1.Tangbikang Granules Improve Diabetic Peripheral Neuropathy by Inhibiting Ferroptosis via AMPK/Nrf2 Signaling Pathway
Zehong YANG ; Tonghua LIU ; Xiaohong MU ; Yaqi ZHANG ; Huizhong BAI ; Lingling QIN ; Xiaolei JIA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):52-60
ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 (AMPK/Nrf2) signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty (ZDF) rats. After successful modeling, the rats were divided into a normal group, a model group, high-, medium-, and low-dose Tangbikang granules groups, and a metformin hydrochloride group. The high-, medium-, and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5, 1.25, 0.625 g·kg-1, respectively. The metformin hydrochloride group received 0.135 g·kg-1 by gavage, while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration, and at 4, 8, 12 weeks. Following the 12-week intervention, the thermal pain threshold and the sciatic nerve conduction velocity (SNCV) were measured. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), and adenosine triphosphate (ATP) in the sciatic nerve were measured using enzyme-linked immunosorbent assay (ELISA). Morphological changes in the sciatic nerve were observed using hematoxylin and eosin (HE) staining, and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 (GPx4) were detected using immunofluorescence (IF) assay. The protein expression levels of p-AMPK, Nrf2, GPx4, and acyl-CoA synthetase long-chain family member 4 (ACSL4) were detected using Western blot. ResultsCompared with the normal group, the model group had significantly higher blood glucose levels after administration and at weeks 4, 8 and 12 (P<0.01). The thermal pain threshold was significantly prolonged (P<0.01), and the SNCV was significantly slowed down (P<0.01). The SOD and ATP levels significantly decreased (P<0.01), while the MDA levels significantly increased (P<0.01). Pathologically, the sciatic nerve fibers in the model group showed a dispersed structure, disordered and sparse arrangement, axonal atrophy, irregular myelin sheath halo, increased and swollen Schwann cell nuclei, obvious endoneurial fibrosis, and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 (P<0.01). Western blot analysis showed significantly decreased protein expression levels of p-AMPK, Nrf2, and GPx4 (P<0.01), and significantly increased expression of ACSL4 (P<0.01) in the model group. Compared with the model group, fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 (P<0.05). The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups (P<0.01). The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups (P<0.01). The SOD levels were significantly elevated in the high-dose Tangbikang granules group (P<0.01). The MDA levels significantly decreased in all Tangbikang granules groups (P<0.01). Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups (P<0.01). The protein expression levels of p-AMPK, Nrf2, and GPx4 were significantly increased (P<0.01), while ACSL4 protein expression significantly decreased (P<0.01). ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.
2.Characteristics of Cerebral Blood Flow in Sleep Deprivation Based on Arterial Spin Labeling
Xiaolei WANG ; Leilei LI ; Bo HAN ; Zeheng SUN ; Keke XIN ; Gang LIN ; Rong ZHANG ; Yuanqiang ZHU ; Yani BAI
Chinese Journal of Medical Imaging 2024;32(7):653-658
Purpose To investigate the difference of cerebral blood flow between sleep deprivation and rest wakefulness.Materials and Methods Fifty subjects were recruited from universities in Xi'an from October 2020 to December 2021.The psychomotor vigilance test(PVT)task was used to measure sustained attention.Arterial spin labeling technique was used to analyze and compare the relative cerebral blood flow(rCBF)between sleep deprivation and rest wakefulness.The correlation between altered rCBF of specific brain regions and PVT task performance after sleep deprivation was analyzed.Results Compared with rest wakefulness,rCBF in bilateral dorsolateral prefrontal lobe,bilateral parietal lobule,left orbital middle frontal gyrus,bilateral middle temporal gyrus,right posterior central gyrus,and bilateral angular gyrus was significantly decreased after sleep deprivation.The rCBF of bilateral thalamus,left precuneus,right medial prefrontal lobe,left posterior cingulate gyrus,and left inferior temporal gyrus was significantly increased(FDR corrected,P<0.05,cluster size≥20 voxels).The changes of rCBF in left dorsolateral prefrontal lobe and right parietal lobule were significantly negatively correlated with the PVT task performance(r=-0.56,P<0.001;r=-0.64,P<0.001),and the change of rCBF of left precuneus was significantly positively correlated with the PVT task performance(r=0.72,P<0.001).Conclusion The abnormal changes of CBF in default mode network,frontoparietal network-related brain regions and thalamic may be the important neural mechanism of sustained attentional decline after sleep deprivation.
