1.Gandouling Regulates PI3K/Akt/mTOR Autophagy Signaling Pathway via LncRNA H19 for Treatment of Wilson Disease Liver Fibrosis
Xin YIN ; Han WANG ; Daiping HUA ; Lanting SUN ; Yunyun XU ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):131-138
ObjectiveTo investigate the potential mechanisms and pathways through which Gandouling (GDL) exerts its effects in the treatment of liver fibrosis in Wilson disease. MethodsSixty male SD rats were randomly divided into six groups: the normal group, the model group, the GDL low-, medium-, and high-dose groups (0.24, 0.48, 0.96 g·kg-1), and the penicillamine group (90 mg·kg-1), with 10 rats in each group. A copper-loaded Wilson disease rat model was established by gavage administration of 300 mg·kg-1 copper sulfate pentahydrate to all groups except the normal group. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathomorphological changes in the liver. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of hyaluronic acid (HA), laminin (LN), procollagen type-Ⅲ peptide (PC-Ⅲ), and collagen type-Ⅳ (C-Ⅳ). Transmission electron microscopy was used to examine the ultrastructure of liver tissues. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the expression levels of liver tissues and serum exosomal long noncoding RNA H19 (LncRNA H19), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR). Western blot analysis was performed to assess the expression levels of PI3K, Akt, mTOR, and their phosphorylated forms, as well as autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B (LC3-Ⅱ/LC3-Ⅰ) in liver tissues. Beclin1 and LC3-Ⅱ fluorescence signal intensity was observed by immunofluorescence. ResultsCompared with the normal group, the model group exhibited inflammatory cell infiltration in hepatocytes, unclear nuclear boundaries with cell cleavage and necrosis, and collagen fiber deposition around confluent areas. The levels of HA, LN, PC-Ⅲ, and C-Ⅳ were significantly elevated (P<0.01). Transmission electron microscopy revealed an increased number of autophagic vesicles, with autophagic lysosomes exhibiting a single-layer membrane structure following degradation of most envelopes. Expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ were significantly increased (P<0.01), and fluorescence signals of Beclin1 and LC3-Ⅱ were markedly enhanced. The protein expression levels of PI3K, Akt, mTOR, p-PI3K, p-Akt, and p-mTOR were reduced (P<0.01), while LncRNA H19 expression was increased (P<0.01), and mRNA expression levels of PI3K, Akt, and mTOR were decreased (P<0.01). After treatment with GDL, the degree of liver fibrosis was significantly improved, with decreased levels of HA, LN, PC-Ⅲ, and C-Ⅳ. The number of autophagic vesicles was significantly reduced, and expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ proteins were lower (P<0.01). The fluorescence signals of Beclin1 and LC3-Ⅱ weakened dose-dependently. The protein levels of PI3K, Akt, mTOR, p-PI3K, p-Akt, and p-mTOR were elevated (P<0.01), while the expression level of LncRNA H19 was reduced (P<0.01). Furthermore, the mRNA expression levels of PI3K, Akt, and mTOR increased (P<0.05, P<0.01). ConclusionGDL may alleviate liver fibrosis and reduce liver injury by regulating the PI3K/Akt/mTOR autophagy signaling pathway via LncRNA H19.
