1.Molecular mechanisms of ligament flavum hypertrophy:analysis based on methylation sequencing and transcriptome integration
Yang HE ; Buyuan TANG ; Changhuai LU
Chinese Journal of Tissue Engineering Research 2025;29(5):1013-1020
BACKGROUND:Ligament flavum hypertrophy is the main cause of lumbar spinal stenosis,which is the result of multiple pathological factors working together.Currently,the molecular mechanism and pathway of action of ligament flavum hypertrophy are unclear,and there is a lack of effective non-surgical treatment options. OBJECTIVE:To investigate the molecular mechanisms of ligament flavum hypertrophy using methylation sequencing and transcriptome integration analysis methods. METHODS:Five normal ligament flavum tissue samples and five hypertrophic ligament flavum tissue samples were collected.Abnormal methylation sites and methylation status were recorded by methylation sequencing and abnormally expressed genes were recorded by transcriptome integration analysis.The genes that showed a negative correlation between methylation level and expression level at the intersection of the two were selected.GO and KEGG enrichment analyses were used to study the major functional pathways and molecular functions of differentially expressed genes.Key genes regulating ligamentum flavum hypertrophy were screened using protein-protein interaction analysis. RESULTS AND CONCLUSION:Methylation sequencing of the two groups of the ligament flavum showed 37 173 hypermethylation sites and 10 583 low methylation sites.Transcriptome integration analysis found 720 abnormally expressed genes,of which 463 were upregulated and 257 were down-regulated.There were 383 overlapping genes,of which 192 genes showed a negative correlation between the methylation level and the expression level.GO functional pathway analysis results showed that molecular function was enriched to 10 terms,cellular component was enriched to 15 terms,and biological process(BP)was enriched to 30 terms.The results of KEGG pathway enrichment analysis showed that 192 genes were mainly enriched to 9 pathways,such as PI3K-Akt signaling pathway,Rap1 signaling pathway,and focal adhesion signaling pathway.The protein-protein interaction analysis identified five genes,PPARG,EGFR,CNR1,TNF and COL11A2,which may be the key genes that regulate ligamentum flavum hypertrophy,and they can influence the occurrence and development of ligamentum flavum hypertrophy mainly through the regulation of tissue fibrosis,cell proliferation and differentiation,inflammatory factor levels,and collagen fiber expression.
2.Improvement of myocardial injury by traditional Chinese medicine:mitochondrial calcium homeostasis mediates macrophage autophagy and pyroptosis pathway
Lingyun LIU ; Guixin HE ; Weibin QIN ; Hui SONG ; Liwen ZHANG ; Weizhi TANG ; Feifei YANG ; Ziyi ZHU ; Yangbin OU
Chinese Journal of Tissue Engineering Research 2025;29(6):1276-1284
BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.
3.A Comparative Study on the Clinical Effects of Short-term and Long-term Spinal Cord Stimulation in Patients with Prolonged Disorders of Consciousness
Fengqiao SUN ; Hongchuan NIU ; Yi YANG ; Jianghong HE ; Yuanli ZHAO
Medical Journal of Peking Union Medical College Hospital 2025;16(2):307-313
To compare the therapeutic effects of short-term spinal cord stimulation (stSCS) and long-term spinal cord stimulation (ltSCS) on patients with prolonged disorders of consciousness(pDoC). Clinical data of patients with pDoC who underwent SCS surgery at Peking University International Hospital from January 2020 to December 2021 were retrospectively included. Patients were divided into the stSCS group and the ltSCS group based on the surgical approach. The Coma recovery scale-revised (CRS-R) was used to assess the level of consciousness before and 3 months after SCS treatment. Based on CRS-R scores, the clinical diagnosis of the patient's level of consciousenss was categorized into four levels: vegetative state, minimally conscious state minus (MCS-), MCS plus (MCS+), and emergence from the minimally conscious state(EMCS). Improvement in the clinical diagnostic level of consciousness was defined as effective treatment, and the therapeutic outcomes of the stSCS and ltSCS groups were compared. 44.8% of patients with pDoC showed improvement in their clinical diagnostic level of consciousness after SCS treatment. Compared to preoperative scores, the CRS-R scores at 3 months postoperatively were significantly increased in both the stSCS and ltSCS groups (both Both stSCS and ltSCS can significantly improve the level of consciousness in patients with pDoC. Compared to ltSCS, stSCS may achieve comparable short-term therapeutic outcomes.
