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.A case report of intraluminal thrombus in proximal vertebral artery
Yang DING ; Yijie CHEN ; Xu ZHENG ; Yigang CHEN ; Jinhua ZHANG
Chinese Journal of Nervous and Mental Diseases 2025;51(4):243-245
Intraluminal thrombus(ILT)at the vertebral artery origin is rare and often missed due to atypical symptoms.However,it poses a high risk of artery-to-artery embolism and severe posterior circulation ischemia.This article reports a case of missed diagnosis of ILT to improve the diagnostic ability.The patient,a 49-year-old male was admitted to emergency department with sudden dizziness accompanied by nausea for 12 hours.Head CT suggested posterior circulation ischemia.Patient was given aspirin 0.2 g/d and atorvastatin 20 mg/d orally and discharged from the hospital.Head MRI in the outpatient department showed a recent infarct in the right cerebellar hemisphere next day.On the 28th,dizziness recurred,accompanied by unsteady walking and right-sided hemisensory numbness.The symptoms persisted and did not improve.He was admitted to the hospital on the 29th.Cervical CTA showed severe stenosis at the origin of the right vertebral artery,filling defect in the distal lumen combined with the Donut sign.Thus,ILT was diagnosed.The drug treatment regimen was adjusted to aspirin 100 mg/d combined with clopidogrel 75 mg/d for a total of 15 weeks.High-resolution MRI of the cervical blood vessels in the outpatient department showed occlusion of the V1-V2 segment of the right vertebral artery.On November 2,endovascular treatment was performed under local anesthesia.At 90 days and 6 months of follow-up after the operation,no recurrence of cerebral ischemia events occurred,and the mRS score was 0.This case highlights the need for vigilance toward ILT in posterior circulation ischemia when initial imaging is inconclusive.Early dynamic CTA(5-7 days)combined with dual antiplatelets may prevent thrombus progression and improve outcomes.
3.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.
4.Effect of portal vein thrombosis on the long-term prognosis of patients with hepatitis B cirrhosis
Keke JIN ; Ying HAN ; Yijie YAN ; Lingna LYU ; Yanna LIU ; Yanglan HE ; Huiguo DING
Chinese Journal of Hepatology 2025;33(3):217-226
Objective:To explore the characteristics of portal vein thrombosis (PVT) formation in patients with hepatitis B cirrhosis and its effect on long-term prognosis.Methods:The clinical data of a cohort of patients with hepatitis B cirrhosis who visited Beijing Youan Hospital from May 2009 to August 2020 were retrospectively analyzed. Enhanced CT examination was used as the standard for diagnosing PVT and its classification. Patients with hepatitis B cirrhosis without PVT at baseline were selected as the research subjects. According to whether PVT was formed during the follow-up period, they were divided into the PVT and control groups including 99 and 168 patients in the PVT and control groups with a follow-up time of 52.0 (46.7, 57.3) months. The changes in baseline and endpoint clinical indicators of the two groups were compared. Kaplan-Meier survival curve, log-rank test, and Cox regression were used to analyze the effect of PVT on prognosis.Results:In the PVT group, 28.28% (28/99) of patients underwent splenectomy, and 74.75% (74/99) did not receive anticoagulation therapy. The main portal vein thrombosis, portal vein branch thrombosis, and thrombosis in both groups accounted for 34.34% (34/99), 23.23% (23/99), and 15.15% (15/99), respectively. The splenic vein or superior mesenteric vein accounted for 27.27% (27/99). PVT was stable in 63.27% (63/99), progressed in 31.31% (31/99), and relieved in 5.05% (5/99) during the follow-up period. The white blood cell, hemoglobin, and platelet counts were all decreased in the PVT group compared with the baseline ( P<0.05). The international normalized ratio (INR) [1.28 (1.14, 1.39) vs. 1.33 (1.19, 1.46), P=0.041] and spleen length [(163.84±30.68) mm vs. (177.26±32.61) mm, P<0.001] was increased compared with the baseline. The proportion of gastroesophageal variceal bleeding was higher in the PVT group than in the control group (57.0% vs. 28.7%, P<0.001), and the constituent ratio of hepatic encephalopathy was not statistically significantly different ( P>0.05). The proportion of patients with ascites in the control group decreased (63.1% vs. 41.7%, P<0.001), while the proportion of patients with ascites in the PVT group was not statistically significantly different ( P>0.05). The incidence of composite clinical endpoint events in the PVT and the control group was 21.21% (21/99) and 4.17% (7/168), respectively ( P<0.05). The incidence of composite clinical endpoint events in PVT patients without anticoagulation and anticoagulation treatment was 25.68% (19/74) and 8.00% (2/25), respectively ( P=0.062). Cox regression analysis found that PVT formation was an independent risk factor for liver-related adverse events in patients with hepatitis B cirrhosis ( HR=9.36, 95% CI: 3.65~24.02, P=0.001). Conclusions:The presence of PVT in patients with hepatitis B cirrhosis is assoliated with worse prognosis. The formation of PVT is closely related to the increased risk of liver-related adverse prognosis in patients with hepatitis B cirrhosis.
