1.Construction and practice of the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine
Zhipeng WU ; Yuqin ZHANG ; Chun YAO ; Minggang WANG ; Na WANG ; Mengru PENG ; Ningfang MO ; Yaqing ZHENG ; Rongzhen ZHANG ; Dewen MAO
Journal of Clinical Hepatology 2025;41(2):370-374
Hepatic encephalopathy is a difficult and critical disease with rapid progression and limited treatment methods in the field of liver disease, and it is urgently needed to make breakthroughs in its pathogenesis. Selection of appropriate prevention and treatment strategies is of great importance in delaying disease progression and reducing the incidence and mortality rates. This article reviews the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine, proposes a new theory of “turbid toxin pathogenesis”, analyzes the scientific connotations of “turbid”, “toxin”, and the theory of “turbid toxin pathogenesis”, and constructs the “four-step” prevention and treatment strategies for hepatic encephalopathy, thereby establishing the new clinical prevention and treatment regimen for hepatic encephalopathy represented by “four prescriptions and two techniques” and clarifying the effect mechanism and biological basis of core prescriptions and techniques in the prevention and treatment of hepatic encephalopathy, in order to provide a reference for the prevention and treatment of hepatic encephalopathy.
2.Hei Xiaoyaosan Improves Learning and Memory Abilities in Alzheimer's Disease Rats by Regulating Cell Apoptosis
Huping WANG ; Jiao YANG ; Yiqin CHEN ; Zhipeng MENG ; Yujie LYU ; Yunyun HU ; Wenli PEI ; Yumei HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):108-115
ObjectiveTo explore the mechanism of Hei Xiaoyaosan in improving the cognitive function in Alzheimer's disease (AD) from cell apoptosis mediated by the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor kappa B (NF-κB) signaling pathway. MethodsFour-month-old SD male rats were randomly assigned into a blank group, a sham group, a model group, a donepezil hydrochloride (0.45 mg·kg-1) group, and high-, medium-, and low-dose (15.30, 7.65, and 3.82 g·kg-1, respectively) Hei Xiaoyaosan groups, with 10 rats in each group. The sham group received bilateral hippocampal injection of 1 μL normal saline, while the other groups received bilateral hippocampal injection of 1 μL beta-amyloid 1-42 (Aβ1-42) solution for the modeling of AD. Rats were administrated with corresponding agents once a day for 42 consecutive days. The Morris water maze test was carried out to assess the learning and memory abilities of rats. Hematoxylin-eosin staining was employed to observe pathological changes in the hippocampus of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of cysteinyl aspartate-specific proteinase-3 (Caspase-3), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax). Western blot was employed to determine the protein levels of PI3K, Akt, and NF-κB. A cell model of AD was established by co-culturing Aβ1-42 and PC12 cells in vitro. Cell viability and apoptosis were detected by the cell-counting kit 8 (CCK-8) assay and flow cytometry (FC), respectively. ResultsAnimal experiments showed that compared with the blank group, the model group had a prolonged escape latency (P<0.01), a reduced number of crossing platforms (P<0.01), disarrangement and a reduced number of hippocampal neurons, up-regulated expression of Bax and Caspase-3, down-regulated expression of Bcl-2 (P<0.01), decreased p-PI3K/PI3K and p-Akt/Akt levels, and an increased p-NF-κB/NF-κB level (P<0.01). Compared with the model group, donepezil hydrochloride and high- and medium-dose Hei Xiaoyaosan shortened the escape latency and increased the number of crossing platforms (P<0.05, P<0.01), improved the arrangement and increased the number of hippocampal neurons, down-regulated the expression levels of Bax and Caspase-3, up-reguated the expression level of Bcl-2 (P<0.05, P<0.01), increased the p-PI3K/PI3K and p-Akt/Akt levels (P<0.05, P<0.01), and reduced the p-NF-κB/NF-κB level (P<0.05, P<0.01). Cell experiments showed that compared with the blank group, the model group exhibited an increased apoptosis rate (P<0.01). Compared with the model group, the serum containing Hei Xiaoyaosan at various doses improved the cell viability (P<0.01), and the serum containing Hei Xiaoyaosan at the high dose decreased the cell apoptosis (P<0.01). ConclusionHei Xiaoyaosan may improve the learning and memory abilities of AD model rats by regulating cell apoptosis, while increasing the vitality and reducing the apoptosis rate of AD model cells via the PI3K/Akt/NF-κB signaling pathway.