3.Effect of Mitochondrial Autophagy in Clinical Diseases and Intervention by Chinese Medicine: A Review
Hongyue MA ; Lin SONG ; Zhongyuan PIAO ; Xiaolei BAI ; Wei CHU ; Yuanwu ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(19):250-257
Mitochondrial autophagy is a process to clear dysfunctional mitochondria in the cytoplasm to maintain the integrity of mitochondrial function and cell homeostasis. Mitochondrial autophagy is a complex physiological process, which can maintain the balance of mitochondrial quality and quantity, cell survival under starvation and harsh conditions, and the stability of the intracellular environment. Its molecular mechanism involves a variety of proteins. Many factors can induce mitochondrial autophagy, such as starvation, oxidative stress, hypoxia, depolarization, and other stresses. The accumulation of unfolded proteins can also induce mitochondrial autophagy. In recent years, as a research hotspot, the abnormality of mitochondrial morphology and function is closely related to the occurrence of a variety of diseases. The research on mitochondrial autophagy and the pathogenesis of clinical diseases has attracted more attention, such as tumors, cardiovascular diseases, liver diseases, nervous system diseases, and glucose metabolism disorders. It has been found that regulating mitochondrial autophagy may inspire the treatment of some diseases. Meanwhile, clinical researchers have paid more attention to traditional Chinese medicine (TCM). As revealed by in-depth research, Chinese medicine has a certain value in regulating mitochondrial autophagy. The research on the pathogenesis of mitochondrial autophagy in related diseases and the intervention of Chinese medicine has found that there are many reports on the regulation of mitochondrial autophagy by Chinese medicine in tumors, cardiovascular diseases, and nervous system diseases. However, the mechanism of mitochondrial autophagy, the balance of mitochondrial autophagy, and the difference in the activation or inhibition of mitochondrial autophagy by Chinese medicine remain unclear. The regulation of mitochondrial autophagy has become a new research target strategy of Chinese medicine in the prevention and treatment of diseases. This paper reviewed the available literature in recent years to provide reference materials for the regulation of mitochondrial autophagy by Chinese medicine and ideas for the follow-up research of Chinese medicine in mitochondrial autophagy.
4.Pharmacological mechanisms of Yishen Xingyang capsule in the treatment of oligoasthenospermia in rats
Chang ZHENGHUI ; Bai XUE ; Tang YIBO ; Liu GUIMIN ; Liu DAN ; Fan XIAOLEI ; Tan TIANYANG ; Liu ZHEJUN ; Li JINSHENG ; Liu ZHENQUAN
Journal of Traditional Chinese Medical Sciences 2021;8(1):52-58
Objective: To investigate the therapeutic effects and pharmacological mechanisms of Yishen Xingyang capsule (YXC) in oligoasthenospermia (OA) rats.Methods: Forty-eight male Sprague-Dawley rats were randomly divided into eight groups of six rats each:normal control (NC);model control (MC);three different positive drug (PD);and low-, medium-, and high-dose YXC groups. A rat model of OA was established by administering glucosides of Triptery-gium wilfordii Hook. F (GTW). After YXC administration, penile erectile function was observed. The epididymis, blood, and testes of the rats were harvested for analysis of sperm quality, sex hormone levels, mitochondrial membrane potential, and the transforming growth factor (TGF)-β1/Smad signaling pathway. Results: Compared with that in the MC group, penile erectile function in the YXC groups and three PD groups increased (all P<.01). Moreover, sperm quality in the YXC groups and three PD groups improved (all P < .001). The levels of testosterone, follicle stimulating hormone, and luteinizing hormone in the three PD and YXC groups increased (all P<.05). The mitochondrial membrane potential in the three PD and YXC groups significantly improved (all P<.001). Furthermore, the YXC and three PD groups showed decreased TGF-β1 expression (all P< .05) compared with the MC group. The high-dose YXC group and three PD groups improved Smad2 and Smad4 expression (all P<.05). Conclusion: YXC improved penile erectile function and sperm quality in OA rats, and the underlying mechanism included increase in sex hormones, inhibition of sperm apoptosis, and regulation of the TGF-β1/Smad signaling pathway. Meanwhile, this study provides a new effective drug option for the treat-ment of OA, which is beneficial to male reproductive health and social harmony.
5. Characteristics and outcomes of primary angiosarcoma
Zhiyang ZHANG ; Yuejuan CHENG ; Xiaolei GONG ; Yuping GE ; Chunmei BAI ; Xiaojun WANG ; Qi MIAO ; Fuquan ZHANG
Chinese Journal of Oncology 2019;41(9):693-697
Objective:
The study was designed to analyze the clinicopanthologic characteristics, treatments and outcomes of a series of patients with primary angiosarcoma.
