1.Effect of Bushen Huoxue Granules (补肾活血颗粒) on the Nrf2/NLRP3 Inflammasome Axis in the Brain Substantia Nigra of Parkinson's Disease Model Mice
Qi CHEN ; Peng WANG ; Yingfan CHEN ; Shaodan LI ; Minghui YANG
Journal of Traditional Chinese Medicine 2025;66(4):390-398
ObjectiveTo explore the possible mechanism of action of Bushen Huoxue Granules (补肾活血颗粒, BHG) in the treatment of Parkinson's disease (PD) through the Nrf2/NLRP3 inflammasome axis. MethodsA total of 84 male C57/BL 6 mice were randomly divided into blank group, model group, Madopar group, dimethyl fumarate group, and low-, medium, and high-dose BHG group, with 12 mice in each group. Except for the blank group, all groups were induced into PD models by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a concentration of 30 mg/ml for 7 consecutive days. The blank group received an equal volume of saline. After model establishment, the low-, medium, and high-dose BHG groups were treated with 1.5, 3, and 6 g/(kg·d) of the BHG by gavage, respectively. The Madopar group was given 0.113 g/(kg·d) of Madopar tablets by gavage, and the dimethyl fumarate group was given 50 mg/(kg·d) of dimethyl fumarate solution. The blank group and the model group were given 10 ml/(kg·d) of distilled water by gavage. Gavage was administered once daily for 14 days. Behavioral changes were evaluated using the open field test (total distance, central area distance, and average speed), rotarod test (time on the rod), and climbing pole test (climbing time). Serum levels of interleukin-1β (IL-1β), interleukin-18 (IL-18), and myeloperoxidase (MPO) were measured by ELISA. Immunohistochemistry was used to detect tyrosine hydroxylase (TH) expression in the brain substantia nigra. Immunofluorescence was used to detect α-synuclein (α-syn) expression. Western Blot was used to detect Nrf2, NLRP3, Caspase-1, and α-syn protein levels in the brain substantia nigra. RT-PCR was used to detect mRNA expression levels of Nrf2, NLRP3, and Caspase-1 in the brain substantia nigra. ResultsCompared with the blank group, the model group showed decreased total distance, central area distance, and average speed, reduced time on the rotarod, prolonged climbing time, reduced TH expression, increased α-syn expression, decreased Nrf2 protein and mRNA expression, increased NLRP3 and Caspase-1 protein and mRNA expression, and elevated serum IL-1β, IL-18, and MPO levels (P<0.05). Compared with the model group, all drug interventions significantly improved the above indicators (P<0.05). There was no significant differences in all indicators between the high-dose BHG group and the Madopar group (P>0.05). Compared with the dimethyl fumarate group, the medium and high-dose BHG groups showed increased Nrf2 mRNA expression in the brain substantia nigra (P<0.05). Compared with the high-dose BHG group, the low-dose group showed decreased total distance, central area distance, and average speed, reduced serum IL-18 levels, decreased α-syn, Nrf2, NLRP3, and Caspase-1 protein levels, and lower Nrf2 mRNA expression (P<0.05). ConclusionThe mechanism by which BHG treat PD may involve activating the Nrf2/NLRP3 inflammasome axis in the brain substantia nigra, thereby reducing neuroinflammation and α-syn aggregation. The high-dose group showed the best effects.