3.Effect of Hei Xiaoyaosan on Neuroinflammation and NLRP3/Caspase-1/GSDMD Signaling Pathway in APP/PS1 Mice
Jun ZHOU ; Mingcheng LI ; Yujie LYU ; Zhipeng MENG ; Yunyun HU ; Huping WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):124-133
ObjectiveTo observe the effects of Hei Xiaoyaosan on the learning and memory abilities of Alzheimer's disease model mice (APP/PS1 mice), and to explore its mechanism through the inflammatory cascade mediated by nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3)/cysteine aspartate-specific protease (Caspase-1)/gasdermin D (GSDMD) signaling pathway. MethodsSPF-grade 4-month-old APP/PS1 mice were randomly divided into the model group, MCC950 group, and Hei Xiaoyaosan high-, medium-, and low-dose groups. C57BL/6J mice were used as the blank group. After 7 days of adaptive feeding, mice in each group were intervened. The Hei Xiaoyaosan high-, medium-, and low-dose groups were given corresponding doses by gavage (25.79, 12.90, 6.45 g·kg-1·d-1), the MCC950 group was intraperitoneally injected with 10 mg·kg-1·2 d-1, and the blank group received the same volume of physiological saline by gavage. After 90 days of intervention, the learning and memory abilities were assessed using the Y maze and Morris water maze tests. The structural changes of hippocampal neurons were observed by hematoxylin-eosin (HE) staining. The expression of amyloid precursor protein (APP) in the hippocampal CA3 region was detected by immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of interleukin (IL)-10, IL-18, and IL-1β in the hippocampus. Western blot was applied to detect the protein expression of NLRP3, Caspase-1, GSDMD, and GSDMD-N in the hippocampus. Immunofluorescence was used to detect the co-localization of GSDMD-N and ionized calcium-binding adapter molecule-1 (Iba-1) in the hippocampus. Results① In the Y maze test, compared with the blank group, the spontaneous alternation rate of the model group was significantly reduced (P<0.01). Compared with the model group, the spontaneous alternation rate in the Hei Xiaoyaosan high- and low-dose groups was significantly increased (P<0.01). ② In the Morris water maze test, during the 1-4 days of the location navigation test, the escape latency time of mice decreased with the extension of training time. On day 4, compared with the blank group, the model group showed a significantly increased escape latency (P<0.05). Compared with the model group, the MCC950 group and the Hei Xiaoyaosan low-dose group showed significantly reduced escape latency (P<0.05). In the spatial exploration experiment, compared with the blank group, the number of platform crossings in the model group was significantly reduced (P<0.01). Compared with the model group, the Hei Xiaoyaosan low-dose group showed significantly increased platform crossings (P<0.05). ③ HE staining showed that, compared with the blank group, the hippocampal CA3 cells of the model group were damaged, arranged loosely and irregularly, swollen, with unclear boundaries, and the nuclei were pyknotic and deeply stained. MCC950 and all doses of Hei Xiaoyaosan improved the hippocampal CA3 cell damage in APP/PS1 mice to varying degrees. ④ Immunohistochemical results indicated that, compared with the blank group, the expression of APP in the hippocampal CA3 region was significantly increased in the model group (P<0.01). MCC950 and all doses of Hei Xiaoyaosan could reduce the expression of APP in the hippocampal CA3 region of APP/PS1 mice (P<0.01). ⑤ ELISA