 8 clusters ranged from 1.49% to 7.69%, with a median of 3.47%. Conclusions The COVID-19 clusters in Lishui imported from domestic in the early stage and later from overseas. Most cases were reported from Qingtian County, were engaged in catering business, and exposed by living with families.