2.The Effect of Qishao Tongbi Capsule (芪芍通痹胶囊) on the Wnt/β-catenin Pathway in a Rat Model of Intervertebral Disc Degeneration
Yumen XUE ; Xilin XU ; Wei HAN ; Jiaben XU ; Wenting XU ; Zelin LIU ; Xiaofeng ZHANG
Journal of Traditional Chinese Medicine 2025;66(1):79-88
ObjectiveTo explore the possible mechanism of Qishao Tongbi Capsule (芪芍通痹胶囊, QTC) in the treatment of intervertebral disc degeneration (IDD). MethodsSeventy-five rats were randomly divided into control group, model group, low-dose QTC group, high-dose QTC group, high-dose QTC +agonist group, with 15 rats in each group. Except for the control group, all other groups were subjected to a fibrous ring puncture to prepare an IDD model. After modeling, rats in low-dose QTC group and high-dose QTC group were given QTC at doses of 0.2 and 0.8 g/(kg·d) by gavage, respectively. Rats in high-dose QTC+ agonist group was given QTC at 0.8 g/(kg·d) and SKL2001 solution at 10 mg/(kg·d) by gavage. The control group and model group were given 10 ml/(kg·d) distilled water by gavage. All treatments were given once a day for 4 consecutive weeks. After treatment, X-ray and magnetic resonance imaging (MRI) were used to detect IDD degree. Hematoxylin-eosin (HE) staining and Safranin O-Fast Green staining were used to observe the morphological changes of the intervertebral disc tissue. Immunohistochemical staining was performed to examine the levels of proteoglycan, type Ⅱ collagen (COL Ⅱ), and matrix metalloproteinase-3 (MMP-3) in the intervertebral disc tissue. Western blotting was used to detect the extracellular matrix (ECM)-related proteins (proteoglycan, COL Ⅱ, MMP-3, MMP-9, MMP-13), aging-related proteins (P53, P21, P16), apoptosis related proteins, including B-cell lymphoma/leukemia 2 (BCL-2), BCL-2 related X protein (BAX), Cleaved Caspase-3, and Wnt/β-catenin pathway related proteins such as Wnt3a, glycogen synthase kinase-3β (GSK-3β) and β-catenin in the intervertebral disc nucleus pulposus (NP) tissue. Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) was used to assess the mRNA expression of Wnt3a, GSK-3β, and β-catenin in intervertebral disc tissue. ResultsCompared with the model group, rats in the low-dose QTC group and high-dose QTC group exhibited improved DHI, decreased Pfirmann grading, and alleviated IDD. The structural integrity of the NP and annulus fibrosus increased, and the number of the NP increased. The levels of proteoglycan, COL Ⅱ, BCL-2 and GSK-3β increased, while the levels of MMP-3, MMP-9, MMP-13, P53, P21, P16, BAX, Cleaved Caspase-3, Wnt3a and β-catenin protein decreased. The mRNA expression of Wnt3a and β-catenin mRNA decreased, while GSK-3β mRNA expression increased (P<0.05). Compared with the low-dose QTC group, the high-dose QTC group showed further improvements in DHI, decrease in Pfirrmann grading (P<0.05), and greater alleviation of IDD. The structural integrity of NP and annulus fibrosus was further enhanced, and the number of NP cells further increased. The levels of proteoglycan, COL Ⅱ, BCL-2 and GSK-3β were higher, while the levels of MMP-3, MMP-9, MMP-13, P53, P21, P16, BAX, Cleaved Caspase-3, Wnt3a and β-catenin were lower. The mRNA expression of Wnt3a and β-catenin decreased, while GSK-3β mRNA expression increased (P<0.05). Compared with the high-dose QTC group, the high-dose QTC +agonist group showed a decrease of DHI, an increase of Pfirmann grading (P<0.05), significant aggravation of IDD, reduction in structural integrity of the NP and annulus fibrosus, a decrease of NP cell count, lower levels of proteoglycan, COL Ⅱ, BCL-2 and GSK-3β, and higher levels of MMP-3, MMP-9, MMP-13, P53, P21, P16, BAX and Cleaved Caspase-3. Additionally, GSK-3β mRNA expression decreased (P<0.05). ConclusionQTC can inhibit NP cell aging, apoptosis, and ECM degradation in IDD rats, and its therapeutic effect may be mediated through the inhibition of the Wnt/β-catenin pathway.
3.Report of 4 cases of IgG4-related urinary diseases and literature review
Fanchao WEI ; Zhaoxiang WANG ; Mengwei XU ; Ruochen QI ; Guohui WANG ; Xiaoyan ZHANG ; Tong XU ; Jingliang ZHANG ; Shuaijun MA ; Weijun QIN ; Lijun YANG ; Shichao HAN
Journal of Modern Urology 2025;30(1):59-63
[Objective] To explore the clinical features of IgG4-related urinary diseases so as to provide reference for the diagnosis and treatment of such diseases. [Methods] The clinical data of 4 cases of IgG4-related urinary system diseases diagnosed and treated in Xijing Hospital of Air Force Medical University during Aug.2019 and Dec.2023 were retrospectively collected.Here, we report on the diagnosis and treatment of these patients, analysing their symptoms, serology, imaging and pathology as well as their treatment and outcomes. [Results] The patients included 2 male and 2 female.The lesions were involved with the retroperitoneum and urinary system.Three patients had symptoms of lumbar pain.The imaging manifestations were complex, including retroperitoneal mass involving urinary system organs in 2 cases, tabdense shadow of the right kidney in 1 case, and simple cystic mass of kidney in 1 case.Serum IgG4 value was not detected before surgery.All patients underwent radical surgical treatment.Postoperative pathology showed fibrous tissue hyperplasia with a large number of plasma cells, lymphocytes, a few neutrophil infiltrates, and lymphoid follicles and obliterated vasculitis in some specimens.The number of IgG4+ plasma cells was more than 10 in all tissues under high power microscope.After surgery, 3 patients had symptoms improved, and serum IgG4 value was within the normal range; 1 patient (patem 3) had elevated IgG4 value during follow-up, received subsequent hormone therapy, and the serum IgG 4 level remained stable. [Conclusion] The symptoms of IgG4-related diseases involving the urinary system are non-specific, and the imaging findings are various, easily confused with other diseases.Early detection of serum IgG4 and biopsy pathology can help clinicians make correct diagnosis in the early stage.
