1.Erjingwan Alleviate Inflammatory Response and Apoptosis in Skeletal Muscle Cells of Sarcopenia via SIRT1/Nrf2/HO-1 Signaling Pathway
Long SHI ; Yang LI ; Hongyu YAN ; Tianle ZHOU ; Zhiwen ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):57-66
ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group, a model group, and groups with different doses of Erjingwan (8,16,32 g·kg-1). The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay (ELISA) was adopted to determine the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum samples of mice, and biochemical tests were conducted to quantify the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) in the serum. The protein and mRNA levels of SIRT1, Nrf2, B-cell lymphoma (Bcl-2), and Bcl-2-associated X protein (Bax) were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), respectively. ResultsAfter 4 weeks of drug intervention, the model group exhibited significant reductions in body weight and grip strength (P0.01) compared with the control group. Compared with the model group, all doses of Erjingwan increased the body weight in mice at week 8 (P0.01) and grip strength from week 6 (P0.01). HE staining revealed clear muscle fiber structure in the control group, muscle fiber rupture and atrophy in the model group, and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group, collagen fiber proliferation and severe fibrosis in the model group, and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group (P0.01). After intervention, the low-dose Erjingwan group exhibited a decreased TNF-α level (P0.05), while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels (P0.01). Biochemical assays revealed that the model group had decreased SOD and GSH levels (P0.01) and an increased MDA level (P0.01) compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels (P0.01) and decreases in MDA level (P0.01), compared with the model group. WB and Real-time PCR results showed that compared with the control group, the model group presented down-regulated protein and mRNA levels of SIRT1, Nrf2, HO-1, and Bcl-2 in the muscle tissue (P0.01) and up-regulated protein and mRNA levels of Bax (P0.01). Compared with the model group, Erjingwan at different doses up-regulated the protein levels of SIRT1, Nrf2, HO-1, and Bcl-2 (P0.01) and down-regulated the protein and mRNA levels of Bax (P0.01) in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 (P0.05, P0.01), and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1, Nrf2, HO-1, and Bcl-2 (P0.01). ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells, improved the antioxidant capacity, and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway, inflammatory response, and apoptosis network.
2.Erjingwan Alleviate Inflammatory Response and Apoptosis in Skeletal Muscle Cells of Sarcopenia via SIRT1/Nrf2/HO-1 Signaling Pathway
Long SHI ; Yang LI ; Hongyu YAN ; Tianle ZHOU ; Zhiwen ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):57-66
ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group, a model group, and groups with different doses of Erjingwan (8,16,32 g·kg-1). The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay (ELISA) was adopted to determine the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum samples of mice, and biochemical tests were conducted to quantify the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) in the serum. The protein and mRNA levels of SIRT1, Nrf2, B-cell lymphoma (Bcl-2), and Bcl-2-associated X protein (Bax) were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), respectively. ResultsAfter 4 weeks of drug intervention, the model group exhibited significant reductions in body weight and grip strength (P0.01) compared with the control group. Compared with the model group, all doses of Erjingwan increased the body weight in mice at week 8 (P0.01) and grip strength from week 6 (P0.01). HE staining revealed clear muscle fiber structure in the control group, muscle fiber rupture and atrophy in the model group, and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group, collagen fiber proliferation and severe fibrosis in the model group, and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group (P0.01). After intervention, the low-dose Erjingwan group exhibited a decreased TNF-α level (P0.05), while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels (P0.01). Biochemical assays revealed that the model group had decreased SOD and GSH levels (P0.01) and an increased MDA level (P0.01) compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels (P0.01) and decreases in MDA level (P0.01), compared with the model group. WB and Real-time PCR results showed that compared with the control group, the model group presented down-regulated protein and mRNA levels of SIRT1, Nrf2, HO-1, and Bcl-2 in the muscle tissue (P0.01) and up-regulated protein and mRNA levels of Bax (P0.01). Compared with the model group, Erjingwan at different doses up-regulated the protein levels of SIRT1, Nrf2, HO-1, and Bcl-2 (P0.01) and down-regulated the protein and mRNA levels of Bax (P0.01) in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 (P0.05, P0.01), and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1, Nrf2, HO-1, and Bcl-2 (P0.01). ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells, improved the antioxidant capacity, and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway, inflammatory response, and apoptosis network.
