1.Graph Neural Networks and Multimodal DTI Features for Schizophrenia Classification: Insights from Brain Network Analysis and Gene Expression.
Jingjing GAO ; Heping TANG ; Zhengning WANG ; Yanling LI ; Na LUO ; Ming SONG ; Sangma XIE ; Weiyang SHI ; Hao YAN ; Lin LU ; Jun YAN ; Peng LI ; Yuqing SONG ; Jun CHEN ; Yunchun CHEN ; Huaning WANG ; Wenming LIU ; Zhigang LI ; Hua GUO ; Ping WAN ; Luxian LV ; Yongfeng YANG ; Huiling WANG ; Hongxing ZHANG ; Huawang WU ; Yuping NING ; Dai ZHANG ; Tianzi JIANG
Neuroscience Bulletin 2025;41(6):933-950
Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans
;
Schizophrenia/pathology*
;
Diffusion Tensor Imaging/methods*
;
Male
;
Female
;
Adult
;
Brain/metabolism*
;
Young Adult
;
Middle Aged
;
White Matter/pathology*
;
Gene Expression
;
Nerve Net/diagnostic imaging*
;
Graph Neural Networks
2.Burden of Headache Disorders in China and its Provinces, 1990-2021.
Zhe LIU ; Xue Hua HU ; Lin YANG ; Jin Lei QI ; Jiang Mei LIU ; Li Jun WANG ; Mai Geng ZHOU ; Peng YIN
Biomedical and Environmental Sciences 2025;38(5):547-556
OBJECTIVE:
To analyze the prevalence and burden of headache disorders in China and its provinces from 1990 to 2021.
METHODS:
Using data from the Global Burden of Disease Study (GBD) 2021, the number of prevalent cases, prevalence rate, disability-adjusted life years (DALYs), and age-standardized DALY rates were analyzed by sex, age group, and province for headache disorders and their subtypes (migraine and tension-type headache [TTH]) between 1990 and 2021. Percentage changes during this period were also estimated.
RESULTS:
In 2021, approximately 426 million individuals in China were affected by headache disorders, with an age-standardized prevalence rate of 27,582.61/100,000. The age-standardized DALY rate for all headache disorders was 487.15/100,000. Between 1990 and 2021, the number of prevalent cases increased by 37.78%, while the prevalence of all headache disorders, migraine, and TTH increased by 6.92%, 7.57%, and 7.86%, respectively. The highest prevalence was observed in the 30-34 age group (39,520.60/100,000). Migraine accounted for a larger proportion of DALYs attributable to headache disorders, whereas TTH has a greater impact on its prevalence. In 2021, the highest age-standardized DALY rates for headache disorders were observed in Heilongjiang (617.85/100,000) and Shanghai (542.86/100,000).
CONCLUSION
The prevalence of headache disorders is increasing in China. Effective health education, improve diagnosis and treatment are essential, particularly for middle-aged working populations and women of childbearing age.
Humans
;
China/epidemiology*
;
Female
;
Male
;
Adult
;
Middle Aged
;
Prevalence
;
Young Adult
;
Adolescent
;
Aged
;
Child
;
Headache Disorders/epidemiology*
;
Disability-Adjusted Life Years
;
Child, Preschool
;
Cost of Illness
;
Infant
;
Aged, 80 and over
3.Colon Dialysis with Yishen Decoction Improves Autophagy Disorder in Intestinal Mucosal Epithelial Cells of Chronic Renal Failure by Regulating SIRT1 Pathway.
Yan-Jun FAN ; Jing-Ai FANG ; Su-Fen LI ; Ting LIU ; Wen-Yuan LIU ; Ya-Ling HU ; Rui-Hua WANG ; Hui LI ; Da-Lin SUN ; Guang ZHANG ; Zi-Yuan ZHANG
Chinese journal of integrative medicine 2025;31(10):899-907
OBJECTIVE:
To explore the mechanism of colon dialysis with Yishen Decoction (YS) in improving the autophagy disorder of intestinal epithelial cells in chronic renal failure (CRF) in vivo and in vitro.