results showed that the levels of IL-18 and IL-1β in the hippocampus of mice in the model group were significantly increased, and IL-10 levels were significantly reduced (P<0.01). Compared with the model group, the IL-18 levels in the MCC950 group and the Hei Xiaoyaosan medium- and low-dose groups were significantly reduced (P<0.01). IL-1β levels in the hippocampus of the MCC950 group and Hei Xiaoyaosan high-, medium-, and low-dose groups were significantly decreased (P<0.01). The IL-10 levels in the hippocampus of the MCC950 group and the Hei Xiaoyaosan medium- and low-dose groups were increased (P<0.05, P<0.01). ⑥ Western blot results showed that compared with the blank group, the protein levels of NLRP3, Caspase-1, GSDMD, and GSDMD-N in the hippocampus of the model group were significantly elevated (P<0.01). Compared with the model group, the content of NLRP3 and Caspase-1 in the hippocampus of the treated groups was decreased (P<0.05, P<0.01). The content of GSDMD in the hippocampus of the Hei Xiaoyaosan high-, medium-, and low-dose groups was reduced (P<0.05, P<0.01), and the content of GSDMD-N in the hippocampus of the Hei Xiaoyaosan medium- and low-dose groups was decreased (P<0.05, P<0.01). ⑦ Immunofluorescence results showed that, compared with the blank group, the co-expression of GSDMD-N and Iba-1 in the hippocampus of the model group was significantly increased (P<0.01). Compared with the model group, the co-expression of GSDMD-N and Iba-1 in the treated groups was significantly reduced (P<0.01). ConclusionHei Xiaoyaosan may regulate the NLRP3/Caspase-1/GSDMD signaling pathway to affect the release of inflammatory factors, alleviate neuroinflammation,improve hippocampal histopathological changes,and improve learning and memory deficits,thus providing potential therapeutic benefits for Alzheimer's disease.
4.Relationship between influencing factors of operation time and postoperative complications in hand-assisted laparoscopic living donor nephrectomy
Hongchen SONG ; Jingcheng LYU ; Yuwen GUO ; Jian ZHANG ; Zhipeng WANG ; Yichen ZHU
Organ Transplantation 2024;15(2):244-250
Objective To identify the influencing factors of operation time of hand-assisted laparoscopic living donor nephrectomy, and to analyze the relationship between influencing factors and the severity of postoperative complications. Methods Clinical data of 91 donors who underwent hand-assisted laparoscopic nephrectomy were retrospectively analyzed. The correlation between preoperative baseline data of donors and operation time was analyzed. The relationship between operation time and postoperative complications was assessed and the threshold of operation time was determined. Results Multiple donor renal arteries, thick perirenal and posterior renal fat, metabolic syndrome, high Mayo adhesive probability (MAP) score and Clavien-Dindo score prolonged the operation time. By analyzing the receiver operating characteristic (ROC) curve, we found that when the operation time was ≥138 min, the incidence of postoperative complications of donors was significantly increased (P<0.05). Conclusions For donors with multiple renal arteries, thick perirenal and posterior renal fat, metabolic syndrome and high MAP score and Clavien-Dindo score, experienced surgeons should be selected to make adequate preoperative preparation and pay close attention after surgery, so as to timely detect postoperative complications and reduce the severity of complications, enhance clinical prognosis of the donors.