3.Association between visual impairment and body mass index in students from rural China.
Hongyu GUAN ; Zhijie WANG ; Yuxiu DING ; Yunyun ZHANG ; Kang DU ; Yaojiang SHI
Singapore medical journal 2025;66(7):362-367
INTRODUCTION:
Visual impairment and obesity remain the major public health issues among school-age students in rural areas of China. Obesity is an underlying risk of vision problems. This study aimed to assess the association between visual impairment and body mass index (BMI) among school-age students in rural northwest China.
METHODS:
This study included 39,385 students from the 4 th to 9 th grade in rural northwest China. From 2018 to 2020, students underwent an assessment of visual acuity (VA) and completed a questionnaire on family demographics, and height and weight measurements. Multiple logistic regression analyses were used to analyse the data.
RESULTS:
The association between visual impairment and BMI groups was significant in the study population ( P = 0.002) and in different groups (at the different educational, provincial and national levels) ( P < 0.001, separately). Multiple logistic regression analyses revealed a positive relationship between visual impairment and obesity in the study population, including those attending primary school, Han students and the residents of Ningxia autonomous region.
CONCLUSION
The association between visual impairment and obesity was significant among school-age students in rural northwest China. There should be implementation of policies to address the problem about visual impairment and obesity among school-age students in rural areas.
Humans
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China/epidemiology*
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Body Mass Index
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Male
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Female
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Rural Population
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Vision Disorders/complications*
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Child
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Adolescent
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Students
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Surveys and Questionnaires
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Logistic Models
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Obesity/complications*
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Visual Acuity
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Cross-Sectional Studies
4.Safety of teriflunomide in Chinese adult patients with relapsing multiple sclerosis: A phase IV, 24-week multicenter study.
Chao QUAN ; Hongyu ZHOU ; Huan YANG ; Zheng JIAO ; Meini ZHANG ; Baorong ZHANG ; Guojun TAN ; Bitao BU ; Tao JIN ; Chunyang LI ; Qun XUE ; Huiqing DONG ; Fudong SHI ; Xinyue QIN ; Xinghu ZHANG ; Feng GAO ; Hua ZHANG ; Jiawei WANG ; Xueqiang HU ; Yueting CHEN ; Jue LIU ; Wei QIU
Chinese Medical Journal 2025;138(4):452-458
BACKGROUND:
Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS.
METHODS:
This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide.
RESULTS:
Eighty-two patients were assigned to variant ( n = 42) and wild type groups ( n = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study.
CONCLUSION:
ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients.
REGISTRATION
NCT04410965, https://clinicaltrials.gov .
Humans
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Crotonates/adverse effects*
;
Toluidines/adverse effects*
;
Nitriles
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Hydroxybutyrates
;
Female
;
Male
;
Adult
;
ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics*
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Middle Aged
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Multiple Sclerosis, Relapsing-Remitting/genetics*
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Prospective Studies
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Young Adult
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Neoplasm Proteins/genetics*
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East Asian People
5.A novel loop-structure-based bispecific CAR that targets CD19 and CD22 with enhanced therapeutic efficacy against B-cell malignancies.
Lijun ZHAO ; Shuhong LI ; Xiaoyi WEI ; Xuexiu QI ; Qiaoru GUO ; Licai SHI ; Ji-Shuai ZHANG ; Jun LI ; Ze-Lin LIU ; Zhi GUO ; Hongyu ZHANG ; Jia FENG ; Yuanyuan SHI ; Suping ZHANG ; Yu J CAO
Protein & Cell 2025;16(3):227-231
6.Greenness evaluation metric for analytical methods and software.
Tong XIN ; Luyao YU ; Wenying ZHANG ; Yingxia GUO ; Chuya WANG ; Zhong LI ; Jiansong YOU ; Hongyu XUE ; Meiyun SHI ; Lei YIN
Journal of Pharmaceutical Analysis 2025;15(7):101202-101202
The focus of green analytical chemistry (GAC) is to minimize the negative impacts of analytical procedures on human safety, human health, and the environment. Several factors, such as the reagents used, sample collection, sample processing, instruments, energy consumed, and the quantities of hazardous materials and waste generated during analytical procedures, need to be considered in the evaluation of the greenness of analytical assays. In this study, we propose a greenness evaluation metric for analytical methods (GEMAM). The new greenness metric is simple, flexible, and comprehensive. The evaluation criteria are based on both the 12 principles of GAC (SIGNIFICANCE) and the 10 factors of sample preparation, and the results are presented on a 0-10 scale. The GEMAM calculation process is easy to perform, and its results are easy to interpret. The output of GEMAM is a pictogram that can provide both qualitative and quantitative information based on color and number.