METHODS:
Thirty male SD rats were randomly divided into normal, CRF, and colonic dialysis with YS groups by a random number table method (n=10). The CRF model was established by orally gavage of adenine 200 mg/(kg•d) for 4 weeks. CRF rats in the YS group were treated with colonic dialysis using YS 20 g/(kg•d) for 14 consecutive days. The serum creatinine (SCr) and urea nitrogen (BUN) levels were detected by enzyme-linked immunosorbent assay. Pathological changes of kidney and colon tissues were observed by hematoxylin and eosin staining. Autophagosome changes in colonic epithelial cells was observed with electron microscopy. In vitro experiments, human colon cancer epithelial cells (T84) were cultured and divided into normal, urea model (74U), YS colon dialysis, autophagy activator rapamycin (Ra), autophagy inhibitor 3-methyladenine (3-MA), and SIRT1 activator resveratrol (Re) groups. RT-PCR and Western blot were used to detect the mRNA and protein expressions of zonula occludens-1 (ZO-1), Claudin-1, silent information regulator sirtuin 1 (SIRT1), LC3, and Beclin-1 both in vitro and in vivo.
RESULTS:
Colonic dialysis with YS decreased SCr and BUN levels in CRF rats (P<0.05), and alleviated the pathological changes of renal and colon tissues. Expressions of SIRT1, ZO-1, Claudin-1, Beclin-1, and LC3II/I were increased in the YS group compared with the CRF group in vivo (P<0.05). In in vitro study, compared with normal group, the expressions of SIRT1, ZO-1, and Claudin-1 were decreased, and expressions of Beclin-1, and LC3II/I were increased in the 74U group (P<0.05). Compared with the 74U group, expressions of SIRT1, ZO-1, and Claudin-1 were increased, whereas Beclin-1, and LC3II/I were decreased in the YS group (P<0.05). The treatment of 3-MA and rapamycin regulated autophagy and the expression of SIRT1. SIRT1 activator intervention up-regulated autophagy as well as the expressions of ZO-1 and Claudin-1 compared with the 74U group (P<0.05).
CONCLUSION
Colonic dialysis with YS could improve autophagy disorder and repair CRF intestinal mucosal barrier injury by regulating SIRT1 expression in intestinal epithelial cells.
Animals
;
Sirtuin 1/metabolism*
;
Drugs, Chinese Herbal/therapeutic use*
;
Autophagy/drug effects*
;
Male
;
Intestinal Mucosa/drug effects*
;
Rats, Sprague-Dawley
;
Epithelial Cells/metabolism*
;
Colon/drug effects*
;
Humans
;
Kidney Failure, Chronic/drug therapy*
;
Signal Transduction/drug effects*
;
Renal Dialysis
;
Rats
;
Kidney/drug effects*
4.CURRENT DISTRIBUTION OF AEDES AEGYPTI IN LEIZHOU PENINSULA,ZHANJIANG CITY,GUANGDONG PROVINCE
Rui-Peng LU ; Jin-Hua DUAN ; Yu-Wen ZHONG ; Hui DENG ; Jun WU ; Li-Ping LIU ; Wei-Xiong YIN ; Feng XING ; Hui HUANG ; Chang-Jie FU ; Zong-Jing CHEN ; Ming-Ji CHENG ; Sheng-Jun HU ; Ya-Ting CHEN ; Wen-Ting GUO ; Li-Feng LIN
Acta Parasitologica et Medica Entomologica Sinica 2025;32(1):16-21
Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.
5.Effects of Rehmanniae Radix Praeparata on striatal neuronal apoptosis in ADHD rats via Bcl-2/Bax/caspase-3 pathway.
Jing WANG ; Kang-Lin ZHU ; Xin-Qiang NI ; Wen-Hua CAI ; Yu-Ting YANG ; Jia-Qi ZHANG ; Chong ZHOU ; Mei-Jun SHI
China Journal of Chinese Materia Medica 2025;50(3):750-757
This study investigated the effects of Rehmanniae Radix Praeparata on striatal neuronal apoptosis in rats with attention deficit hyperactivity disorder(ADHD) based on the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X protein(Bax)/caspase-3 signaling pathway. Twenty-four 3-week-old male spontaneously hypertensive rats(SHR) were randomly divided into a model group, a methylphenidate group(2 mg·kg~(-1)·d~(-1)), and a Rehmanniae Radix Praeparata group(2.4 mg·kg~(-1)·d~(-1)). Age-matched male Wistar Kyoto(WKY) rats were used as the normal control group, with 8 rats in each group. The rats were administered by gavage for 28 days. Body weight and food intake were recorded for each group. The open field test and elevated plus maze test were used to assess hyperactivity and impulsive behaviors. Nissl staining was used to detect changes in striatal neurons and Nissl bodies. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) fluorescence staining was used to detect striatal cell apoptosis. Western blot was employed to detect the expression levels of Bcl-2, Bax, and caspase-3 proteins in the striatum. The results showed that compared with the model group, Rehmanniae Radix Praeparata significantly reduced the total movement distance, average movement speed, and central area residence time in the open field test, and significantly reduced the ratio of open arm entries, open arm stay time, and head dipping in the elevated plus maze test. Furthermore, it increased the number of Nissl bodies in striatal neurons, significantly downregulated the apoptosis index, significantly increased Bcl-2 protein expression and the Bcl-2/Bax ratio, and reduced Bax and caspase-3 protein expression. In conclusion, Rehmanniae Radix Praeparata can reduce hyperactivity and impulsive behaviors in ADHD rats. Its mechanism may be related to the regulation of the Bcl-2/Bax/caspase-3 signaling pathway in the striatum, enhancing the anti-apoptotic capacity of striatal neurons.