5.Effect of PACS-2 on the development of Alzheimer's disease
Yanyun WANG ; Qunying YE ; Jun QIAN ; Zhipeng LIU ; Hongbo LUO ; Yun LI
China Modern Doctor 2024;62(5):11-15
Objective To investigate the involvement of phosphofurin acidic cluster sorting protein-2(PACS-2)in mitochondrial function and apoptosis in N2a/APP695swe cells and further explore the role and significance of PACS-2 in the development of Alzheimer's disease(AD).Methods The CCK8 method was used to analyze the cell survival rate of N2a/APP695swe cells treated with different concentrations of tetrahydroxy stilbene glycoside(TSG)for 48h and to select the appropriate concentration of TSG for subsequent experiments.N2a/WT cells and N2a/APP695swe cells were routinely cultured in vitro,and the experimental cells were divided into 3 groups:blank control group(WT group):N2a/WT cells;model group(APP group):N2a/APP695swe cells;treatment group(TSG group):N2a/APP695swe cells with appropriate concentrations of TSG intervention.TUNEL method to observe apoptosis by fluorescence microscopy;JC-1 method for flow detection of cellular mitochondrial membrane potential;WB to detect protein expression of PACS-2;RT-qPCR to detect PACS-2 mRNA expression.Results CCK8 method was used to analyze the cell survival rate of different concentrations of TSG acting on cells after 48h:the protective effect of 100 μmol/L TSG was the most significant and the difference was statistically significant(P<0.01).The TUNEL method of fluorescence microscopy observed the apoptosis:compared with the WT group,the apoptosis rate of APP group was increased,compared with the APP group,the apoptosis rate of TSG group was decreased,and the differences were statistically significant(P<0.05).The JC-1 method was used to detect the mitochondrial membrane potential of cells:compared with the WT group,the membrane potential of APP group was decreased,compared with the APP group,the membrane potential of TSG group was increased,and the differences were statistically significant(P<0.05);Western blot(WB)detection of PACS-2 protein expression:compared with the WT group,PACS-2 expression was significantly higher in the APP group,and compared with the APP group,PACS-2 expression was significantly lower in the TSG group,with statistically significant differences(P<0.05);The RT-qPCR detected the mRNA expression of PACS-2:the expression of PACS-2 was elevated in the APP group compared with the WT group and decreased in the TSG group compared with the APP group,with statistically significant differences(P<0.05).Conclusion PACS-2 has an important role in the development of AD,and its upregulation may promote the development of AD.The cerebroprotective drug TSG may exert cytoprotective effects by downregulating PACS-2 to inhibit apoptosis and improve mitochondrial function in AD model cells.
6.Hei Xiaoyaosan Regulates Fas/FasL/Caspase-8/Caspase-3 Signaling Pathway to Inhibit Neuronal Apoptosis in AD Rats
Huping WANG ; Yiqin CHEN ; Jiao YANG ; Yunyun HU ; Yujie LYU ; Zhipeng MENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):18-26
ObjectiveTo explore the effect and mechanism of Hei Xiaoyaosan in regulating the tumor necrosis factor receptor superfamily member 6 (Fas)/Fas ligand (FasL)/cysteine protease-8 (Caspase-8)/cysteine protease-3 (Caspase-3) signaling pathway to intervene in neuronal apoptosis and prevent Alzheimer's disease (AD). MethodNinety SPF-grade SD male rats of 4 months old were selected and randomly grouped as follows: 10 rats in the blank group, 10 rats in the sham group (bilateral hippocampus injected with 1 μL normal saline), and 70 rats in the modeling group [bilater hippocampus injected with 1 μL amyloid-beta protein 1-42 (Aβ1-42) solution for the modeling of AD]. Fifty successfully modeled rats were selected and randomly assigned into model, donepezil hydrochloride (0.45 mg·kg-1), and high-, medium-, and low-dose (15.30, 7.65, 3.82 g·kg-1) Hei Xiaoyaosan groups. Rats were administrated with corresponding agents by gavage once a day for 42 days. Terminal-deoxynucleoitidyl transferase-mediated nick end labeling (TUNEL) was employed to observe the apoptosis of neurons in the cortex and hippocampus, and immunohistochemistry (IHC) was used to detect the expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was employed to determine the mRNA levels of Fas, FasL, and Fas-associated protein with death domain (Fadd). Western blot was used to determine the protein levels of Fas, FasL, Fadd, Caspase-3, cleved Caspase-3, Caspase-8, and cleved Caspase-8. ResultCompared with the blank group and sham group, the model group showed increased apoptosis rate in the cortex and hippocampus (P<0.01), elevated Bax level (P<0.01), lowered Bcl-2 level (P<0.01), up-regulated mRNA levels of Fas, FasL, and Fadd in the hippocampus (P<0.01), and up-regulated protein levels of Fas, FasL, Fadd, cleaved Caspase-3, and cleaved Caspase-8 (P<0.01). Compared with the model group, donepezil hydrochloride and Hei Xiaoyaosan at high and medium doses decreased the apoptosis rate in the cortex and hippocampus (P<0.05, P<0.01), lowered the Bax level (P<0.01), elevated the Bcl-2 level (P<0.01), and down-regulated the mRNA levels of Fas, FasL, and Fadd and the protein levels of Fas, FasL, Fadd, cleaved Caspase-3, and cleaved Caspase-8 (P<0.05, P<0.01) in the hippocampus. Low-dose Hei Xiaoyaosan decreased the apoptosis rate in the cortex and hippocampus (P<0.05, P<0.01), lowered the Bcl-2 level (P<0.01), and down-regulated the mRNA levels of FasL and Fadd (P<0.05) and the protein levels of Fas, FasL, Fadd, cleaved Caspase-3, and cleaved Caspase-8 (P<0.05) in the hippocampus. ConclusionHei Xiaoyaosan can protect neurons in the cortex and hippocampus of AD rats by inhibiting the apoptosis mediated by the Fas/FasL/Caspase-8/Caspase-3 signaling pathway.