4.Inner Ear Delivery of Polyamino Acid Nanohydrogels Loaded with Dexamethasone
Pingping AI ; Lidong ZHAO ; Zhaohui TANG ; Chaoliang HE ; Xuesi CHEN ; Shiming YANG ; Nan WU
Medical Journal of Peking Union Medical College Hospital 2025;16(2):370-378
To develop a novel polyamino acid-based nanohydrogel drug delivery system for dexamethasone to enhance its delivery efficiency to the inner ear. A fluorescein-labeled polyglutamic acid-based polyamino acid dexamethasone nanohydrogel was synthesized, and its gelation time was measured. The hydrogel was surgically injected into the round window niche of guinea pigs to determine its degradation time in the middle ear cavity in vivo. The safety, pharmacokinetics, and distribution patterns of dexamethasone in the inner ear were evaluated. The hydrogel exhibited a gelation time of 80 seconds in a 37℃ water bath. In vivo, the hydrogel was almost completely degraded within 7 days in the middle ear cavity of guinea pigs. Transient hearing loss was observed one day after administration, but hearing gradually returned to normal over time. No significant cytotoxicity, vestibular stimulation signs, or pathological abnormalities in spiral ganglion cells were observed. Histopathological examination revealed no significant inflammatory reactions. Pharmacokinetic analysis demonstrated sustained drug release and prolonged dexamethasone activity. Immunofluorescence staining confirmed the distribution of dexamethasone in both the cochlea and vestibular organs. The polyamino acid nanohydrogel exhibits excellent injectability and biodegradability, representing a safe and effective drug delivery system for the inner ear.
5.China’s participation in schistosomiasis control in Africa: value and practice of the trinity model
Jian HE ; Xinyao WANG ; Yuzheng HUANG ; Juma SALEH ; Ally MAYASSA ; Xiaonong ZHOU ; Kun YANG
Chinese Journal of Schistosomiasis Control 2025;37(1):1-7
As a neglected tropical disease, schistosomiasis remains a major public health challenge in underdeveloped areas, notably Africa. Currently, the national schistosomiasis control programmes in Africa mainly depend on foreign aids; however, conventional international aid models have multiple limitations. To enhance the effectiveness and sustainability of global schistosomiasis control programmes, this article proposes a trinity collaboration model based on international rules, China’s experiences and local needs, which is explained with China aid project of schistosomiasis control in Zanzibar as an example. Based on the successful experiences from the national schistosomiasis control programme in China, this model emphasizes the compliance with World Health Organization guidelines and fully considers local actual needs to promote the effectiveness and sustainability of the schistosomiasis control programme through integrating international resources and promoting China’s experience to meet local needs. The successful practice of the China aid project of schistosomiasis control in Zanzibar provides strong evidence that the model is of great theoretical significance and practical value to improve the efficiency of multilateral collaboration and promote global health governance.
6.Trends in global burden due to visceral leishmaniasis from 1990 to 2021 and projections up to 2035
Guobing YANG ; Aiwei HE ; Yongjun LI ; Shan LÜ ; Muxin CHEN ; Liguang TIAN ; Qin LIU ; Lei DUAN ; Yan LU ; Jian YANG ; Shizhu LI ; Xiaonong ZHOU ; Jichun WANG ; Shunxian ZHANG
Chinese Journal of Schistosomiasis Control 2025;37(1):35-43
Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/105, 95% UI: (1.49/105, 4.07/105)], prevalence [0.64/105, 95% UI: (0.37/105, 1.02/105)], mortality [0.51/105, 95% UI: (0, 1.80/105)] and DALYs rates of VL [33.81/105, 95% UI: (0.06/105, 124.09/105)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/105, 95% UI: (0.45/105, 0.72/105); 0.14/105, 95% UI: (0.11/105, 0.18/105)] than among women [0.27/105, 95% UI: (0.21/105, 0.33/105); 0.06/105, 95% UI: (0.05/105, 0.08/105)], and the highest mortality of VL was found among children under 5 years of age [0.24/105, 95% UI: (0.08/105, 0.66/105)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/105, 0.03/105, 0.02/105 and 1.44/105 in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.
