1.Unveiling the renoprotective mechanisms of self-assembled herbal nanoparticles from Scutellaria barbata and Scleromitrion diffusum in acute kidney injury: A nano-TCM approach.
Lunyue XIA ; Qunfang YANG ; Kangzhe FU ; Yutong YANG ; Kaiyue DING ; Yuexue HUO ; Lanfang ZHANG ; Yunong LI ; Borong ZHU ; Peiyu LI ; Yijie HUO ; Liang SUN ; Ya LIU ; Haigang ZHANG ; Tao LIU ; Wenjun SHAN ; Lin ZHANG
Acta Pharmaceutica Sinica B 2025;15(8):4265-4284
Acute kidney injury (AKI) is a critical clinical condition characterized by rapid renal function decline, with high morbidity, mortality, and healthcare costs. Traditional Chinese medicine (TCM) has shown potential effects on mitigating oxidative stress and programmed cell death in AKI models. Scutellaria barbata D. Don (SB) and Scleromitrion diffusum (Willd.) R. J. Wang (SD), a classic TCM herbal pair exhibited anti-inflammatory and antioxidant activities. Using advanced chromatographic separation technology, we enriched the effective fractions of water extracts from SB-SD, obtaining self-assembled herbal nanoparticles (SB and SD nanoparticles, SSNPs) rich in flavonoids and terpenoids. These SSNPs demonstrated robust antioxidant properties in vitro and mitigated AKI progression in vivo by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Oral administration of SSNPs in mice resulted in absorption into the bloodstream, formation of a protein corona, reduced macrophage phagocytosis, and enhanced bioavailability and renal targeting. Furthermore, we investigated the self-assembly principle of SSNPs using representative flavonoids and terpenoids. Kinetic studies and in situ transmission electron microscopy (in situ TEM) revealed that these compounds self-assemble via supramolecular forces like hydrogen bonding and π-π interactions, forming stable nanostructures. This study elucidates the renoprotective effects and mechanisms of SB and SD, and provides a novel approach for the development of TCM-based nanomedicines, highlighting the potential of nano-TCM in AKI treatment.
2.Efficacy of bilateral facial muscle training combined with visual electromyography biofeedback in the treatment of idiopathic facial nerve palsy
Xinyue CAI ; Ling DING ; Yilan MA ; Shihong HU ; Huajun GU ; Longdian GU ; Yijie ZHU ; Jiakun YAN ; Yaoyao ZHENG ; Qingsong MA
Chinese Journal of Clinical Medicine 2025;32(6):1017-1023
Objective To explore the efficacy of bilateral facial muscle training combined with visual electromyography biofeedback on facial nerve function recovery in patients with idiopathic facial nerve palsy. Methods Patients with idiopathic facial nerve palsy admitted to Shanghai Fifth People’s Hospital, Fudan University from July 2022 to July 2024 were selected and randomly divided into a control group and an intervention group. The control group received conventional physical factor therapy, while the intervention group received bilateral facial muscle training combined with visual electromyography biofeedback therapy based on the control group’s regimen. After 20 treatment sessions, the total effective rate, the House-Brackmann (H-B) facial nerve grading system, the Sunnybrook Facial Grading System (SFGS) score, and the average value ratio of maximal amplitudes of bilateral frontalis and zygomaticus muscles were compared between the two groups. Results A total of 90 patients were included, 45 in each group. After 20 treatment sessions, the total effective rate was significantly higher in the intervention group than in the control group (84.4% vs 75.6%, P=0.003). Compared with the control group, the intervention group demonstrated a significantly lower H-B grade (P=0.003) and a higher SFGS score (P=0.001). The average value ratios of maximal amplitudes of the affected versus healthy side frontalis (P=0.013) and zygomatic (P=0.022) muscles were higher in the intervention group than in the control group. Conclusions Bilateral facial muscle training combined with visual electromyography biofeedback is an effective approach for treating idiopathic facial nerve palsy, effectively promoting the recovery of facial nerve function, and improving facial symmetry and facial muscle function.
