1.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.
2.Characteristics and therapeutic strategies of Pott's puffy tumor.
Huiyi DENG ; Zhipeng CHEN ; Xifu WU ; Qintai YANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2024;38(1):83-90
Objective:To explore the characteristics and therapeutic strategies of Pott's puffy tumor(PPT). Methods:The clinical data of two patients with PPT were retrospectively analyzed and combined with the literature, focusing on the comprehensive analysis of perioperative diagnosis and treatment strategies. Both patients underwent muti-disciplinary treatment, including timely administration of sufficient antibiotics capable of penetrating the blood-brain barrier. Early removal of PPT lesions was performed using a combined internal and external approach under nasal endoscopic guidance. Results:After standardized perioperative management, the symptoms of the two patients were completely relieved, with no recurrence after one=year follow=up. Postoperative complications such as frontal pain, numbness, local depression, or scar hyperplasiawere not present. Conclusion:PPT, being relatively rare and severe, requires careful attention. Key strategies for standardized perioperative management include multi-disciplinary consultation, timely and adequate antibiotic administration, and surgical intervention using a combined intranasal and extranasal endoscopic approach for lesion removal.
Humans
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Pott Puffy Tumor/complications*
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Retrospective Studies
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Tomography, X-Ray Computed
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Endoscopy/adverse effects*
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Postoperative Complications
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Anti-Bacterial Agents/therapeutic use*
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Frontal Sinusitis/complications*
3.Autologous ilium graft combination with titanium plate for sternal reconstruction: A case report
Bo YANG ; Bin LI ; Peng JIANG ; Shaobo ZHANG ; Meiyu REN ; Zhipeng SU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(02):329-332
The sternum is the pivotal component of the thoracic cavity. It is connected with the clavicle and ribs on the upper part and both sides respectively, and plays an important role in protecting the stability of the chest wall. Sternal resection usually results in a large segmental chest wall defect that causes the chest wall to float and requires sternal reconstruction. This paper reports a 62 years male patient with thymic squamous cell carcinoma with sternal metastasis, who underwent thymotomy, sternal tumor resection and autologous lilum graft combined with sternal reconstruction by titanium plate after relevant examination was completed and surgical contraindications were eliminated. The patient was followed up for 6 months, the respiratory and motor functions were normal and the thoracic appearance was good.
4.Intervention of muscle strength training combined with neuromuscular electrical stimulation on lower limb function and biomechanical changes in patients with patellofemoral pain
Jing WU ; Yingce YAO ; Xiaowei YANG ; Boshi XUE ; Jianbin ZHAO ; Chen YANG ; Tianfeng LUAN ; Zhipeng ZHOU
Chinese Journal of Tissue Engineering Research 2024;28(9):1365-1371
BACKGROUND:Lower limb peri-knee muscle strength training and neuromuscular electrical stimulation are generally safe and effective rehabilitation methods for patellofemoral joint pain,but the mechanism of their intervention is still unclear. OBJECTIVE:To determine the effect of muscle strength training combined with neuromuscular electrical stimulation on pain,lower extremity function and biomechanical characteristics in patients with patellofemoral pain. METHODS:Thirty-seven patients with patellofemoral pain were randomly divided into muscle strength training combined with electrical stimulation group(trial group,n=19)and muscle strength training group(control group,n=18).Both groups underwent intervention training for 6 weeks,three times a week.The visual analog scale and anterior knee pain scale were used to evaluate the pain level and functional level of the knee.Kinematic and kinetics data during running were collected by using an infrared motion capture system and a three-dimensional force platform simultaneously.A two-way analysis of variance with repeated measures(group*time)was applied to analyze the data. RESULTS AND CONCLUSION:(1)After the intervention,the visual analog scale scores of the trial group and the control group were significantly decreased(P<0.001),and the anterior knee pain scale scores were significantly increased(Ptrial group<0.001,Pcontrol group=0.001)in the trial group and control group.The anterior knee pain scale scores of the trial group were significantly higher compared to the control group after the intervention(P=0.001).(2)The peak knee flexion angle(P=0.011),peak knee extension moment(P<0.001),the peak knee internal rotation moment(P=0.008),the peak patellofemoral stress(P<0.001)and the peak patellofemoral contact force(P<0.001)were significantly decreased in the trial and control groups during running after the intervention compared with those before the intervention.(3)In conclusion,both muscle strength training and muscle strength training combined with electrical stimulation training are helpful to improve the subjective pain and lower limb function of patellofemoral pain patients,enhance the movement pattern during running and reduce the stress of the patellofemoral joint.Compared with muscle strength training alone,muscle strength training combined with electrical stimulation can improve lower limb function more significantly.