7.Hei Xiaoyaosan Affects Synaptic Plasticity of Hippocampal Neurons in APP/PS1 Double Transgenic Mice of AD via cAMP/PKA/NMDAR Signaling Pathway
Yunyun HU ; Yujie LYU ; Zhipeng MENG ; Jiao YANG ; Yiqin CHEN ; Huping WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):27-34
ObjectiveTo explore the effect and mechanism of Hei Xiaoyaosan in modulating the synaptic plasticity in APP/PS1 mice by regulating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/N-methyl-D-aspartate receptor (NMDAR) signaling pathway. MethodTwelve 4-month-old male C57BL/6J mice were selected as the blank control group, and 60 4-month-old male APP/PS1 double transgenic mice were randomized into model, KW-6002 (adenosine receptor antagonist, 3 mg·kg-1), and high-, medium-, and low-dose (22.10, 11.05, 5.53 g·kg-1, respectively) Hei Xiaoyaosan groups, with 12 mice in each group. Mice were administrated with corresponding drugs for 90 days. Transmission electron microscopy was employed to observe the synaptic ultrastructure of hippocampal neurons, and Golgi staining was used to observe the dendritic spine density of neurons in hippocampal CA1 region. Western blot was employed to measure the protein levels of cAMP, PKA, N-methyl-D-aspartate receptors 1, 2A, and 2B (NR1, NR2A, and NR2B, respectively), postsynaptic density protein 95 (PSD95), and synapsin 1 (SYN1). Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was performed to determine the mRNA levels of cAMP, PKA, and NR1. Enzyme-linked immunosorbent assay was employed to determine the content of interleukin-12 (IL-12) and interleukin-4 (IL-4) in the hippocampus. ResultCompared with the blank group, the model group showed blurred boundaries between presynaptic membrane and postsynaptic membrane in hippocampal CA1 region, reduced and scattered synaptic vesicles, and decreased density of postsynaptic membrane, and irregular, disarranged, and loosened dendritic spines of neurons in hippocampal CA1 region (P<0.01). In addition, the model group presented down-regulated protein levels of cAMP, PKA, NR1, NR2A, NR2B, PSD95, and SYN1 and mRNA levels of cAMP, PKA, and NR1, elevated IL-12 level, and lowered IL-4 level in the hippocampus (P<0.01). Compared with the model group, the drug intervention groups showed clear and intact boundaries between presynaptic membrane and postsynaptic membrane in hippocampal CA1 region, increased synaptic vesicles with dense arrangement, increased density of postsynaptic membrane, and improved morphology, arrangement, and density of neuronal dendritic spines (P<0.05, P<0.01). In addition, the drug interventions up-regulated the protein levels of cAMP, PKA, NR1, NR2A, NR2B, PSD95, and SYN1 (P<0.05,P<0.01) and mRNA levels of cAMP, PKA, and NR1 (P<0.01), lowered the IL-12 level (P<0.01), and elevated the IL-4 level (P<0.01) in the hippocampus. ConclusionHei Xiaoyaosan can improve the structure and morphology of hippocampal neurons in APP/PS1 mice by activating the cAMP/PKA/NMDAR signaling pathway and repairing synaptic plasticity.