2.Clinical efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in refractory autoimmune hemolytic anemia
Gang WANG ; Yixin GAO ; Linyan WU ; Liuyan PAN ; Suying HE ; Lijuan ZHOU ; Yongzheng PENG ; Minghui YANG
Chinese Journal of Blood Transfusion 2025;38(10):1348-1354
Objective: To evaluate the safety and efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in the treatment of refractory autoimmune hemolytic anemia (AIHA). Methods: A retrospective analysis was performed on the clinical data of AIHA patients who underwent therapeutic whole blood exchange combined with lymphoplasmapheresis at our hospital from March 2022 to May 2025. Efficacy was assessed by comparing changes in hemoglobin, platelet count, and bilirubin levels before and after treatment. Safety was evaluated by analyzing vital signs before and after the procedure, parameters during the exchange, and adverse reactions. Results: A total of 12 AIHA patients were enrolled, completing 19 exchange procedures. The number of procedures per patient ranged from 1 to 3. The median treatment duration was 67 (65-73) minutes, with a median exchange volume of 2 025 (1 851-2 121) mL, comprising 4.5 (4-6) units of red blood cells and 1 350 (1 200-1 400) mL of plasma. Ten patients achieved partial remission, one achieved complete remission, and one showed no response, yielding an response rate of 91% (11/12). After a single session, hemoglobin increased significantly by 17.58±9.85 g/L (P<0.01), while platelets counts decreased by 45 (17.5, 79)×10
/L (P<0.05), and both systolic and diastolic blood pressure showed a significant elevation (P<0.05). However, no statistically significant differences were observed in total bilirubin, indirect bilirubin, white blood cell count, or heart rate. During the procedures, 4 adverse reactions occurred in 3 patients: one child experienced severe heart rate fluctuation twice consecutively, and two adults developed plasma allergies. All reactions resolved spontaneously without pharmacological intervention. Conclusion: The combination of therapeutic whole blood exchange and lymphoplasmapheresis appears to be a safe and effective treatment for refractory AIHA patients.
3.Effect of Bushen Huoxue Granule (补肾活血颗粒) on Dopamine Homeostasis and ERK/CREB/VMAT2 Signaling Pathways in the Striatum in Parkinson's Disease Model Mice
Hehao SUN ; Yingfan CHEN ; Peng WANG ; Xiaohan GENG ; Yuzhi ZHANG ; Qian ZHANG ; Min LI ; Shaodan LI ; Minghui YANG
Journal of Traditional Chinese Medicine 2025;66(23):2484-2493
ObjectiveTo investigate the possible mechanism of Bushen Huoxue Granule (补肾活血颗粒, BHG) in treating Parkinson's disease (PD) from the perspecitve of dopamine (DA) homeostasis. MethodsSeventy-two mice were randomly divided into blank group, model group, madopar group and BHG low-, medium- and high-dose groups, with 12 mice in each group. Except for the blank group, all mice were administered intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to induce a PD model. On the day following the injection, BHG low-, medium- and high-dose groups were administered BHG at doses of 1.25, 2.5, and 5.0 mg/(g·d) by oral gavage, respectively, while the madopar group received madopar tablets at dose of 0.093 8 mg/(g·d) by oral gavage. The blank group and the model group were given 0.2 ml/10 g of distilled water by gavage. All treatments were given once daily for 14 days. Open field test, pole climbing test and grip test were used to evaluate the behavior of mice in each group. Immunohistochemistry was used to detect the expression of tyrosine hydroxylase (TH) in striatum. Nissl staining was used to detect the activity of striatal neurons. The contents of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in striatum were detected by ultra performance liquid chromatography tandem mass spectrometry. The number and volume of synaptic vesicles were observed by transmission electron microscope. The expression of vesicular monoamine transporter 2 (VMAT2) in striatum was detected by immunofluorescence. Western Blot was used to detect the expression of extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), cAMP response element-binding protein (CREB), phosphorylated CREB (p-CREB) and VMAT2 in striatum. ResultsCompared to the blank group, mice in the model group showed a significant decline in total distance and average speed in the open field test, along with an increase in total resting time; in the pole test, both the time required for the mice to turn completely downward (T-turn) and the total time taken to reach the bottom of the pole (T-total) were prolonged; forelimb grip strength was reduced; in the striatum, the mean optical density of TH, the average fluorescence intensity of VMAT2 protein, and DA content all decreased, while the number of striatal neurons was reduced, and the DOPAC/DA ratio was elevated; the levels of p-ERK/ERK, p-CREB/CREB, and VMAT2 in the striatum significantly decreased (P<0.01); transmission electron microscopy revealed that both the number and volume of synaptic vesicles in striatal neurons were markedly reduced. Compared to the model group, mice in the madopar group and BHG low-, medium- and high-dose groups showed significant improvements in all the above indicators (P<0.05 or P<0.01). Compared to madopar group, the BHG high-dose group exhibited increased DA content and elevated p-CREB/CREB ratio in the striatum (P<0.05). Compared to the BHG low-dose group, the BHG high-dose group showed increased total distance and mean velocity, decreased total resting time, T-turn, and T-total, as well as enhanced forelimb grip strength; moreover, the average fluorescence intensity of VMAT2 protein, DA content, p-ERK/ERK, p-CREB/CREB, and VMAT2 levels in the striatum were all significantly elevated (P<0.05 or P<0.01). ConclusionBHG may restore DA homeostasis and alleviate the damage of dopaminergic neurons by regulating ERK/CREB/VMAT2 signaling pathway.