5.A case report of intraluminal thrombus in proximal vertebral artery
Yang DING ; Yijie CHEN ; Xu ZHENG ; Yigang CHEN ; Jinhua ZHANG
Chinese Journal of Nervous and Mental Diseases 2025;51(4):243-245
Intraluminal thrombus(ILT)at the vertebral artery origin is rare and often missed due to atypical symptoms.However,it poses a high risk of artery-to-artery embolism and severe posterior circulation ischemia.This article reports a case of missed diagnosis of ILT to improve the diagnostic ability.The patient,a 49-year-old male was admitted to emergency department with sudden dizziness accompanied by nausea for 12 hours.Head CT suggested posterior circulation ischemia.Patient was given aspirin 0.2 g/d and atorvastatin 20 mg/d orally and discharged from the hospital.Head MRI in the outpatient department showed a recent infarct in the right cerebellar hemisphere next day.On the 28th,dizziness recurred,accompanied by unsteady walking and right-sided hemisensory numbness.The symptoms persisted and did not improve.He was admitted to the hospital on the 29th.Cervical CTA showed severe stenosis at the origin of the right vertebral artery,filling defect in the distal lumen combined with the Donut sign.Thus,ILT was diagnosed.The drug treatment regimen was adjusted to aspirin 100 mg/d combined with clopidogrel 75 mg/d for a total of 15 weeks.High-resolution MRI of the cervical blood vessels in the outpatient department showed occlusion of the V1-V2 segment of the right vertebral artery.On November 2,endovascular treatment was performed under local anesthesia.At 90 days and 6 months of follow-up after the operation,no recurrence of cerebral ischemia events occurred,and the mRS score was 0.This case highlights the need for vigilance toward ILT in posterior circulation ischemia when initial imaging is inconclusive.Early dynamic CTA(5-7 days)combined with dual antiplatelets may prevent thrombus progression and improve outcomes.
6.Effect of portal vein thrombosis on the long-term prognosis of patients with hepatitis B cirrhosis
Keke JIN ; Ying HAN ; Yijie YAN ; Lingna LYU ; Yanna LIU ; Yanglan HE ; Huiguo DING
Chinese Journal of Hepatology 2025;33(3):217-226
Objective:To explore the characteristics of portal vein thrombosis (PVT) formation in patients with hepatitis B cirrhosis and its effect on long-term prognosis.Methods:The clinical data of a cohort of patients with hepatitis B cirrhosis who visited Beijing Youan Hospital from May 2009 to August 2020 were retrospectively analyzed. Enhanced CT examination was used as the standard for diagnosing PVT and its classification. Patients with hepatitis B cirrhosis without PVT at baseline were selected as the research subjects. According to whether PVT was formed during the follow-up period, they were divided into the PVT and control groups including 99 and 168 patients in the PVT and control groups with a follow-up time of 52.0 (46.7, 57.3) months. The changes in baseline and endpoint clinical indicators of the two groups were compared. Kaplan-Meier survival curve, log-rank test, and Cox regression were used to analyze the effect of PVT on prognosis.Results:In the PVT group, 28.28% (28/99) of patients underwent splenectomy, and 74.75% (74/99) did not receive anticoagulation therapy. The main portal vein thrombosis, portal vein branch thrombosis, and thrombosis in both groups accounted for 34.34% (34/99), 23.23% (23/99), and 15.15% (15/99), respectively. The splenic vein or superior mesenteric vein accounted for 27.27% (27/99). PVT was stable in 63.27% (63/99), progressed in 31.31% (31/99), and relieved in 5.05% (5/99) during the follow-up period. The white blood cell, hemoglobin, and platelet counts were all decreased in the PVT group compared with the baseline ( P<0.05). The international normalized ratio (INR) [1.28 (1.14, 1.39) vs. 1.33 (1.19, 1.46), P=0.041] and spleen length [(163.84±30.68) mm vs. (177.26±32.61) mm, P<0.001] was increased compared with the baseline. The proportion of gastroesophageal variceal bleeding was higher in the PVT group than in the control group (57.0% vs. 28.7%, P<0.001), and the constituent ratio of hepatic encephalopathy was not statistically significantly different ( P>0.05). The proportion of patients with ascites in the control group decreased (63.1% vs. 41.7%, P<0.001), while the proportion of patients with ascites in the PVT group was not statistically significantly different ( P>0.05). The incidence of composite clinical endpoint events in the PVT and the control group was 21.21% (21/99) and 4.17% (7/168), respectively ( P<0.05). The incidence of composite clinical endpoint events in PVT patients without anticoagulation and anticoagulation treatment was 25.68% (19/74) and 8.00% (2/25), respectively ( P=0.062). Cox regression analysis found that PVT formation was an independent risk factor for liver-related adverse events in patients with hepatitis B cirrhosis ( HR=9.36, 95% CI: 3.65~24.02, P=0.001). Conclusions:The presence of PVT in patients with hepatitis B cirrhosis is assoliated with worse prognosis. The formation of PVT is closely related to the increased risk of liver-related adverse prognosis in patients with hepatitis B cirrhosis.
7.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.
8.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.
9.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.
10.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.

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