4.Morphologic and functional effect of core training combined with respiratory training on multifidus and transversus abdominis in patients with lumbar disc herniation
Jianing SONG ; Xiaole LOU ; Huan LIU ; Xue HAN ; Lei XU ; Min WANG
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):107-116
ObjectiveTo explore the effect of respiratory training based on core stabilization training on lumbar disc herniation. MethodsFrom January, 2023 to October, 2024, 96 patients with lumbar disc herniation admitted to the First Affiliated Hospital of Bengbu Medical University were divided into control group (n = 32), core group (n = 32) and respiratory group (n = 32). All the groups underwent conventional rehabilitation therapy, with core stabilization training in the core group and respiratory training combined with core stabilization training in the respiratory group, additionally, for four weeks. Before and after training, the scores of Visual Analogue Scale, Japanese Orthopaedic Association (JOA) and Oswestry Dysfunction Index (ODI) were compared, the average electromyographic value (AEMG) and root mean square (RMS) value of the multifidus and transversus abdominis were detected by surface electromyography (sEMG); and the thickness of the multifidus and transversus abdominis were measured by musculoskeletal ultrasonography bilaterally. ResultsThe intra-group effect (F > 597.796, P < 0.001), inter-group effect (F > 16.535, P < 0.001) and interaction effect (F > 49.622, P < 0.001) were significant in the scores of VAS, JOA and ODI; which were better in the respiratory group than in the control group and the core group (P < 0.05), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 7971.631, P < 0.001), inter-group effect (F > 177.760, P < 0.001) and interaction effect (F > 478.771, P < 0.001) were significant in the thickness of the transversus abdominis and multifidus; which were better in the respiratory group than in the control group and the core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 144303.007, P < 0.001), inter-group effect (F > 1495.458, P < 0.001) and interaction effect (F > 3121.361, P < 0.001) were significant in the RMS of the multifidus and transversus abdominis; which were better in the respiratory group than in the control group and the core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 1890.532, P < 0.001), inter-group effect (F > 607.132, P < 0.001) and interaction effect (F > 824.923, P < 0.001) were significant in the AEMG of the multifidus and transversus abdominis; which were better in the respiratory group than in the control group and core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). ConclusionCore training combined with respiratory training can more effectively reduce pain and improve dysfunction by enhancing the strength and control of the core muscles, thus improving the quality of life of patients with lumbar disc herniation.
5.Effect of fine particulate matter exposure in the air on dyslipidemia among primary school students in two privinces and cities of China
ZHU Yuanduo, HAN Yingying, LI Dandan, ZHANG Jingwei, XU Yanlong
Chinese Journal of School Health 2025;46(1):115-118
Objective:
To analyze the association between fine particulate matter (PM2.5) exposure in the air and dyslipidemia among primary school students, in order to provide the evidencebased support for the prevention and control of chronic diseases in children.
Methods:
The random sampling method was used to select 625 students from two primary schools in Anhui Province and Tianjin City from May to June 2024. Based on the home address, the annual average exposure levels of PM2.5 were obtained in 3 years before investigation, 2 years before investigation, and the past year before investigation. Fasting blood samples were collected for the detection of total cholesterol, triglycerides (TG), highdensity lipoprotein cholesterol and lowdensity lipoprotein cholesterol. Linear regression modeling was used to analyze the association between PM2.5 exposure and dyslipidemia among primary school students.