4.Research on the resistance of hepatitis B virus to core protein allosteric modulators
Zechun YANG ; Yuanyuan LIU ; Minghui LIANG ; Hewang WANG ; Jie YANG ; Peng ZHAN ; Haiyong JIA
Journal of China Pharmaceutical University 2025;56(6):700-709
Hepatitis B virus (HBV) infection represents a significant global health challenge. Current therapeutic options, such as interferon and nucleoside analogues (NAs), are limited by issues including long-term medication toxicity, the virus's propensity to develop drug resistance, and the inability to eradicate covalently closed circular DNA (cccDNA). Core protein allosteric modulators (CpAMs), as an emerging class of anti-HBV drugs, target HBcAg to interfere with capsid assembly. This not only blocks viral nucleocapsid formation and inhibits viral replication but also indirectly destabilizes the cccDNA pool, while exhibiting a relatively high genetic barrier to resistance. This article systematically evaluates HBV drug resistance to CpAMs and proposes anti-resistance strategies, including the combination of nucleoside analogues with CpAMs, enhancing protein-drug interactions, targeting HBcAg degradation, designing multi-target inhibitors, and employing combination therapy. Looking ahead, the integration of structural biology, computational chemistry, and immunotherapy will offer innovative approaches for developing novel, highly effective, and low-resistance inhibitors, thereby advancing the functional cure of hepatitis B.
5.Effect of the impaction of posterior wall on the prognosis following open reduction and internal fixation for fractures of acetabular posterior wall
Yufeng GE ; Feng GAO ; Chao TU ; Gang LIU ; Minghui YANG ; Xu SUN ; Zhelun TAN ; Yimin CHEN ; Weidong PENG ; Xinbao WU
Chinese Journal of Orthopaedic Trauma 2024;26(3):188-193
Objective:To evaluate the effect of the impaction of posterior wall on the prognosis following open reduction and internal fixation for fractures of acetabular posterior wall.Methods:A retrospective study was conducted to analyze the data from the 83 patients with fracture of acetabular posterior wall who had been consecutively treated by open reduction and internal fixation at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital from January 2017 to December 2020. The patients were divided into 2 groups based on involvement of posterior wall impaction. In the impaction group of 33 cases, there were 26 males and 7 females with an age of (47.4±11.6) years; in the non-impaction group of 50 cases, there were 43 males and 7 females with an age of (41.3±12.0) years. The quality of postoperative fracture reduction, the function of the affected hip at the last follow-up, and the complication rate during follow-up were compared between the 2 groups. Multifactorial binary logistic regression and age subgroups were used to analyze the effects of posterior wall impaction on functional outcomes.Results:The age, rate of associated injuries in other body parts, and rate of posterior wall comminution in the impaction group were significantly higher than those in the non-impaction group ( P<0.05), but there was no statistically significant difference in other general data of patients between the 2 groups ( P>0.05). All patients were followed up for (44.5±13.3) months after surgery. The rate of anatomical reduction in the non-impaction group (96.0%, 48/50) was significantly higher than that in the impaction group (57.6%, 19/33) ( P<0.05), and the good and excellent rate by the modified Merle d'Aubigné & Postel scale at the last follow-up in the non-impaction group (84.0%, 42/50) was significantly higher than that in the impaction group (51.5%, 17/33) ( P<0.05). There was no significant difference in the incidence of complications between the 2 groups ( P>0.05). After adjusting for age and gender, the difference in hip function was still significantly different between the 2 groups ( OR=0.23, 95% CI: 0.06 to 0.79, P=0.020). The effect of posterior wall impaction on functional outcomes was statistically significant in patients aged ≥50 years ( P=0.008), whereas the difference was not statistically significant in patients aged <50 years ( P=0.194). Conclusions:Compared with non-impaction ones, acetabular fractures of posterior wall impaction tend to lead to poorer quality of reduction, which in turn affects the postoperative recovery of hip joint function. The impact of impaction fractures on functional recovery is more significant in patients aged 50 years and above.
