1.Characteristics of mitochondrial translational initiation factor 2 gene methylation and its association with the development of hepatocellular carcinoma
Huajie XIE ; Kai CHANG ; Yanyan WANG ; Wanlin NA ; Huan CAI ; Xia LIU ; Zhongyong JIANG ; Zonghai HU ; Yuan LIU
Journal of Clinical Hepatology 2025;41(2):284-291
ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 (MTIF2) gene methylation and its association with the development and progression of hepatocellular carcinoma (HCC). MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples, including survival curve analysis, methylation signature analysis, the association of tumor signaling pathways, and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level, and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races, ethnicities, BMI levels, and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation (hazard ratio [HR]=0.492, P<0.001), while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels (P>0.05). The methylation profile of the MTIF2 gene based on different ages, sexes, BMI levels, races, ethnicities, and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age, and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population (P<0.05); the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ (P<0.05). Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population (P<0.05). ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.
2.Palpitations, Shortness of Breath, Weakness in Limbs, Edema, and Dyspnea: A Rare Inflammatory Myopathy with Positive Aniti-mitochondrial Antibodies and Cardiac Involvement
Chunsu LIANG ; Xuchang ZHANG ; Ning ZHANG ; Lin KANG ; Xiaohong LIU ; Jiaqi YU ; Yingxian LIU ; Lin QIAO ; Yanli YANG ; Xiaoyi ZHAO ; Ruijie ZHAO ; Na NIU ; Xuelian YAN
Medical Journal of Peking Union Medical College Hospital 2025;16(1):248-255
This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.
3.Liver histopathological features of HBeAg-negative patients in the indeterminate phase of low-viral-load chronic hepatitis B virus infection
Lulu ZHOU ; Bing DONG ; Jiejing XIN ; Guanghua XU ; Na LIU
Journal of Clinical Hepatology 2025;41(1):52-56
ObjectiveTo investigate the liver histopathological features of HBeAg-negative patients in the indeterminate phase of low-viral-load chronic hepatitis B virus (HBV) infection. MethodsA total of 271 patients with low-viral-load HBeAg-negative chronic HBV infection who underwent liver biopsy in Department of Infectious Diseases, Affiliated Hospital of Yan’an University, from September 2013 to June 2021 were enrolled as subjects, and the degree of liver injury was compared between patients based on age, sex, presence or absence of the family history of hepatitis B, HBsAg, and alanine aminotransferase (ALT) level. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 271 patients with HBeAg-negative chronic HBV infection, 86 patients (31.73%) grade≥A2 liver inflammatory activity, 72 (26.57%) had a liver fibrosis stage of ive, and 112 (41.33%) had moderate or severe liver histological injury. The proportion of patients with grade≥A2 liver inflammatory activity in the patients with ALT>20 U/L was significantly higher than that in the patients with ALT≤20 U/L (χ2=3.938, P=0.047). There were no significant differences in the proportion of patients with grade≥A2 liver inflammatory activity between the patients with different ages, sexes, family history of hepatitis B, HBsAg levels (all P>0.05),there were no significant differences in the proportion of patients with a liver fibrosis stage of ≥F2 between the patients with different ages, sexes, family history of hepatitis B, HBsAg, and ALT levels (all P>0.05), and the stratified analysis of patients aged≤30 years and patients without the family history of hepatitis B showed no statistical significance between groups (all P>0.05). There was no significant difference in the degree of liver histological injury between the patients with different ages, sexes, family history of hepatitis B, HBsAg, and ALT levels (all P>0.05). ConclusionSignificant liver injury is observed in more than 40% of the patients with low-viral-load HBeAg-negative chronic HBV infection, and there is no significant difference in the degree of liver histological injury between the patients with different ages, sexes, family history of hepatitis B, HBsAg, and ALT levels. Even for the patients aged≤30 years who deny the family history of hepatitis B, there is still a considerable proportion of patients with liver injury, which should be taken seriously by clinicians.
