1.Correlation Between Traditional Chinese Medicine Syndrome Type of Unstable Angina Pectoris and Iron Metabolism Indices
Jiye CHEN ; Min WU ; Changxin SUN ; Xiaonan ZHANG ; Zeping WANG ; Longtao LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):126-136
ObjectiveTo investigate the correlation between iron metabolism parameters and various syndrome types of unstable angina pectoris (UAP). MethodsA cross-sectional study was conducted from October 2021 to October 2023, encompassing 213 patients diagnosed with UAP at Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences. Additionally, 30 healthy individuals were selected as control cases. Single-factor analysis was used to investigate the differences in clinical data among different Traditional Chinese Medicine (TCM) syndrome types of UAP and their correlation with iron metabolism indices. The study conducted a comparative analysis of the aforementioned clinical data among patients with and without heat-toxic and blood-stasis syndrome. Logistic regression was used to analyze the correlation between TCM syndrome types and related factors. The receiver operator characteristic (ROC) curve was employed to assess the predictive value of iron metabolism indices, along with their sensitivity and specificity. ResultsCompared to those in the control group, serum iron (SI) and serum ferritin (SF) levels were significantly increased in the UAP group (P<0.01), while transferrin (TRF) and total iron binding capacity (TIBC) levels were decreased (P<0.01). However, there was no significant difference in unsaturated iron binding capacity (UIBC). Multivariate binary Logistic regression analysis identified apolipoprotein A1 (ApoA1), homocysteine (HCY), high-sensitivity C-reactive protein (hs-CRP), and SF as independent influencing factors for the UAP patients (P<0.05, P<0.01). Additionally, statistically significant differences were observed in SI, SF, TRF, and TIBC among 213 patients with different TCM types (P<0.01). Patients with heat-toxic and blood-stasis syndrome had higher SI and SF values than those without the syndrome (P<0.01), while their TIBC and TRF values were lower (P<0.01). Multivariate binary logistic regression analysis showed that SI and LDL-C levels were closely associated with the differentiation of heat-toxic and blood-stasis syndrome. ConclusionUAP patients often experience iron metabolism disorders, and the heat-toxic and blood-stasis syndrome are significantly correlated with iron metabolism parameters. The SI and LDL-C levels have high specificity and sensitivity in diagnosing heat-toxic and blood-stasis syndrome.
2.Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy.
Yue ZHANG ; Jingwen GAO ; Na LI ; Peng XU ; Shimeng QU ; Jinqian CHENG ; Mingrui WANG ; Xueru LI ; Yaheng SONG ; Fan XIAO ; Xinyu YANG ; Jihong LIU ; Hao HONG ; Ronghao MU ; Xiaotian LI ; Youmei WANG ; Hui XU ; Yuan XIE ; Tianming GAO ; Guangji WANG ; Jiye AA
Acta Pharmaceutica Sinica B 2024;14(2):667-681
Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.
3.Pathogenesis and Traditional Chinese Medicine Prevention and Treatment Strategy of Refractory Angina Based on Theory of Stasis and Toxin
Dexiu LI ; Xiaoya LI ; Jiye CHEN ; Changxin SUN ; Lanqing HU ; Jingyi ZHANG ; Longtao LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):234-240
Refractory angina is characterized by recurrent and persistent angina with a duration of not less than three months, which is related to reversible ischemia and hypoxia caused by coronary stenosis and obstruction. It mainly involves obstructive coronary artery disease and non-obstructive coronary artery disease with coronary artery spasm and coronary microvascular dysfunction. “Stasis and toxin” play an important role in the pathogenesis of cardiovascular diseases. The pathogenesis of stasis and toxin is stubborn filthy turbidity featured by slow accumulation and sudden onset,and rapid changes,which coincides with the characteristics of refractory angina which is complex and changeable,prolonged and difficult to cure. The pathogenesis of refractory angina involves a combination of underlying deficiency and excessive manifestation, with "stasis and toxin" playing a crucial role as an important pathological factor in the whole process of refractory angina. Traditional Chinese medicine (TCM) employs a holistic approach known as "activating blood circulation and removing toxins", which is supplemented by various methods to tonify Qi and warm Yang, nourish the kidneys and invigorate the spleen, clear heat and transform phlegm. This approach applies anti-inflammatory measures, regulates lipid metabolism, inhibits oxidative stress and thrombus formation, protects endothelial function in blood vessels, as well as establishes collateral circulation for the prevention and treatment of refractory angina. Therefore,based on the theory of "stasis and toxin",combined with TCM theory and modern medical research,this paper discusses the pathogenesis of refractory angina and the prevention and treatment strategy of TCM,and elucidates the reasons for the difficulty in curing refractory angina and the relationship between refractory angina and common angina pectoris,coronary microvascular dysfunction,coronary artery spasm and obstructive coronary artery disease,hoping to provide certain theoretical basis and clinical ideas for the prevention and treatment of refractory angina with TCM.