Animals
;
Male
;
Apoptosis/drug effects*
;
Rats
;
Drugs, Chinese Herbal/administration & dosage*
;
Caspase 3/genetics*
;
Proto-Oncogene Proteins c-bcl-2/genetics*
;
bcl-2-Associated X Protein/genetics*
;
Rehmannia/chemistry*
;
Attention Deficit Disorder with Hyperactivity/physiopathology*
;
Signal Transduction/drug effects*
;
Neurons/cytology*
;
Rats, Inbred SHR
;
Rats, Inbred WKY
;
Humans
;
Corpus Striatum/cytology*
;
Plant Extracts
6.Integrated multiomics reveal mechanism of Aidi Injection in attenuating doxorubicin-induced cardiotoxicity.
Yan-Li WANG ; Yu-Jie TU ; Jian-Hua ZHU ; Lin ZHENG ; Yong HUANG ; Jia SUN ; Yong-Jun LI ; Jie PAN ; Chun-Hua LIU ; Yuan LU
China Journal of Chinese Materia Medica 2025;50(8):2245-2259
The combination of Aidi Injection(ADI) and doxorubicin(DOX) is a common strategy in the treatment of cancer, which can achieve synergistic anti-tumor effects while attenuating the cardiotoxicity caused by DOX. This study aims to investigate the mechanism of ADI in attenuating DOX-induced cardiotoxicity by multi-omics. DOX was used to induce cardiotoxicity in mice, and the cardioprotective effects of ADI were evaluated based on biochemical indicators and pathological changes. Based on the results, transcriptomics, proteomics, and metabolomics were employed to analyze the changes of endogenous substances in different physiological states. Furthermore, data from multiple omics were integrated to screen key regulatory pathways by which ADI attenuated DOX-induced cardiotoxicity, and important target proteins were selected for measurement by ELISA kits and immunohistochemical analysis. The results showed that ADI significantly reduced the levels of cardiac troponin T(cTnT) and N-terminal pro-B-type natriuretic peptide(NT-proBNP) and effectively ameliorated myocardial fibrosis and intracellular vacuolization, indicating that ADI showed therapeutic effect on DOX-induced cardiotoxicity. The transcriptomics analysis screened out a total of 400 differentially expressed genes(DEGs), which were mainly enriched in inflammatory response, oxidative stress, and myocardial fibrosis. After proteomics analysis, 70 differentially expressed proteins were selected, which were mainly enriched in the inflammatory response, cardiac function, and energy metabolism. A total of 51 differentially expressed metabolites were screened by the metabolomics analysis, and they were mainly enriched in multiple signaling pathways, including the inflammatory response, lipid metabolism, and energy metabolism. The integrated data of multiple omics showed that linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism pathways played an important role in DOX-induced cardiotoxicity, and ADI may exert therapeutic effects by modulating these pathways. Target validation experiments suggested that ADI significantly regulated abnormal protein levels of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), prostaglandin H2(PGH2), and prostaglandin D2(PGD2) in the model group. In conclusion, ADI may attenuate DOX-induced cardiotoxicity by regulating linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism, thus alleviating inflammation of the body.
Doxorubicin/toxicity*
;
Animals
;
Mice
;
Cardiotoxicity/genetics*
;
Drugs, Chinese Herbal/administration & dosage*
;
Male
;
Proteomics
;
Metabolomics
;
Injections
;
Humans
;
Multiomics
7.Early clinical observation of the efficacy of a three-stage traditional Chinese medicine external treatment plan for talus Bone bruises caused by acute ankle sprain.