4.2023 National Report on Rehabilitation Medicine Services, Quality and Safety in Medical Care System
Jingyu LIU ; Yanyan YANG ; Yuanmingfei ZHANG ; Xiaoxie LIU ; Na ZHANG ; Zhiliang ZHANG ; Mouwang ZHOU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):1-20
ObjectiveTo describe the medical services quality and safety of rehabilitation medicine departments in general hospitals and rehabilitation hospitals in 2022 from the aspects of structure, link and outcome quality. MethodsThrough the National Clinical Improvement System of the National Health Commission, all secondary and above general hospitals and rehabilitation hospitals were investigated in 2022, the relevant data from 7 250 hospitals, including traditional Chinese medicine hospitals and integrated traditional Chinese and Western medicine hospitals in 2022. A total of 3 153 sampling hospitals that equipped with rehabilitation medicine wards were included for analysis. ResultsAmong the 7 250 general hospitals surveyed this year, only 3 277 equipped with rehabilitation wards. In general hospitals, the average number of physicians per bed in 56.46% hospitals, the average number of rehabilitation therapists per bed in 77.67% hospitals, and the average number of nurses per bed in 51.18% hospitals did not meet the national requirements. The rates of early rehabilitation intervention were 13.98%, 20.82% and 21.36% respectively in the department of orthopedics, department of neurology and department of intensive care in general hospitals. The average activity of daily living improvement rate of discharged patients from rehabilitation departments of general hospitals was 77.69%, and that of discharged patients from rehabilitation specialized hospitals was 66.78%. ConclusionThere are insufficient allocation of wards and facility scales in the department of rehabilitation medicine, a shortage of human resources for rehabilitation services, inadequate integration of rehabilitation services with clinical services, and there is still scope for enhancing the effect and efficiency of rehabilitation services. It is recommended to expand the scale of rehabilitation services and improve discipline construction; increase the quantity and quality of rehabilitation human resources; incorporate rehabilitation services into the health service system; establish and modify clinical rehabilitation guidelines and technical specifications; and construct a rehabilitation medical information platform.
5.Structure, content and data standardization of rehabilitation medical records
Yaru YANG ; Zhuoying QIU ; Di CHEN ; Zhongyan WANG ; Meng ZHANG ; Shiyong WU ; Yaoguang ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Jian YANG ; Na AN ; Yuanjun DONG ; Xiaojia XIN ; Xiangxia REN ; Ye LIU ; Yifan TIAN
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):21-32
ObjectiveTo elucidate the critical role of rehabilitation medical records (including electronic records) in rehabilitation medicine's clinical practice and management, comprehensively analyzed the structure, core content and data standards of rehabilitation medical records, to develop a standardized medical record data architecture and core dataset suitable for rehabilitation medicine and to explore the application of rehabilitation data in performance evaluation and payment. MethodsBased on the regulatory documents Basic Specifications for Medical Record Writing and Basic Specifications for Electronic Medical Records (Trial) issued by National Health Commission of China, and referencing the World Health Organization (WHO) Family of International Classifications (WHO-FICs) classifications, International Classification of Diseases (ICD-10/ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI Beta-3), this study constructed the data architecture, core content and data standards for rehabilitation medical records. Furthermore, it explored the application of rehabilitation record summary sheets (home page) data in rehabilitation medical statistics and payment methods, including Diagnosis-related Groups (DRG), Diagnosis-Intervention Packet (DIP) and Case Mix Index. ResultsThis study proposed a systematic standard framework for rehabilitation medical records, covering key components such as patient demographics, rehabilitation diagnosis, functional assessment, rehabilitation treatment prescriptions, progress evaluations and discharge summaries. The research analyzed the systematic application methods and data standards of ICD-10/ICD-11, ICF and ICHI Beta-3 in the fields of medical record terminology, coding and assessment. Constructing a standardized data structure and data standards for rehabilitation medical records can significantly improve the quality of data reporting based on the medical record summary sheet, thereby enhancing the quality control of rehabilitation services, effectively supporting the optimization of rehabilitation medical insurance payment mechanisms, and contributing to the establishment of rehabilitation medical performance evaluation and payment based on DRG and DIP. ConclusionStructured rehabilitation records and data standardization are crucial tools for quality control in rehabilitation. Systematically applying the three reference classifications of the WHO-FICs, and aligning with national medical record and electronic health record specifications, facilitate the development of a standardized rehabilitation record architecture and core dataset. Standardizing rehabilitation care pathways based on the ICF methodology, and developing ICF- and ICD-11-based rehabilitation assessment tools, auxiliary diagnostic and therapeutic systems, and supporting terminology and coding systems, can effectively enhance the quality of rehabilitation records and enable interoperability and sharing of rehabilitation data with other medical data, ultimately improving the quality and safety of rehabilitation services.