Results:
The rate of dyslipidemia among primary school students was 14.72% in the present study. The results of linear regression analysis showed that the TG increased by 0.019(95%CI=0.012-0.025),0.023(95%CI=0.016-0.030) and 0.021(95%CI=0.014-0.027) mmol/L for every 1 μg/m3 increase of PM2.5 in the past year before investigation, 2 years before investigation and 3 years before investigation respectively (P<0.05). The results of binary Logisitic analysis showed that the risks of dyslipidemia in primary school students were positively correlated with PM2.5 mass concentration in the past year before investigation, 2 years before investigation, and 3 years before investigation [OR(95%CI)=1.06(1.02-1.11), 1.06(1.01-1.12), 1.06(1.01-1.11), P<0.05].
Conclusions
PM2.5 exposure is associated with increased risk of dyslipidemia among primary school students. To protect the health of primary school students, effective measures should be taken to improve air quality.
6.Evaluation of the comprehensive intervention effect on lunch for primary and secondary school students in Minhang District of Shanghai
HU Yuhuan, ZANG Jiajie, XU Huilin, GUO Qi, HAN Yan, TANG Hongmei, YING Fangjia, LIANG Hao
Chinese Journal of School Health 2025;46(2):191-195
Objective:
To evaluate the comprehensive intervention effect of lunch for primary and secondary school students in Minhang District, so as to provide a theoretical and practical basis for lunch intervention in school.
Methods:
From October to December 2023, a convenience sampling method was used to select 1 937 students from one primary and secondary school in Minhang District.A comprehensive intervention measure focusing on "reducing oil and salt" for lunch recipe optimization and nutrition education was carried out, and a questionnaire survey was conducted to evaluate the intervention effect three months later. Chi square test and Wilcoxon rank test were used to compare the data before and after the intervention.
Results:
After intervention, the use of cooking oil and salt, the supply of protein and fat in primary and secondary school lunches were reduced, and had no obvious impact on energy and other major nutrients. After intervention, compared to before intervention, the proportion of primary school students who felt that lunch was greasy decreased (8.9%, 6.2%, χ 2=4.35), and the proportion of primary and secondary school students who felt that lunch were delicious decreased significantly (33.2%, 23.2%; 63.9%, 53.5%, χ 2=26.39, 17.52) ( P < 0.05 ). Secondary school students also felt reduced variety of food ingredients (46.9%, 38.3%, χ 2=16.05, P <0.05). In addition, after intervention, the total surplus rate of primary school students meals decreased (7.4%, 4.4%, χ 2=5.73), mainly reflected in the decrease of the surplus rate of staple foods (7.1%, 2.4%, χ 2=17.39), while the surplus rate of vegetable dishes increased ( 16.0 %, 21.2%, χ 2=6.01) ( P <0.05). Although there was no significant change in the total surplus rate of meals for secondary school students, the surplus rate of staple foods decreased (12.9%, 5.4%, χ 2=33.52), while the surplus rates of meat and vegetable dishes increased (11.2%, 26.9%; 17.5%, 33.2%, χ 2=74.26, 61.88) ( P <0.05). After intervention, there was no statistically significant difference in the overweight and obesity rates of primary school students ( χ 2=0.11,0.43) and secondary school students ( χ 2=0.01,0.00) compared to before intervention( P >0.05). After intervention, the lung capacity of primary school students [1 564 (1 269,1 890) mL] and sitting forward flexion [11.3 (7.6, 15.2) cm] increased compared to before intervention [1 522 (1 259, 1 819 ) mL, 10.5 (6.3, 13.5) cm] ( Z =2.20, 4.68, P <0.01), but there was no statistically significant difference in lung capacity and sitting forward flexion of secondary school students before and after intervention ( Z =-0.46, -0.08, P >0.05).
Conclusion
The comprehensive intervention of school lunch has promoted a significant decrease in the use of oil and salt in lunch and improved the quality of recipes, and has a positive impact on the situation of leftover lunch and the health of students to a certain extent.
7.Progress on antisense oligonucleotide in the field of antibacterial therapy
Jia LI ; Xiao-lu HAN ; Shi-yu SONG ; Jin-tao LIN ; Zhi-qiang TANG ; Zeng-ming WANG ; Liang XU ; Ai-ping ZHENG
Acta Pharmaceutica Sinica 2025;60(2):337-347
With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.