8.Hei Xiaoyaosan Regulates RAS/RAF/MEK/ERK Signaling Pathway to Ameliorate Oxidative Stress in Rat Model of AD
Huping WANG ; Yujie LYU ; Yunyun HU ; Zhipeng MENG ; Jiao YANG ; Yiqin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):35-42
ObjectiveTo investigate the role and mechanism of Hei Xiaoyaosan in intervening in oxidative stress in the rat model of Alzheimer's disease (AD) via modulating the rat sarcoma (RAS)/rapidly accelerating fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway. MethodOne hundred 4-month-old SPF-grade Wistar male rats were randomly grouped as follows: 10 in the blank group, 10 in the sham group (bilateral hippocampus injected with 1 μL normal saline), and 80 in the modeling group [bilateral hippocampus injected with 1 μL amyloid beta protein 1-42 (Aβ1-42) solution for the modeling of AD]. Fifty rats qualified for modeling were selected and randomized into the model, donepezil hydrochloride (0.5 mg·kg-1), and high-, medium-, and low-dose (15.30, 7.65, 3.82 g·kg-1, respectively) Hei Xiaoyaosan groups. The rats were administrated with corresponding drugs by gavage once a day for 42 consecutive days. At the end of gavage, Morris water maze test was performed to examine the learning and memory abilities of the rats, and Nissl staining was used to observe the pathological changes of neurons in CA3 region of the hippocampus. The immunofluorescence assay was used to observe Aβ deposition and tau phosphorylation. Western blot was employed to determine the protein levels of RAS, RAF, phosphorylated (p)-RAF, MEK, p-MEK, ERK, and p-ERK in the hippocampal tissue. Biochemical methods were used to determine the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) in the hippocampal tissue. ResultCompared with the sham group, the model group showed prolonged escape latency (P<0.01), shortened swimming distance in the target quadrant (P<0.01), reduced and uneven stained Nissl bodies, enhanced fluorescence intensity of Aβ and p-tau (P<0.01), up-regulated protein levels of RAS, p-RAF, p-MEK, and p-ERK in the hippocampal tissue (P<0.01), increased ROS and MDA content (P<0.01), and decreased SOD activity (P<0.01) on day 5. Compared with the model group, donepezil hydrochloride and high-, medium-, and low-dose Hei Xiaoyaosan shortened the escape latency (P<0.01), increased the swimming distance in the target quadrant (P<0.01), improved the arrangement, morphology, and structures of neurons and the number and distribution of Nissl bodies, decreased the fluorescence intensity of Aβ and p-tau (P<0.01), up-regulated the protein levels of RAS, p-RAF, p-MEK, and p-ERK (P<0.05, P<0.01), decreased the ROS and MDA content (P<0.01), and increased the SOD activity (P<0.01) on day 5. ConclusionHei Xiaoyaosan may ameliorate oxidative stress, reduce Aβ and p-tau levels, and inhibit hippocampal neuronal damage by regulating the RAS/RAF/MEK/ERK signaling pathway, thus improving learning and memory abilities.
9.Hei Xiaoyaosan in Treating Alzheimer's Disease: A Review
Yujie LYU ; Yunyun HU ; Zhipeng MENG ; Yiqin CHEN ; Jiao YANG ; Huping WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):43-50
Alzheimer's disease (AD) is a neurodegenerative disease that predominantly affects the elderly. It belongs to the category of dementia in traditional Chinese medicine (TCM), with the onset and progression closely associated with the functions of the kidney, liver, and spleen. The classic TCM formula Hei Xiaoyaosan, which regulates the three Yin of liver, spleen, and kidney, shows broad prospects in treating neurodegenerative diseases. This article reviews the experimental studies reported in the past decade to summarize the mechanisms of Hei Xiaoyaosan and its active components in intervening in AD. Hei Xiaoyaosan can treat AD via multiple targets, levels, and aspects comprehensively. The clinical studies have demonstrated that Hei Xiaoyaosan alone or in combination with other therapies has a definite therapeutic effect on AD. Specifically, it can ameliorate the cognitive impairment, mitigate oxidative stress, and inhibit the overexpression of soluble apoptotic factors in AD patients. This review aims to provide a theoretical basis for the treatment of AD with Hei Xiaoyaosan and explore new research directions. Moreover, it gives new insights into the clinical application of Hei Xiaoyaosan and the development of products with both medicinal and edible values.