7.Recent advances, strategies, and future perspectives of peptide-based drugs in clinical applications.
Qimeng YANG ; Zhipeng HU ; Hongyu JIANG ; Jialing WANG ; Han HAN ; Wei SHI ; Hai QIAN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(1):31-42
Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans
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Peptides/pharmacology*
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Animals
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Neoplasms/drug therapy*
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Drug Discovery
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Neurodegenerative Diseases/drug therapy*
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Diabetes Mellitus/drug therapy*
8.Effect of enriched environment combined with acupuncture at head points on behavior in rats with autism spectrum disorder
Zichen MU ; Qiang TANG ; Yunqiu SHI ; Yan WANG ; Shuwei ZHU ; Ya'nan ZHUANG ; Danshuang XU ; Hongyu LI ; Baolong LI ; Chunyan ZHANG ; Mengke YUAN
Chinese Journal of Rehabilitation Theory and Practice 2024;30(2):176-182
ObjectiveTo observe the effect of enriched environment (EE) combined with acupuncture at head point (HA) on behavior in rats with autism spectrum disorder. MethodsHealthy female Wistar rats were given peritoneal injection of sodium valproate at 12.5 days of gestation. Twenty-four male offspring rats were randomly selected and then randomly divided into model group (n = 6), EE group (n = 6), HA group (n = 6) and EE combined with HA group (the combined group, n = 6). Six male offspring rats born from female mice injected with the same amount of saline intraperitoneally were as control group. After four weeks of treatment, all the five groups were tested with three-chamber test and marble burying test, and the sociability index, the social novelty index and the number of buried marbles were recorded. The levels of interleukin (IL)-1β and IL-6 in peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). ResultsAfter treatment, compared with the model group, the sociability index and the social novelty index improved (P < 0.05), the number of buried marbles reduced (P < 0.05), and the levels of IL-6 and IL-1β in peripheral blood decreased in EE group, HA group and the combined group (P < 0.05); while the combined group was the best (P < 0.01). ConclusionBoth EE or acupuncture at HA could improve behavioral symptoms, and reduce the expression of inflammatory factors in rats with autism spectrum disorder. The combination of the two methods showed the best result.
9.Modified Xiaoyaosan Alleviates Depression-like Behaviors by Regulating Activation of Hippocampal Microglia Cells in Rat Model of Juvenile Depression
Jiayi SHI ; Yun XIANG ; Ziyang ZHOU ; Dahua WU ; Feng QIU ; Chang LEI ; Hongyu ZENG ; Kaimei TAN ; Hongqing ZHAO ; Dong YANG ; Yuhong WANG ; Pengxiao GUO ; Xiuli ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):46-56
ObjectiveTo investigate the mechanism of Baihuan Xiaoyao Decoction (Xiaoyaosan added with Lilii Bulbus and Albiziae Cortex) in alleviating depression-like behaviors of juvenile rats by regulating the polarization of microglia. MethodSixty juvenile SD rats were randomized into normal control, model, fluoxetine, and low-, medium-, and high-dose (5.36, 10.71, 21.42 g·kg-1, respectively) Baihuan Xiaoyao decoction groups. The rat model of juvenile depression was established by chronic unpredictable mild stress (CUMS). The sucrose preference test (SPT) was carried out to examine the sucrose preference of rats. Forced swimming test (FST) was carried out to measure the immobility time of rats. The open field test (OFT) was conducted to measure the total distance, the central distance, the number of horizontal crossings, and the frequency of rearing. Morris water maze (MWM) was used to measure the escape latency and the number of crossing the platform. The immunofluorescence assay was employed to detect the expression of inducible nitric oxide synthase (iNOS, the polarization marker of M1 microglia) and CD206 (the polarization marker of M2 microglia). Real-time polymerase chain reaction was employed to determine the mRNA levels of