6.Multi-Voiced Narrative of Home-Based Palliative Care:Report of One Case
Xiaotian ZHANG ; Zidan WANG ; Minghui WANG ; Lingling WU ; Peng YUE
Acta Academiae Medicinae Sinicae 2024;46(1):68-71
Terminally ill patients face multiple difficulties in home care.Home-based palliative care ad-hering to the concept of whole-person,whole-family,whole-team,and whole-course care is able to meet the needs of terminally ill patients and their families.In this paper,we reported the care history and home-based pal-liative care process of a patient with end-stage breast tumor and summarized the experience,aiming to provide reference for the future work of home-based palliative care.
7.Predictive value of serum hs-cTnT levels for major adverse cardiovascular events in patients with chronic coronary syndrome after PCI
Yaxin XU ; Ru LIU ; Qizhe WANG ; Xiaopan LI ; Yuxiang DAI ; Minghui PENG ; Sunfang JIANG
Chinese Journal of General Practitioners 2024;23(10):1029-1036
Objective:To investigate the correlation of serum high-sensitivity cardiac troponin T (hs-cTnT) level with major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI) and to explore its predictive value.Methods:It was a case-control study. Clinical data of 731 patients with CCS who underwent PCI in the Affiliated Zhongshan Hospital of Fudan University between May 2019 and April 2020 were retrospectively analyzed. Baseline clinical characteristics and pre/postoperative laboratory results were gathered, and patients were followed up and the incidence of MACE was documented. The correlation of serum hs-cTnT levels with MACE was analyzed, and the threshold of hs-cTnT for predicting the occurrence of MACE was determined.Results:Among 731 patients there were 560 males (76.61%) with the age of (64.05±9.48) years. Patients were followed up for 29.9 (18.8, 35.3) months, and MACE occurred in 216 cases (MACE group), and did not occur in 515 cases (control group). The X-tile software analysis showed that the optimal cutoff value of post-PCI hs-cTnT was 4.17×upper reference limit (URL) for predicting MACE ( P=0.033). Multivariate Cox regression analysis revealed that postoperative cTnT>6×URL was an independent risk factor for MACE in CCS patients after PCI ( HR=1.87, 95% CI: 1.19-2.94, P=0.007). The net reclassification index pairwise comparison results indicated that hs-cTnT>6×URL had the better predictive performance for MACE in CCS patients after PCI compared to 7×URL, 8×URL, 9×URL, 10×URL and 15×URL (all P<0.05). Conclusion:Postoperative hs-cTnT>6×URL is an independent risk factor for MACE in CCS patients after PCI, and hs-cTnT>6×URL is the optimal threshold for predicting the risk of MACE.