7.Etiological characteristics and molecular evolution of the first mpox case in Huai’an City of Jiangsu Province
Pengfei YANG ; Fang HE ; Qingli YAN ; Heyuan GENG ; Tong GAO ; Qiang GAO ; Chenglong XIONG ; Haiyan PENG
Chinese Journal of Schistosomiasis Control 2025;37(1):85-92
Objective To analyze the virus subtypes, molecular evolutional and molecular transmission network features of the first confirmed mpox case in Huai’an City, Jiangsu Province, so as to provide insights into understanding of the transmission and evolution dynamics of mpox virus and formulation of the mpox control strategy in the city. Methods Genomic DNA was extracted from swabs of the first confirmed mpox case’s skin lesions in Huai’an City, and the amplicon sequencing library was constructed using the hypersensitive mpox virus whole-genome capture kit. High-throughput sequencing was performed using the GridION X5 nanopore sequencer on the Nanopore sequencing platform, and single nucleotide polymorphism (SNP) analysis of mpox virus genome sequences was performed following sequence assembly. In addition, phylogenetic analysis, genetic genealogy and molecular traceability analysis were performed. Results The virus whole genome sequence of the first confirmed mpox case was successfully obtained by high-throughput sequencing, with a full length of 197 182 bp, and was named hMpxV/China/JS-HA01/2023, which belonged to the clade IIb (West African clade) lineage B.1.3. Compared with the mpox virus reference sequence MPXV-M5312_HM12_Rivers-001 (GenBank accession number: NC_063383), the genome sequence of the Huai’an virus isolate carried 86 SNPs, including 40 SNPs in the coding region as non-synonymous mutations and 73 SNPs as nucleotide mutations caused by APOBEC3 (APOBEC3). Of the 97 mpox virus gene sequences, 79 sequences were included in the molecular network (81.44%), and the threshold of the genetic distance accessed to the network was 0.35/105. There were two large molecular transmission clusters and one scattered cluster in the molecular transmission network of the mpox virus, andthehMpxV/China/JS-HA01/2023 sequence was located in the large cluster. The 97 gene sequences formed 92 haplotypes, including three shared haplotypes Hap_4, Hap_6 and Hap_38, and an exclusive haplotype Hap_1 of hMpxV/China/JS-HA01/2023 generated from mutation of the exclusive haplotype Hap_43, while the exclusive haplotype Hap_43 was generated from mutation of the shared haplotype Hap_38. Conclusions The whole genome sequence of the mpox virus isolated from the first confirmed mpox case in Huai’an City has been successfully obtained, and the molecular evolutionary and molecular transmission network characteristics of the virus have been preliminarily understood.
8.Research on The Construction and Application of Multiple Fluorescence Amplification System for Three Kinds of Stains
Yi-Fan BAI ; He-Miao ZHAO ; Jing CHEN ; Hong-Di LIU ; Rui-Qin YANG ; Chong WANG
Progress in Biochemistry and Biophysics 2025;52(4):982-994
ObjectiveA multiplex amplification system was constructed based on the capillary electrophoresis platform for simultaneous detection of saliva, semen, and vaginal secretions using tissue-specific RNA markers. The aim of this study is to identify the tissue origin of suspicious body fluid stains found at crime scenes and determine whether the body fluid stains at the crime scene are one or several types among saliva, semen, and vaginal secretions. MethodsThirty saliva samples, forty semen samples, and forty vaginal secretion samples (half from 2015 and half from 2024) were collected from healthy adult volunteers. Through primer designing, system formulation, and PCR condition optimization, a multiplex fluorescent amplification system was constructed. The specificity, sensitivity, and detection ability for mixed samples of this system were investigated, and it was tested using real crime scene materials. In the primer design stage, to reduce the requirements for RNA template quality, the amplification products were set within 80-300 bp. In the system formulation stage, dominant and subordinate primers were mainly considered. By reducing the concentration of dominant primers and increasing that of subordinate primers, a capillary electrophoresis spectrum with an appropriate peak height ratio was finally obtained. Additionally, gradient experiments were designed to adjust the concentrations of PCR reagents and PCR amplification conditions, and multiple versions of DNA amplification enzymes were optimized to achieve the best experimental results. ResultsThrough statistical analysis, there was no significant difference in the capillary electrophoresis of the 3 types of body fluid samples from the two years (2015 and 2024), demonstrating that the sample preservation method in this study can preserve samples for a relatively long time. The composite amplification system constructed in this study exhibited high specificity for all 3 types of body fluid, with no cross-reactions between the markers of each type of body fluid. The minimum detection thresholds for the 3 types of body fluid reached 0.002 9, 0.001 5, and 0.42 mg/L, respectively. This system also had a high degree of discrimination for mixed samples, especially for semen-saliva mixtures, where each body fluid marker could still be successfully detected when the concentration ratio of semen to saliva was 100:1. Meanwhile, in the two actual cases presented in this article, the application of this composite amplification system performed outstandingly. ConclusionThe composite amplification detection system constructed in this study can achieve the correct screening of saliva, semen, and vaginal secretions, overcoming the problems such as low specificity and sensitivity of marker tests and unbalanced RFU values of each marker in previous studies. The specificity and sensitivity meet the practical work requirements, and the operation is simple. It provides an analytical and identification method for body fluid stains in actual case and is applicable to the identification of the tissue origin of biological evidence at crime scenes involving sexual assault, indecent assault, and other criminal acts. In the future, more types of body fluid markers will be screened to expand the types of body fluids detected by the system, and body fluid-specific cSNP and cInDel genetic markers will be introduced to infer the sources (individuals and types) of mixed and complex stains more accurately.