4.Pathogenesis of Atherosclerotic Vulnerable Plaque Based on Relationship Between Theory of ''Stasis and Toxin'' and Efferocytosis
Jiye CHEN ; Xiaoya LI ; Zongliang YU ; Xin LI ; Lanqing HU ; Changxin SUN ; Longtao LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(1):188-193
Atherosclerosis is a vascular disease characterized by arterial occlusion formed by the pathological accumulation of pathological vascular cells and apoptotic cell debris. Atherosclerotic vulnerable plaque is an important pathological basis for inducing severe thrombotic cardiovascular events, and the study of its etiology and pathogenesis has always been a hot issue in the field of cardiovascular research. Efferocytosis is a new type of programmed death cell removal, which refers to the process of macrophages phagocytosing and degrading apoptotic cells to prevent secondary necrosis. It is a key homeostatic mechanism in the body's physiological process. In the pathological state, the dysfunction of efferocytosis causes the pathological accumulation of apoptotic cells and necrotic debris, leading to the occurrence of secondary cell necrosis and the continuous release of intracellular toxic content and inducing inflammatory regression disorders and cholesterol metabolism disorders, which are closely related to the occurrence and development of atherosclerotic vulnerable plaques. The theory of ''blood stasis and toxin'' is an important theory of traditional Chinese medicine (TCM) to explain the occurrence and development of atherosclerosis. Atherosclerosis starts from the pathological state of blood stagnation. Prolonged blood stagnation leads to blood stasis and toxic substances. Blood stasis and toxic pathogens interact with each other in blood vessels and eventually form plaques in blood vessels. The theory of ''blood stasis and toxin causing a catastrophe'' is an important understanding of the occurrence and development of acute cardiovascular events. From the perspective of TCM theory, the pathophysiological mechanism of efferocytosis is similar to the etiology and pathogenesis of the ''blood stasis and toxin'' in TCM. Therefore, this paper took the theory of ''blood stasis and toxin'' as the breakthrough point to explore the mechanism of efferocytosis in atherosclerotic vulnerable plaques, and proposed a detoxification and blood circulation method to regulate cell burial to prevent and treat atherosclerotic vulnerable plaques. The research strategy aims to provide new ideas and theoretical basis for the prevention and treatment of atherosclerosis by detoxification and blood circulation.
5.Effects of the combination of acupuncture and medication on orthostatic hypotension after incomplete cervical spinal cord injury
Jiye LIU ; Hong MENG ; Jiahe WANG
Journal of Acupuncture and Tuina Science 2023;21(1):59-65
Objective: To observe the effect of the combination of acupuncture and medication on orthostatic hypotension after incomplete cervical spinal cord injury. Methods: Ninety-two patients with orthostatic hypotension after incomplete cervical spinal cord injury were divided into two groups according to the random number table method, with 46 cases in each group. The control group was treated with oral midodrine hydrochloride on the basis of conventional treatment, and the observation group was treated with acupuncture in addition to the intervention used in the control group. Both groups were treated for 4 weeks. The changes in supine and orthostatic blood pressures, motor and sensory scores, quadriplegic function index score, clinical efficacy, and safety evaluation were observed. Results: During the treatment, 2 cases dropped out in the observation group, and 3 cases dropped out in the control group. After 4 weeks of treatment, the clinical efficacy of the observation group was better than that of the control group (P<0.05). After treatment, the supine systolic blood pressure and diastolic blood pressure in the two groups had no significant changes (P>0.05), while the orthostatic systolic blood pressure and diastolic blood pressure, the motor and sensory scores, and the quadriplegic function index score were significantly higher than those before treatment (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05). Adverse reactions were mild in both groups. Conclusion: The combination of acupuncture and medication can significantly improve the orthostatic blood pressure, motor and sensory function and daily living ability of patients with orthostatic hypotension after incomplete cervical spinal cord injury, and it is safe and reliable.