iNOS, CD206, pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] and anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus. Western blotting was employed to determine the protein levels of iNOS and CD206 in the hippocampus. The levels of IL-4 and IL-6 in the hippocampus were detected by enzyme-linked immunosorbent assay. ResultCompared with the normal control group, the model rats showed a reduction in sucrose preference (P<0.05), an increase in immobility time (P<0.05), decreased motor and exploratory behaviors (P<0.05), and weakened learning and spatial memory (P<0.05). In addition, the model rats showed up-regulated mRNA and protein levels of iNOS and mRNA levels of IL-1β, IL-6, and TNF-α (P<0.05). Compared with the model group, Baihuan Xiaoyao decoction increased the sucrose preference value (P<0.05), shortened the immobility time (P<0.01), increased the motor and exploratory behaviors (P<0.05), and improved the learning and spatial memory (P<0.01). Furthermore, the decoction down-regulated the positive expression and protein level of iNOS, lowered the levels of TNF-α, IL-1β, and IL-6 (P<0.01), promoted the positive expression of CD206, and elevated the levels of IL-4 and IL-10 (P<0.01) in the hippocampus of the high dose group. Moreover, the high-dose Baihuan Xiaoyao decoction group had higher sucrose preference value (P<0.01), shorter immobility time (P<0.01), longer central distance (P<0.01), stronger learning and spatial memory (P<0.01), higher positive expression and protein level of iNOS (P<0.01), lower levels of TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), lower positive expression and mRNA level of iNOS (P<0.05), and higher levels of IL-4 and IL-10 (P<0.05, P<0.01) than the fluoxetine group. ConclusionBaihuan Xiaoyao decoction can improve the depression-like behavior of juvenile rats by inhibiting the M1 polarization and promoting the M2 polarization of microglia in the hippocampus.
10.Construction of evidence graph for modifiable risk factors for diabetic retinopathy
Shuyuan SHI ; Qingxin ZHOU ; Hongyu SUN ; Siyan ZHAN ; Feng SUN ; Shuyan ZHANG
Chinese Journal of Epidemiology 2024;45(12):1736-1744
Objective:Diabetic retinopathy (DR) has been reported as the leading cause of blindness among diabetic adults, which is closely related to poor quality of life and increased burden of disability. This study aimed to aggregate the optimally available evidence on modifiable risks of DR.Methods:Until June 2023, PubMed, Cochrane Library, CNKI, and Wanfang databases were used to retrieve Meta-analysis about various risk factors for DR, and Meta-analysis were analyzed and summarized. R 4.3.2 software was used for each Meta-analytic association to calculate the effect size, 95% CI, heterogeneity, small-study effects, excess significance bias, and 95% prediction intervals. The credibility of significant evidence was graded. Results:We captured 23 eligible papers (72 associations) covering a wide range of medication use, concomitant diseases, daily intervention, biomarkers, lifestyle, and physical measurement index. Among them, higher HbA1c variability ( RR=1.45, 95% CI: 1.26-1.66) and urine microalbumin positive ( OR=2.44, 95% CI: 1.99-2.97) were convincing (grade Ⅰ) evidence, and insulin use ( RR=3.48, 95% CI: 2.14-5.67) was highly suggestive (grade Ⅱ) evidence. Moreover, hypertension ( OR=2.03, 95% CI: 1.06-3.97), poor glycemic control ( OR=4.35, 95% CI: 1.47-12.85), positive macroalbuminuria ( OR=8.42, 95% CI: 3.52-20.15), long sleep duration ( OR=2.05, 95% CI: 1.37-3.05), vitamin D deficiency ( OR=2.02, 95% CI: 1.17-3.50), periodontitis ( OR=4.51, 95% CI: 1.76-11.55) were the main risk factors for DR. Intensive blood pressure intervention ( RR=0.78, 95% CI: 0.65-0.94), dietary control ( OR=0.64, 95% CI: 0.47-0.89) and moderate intensity physical activity ( RR=0.76, 95% CI: 0.59-0.97) yielded significant protective associations with DR. Conclusions:Intensive blood pressure glycemic control, and a healthy lifestyle pattern could reduce the risk of DR. This study provides the evidence to identify high-risk populations and recommends rational treatment options and healthy living interventions.

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