Methods:
The clinical, surgical and pathological data and treatment of 68 patients with pathologically confirmed angiosarcoma admitted to Peking Union Medical College Hospital from January 1990 to June 2017 was retrospectively analyzed. Kaplan-Meier method and Log rank test were used for univariate survival analysis and Cox regression model was used for multivariate survival analysis.
Results:
A total of 68 patients were enrolled, 38 were male, 30 were female. The median age at diagnosis was 50.5 years. The time from symptom onset to diagnosis was (7.5±7.5) months. The primary sites included face and scalp, breast, chest wall, lung, heart, liver, spleen, extremities, bones and so on. At diagnosis, the mean size of tumors were (7.4±7.3) cm, 28 patients (41.2%) had localized disease (stage Ⅰ+ Ⅱ) and 40 patients had metastatic disease (stage Ⅲ+ Ⅳ). There were 37 patients treated with surgery alone, three receiving radiotherapy alone, five receiving chemotherapy alone and sixteen receiving comprehensive treatment with 5 underwent surgery plus radiotherapy, three treated by surgery plus chemotherapy, four had surgery plus interventional therapy, two had chemoradiotherapy, one had radiotherapy and interventional therapy and 1 had surgery plus chemoradiotherapy and targeted therapy. Five patients received only palliative treatment, and 2 patients lost follow-up after diagnosed. Fifty patients were followed up with a median overall survival time of 8.5 months. The median survival time of patients with metastatic angiosarcoma was 6.6 months, significantly shorter than that of patients with localized disease (15.0 months,
6.Effect of schisandrin on learning and memory abilities and their mechanism in APP/PS1 dual transgenic dementia mice
Zhongyuan PIAO ; Lin SONG ; Lifen YAO ; Ye PENG ; Xiaolei BAI ; Shuilan YU
Chinese Journal of Neuromedicine 2019;18(4):325-330
Objective To investigate the effect of schisandrin (SCH) treatment on learning and memory abilities and their mechanism in APP/PS1 dual transgenic dementia mice,and explore the effect of Chinese medicine on Alzheimer's disease (AD).Methods Thirty-five APP/PS1 dementia mouse models were randomly assigned into APP/PS1 model group (n=17) and APP/PS1+SCH group (n=18);another 10 male C57BL/6J mice were chosen as blank control group.The mice in the APP/PS1+SCH group were given intragastric administration of SCH at 2.6 mg/(kg· d) for 30 d;the mice in the APP/PS1 model group and blank control group were treated with distilled water for 30 d.The learning and memory abilities of these APP/PS1 mice (n=7) were detected by Morris water maze.Mice from the three groups were sacrificed;Nissl staining was used to observe Nissl bodies of neurons in brain tissues;real-time fluorescence quantitative PCR (qPCR) was used to detect the mRNA content of terminal glycosylationend products receptor (RAGE) in brain tissues;Western blotting was used to detect the expressions of RAGE and phosphorylated P38 mitogen-activated protein kinase (p-p38) in brain tissues.Results (1) The results of water maze space exploration experiment showed that the times of crossing the platform area in the three groups were statistically significant (P<0.05);as compared with the APP/PS1 modelgroup,the times of crossing the platform area in the APP/PS1+SCH group were significantly increased (P<0.05).(2) Nissl staining results showed that the contents of Nissl bodies in the hippocampal CA1 area and cortical neurons of the APP/PS 1 model group were significantly reduced,with light staining and cell body atrophy;the lesions in mice of the APP/PS1+SCH group were less severe than those of APP/PS1 model group,some neurons were atrophic,and the content of the neuronal nileite bodies in the hippocampal CA1 region was relatively abundant.(3) The qPCR results showed that there were statistically significant differences in RAGE mRNA expression levels in the cortex and hippocampus of the three groups (P<0.05);as compared with the APP/PS1 model group,the APP/PS1+SCH group had significantly reduced RAGE mRNA expression in the hippocampal area (P<0.05).(4) Western blotting results showed that RAGE and p-p38 protein expression levels in two parts of mice of APP/PS1+SCH group were significantly reduced as compared with those in the APP/PS1 model group (P<0.05).Conclusion SCH may improve the functional status of hippocampal and cortical neurons and improve the spatial exploratory memory ability of APP/PS1 mice by down regulating the RAGE and P38 expressions.