6.Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in non-small cell lung cancer.
Chenxue MAO ; Juan CHEN ; Ting ZOU ; Yuankang ZHOU ; Junyan LIU ; Xi LI ; Xiangping LI ; Min LI ; Pinhua PAN ; Wei ZHUO ; Yang GAO ; Shuo HU ; Desheng XIAO ; Lin WU ; Zhan WANG ; Heng XU ; Wen YANG ; Yingjie XU ; Haihua XIAO ; Kazuhiko HANADA ; Wei ZHANG ; Honghao ZHOU ; Jiye YIN ; Zhaoqian LIU
Acta Pharmaceutica Sinica B 2022;12(3):1514-1522
To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.
7.Tumor-targeting intravenous lipid emulsion of paclitaxel:Characteristics,stability,toxicity,and toxicokinetics
Jun YE ; Lin LI ; Jiye YIN ; Hongliang WANG ; Renjie LI ; Yanfang YANG ; Yongbiao GUAN ; Xuejun XIA ; Yuling LIU
Journal of Pharmaceutical Analysis 2022;12(6):901-912
Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and tox-icokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.
8.Epidemiological characteristics of an epidemic of 2019-nCoV Omicron variant infection in Beijing
Yamin SUN ; Feng LIU ; Wei CAI ; Lina JIN ; Li GUO ; Run CAI ; Rujing SHI ; Fangyao LIU ; Chu JIANG ; Jiye FU ; Yang PAN ; Xiangfeng DOU ; Shuangsheng WU
Chinese Journal of Epidemiology 2022;43(12):1881-1886
Objective:To analyze the epidemiological characteristics and transmission chain of an epidemic of COVID-19 in Haidian district, Beijing.Methods:Descriptive epidemiological method was used to analyze the epidemiological characteristics of the epidemic, and field investigation and big data technology were used to analyze the transmission chain of the epidemic.Results:From April 27 to May 13, 2022, an epidemic of COVID-19 occurred in Haidian district. The strains isolated from the cases were identified by whole genome sequencing as Omicron variant (BA.2.2 evolutionary branch). A total of 38 infection cases were detected, including 34 confirmed cases and 4 asymptomatic cases. Most cases were mild ones (88.2%), no severe, critical or death cases occurred. The early clinical symptoms were mainly sore throat (50.0%) and cough (29.4%). The epidemic lasted for 17 days, resulting in 7 generations of the cases and involving 3 community transmissions, 2 working place transmissions and 8 family transmissions; the main infection routes were co-residence (47.6%) and co-space exposure (31.6%). The intergenerational interval M( Q1, Q3)was 3 (1, 6) days. The overall secondary attack rate was 1.5% (37/2 482), and the family secondary attack rate was 36.7% (18/49). Conclusions:The cases in this COVID-19 epidemic caused by Omicron variant had mild clinical symptoms, but the case clustering in families and communities was obvious, the transmission was rapid, and the risk for co-space exposure was high. It is necessary to use information technology to identify close contacts in the local population for the rapid and effective blocking of the epidemic spread.