Mei-Qi YU ; Lei ZHANG ; Tian-Xin CHEN ; Ting-Ting DONG ; Yan LI ; Jun-Ying WU ; Bo JIANG ; Sheng ZHANG ; Xiao-Hua LIU ; Jin SUN ; Qing-Lin WANG
China Journal of Orthopaedics and Traumatology 2025;38(8):835-841
OBJECTIVE:
To explore the early clinical efficacy of a three-stage external treatment with traditional Chinese medicine (TCM) in the treatment of talar bone contusion caused by acute ankle sprain.
METHODS:
A retrospective analysis was performed on 360 patients with primary lateral ankle sprain admitted from September 2021 to July 2024. Patients with talar bone contusion were selected based on MRI examination, and 73 cases were finally included. According to different treatment methods, they were divided into the observation group and the control group. The observation group consisted of 35 cases, including 16 males and 19 females, aged 24 to 37 years old with an average of (30.34±2.68) years old, and received the three-stage external TCM treatment combined with the "POLICE" protocol. The control group included 38 cases, including 18 males and 20 females, aged 24 to 35 years old with an average of (29.87±2.57) years old, and was treated with the "POLICE" protocol alone. The volume of bone marrow edema (BME) area shown by MRI before treatment and 6 weeks after treatment was measured using 3D Slicer software, and the BME improvement rate was calculated. The "Figure of 8" measurement method was used to assess ankle swelling before treatment and at 1 and 3 weeks after treatment. The visual analogue scale (VAS) was used to evaluate ankle pain before treatment and at 1 and 6 weeks after treatment. At 6 weeks after treatment, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Karlsson ankle function score system were used to evaluate the improvement of ankle function.
RESULTS:
A total of 73 patients with talar bone contusion caused by ankle sprain completed the 6-week follow-up. At 6 weeks after treatment, the BME improvement rate in the observation group was (39.18±0.06)%, which was higher than (26.75±0.03)% in the control group, with a statistically significant difference (P<0.05). After 1 week of treatment, the VAS score in the observation group was (2.89±0.72) points, lower than (3.37±0.79) points in the control group, and the difference was statistically significant (P<0.05). The ankle swelling degree in the observation group was (50.20±3.19) cm, lower than (52.00±3.60) cm in the control group, with a statistically significant difference (P<0.05). After 3 weeks of treatment, there was no statistically significant difference in ankle swelling between the two groups. At 6 weeks after treatment, there was no statistically significant difference in VAS scores between the two groups. At 6 weeks after treatment, the AOFAS ankle-hindfoot score and Karlsson score in the observation group were (87.43±4.18) and (82.77±5.93) points, respectively, which were higher than (82.92±4.87) and (76.45±6.85) points in the control group, with statistically significant differences (P<0.05). According to the AOFAS ankle-hindfoot score, 8 cases were excellent and 27 cases were good in the observation group;2 cases were excellent, 33 cases were good, and 3 cases were fair in the control group. The difference between the two groups was statistically significant (χ2=7.089, P=0.029).
CONCLUSION
The three-stage external TCM treatment combined with the "POLICE" protocol has a significant early clinical efficacy. It can significantly reduce ankle pain and swelling in patients with bone contusion caused by acute lateral ankle sprain, promote the absorption of bone marrow edema, and accelerate the recovery of ankle function.
Ankle Injuries/drug therapy*
;
Drugs, Chinese Herbal/administration & dosage*
;
Talus/injuries*
;
Retrospective Studies
;
Administration, Cutaneous
;
Magnetic Resonance Imaging
;
Humans
;
Male
;
Female
;
Young Adult
;
Adult
;
Contusions/etiology*
;
Visual Analog Scale
;
Musculoskeletal Pain/etiology*
;
Recovery of Function/drug effects*
;
Treatment Outcome
;
Follow-Up Studies
8.Comparative efficacy of two hemopurification filters for treating intra-abdominal sepsis: A retrospective study.
Ye ZHOU ; Ming-Jun LIU ; Xiao LIN ; Jin-Hua JIANG ; Hui-Chang ZHUO
Chinese Journal of Traumatology 2025;28(5):352-360
PURPOSE:
To compare the efficacy of continuous renal replacement therapy (CRRT) using either oXiris or conventional hemopurification filters in the treatment of intra-abdominal sepsis.