3.Mechanism of CD137 signal regulating P53/P21 pathway to promote senescence of vascular smooth muscle cells
Yijie YU ; Yu JIANG ; Shu DING ; Bo LI ; Xinggang CUI ; Wei YUAN ; Zhiyin DAI ; Wei ZHONG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(1):76-80
Objective To explore the mechanism by which CD137 signal regulates the aging of vas-cular smooth muscle cells(VSMCs).Methods Thirty 8-week-old male C57BL/6J mice were ran-domly divided into a young group(8 weeks old)and an aged group(80 weeks old),with 30 mice in each group.After corresponding periods of feeding,the mice were euthanized,and the plasma and aortic blood vessels were isolated.In the cell experiments,normal VSMCs were divided into a control group,bleomycin(BLM)group,combined agonist group,and combined inhibitor group.The cellular senescence level of VSMCs was assessed using a cellular senescence β-galactosidase staining kit.Western blotting and PCR were employed to examine the expression of senescence-related proteins in tissues and cells,while ELISA was utilized to measure the expression of senes-cence-related inflammatory factors.Results The expression of CD137 and γ-H2AX in the aorta was significantly higher,while that of PCNA was obviously lower in the aged group than the young group(P<0.05).The plasma level of CD137 was notably higher in the aged group than the young group(154.0±4.1 pg/ml vs 98.0±2.3 pg/ml,P<0.05).Compared with the normal control group,there were significantly more aged VSMCs in the BLM group(P<0.05).While,treatment of combined agonist resulted in larger amount of aged VSMCs when compared with the BLM group(P<0.05),which was reversed by combined inhibitor treatment(P<0.05).The levels of TNF-α,IL-6 and IL-1β were significantly elevated in the BLM group than the normal control group(P<0.05).The combined agonist group had even higher levels of TNF-α,IL-6,and IL-1βthan the BLM group(P<0.05),but the levels were decreased in the combined inhibitor group(P<0.05).Compared with the normal control group,the expression of Bcl-2,γ-H2AX,P53,and P21 were significantly increased in the BLM group,combined agonist group,and combined inhibi-tor group,while that of PCNA was significantly decreased(P<0.05).Compared with the BLM group,the expression of P53 and P21 in the combined agonist group showed an increase(P<0.05),and the expression of P53 was significantly decreased in the combined inhibitor group(P<0.05).Conclusion CD137 signal regulates the P53/P21 pathway to promote VSMC aging.
4.Risk factors for arrhythmia after robotic cardiac surgery: A retrospective cohort study
Wenjun WU ; Renzhong DING ; Jianming CHEN ; Ye YUAN ; Yi SONG ; Manrong YAN ; Yijie HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(05):745-750
Objective To investigate the risk factors for arrhythmia after robotic cardiac surgery. Methods The data of the patients who underwent robotic cardiac surgery under cardiopulmonary bypass (CPB) from July 2016 to June 2022 in Daping Hospital of Army Medical University were retrospectively analyzed. According to whether arrhythmia occurred after operation, the patients were divided into an arrhythmia group and a non-arrhythmia group. Univariate analysis and multivariate logistic analysis were used to screen the risk factors for arrhythmia after robotic cardiac surgery. Results A total of 146 patients were enrolled, including 55 males and 91 females, with an average age of 43.03±13.11 years. There were 23 patients in the arrhythmia group and 123 patients in the non-arrhythmia group. One (0.49%) patient died in the hospital. Univariate analysis suggested that age, body weight, body mass index (BMI), diabetes, New York Heart Association (NYHA) classification, left atrial anteroposterior diameter, left ventricular anteroposterior diameter, right ventricular anteroposterior diameter, total bilirubin, direct bilirubin, uric acid, red blood cell width, operation time, CPB time, aortic cross-clamping time, and operation type were associated with postoperative arrhythmia (P<0.05). Multivariate binary logistic regression analysis suggested that direct bilirubin (OR=1.334, 95%CI 1.003-1.774, P=0.048) and aortic cross-clamping time (OR=1.018, 95%CI 1.005-1.031, P=0.008) were independent risk factors for arrhythmia after robotic cardiac surgery. In the arrhythmia group, postoperative tracheal intubation time (P<0.001), intensive care unit stay (P<0.001) and postoperative hospital stay (P<0.001) were significantly prolonged, and postoperative high-dose blood transfusion events were significantly increased (P=0.002). Conclusion Preoperative direct bilirubin level and aortic cross-clamping time are independent risk factors for arrhythmia after robotic cardiac surgery. Postoperative tracheal intubation time, intensive care unit stay, and postoperative hospital stay are significantly prolonged in patients with postoperative arrhythmia, and postoperative high-dose blood transfusion events are significantly increased.