5.Core stability training reduces risk of anterior cruciate ligament injury in landing movements
Boshi XUE ; Changrui LIN ; Liangliang ZHENG ; Chen YANG ; Zhipeng ZHOU
Chinese Journal of Tissue Engineering Research 2024;28(16):2467-2472
BACKGROUND:Studies have shown that poor dynamic postural control may lead to abnormal movement patterns during exercise,which may increase the risk of lower limb joint and anterior cruciate ligament injury.The stability of the body core is the basis of good dynamic postural control. OBJECTIVE:To investigate the effects of core stability training on dynamic postural control and risk of injury in landing movements,and to compare the differences in training effects between genders. METHODS:Thirty-five college students(male=19,female=16)were recruited for 6 weeks of core stability training.The results of the Y balance test,trunk extensor endurance test,trunk flexor endurance test,lateral bridge endurance test,and landing error scoring system were analyzed before and after training. RESULTS AND CONCLUSION:The 6-week core stability training could improve trunk extensor endurance(P<0.001),flexor endurance(P<0.001),and lateral abdominal muscle endurance(P<0.001).Core stability training could improve forward distance(P=0.026),backward inward distance(P<0.001),backward outward distance(P=0.005)and comprehensive score(P<0.001)of Y balance test for male and female college students.Landing error scoring system scores of both male and female college students significantly decreased after 6 weeks of core stability training(P<0.001)while increasing knee(P<0.001)and hip flexion angles(P<0.001),decreasing knee valgus angle(P<0.001)at the moment of touchdown,and could increase the maximum knee flexion angle(P<0.001)and decrease the maximum knee valgus angle(P<0.001).It is concluded that core stability training improves dynamic postural control and improves landing movement patterns,suggesting that it may help reduce the risk of anterior cruciate ligament injury.There are no sex differences in core stability training in terms of increased trunk flexor endurance,lateral bridge muscle group endurance,improved dynamic postural control,and reduced risk of anterior cruciate ligament injury.
6.Analysis of clinical characteristics and risk factors for delayed diagnosis of tuberculosis in children
Yilin WANG ; Qi SUN ; Zhuo QIAN ; Jingyue LI ; Shiyue MEI ; Hengmiao GAO ; Junwen YANG ; Zhipeng JIN
Chinese Journal of Infection and Chemotherapy 2024;24(5):507-514
Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1%.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children>5 years old(P<0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough>2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P<0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P<0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95%CI:1.677-29.754)],mixed infection(OR=3.812,95%CI:1.185-12.260),severe disease(OR=3.697,95%CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95%CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.
7.Real-world study on piperacillin-tazobactam in the treatment of complicated urinary tract infection in adults
Yi YANG ; Ming LI ; Na LI ; Zhipeng WEN ; Bing ZHAO
China Pharmacy 2024;35(14):1753-1758
OBJECTIVE To investigate the efficacy and safety of piperacillin-tazobactam in the treatment of complicated urinary tract infection (cUTI) in adults. METHODS Retrospective analysis was performed on the data of 352 cUTI adult patients in our hospital from January 1, 2021 to December 31, 2023. All patients received piperacillin-tazobactam. The detection of pathogens in patients, the clinical efficacy and microbial clearance rate after treatment, the occurrence of adverse drug reactions and treatment cost were observed in all patients. RESULTS Of the 352 patients, pathogen culture results of 54 patients were detected, mainly Escherichia coli producing extended-spectrum beta-lactamases. The clinical effective rate was 94.3%, the microbial clearance rate was 81.5%, and the incidence of adverse reactions was 1.4%. The percentage of male effective patients in urinary surgery department was significantly higher than invalid patients, while the proportion of transplant treatment and the proportion of patients with concomitant kidney transplantation were significantly lower than invalid patients (P<0.05). There was no significant difference in clinical effective rate between the two groups after those patients were divided into target treatment group and empirical treatment group according to the sensitivity of pathogen to piperacillin-tazobactam (P=0.902 5). CONCLUSIONS Piperacillin-tazobactam is effective and safe in the treatment of cUTI.
8.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.
9.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.
10.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.

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