9.Concept,Organizational Structure,and Medical Model of the Traditional Chinese Medicine Myocardial Infarction Unit
Jun LI ; Jialiang GAO ; Jie WANG ; Zhenpeng ZHANG ; Xinyuan WU ; Ji WU ; Zicong XIE ; Jingrun CUI ; Haoqiang HE ; Yuqing TAN ; Chunkun YANG
Journal of Traditional Chinese Medicine 2025;66(9):873-877
The traditional Chinese medicine (TCM) myocardial infarction (MI) unit is a standardized, regulated, and continuous integrated care unit guided by TCM theory and built upon existing chest pain centers or emergency care units. This unit emphasizes multidisciplinary collaboration and forms a restructured clinical entity without altering current departmental settings, offering comprehensive diagnostic and therapeutic services with full participation of TCM in the treatment of MI. Its core medical model is patient-centered and disease-focused, providing horizontally integrated TCM-based care across multiple specialties and vertically constructing a full-cycle treatment unit for MI, delivering prevention, treatment, and rehabilitation during the acute, stable, and recovery phases. Additionally, the unit establishes a TCM-featured education and prevention mechanism for MI to guide patients in proactive health management, reduce the incidence of myocardial infarction, and improve quality of life.
10.Analysis of unqualified ALT results in the initial screening and re-examination of blood donors in Changchun, China
Min HE ; Jingru CUI ; Zhiyong WANG ; Yang MA
Chinese Journal of Blood Transfusion 2025;38(4):495-501
[Objective] To investigate the non-pathological influencing factors of the unqualified alanine aminotransferase (ALT) in the initial screening of blood donors in Changchun and the laboratory re-examination, so as to provide evidence for reducing the deferral of blood donors and the discarding of blood due to ALT disqualification. [Methods] The unqualified results of ALT from the laboratory of our center from September 1, 2023 to October 31, 2024 were collected. The unqualified rates of ALT were statistically analyzed according to the blood collection sites and the initial screening detection equipment. The samples after ALT pre-donation screening were tested in the laborator, and the unqualified rates of ALT in the initial screening and the laboratory, the non-conformity rate of the results and the distribution range of ALT values were statistically analyzed according to the blood collection sites and the initial screening detection equipment. A questionnaire survey was conducted on the blood donors before blood collection to statistically analyze the influence of the blood donors' living habits and diet on ALT test results. [Results] The statistical analysis of the unqualified rate of ALT in the laboratory showed statistically significant differences in the ALT disqualification rates among different blood collection sites and different initial screening detection devices (P<0.05). Comparison of the ALT unqualified rate for the same type of equipment at different sites showed that for Equipment 1, there were differences between the combined blood collection house and the whole blood house, and between the combined blood collection house and the blood donation vehicle (P<0.05); for Equipment 2, there were differences between the combined blood collection house and the blood donation vehicle, and between the whole blood house and the blood donation vehicle (P<0.05); there were no significant differences among other groups with the same equipment. The initial screening and the laboratory test results for the same samples were compared, with unqualified rates of ALT of 16.29% and 13.01%, respectively. There were statistically significant differences in the unqualified rates of ALT among different blood collection sites (P<0.05), but no significant differences in the ALT test results among different detection equipment (P>0.05).. The non-conformity rate between the initial screening and the laboratory results was 5.26%, of which 81.15% (99/122) were unqualified in the initial screening but qualified in the laboratory. There were statistically significant differences in those unqualified in the initial screening but qualified in the laboratory among different blood collection sites and different detection equipment (P<0.05). The median ALT level in the initial screening was 29.0 U/L (with a 5%-95% range of 14-75 U/L), and the median ALT level in the laboratory was 19 U/L (with a 5%-95% range of 8-65 U/L). The results of the questionnaire survey showed that 33.3% (2/6) of those who consumed alcohol within 24 hours before blood donation had unqualified ALT, and 10% (1/10) of those who stayed up late the night before blood donation had unqualified ALT. [Conclusion] The unqualified rates of ALT in the initial screening before blood collection and the laboratory re-examination of blood donors in Changchun are closely related to the blood collection sites, detection equipment, detection environment, detection personnel, samples, ALT thresholds and detection time. Drinking alcohol and staying up late within 24 hours before blood donation increase the risk of unqualified ALT detection.

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