6.Design, synthesis and antifungal and antitumor activity research of novel Hsp90 inhibitors
Qiao SHI ; Guiyan HAN ; Junteng ZHANG ; Na LIU
Journal of Pharmaceutical Practice and Service 2025;43(3):124-135
Objective To design and synthesize novel Hsp90 inhibitors with dual functions of synergistically enhancing the antifungal activity of fluconazole (FLC) against drug-resistant fungi and anti-tumor activity based on the Hsp90 inhibitor Ganetespib. Methods The previous research found that Ganetespib had a good synergistic anti-resistant fungal activity with FLC, with a fractional inhibitory concentration index (FICI) of 0.023 to 0.039. In this study, structural modifications were made to Ganetespib by replacing its indole ring with a phenyl ring containing different substituents to design and synthesize a series of new compounds. The in vitro synergistic anti-resistant fungal activity against C. albicans 0304103 in combination with FLC, anti-tumor activity (against HEL, HL60 and A549 cells), and Hsp90α inhibition activity were determined to explore their structure-activity relationship and mechanism of action. Results The chemical structures of 19 new compounds were confirmed by 1H NMR, 13C NMR and HRMS. Most of the compounds exhibited strong Hsp90α inhibitory activity, good synergistic activity against drug-resistant fungi in combination with FLC and anti-tumor activity. The substitution of electron-donating groups on the benzene ring was beneficial to enhancing the synergistic activity against drug-resistant fungi in combination with FLC. Among them, compounds F3 and F5 showed excellent synergistic activity against drug-resistant fungi in combination with FLC (FICI were both 0.047) and anti-tumor activity (IC50 were 0.025 to 0.15 μmol/L and 0.021 to 0.23 μmol/L respectively), and could down-regulate the expression levels of drug resistance genes and efflux pump genes in fungi, inhibit the formation of fungal biofilms, and arrest the cell cycle of HEL cells at G0/G1 phase. Conclusion The novel Hsp90 inhibitors such as F3 and F5 could both effectively exert the dual activities of synergizing with FLC to combat drug-resistant fungi and fight against tumors, which provided a new idea for the development of new drugs with dual functions of synergizing with FLC to combat drug-resistant fungi and fight against tumors.
7.Bibliometric analysis of studies on myopia in preschool children in the last 20 years
Na YUAN ; Yuxia LIU ; Lingjun WEI ; Haitao ZHENG
International Eye Science 2025;25(4):558-564
AIM: To identify research articles on myopia in preschool children and explore its current status and development trends based on bibliometric analysis.METHODS: Data from the Web of Science Core Collection database were analyzed using the search term “TS=Preschool children myopia” to retrieve all relevant publications from January 1, 2004, to December 31, 2023.RESULTS: A total of 171 articles were included in the analysis. China was identified as the leading country in terms of publication volume, making significant contributions to this field. The National University of Singapore and Nanjing Medical University were recognized as key institutions at the forefront of this research. Investigative Ophthalmology & Visual Science and Ophthalmology emerged as the journals with the highest citation frequencies. High-frequency keywords highlighted the current status and future directions of myopia research in preschool children. Specifically, “prevalence”, “refractive error” and “risk factors” were identified as potential focal points for future investigations.CONCLUSION: This study provides a comprehensive bibliometric analysis of global literature on myopia in preschool children. It identifies the most frequently cited articles in this field, outlines the global research landscape, and highlights emerging hotspots and trends. These findings offer valuable insights and directions for researchers and practitioners focusing on this area.