5.Role of group 3 innate lymphoid cells in skin wound healing and underlying mechanisms
Wei ZHANG ; Xingyu MU ; Qianru HANG ; Yijie HUANG ; Tengjiao XU ; Xiaojie HE ; Yan DING
Chinese Journal of Dermatology 2024;57(6):516-523
Objective:To investigate the role of group 3 innate lymphoid cells (ILC3) in skin wound healing, and to explore the underlying mechanisms.Methods:Twenty-four 5-week-old male C57BL/6 mice were randomly and equally allocated into 3 groups: the skin wound + ILC3 inhibitor group (referred to as ILC3 inhibitor group), the skin wound group, and the control group, with 8 mice in each group. Four days before the establishment of the wound model, mice in the ILC3 inhibitor group were intraperitoneally injected with 1 μg of ILC3 inhibitor every 2 days for a total of 2 doses, mice in the skin wound group were injected with an equal volume of physiological saline solution, and mice in the control group were fed normally. To establish a mouse skin wound model, a full-thickness circular incision with a diameter of 0.6 cm was made around the midpoint of the dorsal midline using a biopsy punch after the intraperitoneal injection of anesthetics, which was histologically confirmed to be a full-thickness injury. The size of the wounds was observed and recorded, photographs of the wounds were taken on days 0, 1, 3, 5, 7, and 9 after wounding, and corresponding wound healing rates were calculated. On day 9 after wounding, tissue samples were collected from the wound edges, and subjected to flow cytometry analysis to quantify ILC3 infiltrating around the skin wound, and hematoxylin and eosin (HE) staining was performed to assess the healing status of the skin wounds. Real-time quantitative polymerase chain reaction (qRT-PCR) was conducted to determine the mRNA expression of vitamin D receptor (VDR), Notch1, tumor necrosis factor-alpha (TNF-α), interleukin (IL) -17A, IL-17F, and IL-22 in the wound-edge tissues, and Western blot analysis to determine their protein expression. Statistical analysis was carried out by using one-way analysis of variance and t test. Results:On day 9 after wounding, the skin wound group showed an increased number of ILC3 in the wound-edge tissues (5.31% ± 1.47% vs. 3.10% ± 0.54%, P < 0.01), increased mRNA and protein expression of TNF-α, IL-22, IL-17A, and IL-17F (all P < 0.05), but decreased mRNA and protein expression of VDR (both P < 0.05) compared with the control group; the protein expression of Notch1 was significantly higher in the skin wound group than in the control group ( P < 0.05), but there was no significant difference in its mRNA expression between the two groups ( P > 0.05). On days 1, 3 and 5, the wound healing rates were significantly higher in the ILC3 inhibitor group (45.17% ± 9.90%, 61.58% ± 11.61%, 75.61% ± 9.12%, respectively) than in the skin wound group (25.87% ± 10.96%, 47.78% ± 13.81%, 64.55% ± 10.29%, respectively, all P < 0.05). On day 9, the ILC3 inhibitor group showed a decreased number of ILC3 around the wound (2.69% ± 0.95%, P < 0.01), decreased mRNA and protein expression of TNF-α, IL-22, IL-17A, and IL-17F in the wound-edge tissues (all P < 0.05), but increased mRNA and protein expression of Notch1 and VDR in the wound-edge tissues (all P < 0.05) compared with the skin wound group. On day 9 after wounding, histopathological examination with HE staining revealed continuous and intact epithelial structure, as well as dense and neatly arranged collagen fibers in the ILC3 inhibitor group, and the structures of hair follicles, blood vessels, and sebaceous glands were similar to those in the control group. Conclusions:Skin ILC3 infiltrated local wounds and were involved in the skin wound healing process through inflammatory factors such as TNF-α, IL-17A, IL-17F, and IL-22. Downregulating the number of ILC3 may promote skin wound healing by activating VDR and Notch1, as well as inhibiting the TNF-α signaling pathway and the expression of downstream inflammatory factors.
6.Immunometabolic rewiring in macrophages for periodontitis treatment via nanoquercetin-mediated leverage of glycolysis and OXPHOS.