METHODS:
We conducted a retrospective analysis of septic patients with severe intra-abdominal infections admitted to our hospital from October 2019 to August 2023. Patients who meet the criteria for intra-abdominal sepsis based on medical history, symptoms, physical examination, and laboratory/imaging findings were included.
EXCLUSION CRITERIA:
pregnancy, terminal malignancy, prior CRRT before intensive care unit admission, pre-existing liver or renal failure. Heart rate (HR), mean arterial pressure, oxygenation index, lactic acid level (Lac), platelet count (PLT), neutrophil percentage, serum levels of procalcitonin, C-reactive protein, interleukin (IL)-6, norepinephrine dosage, acute physiology and chronic health evaluation II (APACHE II), and sequential organ failure assessment (SOFA) scores before and after 24 h and 72 h of treatment, as well as ventilator use time, hemopurification treatment time, intensive care unit and hospital lengths of stay, and 14-day and 28-day mortality were compared between patients receiving CRRT using either oXiris or conventional hemofiltration. Statistical analysis was performed using SPSS Statistics 26.0 software, including the construction of predictive models via logistic regression equations and repeated measures ANOVA.
RESULTS:
Baseline values including time to antibiotic administration, time to source control, and time to initiation of CRRT were similar between the 2 groups (all p>0.05). Patients receiving conventional CRRT exhibited significant changes in HR but of none of the other indexes at the 24 h and 72 h time points (p=0.041, p=0.026, respectively). The oXiris group showed significant improvements in HR, Lac, IL-6, and APACHE II score 24 h after treatment (p<0.05); after 72 h, all indexes were improved except PLT (all p<0.05). Intergroup comparison disclosed significant differences in HR, Lac, norepinephrine dose, APACHE II, SOFA, neutrophil percentage, and IL-6 after 24 h of treatment (p<0.05). Mean arterial pressure, serum levels of procalcitonin, C-reactive protein, SOFA score, and norepinephrine dosage were similar between the 2 groups at 24 h (p>0.05). Except for HR, oxygenation index, and PLT, post-treatment change rates of △ (%) were significantly greater in the oXiris group (p < 0.05). Duration of ventilator use, CRRT time, and intensive care unit and hospital lengths of stay were similar between the 2 groups (p>0.05). The 14-day mortality rates of the 2 groups were similar (p=0.091). After excluding patients whose CRRT was interrupted, 28-day mortality was significantly lower in the oXiris than in the conventional group (25.0% vs. 54.2%; p=0.050). The 28-day mortality rate increased by 9.6% for each additional hour required for source control and by 21.3% for each 1-point increase in APACHE II score.
CONCLUSIONS
In severe abdominal infections, the oXiris filter may have advantages over conventional CRRT, which may provide an alternative to clinical treatment. Meanwhile, early active infection source control may reduce the case mortality rate of patients with severe abdominal infections.
Humans
;
Retrospective Studies
;
Female
;
Male
;
Middle Aged
;
Sepsis/mortality*
;
Aged
;
Adult
;
Continuous Renal Replacement Therapy/methods*
;
Intraabdominal Infections/mortality*
;
APACHE
;
Organ Dysfunction Scores
;
Intensive Care Units
;
Treatment Outcome
9.The addition of 5-aminolevulinic acid to HBSS protects testis grafts during hypothermic transportation: a novel preservation strategy.
Meng-Hui MA ; Pei-Gen CHEN ; Jun-Xian HE ; Hai-Cheng CHEN ; Zhen-Han XU ; Lin-Yan LV ; Yan-Qing LI ; Xiao-Yan LIANG ; Gui-Hua LIU
Asian Journal of Andrology 2025;27(4):454-463
The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male
;
Animals
;
Testis/cytology*
;
Aminolevulinic Acid/pharmacology*
;
Mice
;
Organ Preservation/methods*
;
Organ Preservation Solutions/pharmacology*
;
Cryopreservation/methods*
10.Study on Differential DNA Methylation Profiles of Patients with High-Altitude Polycythemia.
Jun-Hua JI ; Min YANG ; Yan JIANG ; Ting-Xian YANG ; Xiao-Jing MA ; Qi-Chao YIN ; Hong-Wei YIN ; Lin-Hua JI
Journal of Experimental Hematology 2025;33(2):580-586
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

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