8.Bugansan Regulates R-spondin1/Wnt3a-mediated Intestinal Injury to Ameliorate Digestion and Absorption Dysfunction in Rat Model of Aging Induced by D-galactose
Yixuan WANG ; Ran HUO ; Jin TIAN ; Fang FANG ; Na LIU ; Jiepeng WANG ; Chaoyi FANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):19-27
ObjectiveTo elucidate the correlation between alterations in digestion and absorption functions and hepatic deficiency states in aging rats based on the R-spondin1/Wnt3a signaling pathway, and reveal the intervention mechanism of Bugansan. MethodsForty-eight SPF-grade male SD rats were randomly assigned to six groups: blank control, model, low-, medium-, and high-dose (7.03, 14.06, 28.12 g·kg-1, respectively) Bugansan, and vitamin E (suspension, 27 mg·kg-1), with 8 rats in each group. The rat model of aging was established by intraperitoneal injection of D-galactose (400 mg·kg-1), while the blank control group was injected with normal saline. Since the day of modeling, rats in intervention groups received corresponding agents by gavage, and those in blank control and model groups received an equal volume of normal saline (10 mL·kg-1). General biological features such as fur color, activity, body mass, water intake, and food intake were observed. Meanwhile, the content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the serum were measured to assess aging. Grip strength and the content of total bile acids (TBA) and the activity of α-amylase (AMY) in the serum were measured to evaluate hepatic deficiency states. The activity of β-galactosidase (β-gal) in the duodenum was measured to evaluate intestinal senescence. The levels of glucagon-like peptide-1 (GLP-1), vasoactive intestinal peptide (VIP), and D-xylose in the serum were determined to assess digestion and absorption functions of the small intestine. Hematoxylin-eosin staining was conducted to observe pathological changes of the duodenum to assess the small intestine damage. Immunohistochemical staining was employed to visualize the expression of B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) and leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) in the duodenal tissue. Moreover, Real-time quantitative polymerase chain reaction (Real-time PCR) was utilized to quantify the mRNA levels of Ki67, Bmi1, and Lgr5 to assess proliferation and regeneration of the small intestine. Additionally, the mRNA levels of R-spondin1, Wnt3a, β-catenin, and glycogen synthase kinase-3β (GSK-3β) and the protein levels of R-spondin1, Wnt3a, β-catenin, and phosphorylated GSK-3β (p-GSK-3β) in the duodenum were determined by Real-time PCR and Western blot, respectively, to analyze the mechanisms of intestinal digestion and absorption dysfunction in aging rats and the regulatory characteristics of Bugansan. ResultsCompared with blank control group, the model group showed decreases in body mass, water intake, food intake, grip strength, activities of SOD, GSH-Px, and AMY in the serum and content of GLP-1, VIP and D-xylose in the serum (P<0.05), increases in the content of MDA and TBA in the serum and β-gal activity in the duodenum (P<0.05), reductions in villus length, villus width, crypt depth, and villi/crypt (V/C) value, down-regulated mRNA and protein levels of Ki67, Lgr5, Bmi1, R-spondin1, Wnt3a, β-catenin, and up-regulated level of GSK-3β, phosphorylation (p)-GSK-3β (P<0.05). Compared with the model group, Bugansan increased the body mass, water intake, food intake, grip strength, and activities of SOD, GSH-Px, and AMY and levels of GLP-1, VIP and D-xylose in the serum (P<0.05), while decreasing the content of MDA and TBA in the serum and β-gal activity in the duodenum (P<0.05). Furthermore, Bugansan increased the villus length, villus width, crypt depth, and V/C value, up-regulated the mRNA and protein levels of Ki67, Lgr5, Bmi1, R-spondin1, Wnt3a, β-catenin, and down-regulated the level of GSK-3β and p-GSK-3β (P<0.05). ConclusionAging rats exhibit obvious impairments in digestion and absorption functions, accompanied by a state of hepatic deficiency. The traditional Chinese medicine approach of tonifying liver Qi effectively ameliorates aging-related changes by modulating the R-spondin1/Wnt3a signaling pathway to mitigate intestinal senescence and enhance digestion and absorption functions, ultimately contributing to the delay of aging.
9.Application of ultra-wide-field swept-source optical coherence tomography angiography in patients with diabetic retinopathy and diabetic kidney disease
Zhutao LIU ; Beibei HAN ; Wen YU ; Na LI ; Tian ZHANG
International Eye Science 2025;25(5):819-825
AIM: To analyze the clinical utility and value of the ultra-wide-field swept-source optical coherence tomography angiography(UWF-SS-OCTA)technique in changes of blood flow density and thickness in the central and peripheral regions of the retina and choroid in patients with nonproliferative diabetic retinopathy(NPDR)with or without diabetic kidney disease(DKD).METHODS: Cross-sectional study. Totally 50 cases(50 eyes)of diabetes mellitus(DM)that visited our hospital between June 2023 and June 2024 were included. They were divided into three groups: NPDR combined with DKD group(DKD group, n=20), NPDR without DKD group(NDKD group, n=20), and DM without retinopathy group(DM group, n=10, which served as control). In order to investigate the impact of DKD on ocular microangiopathy in NPDR patients, the retina and choroid within 24 mm×20 mm of the scan were separated into central and peripheral areas using the 3×3 nine-grid partition option that comes with UWF-SS-OCTA, and the parameters were then quantitatively assessed.RESULTS:The central and peripheral blood flow density of the choroidal capillary layer(CCP)was statistically significant between the DM group and the DKD group(t=3.93, P=0.0003; t=3.34, P=0.0016), and between the NDKD group and the DKD group(t=-3.06, P=0.003; t=-2.55, P=0.013), but there was no statistically significant difference between the DM group and the NDKD group(t=1.44, P=0.157; t=1.26, P=0.21). The mid-large choroidal vessel(MLCV)showed a progressive decline in central and peripheral blood flow density in the DM, NDKD, and DKD groups(F=13.74, 19.03, all P<0.0001). The DM, NDKD, and DKD groups saw a progressive decrease in central and peripheral choroidal thickness(CT; F=10.72, P=0.0001; F=13.12, P<0.001).CONCLUSION:CCP, MLCV, and CT can be used as visual indicators to identify impaired renal function in patients with NPDR. UWF-SS-OCTA can support the development of precise and noninvasive monitoring and treatment technology for diabetic ocular microangiopathy, while also offering a scientific foundation for the joint management of DR and DKD.