Yi ZHANG ; Junyu SHI ; Jie ZHU ; Xinxin DING ; Jianxu WEI ; Xue JIANG ; Yijie YANG ; Xiaomeng ZHANG ; Yongzhuo HUANG ; Hongchang LAI
Acta Pharmaceutica Sinica B 2024;14(11):5026-5036
Periodontitis is a chronic inflammatory disease marked by a dysregulated immune microenvironment, posing formidable challenges for effective treatment. The disease is characterized by an altered glucose metabolism in macrophages, specifically an increase in aerobic glycolysis, which is linked to heightened inflammatory responses. This suggests that targeting macrophage metabolism could offer a new therapeutic avenue. In this study, we developed an immunometabolic intervention using quercetin (Q) encapsulated in bioadhesive mesoporous polydopamine (Q@MPDA) to treat periodontitis. Our results demonstrated that Q@MPDA could reprogram inflammatory macrophages to an anti-inflammatory phenotype (i.e., from-M1-to-M2 repolarization). In a murine periodontitis model, locally administered Q@MPDA reduced the presence of inflammatory macrophages, and decreased the levels of inflammatory cytokines (IL-1β and TNF-α) and reactive oxygen species (ROS) in the periodontium. Consequently, it alleviated periodontitis symptoms, reduced alveolar bone loss, and promoted tissue repair. Furthermore, our study revealed that Q@MPDA could inhibit the glycolysis of inflammatory macrophages while enhancing oxidative phosphorylation (OXPHOS), facilitating the shift from M1 to M2 macrophage subtype. Our findings suggest that Q@MPDA is a promising treatment for periodontitis via immunometabolic rewiring.
7.Psychological characteristics of vocational selection for college students with disabilities
Xiaoqing FANG ; Xuemei DING ; Yijie WANG ; Xinzheng LI ; Xiaoli ZHANG
Chinese Journal of Rehabilitation Theory and Practice 2023;29(10):1227-1232
ObjectiveTo investigate the psychological tendency characteristics of vocational selection for college students with disabilities. MethodsA total of 155 college students with disabilities in four colleges and universities were investigated using Psychological Tendencies of Vocational Selection for College Students with Disabilities (PTVS). ResultsA total of 151 questionnaires returned finally. The principal component analysis extracted four factors, namely profession, capability, parental occupation and parental education, with a cumulative contribution rate of 74.98%. Clustering analysis clustered three categories, namely vocational capability and parental education dominated, profession and capability dominated, and profession dominated, which accounted for 20.5%, 31.1% and 48.3%, respectively. There were significant differences among the three categories in the dimensions of personal cognition, employment tendency, employment affect and employment will of PTVS (F > 7.021, P < 0.01). ConclusionThere are four dimensions of PTVS, i.e., the dimension of profession, the dimension of capability, the dimension of parental occupation and the dimension of parental education; while the PTVS could be divided into three categories, i.e., vocational capability and parental education dominated, profession and capability dominated, and profession dominated. For college students with disabilities, accurate career counseling and guidance should be provided according to the psychological structure of vocational selection and PTVS.
8.Clinical and genetic analysis of a child with Cerebral creatine deficiency syndrome due to variant of SLC6A8 gene.
Yunjiang ZHANG ; Yifeng DING ; Yijie LI ; Shuizhen ZHOU
Chinese Journal of Medical Genetics 2023;40(11):1397-1403
OBJECTIVE:
To explore the clinical features and genetic variant in a child with Cerebral creatine deficiency syndrome (CCDS).
METHODS:
A child who had presented at the Affiliated Children's Hospital of Fudan University on March 5, 2021 was selected as the study subject. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing. The level of creatine in the brain was determined by magnetic resonance spectroscopy.
RESULTS:
The patient, a 1-year-and-10-month male, had presented with developmental delay and epilepsy. Both his mother and grandmother had a history of convulsions. MRS showed reduced cerebral creatine in bilateral basal ganglia and thalamus. The child was found to harbor a hemizygous splicing variant of the SLC6A8 gene, namely c.1767+1_1767+2insA, which may lead to protein truncation. The variant was not found in the public databases. Both his mother and grandmother were heterozygous carriers for the same variant.
CONCLUSION
The hemizygous c.1767+1_1767+2insA variant of the SLC6A8 gene probably underlay the CCDS in this child. Discovery of the novel variant has also expanded the mutational spectrum of the SLC6A8 gene.
Humans
;
Male
;
Amino Acid Metabolism, Inborn Errors
;
Brain
;
Creatine/genetics*
;
Heterozygote
;
Mothers
;
Nerve Tissue Proteins
;
Plasma Membrane Neurotransmitter Transport Proteins/genetics*
;
Infant
9.Cassiae Semen improves non-alcoholic fatty liver disease through autophagy-related pathway.