7.Characteristics and outcomes of primary angiosarcoma
Zhiyang ZHANG ; Yuejuan CHENG ; Xiaolei GONG ; Yuping GE ; Chunmei BAI ; Xiaojun WANG ; Qi MIAO ; Fuquan ZHANG
Chinese Journal of Oncology 2019;41(9):693-697
Objective The study was designed to analyze the clinicopanthologic characteristics, treatments and outcomes of a series of patients with primary angiosarcoma. Methods The clinical, surgical and pathological data and treatment of 68 patients with pathologically confirmed angiosarcoma admitted to Peking Union Medical College Hospital from January 1990 to June 2017 was retrospectively analyzed. Kaplan?Meier method and Log rank test were used for univariate survival analysis and Cox regression model was used for multivariate survival analysis. Results A total of 68 patients were enrolled, 38 were male, 30 were female. The median age at diagnosis was 50.5 years. The time from symptom onset to diagnosis was (7.5±7.5) months. The primary sites included face and scalp, breast, chest wall, lung, heart, liver, spleen, extremities, bones and so on. At diagnosis, the mean size of tumors were ( 7.4 ± 7.3) cm, 28 patients (41.2%) had localized disease (stage Ⅰ+Ⅱ) and 40 patients had metastatic disease ( stage Ⅲ+ Ⅳ). There were 37 patients treated with surgery alone, three receiving radiotherapy alone, five receiving chemotherapy alone and sixteen receiving comprehensive treatment with 5 underwent surgery plus radiotherapy, three treated by surgery plus chemotherapy, four had surgery plus interventional therapy, two had chemoradiotherapy, one had radiotherapy and interventional therapy and 1 had surgery plus chemoradiotherapy and targeted therapy. Five patients received only palliative treatment, and 2 patients lost follow?up after diagnosed. Fifty patients were followed up with a median overall survival time of 8.5 months. The median survival time of patients with metastatic angiosarcoma was 6.6 months, significantly shorter than that of patients with localized disease (15.0 months, P=0.020). The median survival time of patients with cardiac angiosarcoma was 3.0 months, significantly shorter than that of patients with angiosarcoma at other sites (11.5 months, P=0.010). The median survival time of patients receiving comprehensive treatment was 31.0 months, significantly longer than that of patients without comprehensive treatment ( 5.6 months, P=0.007). Multivariate analysis showed that staging, heart occurrence and comprehensive treatment were independent factors for the prognosis of primary angiosarcoma (all P<0.05). Conclusions Angiosarcoma is a rare malignancy, and patients with metastatic disease or cardiac occurence have poor prognosis. Comprehensive treatment can improve the prognosis of patients with angiosarcoma.
8.Characteristics and outcomes of primary angiosarcoma
Zhiyang ZHANG ; Yuejuan CHENG ; Xiaolei GONG ; Yuping GE ; Chunmei BAI ; Xiaojun WANG ; Qi MIAO ; Fuquan ZHANG
Chinese Journal of Oncology 2019;41(9):693-697
Objective The study was designed to analyze the clinicopanthologic characteristics, treatments and outcomes of a series of patients with primary angiosarcoma. Methods The clinical, surgical and pathological data and treatment of 68 patients with pathologically confirmed angiosarcoma admitted to Peking Union Medical College Hospital from January 1990 to June 2017 was retrospectively analyzed. Kaplan?Meier method and Log rank test were used for univariate survival analysis and Cox regression model was used for multivariate survival analysis. Results A total of 68 patients were enrolled, 38 were male, 30 were female. The median age at diagnosis was 50.5 years. The time from symptom onset to diagnosis was (7.5±7.5) months. The primary sites included face and scalp, breast, chest wall, lung, heart, liver, spleen, extremities, bones and so on. At diagnosis, the mean size of tumors were ( 7.4 ± 7.3) cm, 28 patients (41.2%) had localized disease (stage Ⅰ+Ⅱ) and 40 patients had metastatic disease ( stage Ⅲ+ Ⅳ). There were 37 patients treated with surgery alone, three receiving radiotherapy alone, five receiving chemotherapy alone and sixteen receiving comprehensive treatment with 5 underwent surgery plus radiotherapy, three treated by surgery plus chemotherapy, four had surgery plus interventional therapy, two had chemoradiotherapy, one had radiotherapy and interventional therapy and 1 had surgery plus chemoradiotherapy and targeted therapy. Five patients received only palliative treatment, and 2 patients lost follow?up after diagnosed. Fifty patients were followed up with a median overall survival time of 8.5 months. The median survival time of patients with metastatic angiosarcoma was 6.6 months, significantly shorter than that of patients with localized disease (15.0 months, P=0.020). The median survival time of patients with cardiac angiosarcoma was 3.0 months, significantly shorter than that of patients with angiosarcoma at other sites (11.5 months, P=0.010). The median survival time of patients receiving comprehensive treatment was 31.0 months, significantly longer than that of patients without comprehensive treatment ( 5.6 months, P=0.007). Multivariate analysis showed that staging, heart occurrence and comprehensive treatment were independent factors for the prognosis of primary angiosarcoma (all P<0.05). Conclusions Angiosarcoma is a rare malignancy, and patients with metastatic disease or cardiac occurence have poor prognosis. Comprehensive treatment can improve the prognosis of patients with angiosarcoma.