10.Effects of isorhamnetin on the development of gastric cancer by up-regulating SLC25A25-AS1
Yang ZHANG ; Jing WANG ; Lisha NA ; Aoran ZENG ; Bowen PANG ; Yulin LIU
China Pharmacy 2025;36(8):932-938
OBJECTIVE To explore the effects of isorhamnetin on the development of gastric cancer through up-regulation of solute carrier family 25 member 25 antisense RNA 1(SLC25A25-AS1). METHODS Using BALB/c nude mice as the subjects, the xenograft tumor model was established by subcutaneously inoculating human gastric cancer MKN28 cells into the axillary region. The effects of low and high doses of isorhamnetin (20 and 40 mg/kg) on the tumor volume and mass in nude mice were investigated. MKN28 cells were selected and divided into control group, isorhamnetin group (70 μmol/L, similarly hereinafter), isorhamnetin+knocking down negative control group, isorhamnetin+knocking down SLC25A25-AS1 group, isorhamnetin+ overexpression negative control group and isorhamnetin+overexpressing SLC25A25-AS1 group. Effects of knocking down/ overexpressing SLC25A25-AS1 on viability, apoptosis, migration and invasion ability of isorhamnetin-treated cells were detected. After verifying the targeting relationships between microRNA-212-3p (miR-212-3p) and SLC25A25-AS1, as well as phosphatase and tensin homologue deleted on chromosome 10 (PTEN), the effects of knocking down/overexpressing SLC25A25-AS1 on the expression of miR-212-3p, PTEN mRNA, and PTEN protein in isorhamnetin-treated cells were investigated. RESULTS Compared with the model control group, tumor volume and mass of nude mice in the isorhamnetin low-dose and high-dose groups were reduced significantly, and the isorhamnetin high-dose group was significantly lower than the isorhamnetin low-dose group (P<0.05). miR-212-3p had targeting relationships with SLC25A25-AS1 and PTEN. Compared with the control group, the cell viability (intervened for 24, 48 h), migration number, invasion number and miR-212-3p expression of cells in the isorhamnetin group, isorhamnetin+knocking down negative control group and isorhamnetin+overexpressing negative control group were significantly reduced or decreased or down-regulated, while the apoptosis rate, mRNA and protein expressions of PTEN were significantly increased or up-regulated (P<0.05). Compared with isorhamnetin group and isorhamnetin+knocking down negative control group, the cell viability, migration number, invasion number and miR-212-3p expression of cells in the isorhamnetin+knocking down SLC25A25-AS1 group were significantly increased or up- regulated, while the apoptosis rate, mRNA and protein expressions of PTEN were significantly reduced or down-regulated (P< 0.05). Compared with isorhamnetin group and isorhamnetin+overexpressing negative control group, the cell viability, migration number, invasion number and miR-212-3p expression of cells in isorhamnetin+overexpressing SLC25A25-AS1 group were significantly reduced or decreased or down-regulated, while the apoptosis rate, PTEN mRNA and protein expressions were significantly increased or up-regulated (P<0.05). CONCLUSIONS Isorhamnetin may inhibit the development of gastric cancer by up-regulating the expression of SLC25A25-AS1, down-regulating miR-212-3p, and up-regulating the expression of PTEN, which is a downstream target of miR-212-3p.

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