9.Study on the Activity of Lycorine to the in vivo Apoptosis of Tumor Cells in H 22-bearing Mice and Its Mechanism
Guosong XIN ; Jing ZHANG ; Jiye LI ; Yubin JI ; Bin LIU ; Jun LI ; Yingxiang CHEN ; Miao YU
China Pharmacy 2021;32(5):571-577
OBJECTIVE:To investigate the activity of lycorine to the in vivo apoptosis of tumor cells in H 22-bearing mice and its mechanism. METHODS :Kunming mice were inoculated subcutaneously with ascites of H 22 hepatoma mice in the armpit of forelimb to establish solid tumor model. After modeling ,mice were randomly divided into negative control group ,positive control group(hydroxycamptothecin 6 mg/kg),lycorine low-dose ,medium-dose and high-dose groups (10,20,40 mg/kg),with 10 mice in each group. Negative control group was given constant volume of normal saline intragastrically ,and administration groups were given relevant medicine intragastrically ,once a day ,for consecutive 7 days. After last medication ,the weight of tumor was detected and anti-tumor rate was calculated. Ascites tumor model of mice was established by intraperitoneal injection of H 22 hepatoma mice ascites ,and then were grouped with same method and given relevant medicine as above. After last medication , survival time of mice was recorded and the life prolongation rate was calculated. The early apoptotic rate of tumor cells in mice was detected by flow cytometry. On the basis of normal control group (normal mice without tumor ),the mitochondrial membrane permeability of tumor cells in each group was investigated by Calcein AM staining. The changes of mitochondrial potential were investigated by Rhodamine 123 staining. Colorimetry and Western blot assay were adopted to detect the Caspase-3 activity and expression of apoptosis-related protein (Bcl-2,Bax,Cyt-C and Caspase- 9). RESULTS :Compared with negative control UN- group,the tumor weight of positive control group and lycorine PYSCT-2017208) groups were decreased significantly ,while the survival time was significantly prolonged ,and the early apoptotic rate of tumor cells was significantly increased (P<0.05 or P<0.01);the anti-tumor rates were 39.41% , 23.36% , 36.50% , 56.93%,and life prolonga tion rates were 49.23%,29.09%, E-mail:ym913@yahoo.com.cn 50.19%,69.08%. Compared with normal control group ,the mitochondrial membrane permeability ,Caspase-3 protein activity and protein expression of Cyt-C and Caspase- 9 were significantly increased,while the mitochondrial membrane potential and Bcl- 2/Bax ratio were decreased significantly (P<0.05 or P<0.01). Compared with negative control group ,mitochondrial membrane permeability and Bcl- 2/Bax ratio were decreased significantly in administration groups ,while mitochondrial permeability ,Caspase-3 protein activity and protein expression of Cyt-C and Caspase- 9 were significantly increased (P<0.05 or P<0.01). CONCLUSIONS :Lycorine can induce the apoptosis of tumor cells in H22-bearing mice ,the effects of which may be associated with opening mitochondrial membrane permeability transition pore to increase mitochondrial permeability , decreasing mitochondrial membrane potential and up-regulating the expression of apoptosis-related proteins.
10.Use of autologous left renal vein as a graft vessel for reconstruction after portal vein-superior mesenteric vein resection in pancreaticoduodenectomy
Weizheng REN ; Xianlei XIN ; Zhiwei LIU ; Jiye CHEN ; Shouwang CAI
Chinese Journal of Hepatobiliary Surgery 2021;27(5):350-353
Objective:To study the use of left renal vein as a graft vessel in reconstruction after portal vein/superior mesenteric vein (PV-SMV) resection in pancreaticoduodenectomy.Methods:A retrospective study was conducted on 5 of these patients who underwent surgery from July 2008 to December 2017 at Chinese PLA General Hospital. The operative, complication and follow-up data were analysed.Results:There were 4 males and 1 female, with an average age of 57 (33-72) years. The mean operative time was 6.8 (5.4-9.1) h and the mean tumor size was 3.8 (2.8-4.8) cm. The average length of the PV-SMV defect left after resection was 3.8 (3.2-4.6) cm. The average length of the left renal vein used was 3.4 (3.0-4.1) cm. The operations were carried out in 3 patients with pancreatic cancer and in 2 patients with colon cancer pancreatic metastasis. The average postoperative hospital stay was 12 (10-25) days. Perioperative complications included 1 patient each with ascites, diarrhea and delayed gastric emptying. The creatinine levels ranged from 70-98 μmol/L preoperatively, with a transient creatinine rise to 80-156 μmol/L after operation and became 62-107 μmol/L upon discharge from hospital. The follow-up time was 4.3-17.8 months. Two patients died of recurrence/metastasis at 14.2 and 17.8 months after surgery.Conclusions:The left renal vein has the appropriate diameter and rich collateral branches. It has a sufficient length and it is conveniently located in the surgical field. This study showed that there was a minimal effect on renal function after its excision, and it can be used as a graft vessel for reconstruction in pancreaticoduodenectomy after PV-SMV resection.

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