10.Analysis of risk factors and their warning effectiveness for meniscus tear secondary to delayed anterior cruciate ligament reconstruction
Kai DING ; Yujing YAO ; Zhipeng LI ; Lei WANG ; Changyuan GU ; Hao SHU ; Luning SUN
Chinese Journal of Trauma 2024;40(3):229-235
Objective:To investigate the risk factors and their warning effectiveness for meniscus tear secondary to delayed anterior cruciate ligament (ACL) reconstruction.Methods:A retrospective cohort study was conducted to analyze the clinical data of 114 patients (114 knees) with ACL injury, who were admitted to Affiliated Hospital of Nanjing University of Chinese Medicine from December 2018 to December 2023, including 78 males and 36 females, aged 11-50 years [29(21, 35)years]. The patients were divided into tear group ( n=46) and non-tear group ( n=68) according to whether combined with meniscus tear or not during the surgery. Gender, age, duration of disease, smoking history, Body Mass Index (BMI), cause of injury, mechanism of injury, side of the injury, Beighton score, difference of KT-2000 examination, Tegner activity scale of the knee joint, anterior tibial translation sign, medial posterior tibial slope angle, lateral posterior tibial slope angle, and pivot shift grading of the patients in the two groups were recorded. Correlations between the above-mentioned indicators and occurrence of meniscus tear secondary to delayed ACL reconstruction were assessed. In the meantime, the independent risk factors were determined by univariate and multivariate binary logistic regression analysis. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to evaluate the warning effectiveness of each risk factor for meniscal tear secondary to delayed ACL reconstruction. Results:Univariate analysis showed correlation of duration of disease, BMI, Tegner activity scale of the knee joint, medial posterior tibial slope angle, lateral posterior tibial slope angle and high-grade pivot shift with occurrence of meniscus tear secondary to delayed ACL reconstruction ( P<0.01). The results of multivariate binary logistic regression analysis showed that the duration of disease ≥14.5 weeks ( OR=1.20, 95% CI 1.05, 1.38, P<0.01), BMI≥26.9 kg/m 2 ( OR=1.36, 95% CI 1.03, 1.81, P<0.05), Tegner activity scale of the knee joint ≥4 points ( OR=2.29, 95% CI 1.18, 4.46, P<0.05), medial posterior tibial slope angle ≥11.2° ( OR=2.27, 95% CI 1.06, 4.89, P<0.05) and high-grade pivot shift ( OR=0.03, 95% CI 0.01, 0.03, P<0.05) were significantly correlated with occurrence of meniscus tear secondary to delayed ACL reconstruction. Results of ROC curve analysis showed that the medial posterior tibial slope angle (AUC=0.86, 95% CI 0.80, 0.93) and duration of disease (AUC=0.85, 95% CI 0.77, 0.92) had good warning value, BMI (AUC=0.78, 95% CI 0.69, 0.87) and Tegner activity scale of the knee joint (AUC=0.73, 95% CI 0.64, 0.83) had ordinary warning value, and the warning value of high-grade pivot shift (AUC=0.60, 95% CI 0.49, 0.71) was the lowest. The combination of the risk factors revealed superior warning effectiveness for meniscus tear second to delayed ACL reconstruction (AUC=0.97, 95% CI 0.96, 1.00). Conclusions:The duration of disease ≥14.5 weeks, BMI ≥26.9 kg/m 2, Tegner score ≥4 points, medial posterior tibial slope angle ≥11.2°and high-grade pivot shift are independent risk factors for meniscus tear secondary to delayed ACL reconstruction. The medial posterior tibial slope angle and duration of disease have good warning value, BMI and Tegner scores have ordinary warning value and high-grade pivot shift has the lowest warning value. The combination of the above risk factors has better warning effectiveness for meniscus tear secondary to delayed ACL reconstruction.

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