Mingning DING ; Fei ZHOU ; Yijie LI ; Chuanyang LIU ; Yiqing GU ; Jianzhi WU ; Guifang FAN ; Yajing LI ; Xiaojiaoyang LI
Chinese Herbal Medicines 2023;15(3):421-429
OBJECTIVE:
Cassiae Semen (CS, Juemingzi in Chinese) has been used for thousands of years in ancient Chinese history for relieving constipation, improving liver function as well as preventing myopia. Here we aimed to elucidate the anti-steatosis effect and underlying mechanism of CS against non-alcoholic fatty liver disease (NAFLD).
METHODS:
High-performance liquid chromatography (HPLC) was used to identify the major components of CS water extract. Mice were fed with a high-fat and sugar-water (HFSW) diet to induce hepatic steatosis and then treated with CS. The anti-NAFLD effect was determined by measuring serum biomarkers and histopathology staining. Additionally, the effects of CS on cell viability and lipid metabolism in oleic acid and palmitic acid (OAPA)-treated HepG2 cells were measured. The expression of essential genes and proteins involved in lipid metabolism and autophagy signalings were measured to uncover the underlying mechanism.
RESULTS:
Five compounds, including aurantio-obtusin, rubrofusarin gentiobioside, cassiaside C, emodin and rhein were simultaneously identified in CS extract. CS not only improved the diet-induced hepatic steatosis in vivo, as indicated by decreased number and size of lipid droplets, hepatic and serum triglycerides (TG) levels, but also markedly attenuated the OAPA-induced lipid accumulation in hepatocytes. These lipid-lowering effects induced by CS were largely dependent on the inhibition of fatty acid synthase (FASN) and the activation of autophagy-related signaling, including AMP-activated protein kinase (AMPK), light chain 3-II (LC3-II)/ LC3-1 and autophagy-related gene5 (ATG5).
CONCLUSION
Our study suggested that CS effectively protected liver steatosis via decreasing FASN-related fatty acid synthesis and activating AMPK-mediated autophagy, which might become a promising therapeutic strategy for relieving NAFLD.
10.Serum metabolomics in latent pneumoconiosis tuberculosis patients based on ultra performance liquid chromatography tandem quadrupole time of flight mass spectrometry
Fangda PENG ; Yijie WANG ; Bo ZHANG ; Hongliang GAO ; Aihua TANG ; Qingjun QIAN ; Chunguang DING
Chinese Journal of Industrial Hygiene and Occupational Diseases 2020;38(4):246-250
Objective:To explore the non-target metabonomics of serum in worker's pneumoconiosis (CWP) patients with latent tuberculosis and the biomarkers of latent tuberculosis infection of pneumoconiosis.Methods:In December 2018, 39 CWP inpatients from a hospital in Beijing were taken as subjects. The subjects were screened for latent tuberculosis using the in vitro release test of mycobacterium tuberculosis-interferon (IGRAs) test. According to the screening results, 21 positive patients with latent tuberculosis infection were selected as the latent tuberculosis group of pneumoconiosis. While 18 negative patients with CWP alone were selected as the pneumoconiosis group. Polarity components of metabolites were analyzed by UPLC-QTOF/MS. The data was processed with Progenesis QI software for multidimensional statistical analysis. Identification of structure of differential metabolites were matched through accurate mass and secondary mass spectrum. Searching the Human Metabolome Database (HMDB) , differential metabolites were imported into MetaboAnalyst 4.0 to analyze the metabolic pathways.Results:All 42 differential metabolites were screened out. Excepted for exogenous metabolites, 14 endogenous differential metabolites were identified. Compared with the pneumoconiosis group, 6 metabolites including PC [18∶4 (6Z, 9Z, 12Z, 15Z) /P-18∶1 (11Z) ], 3-Oxododecanoyl-CoA in the latent tuberculosis group were up-regulated, while 8 metabolites including the Stearoyl-CoA, (2S) -Pristanoyl-CoA were down-regulated. These results might be related to lipid, fatty acid and arachidonic acid metabolism pathways.Conclusion:There are significant differences in serum metabonomics between the patients with latent tuberculosis of pneumoconiosis and the patients with ordinary pneumoconiosis, which provide a reference for the study of biomarkers for the diagnosis of latent tuberculosis infection of pneumoconiosis.

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