9.Dosimetric comparison of combined intracavitary/interstitial brachytherapy planning using three different kinds of optimization methods in locally advanced cervical cancer
Kaiqiang CHEN ; Hongqiang YOU ; Qixin LI ; Xiaolei NI ; Wenjuan CHEN ; Xiuchun ZHANG ; Penggang BAI ; Ye CAO ; Jihong CHEN
Chinese Journal of Radiological Medicine and Protection 2018;38(3):215-219
Objective To compare and analyze the dosimetric discrepancy of combind intracavitary/interstitial brachytherapy using three different kinds of optimization method in locally advanced cervical cancer.Methods Totally 20 cases of locally advanced cervical cancer were selected and divided into three groups according to different optimization method which include manual optimization group (MO) based on graphical optimization,inverse planning simulated annealing (IPSA 1)based on simulated annealing optimization algorithm,IPSA 2 based on IPSA 1 with limitation on maximum dose of target.The dose volume histogram parameters of the targets (V200,V150,V100,D100,D90,HI) and the OARs(D0.1 cm3,D1 cm3 and D2 cm3) were analyzed.Results For CTV,compared with MO,there was no significantly statistical difference in D100between IPSA 1 and IPSA 2(P > 0.05).However,V200,V150,V100 and HI for ISPA1 were better than for ISPA2 (t =-3.422-9.910,P < 0.05).In addition,V100 and D100 in ISPA1 were better than in ISPA2 (t =7.238,5.032,P <0.05).For OARs,D0.1 cm3,D1 cm3 and D2 cm3 in rectum,bladder,sigmoid colon of both ISPA 1 and ISPA 2 were dramatically lower than those of MO (t =2.235 5.819,P < 0.05),without significantly statistical difference found between ISPA1 and ISPA2.Conclusions For combined intracavitary/interstitial brachytherapy in locally advanced cervical cancer,all treatment plans based on three different kinds of optimization methods can meet the clinical need.Moreover,inverse optimization can ensure dose coverage over target and reduce maximum dose of rectum,bladder and sigmoid colon.
10.Evaluation of ventricular systolic function in patients with rheumatoid arthritis using two-dimensional speckle tracking echocardiography
Xiashan ZHANG ; Guojun ZHAO ; Zhian LI ; Shasha DUAN ; Yilu SHI ; Xiaolei WANG ; Si HA ; Yong WANG ; Lijie BAI ; Hongbin LI
Chinese Journal of Ultrasonography 2016;(1):19-23
Objective To evaluate the left ventricular and right ventricular systolic function by two‐dimensional speckle tracking echocardiography ( 2D‐STE) in patients with rheumatoid arthritis ( RA ) . Methods Fifty five patients with RA and 50 healthy subjects were received echocardiography . 2D‐STE were applied for all the subjects to obtain left ventricular global longitudinal strain ( LVGLS) and right ventricular global longitudinal strain ( RVGLS) .Tricuspid annular plane systolic excursion ( TAPSE) and the change ratio of right ventricular area ( RVACR) were measured by echocardiography . The anti‐cyclic citrullinated peptide antibodies ( anti‐CCP‐II) ,rheumatoid factor ( RF) ,C‐reactive protein ( CRP) and erythrocyte sedimentation rate ( ESR) were detected in both group . The LVGLS and RVGLS in RA group were used to conduce correlation analysis with the level of anti‐CCP‐II ,RF ,CRP , ESR and the duration of disease . Results There was a significant decrease in RVGLS and LVGLS in RA group compared with control group( P <0 .05) . However there was no statistical differenc in TAPSE and RVACR between RA and control group( P > 0 .05) . The anti‐CCP‐II ,RF ,CRP and ESR in RA group increased significantly compared with control group ( P < 0 .001 ) . The result of correlation analysis showed there was no correlation between RVGLS ,LVGLS and anti‐CCP‐II ,RF ,CRP ,ESR in RA group . However ,RVGLS and LVGLS were negatively correlated with the duration of disease . Conclusions LVGLS and RVGLS in RA patients were lower than those in healthy people ,strain decreases with the extension of disease duration ,2D‐STE may be an efficacious assessment to assess left ventricular and right ventricular systolic function in patients w ith RA .

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