8.Effect of self-made Bitong Ointment combined with umbilical dressing of traditional Chinese medicine in treatment of children with pediatric allergic rhinitis differentiated as type of latent heat in the lung meridian
Guihua YANG ; Songqing KANG ; Lina PENG ; Minghui ZHANG
Journal of Clinical Medicine in Practice 2024;28(6):69-73
Objective To investigate the therapeutic effect of self-made Bitong Ointment combined with umbilical dressing of traditional Chinese medicine in the treatment of children with pediatric allergic rhinitis differentiated as type of latent heat in the lung meridian. Methods Eighty children with allergic rhinitis differentiated as type of latent heat in the lung meridian were randomly divided into observation group and control group, with 40 cases in each group. The control group was treated with loratadine, while the observation group was additionally treated with self-made Bitong Ointment and umbilical dressing of traditional Chinese medicine. After 4 weeks of treatment, the clinical effect, TCM syndrome score, airway stress response, inflammatory factors, and therapeutic safety were evaluated. Results The total effective rate in the observation group was 95.00% (38/40), which was higher than 77.50% (31/40) in the control group. After treatment, the scores of main TCM syndromes such as frequent sneezing, clear and thin nasal discharge, decreased sense of smell, shortness of breath, and reluctance to speak in the observation group were lower than those in the control group. After treatment, the levels of indicators of airway stress response such as exhaled nitric oxide (FeNO), lipid peroxide (LHP) and inducible nitric oxide synthase (iNOS) in the observation group were lower than those in the control group. After treatment, the levels of inflammatory factors such as monocyte chemoattractant protein-4 (MCP-4), cysteinyl leukotriene receptor 1 (CysLTR1), and interleukin-9 (IL-9) in the observation group were significantly lower than those in the control group (
9.Enhancement of oligodendrocyte autophagy alleviates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in rats.
Huiyang WANG ; Yueyang LIU ; Zhenkun GUO ; Minghui CUI ; Peng PANG ; Jingyu YANG ; Chunfu WU
Acta Pharmaceutica Sinica B 2023;13(5):2107-2123
Cognitive impairment caused by chronic cerebral hypoperfusion (CCH) is associated with white matter injury (WMI), possibly through the alteration of autophagy. Here, the autophagy-lysosomal pathway (ALP) dysfunction in white matter (WM) and its relationship with cognitive impairment were investigated in rats subjected to two vessel occlusion (2VO). The results showed that cognitive impairment occurred by the 28th day after 2VO. Injury and autophagy activation of mature oligodendrocytes and neuronal axons sequentially occurred in WM by the 3rd day. By the 14th day, abnormal accumulation of autophagy substrate, lysosomal dysfunction, and the activation of mechanistic target of rapamycin (MTOR) pathway were observed in WM, paralleled with mature oligodendrocyte death. This indicates autophagy activation was followed by ALP dysfunction caused by autophagy inhibition or lysosomal dysfunction. To target the ALP dysfunction, enhanced autophagy by systemic rapamycin treatment or overexpression of Beclin1 (BECN1) in oligodendrocytes reduced mature oligodendrocyte death, and subsequently alleviated the WMI and cognitive impairment after CCH. These results reveal that early autophagy activation was followed by ALP dysfunction in WM after 2VO, which was associated with the aggravation of WMI and cognitive impairment. This study highlights that alleviating ALP dysfunction by enhancing oligodendrocyte autophagy has benefits for cognitive recovery after CCH.
10.Study on safety performance and condition-suggestion accuracy of the symptom assessment mobile applications
Shanzhu ZHU ; Sunfang JIANG ; Juan SHOU ; Zhigang PAN ; Yu ZHANG ; Minghui PENG ; Hua YANG ; Stephen GILBERT
Chinese Journal of General Practitioners 2023;22(3):288-294
Objective:To compare the breadth of condition coverage, accuracy of suggested conditions and appropriateness of urgency advice of the 8 symptom assessment mobile applications (APPs) available on the Chinese market.Methods:The APPs were assessed using 200 primary care vignettes and were measured against the vignettes′ standard. The primary outcome measures were proportion of conditions covered by an APP, proportion of vignettes with the correct primary diagnosis,and proportion of safe urgency advice.Results:For APPs assessed,condition-coverage was from 29.0%(58/200)to 99.5%(199/200), top-3 suggestion accuracy was from 8.5%(17/200) to 61.5%(123/200), the proportion of safe urgency advice was from 84.8%(167/197) to 99.5% (198/199).Conclusions:The APPs showed a wide range of coverage, safety performance and condition-suggestion accuracy. Symptom assessment APPs with good performance could be used by general practitioners as supporting tools. However, even symptom assessment APPs with excellent performance need to be further assessed in a real clinical environment.


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