8.Construction of Multidimensional Evaluation System for Health Status in Modern China's Ideal Life
Rui XU ; Han ZHOU ; Zhong WANG ; Yongyan WANG
Journal of Traditional Chinese Medicine 2025;66(7):657-662
The evolving health demands of contemporary society urgently call for adaptive adjustments in health policies and a comprehensive enhancement of perspectives, horizons, and viewpoints. Grounded in the solid foundation of traditional Chinese culture, this paper proposed a multidimensional evaluation system for assessing the health status of modern China's ideal life. Drawing upon the philosophical insights of Confucianism, Daoism, Mohism, Song-Ming Neo-Confucianism, and their subsequent developments, as well as core cultural values such as harmony (和), happiness (福), and joy (乐), this system established a fundamental framework for evaluating health in modern ideal life. The framework consists of eight indices, i.e. harmony index, diligence index, peace of mind index, happiness index, compassion index, innovation index, fulfillment index, and adaptability index. The purpose of constructing this system is to comprehensively and deeply reflect the physical and mental characteristics and behavioral patterns of the Chinese population, and to provide a holistic evaluation framework for advancing the foundation of health in modern ideal life, offering solid scientific support for formulating health policies that align with China's national context.
9.Quality assessment of guidelines/consensuses on traditional Chinese medicine/integrated traditional Chinese and Western medicine diagnosis and treatment of nonalcoholic fatty liver disease
Ruimin JIAO ; Jingjie ZHAO ; Juanjuan LI ; Wei CHEN ; Chaoru HAN ; Li LI ; Chunjun XU ; Hong YOU
Journal of Clinical Hepatology 2025;41(3):446-452
ObjectiveTo evaluate the methodological quality and reporting quality of published guidelines/consensuses on traditional Chinese medicine (TCM)/integrated traditional Chinese and Western medicine diagnosis and treatment of nonalcoholic fatty liver disease (NAFLD), and to provide a basis for formulating guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD in the future. MethodsDatabases including PubMed, Embase, Web of Science, CNKI, Wanfang Data, and CBM and the websites of China Association of Chinese Medicine and China Association of Integrative Medicine were searched for related articles published up to September 1, 2024. Two clinical researchers independently assessed the methodological quality and reporting quality of the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD by using Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) and Reporting Items for Practice Guidelines in Healthcare (RIGHT). ResultsA total of nine guidelines/consensuses were included after literature screening, with four guidelines and five expert consensuses. The scores of different domains assessed by AGREE Ⅱ for the nine guidelines/consensuses were as follows: scope and purpose (47.1%), stakeholder involvement (41.0%), rigor of development (21.6%), clarity of presentation (40.2%), applicability (19.0%), and editorial independence (19.6%). The recommendation level of the articles was B level (recommended after revision) for four articles and C level (not recommended) for five articles. The RIGHT assessment showed high reporting rates for “Basic Information” and “Background”, while other areas needed to be improved. Currently, there was no international standard for the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD, and the quality of these guidelines/consensuses needed to be enhanced to ensure comprehensiveness and credibility. ConclusionThere is still potential for improving the quality of guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD, and AGREE Ⅱ and RIGHT checklists should be strictly followed to ensure the fairness, scientific rigor, and transparency of these guidelines/consensuses.
10.Investigation of Helicobacter pylori infection and analysis of risk factors in permanent residents in a certain area
Xuemei XU ; Jun LIU ; Lamei HAN ; Danni LU ; Ting HE
Journal of Public Health and Preventive Medicine 2025;36(2):78-81
Objective To analyze the status and risk factors of Helicobacter pylori (Hp) infection in permanent residents in a certain area. Methods The clinical data of 6 792 permanent residents surveyed from January 2021 to December 2023 were retrospectively analyzed. All subjects underwent 13C-urea breath test,and relevant general information was collected to analyze Hp infection status. According to whether Hp infection occurred, they were divided into positive group (n=4 283) and negative group (n=2 509). The differences in general information, living habits, and dietary habits between the two groups of subjects were analyzed, and multivariate logistic regression analysis was conducted. Results Among the 6 792 permanent residents surveyed from January 2021 to December 2023, 4283 were positive for 13C-urea breath test, accounting for 63.05% of the total. There were statistically significant differences in age distribution, gender, BMI, tableware cleaning, personal hygiene products use, chopsticks use, and raw food and vegetable cleaning between the positive group and the negative group (P<0.05). The single factors of Hp infection were substituted into multivariate logistic regression analysis equation, and it was found that age ≥45 years old, male, BMI≥24, no use of detergents to clean utensils, sharing personal hygiene products, not using public chopsticks, having a habit of eating raw food, and not cleaning vegetables before eating were independent risk factors for Hp infection. Conclusion The positive rate of Hp infection in this area is relatively high, and the infection factors are related to age, gender, and some lifestyle and dietary habits.


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