1.Components and Brain-protective Effect of Chuanxiong Rhizoma-Paeoniae Radix Rubra in Improving Ischemic Stroke Based on UPLC-Q-TOF-MS
Qizhong JIN ; Jie ZHANG ; Lijuan XIU ; Fan XU ; Lei WANG ; Ning WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):20-29
ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra(CRPRR) that cross the blood-brain barrier in rats with ischemic stroke, their brain-protective effects, and their impact on inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-18 (IL-18) based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion (MCAO/R) method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups: sham operation group, model group, low-, medium-, and high-dose CRPRR groups (1.35, 2.7, 5.4 g·kg-1, respectively), and an edaravone group (5 mg·kg-1), with 12 rats in each group. The sham and model groups received normal saline, while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method, open field test, Morris water maze, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (HE) staining, and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR, namely paeoniflorin, senkyunolide F, senkyunolide G, paeonimetabolin Ⅰ, paeoniflorin derivative, senkyunolide H, benzoylpaeoniflorin, senkyunolide A, and ligustilide. Animal experiment results showed that compared with the sham operation group, the model group exhibited disordered neuronal arrangement, severe vacuolation, nuclear pyknosis, and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased (P<0.01), while platform crossings were significantly decreased (P<0.01), and clear infarct areas were present (P<0.01). Serum levels and protein expression of TNF-α, IL-1β, and IL-18 were significantly elevated (P<0.01). Compared with the model group, all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level, with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores (P<0.01), while the low-, medium-, and high-dose groups significantly reduced the number of central crossings (P<0.01) and infarct volume (P<0.01), and decreased TNF-α, IL-1β, and IL-18 levels (P<0.05, P<0.01) compared with the model group. Furthermore, the medium- and high-dose groups significantly reduced TNF-α protein expression (P<0.05,P<0.01), and the high-dose group significantly reduced IL-1β and IL-18 protein expression (P<0.01). ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α, IL-1β, and IL-18, as well as the presence of nine active chemical constituents in cerebrospinal fluid, namely paeoniflorin, senkyunolide F, senkyunolide G, paeonimetabolin Ⅰ, paeoniflorin derivative, senkyunolide H, benzoylpaeoniflorin, senkyunolide A, and ligustilide, which are closely related to their brain-protective effects.
2.Components and Brain-protective Effect of Chuanxiong Rhizoma-Paeoniae Radix Rubra in Improving Ischemic Stroke Based on UPLC-Q-TOF-MS
Qizhong JIN ; Jie ZHANG ; Lijuan XIU ; Fan XU ; Lei WANG ; Ning WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):20-29
ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra(CRPRR) that cross the blood-brain barrier in rats with ischemic stroke, their brain-protective effects, and their impact on inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-18 (IL-18) based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion (MCAO/R) method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups: sham operation group, model group, low-, medium-, and high-dose CRPRR groups (1.35, 2.7, 5.4 g·kg-1, respectively), and an edaravone group (5 mg·kg-1), with 12 rats in each group. The sham and model groups received normal saline, while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method, open field test, Morris water maze, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (HE) staining, and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR, namely paeoniflorin, senkyunolide F, senkyunolide G, paeonimetabolin Ⅰ, paeoniflorin derivative, senkyunolide H, benzoylpaeoniflorin, senkyunolide A, and ligustilide. Animal experiment results showed that compared with the sham operation group, the model group exhibited disordered neuronal arrangement, severe vacuolation, nuclear pyknosis, and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased (P<0.01), while platform crossings were significantly decreased (P<0.01), and clear infarct areas were present (P<0.01). Serum levels and protein expression of TNF-α, IL-1β, and IL-18 were significantly elevated (P<0.01). Compared with the model group, all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level, with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores (P<0.01), while the low-, medium-, and high-dose groups significantly reduced the number of central crossings (P<0.01) and infarct volume (P<0.01), and decreased TNF-α, IL-1β, and IL-18 levels (P<0.05, P<0.01) compared with the model group. Furthermore, the medium- and high-dose groups significantly reduced TNF-α protein expression (P<0.05,P<0.01), and the high-dose group significantly reduced IL-1β and IL-18 protein expression (P<0.01). ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α, IL-1β, and IL-18, as well as the presence of nine active chemical constituents in cerebrospinal fluid, namely paeoniflorin, senkyunolide F, senkyunolide G, paeonimetabolin Ⅰ, paeoniflorin derivative, senkyunolide H, benzoylpaeoniflorin, senkyunolide A, and ligustilide, which are closely related to their brain-protective effects.
3.Effects of computerized cognitive remediation therapy combined with social skill training on the negative symptoms of schizophrenia
Xianli FAN ; Zhenning WU ; Kewen WU ; Yutao ZHANG ; Lijuan BAI ; Yan WANG ; Dongmei YAN ; Xiu WU ; Huifang BAI ; Zhirui LI
Chinese Journal of Primary Medicine and Pharmacy 2023;30(2):235-239
Objective:To investigate the effects of computerized cognitive remediation therapy (CCRT) combined with social skill training on the improvement of negative symptoms of schizophrenia.Methods:A total of 102 schizophrenic patients who received treatment in Shanxi Province Social Welfare Kangning Psychiatry Hospital from March 2019 to June 2021 were included in this study. They were randomly divided into an intervention group and a control group ( n = 51/group). During the intervention process, because of the reasons such as midway discharge, only 93 patients were included in the final analysis, consisting of 47 patients in the intervention group and 46 patients in the control group. All patients received social skills training. Patients in the intervention group received 8-week CCRT. The Positive and Negative Syndrome Scale and Social Skills Checklist were used to evaluate curative effect in the two groups. Results:After treatment, total score of the Positive and Negative Syndrome Scale and the score of negative symptoms in the intervention group were (46.36 ± 9.33) points and (11.15 ± 3.53) points, respectively, which were significantly lower than (51.06 ± 10.26) points and (16.42 ± 4.75) points in the control group ( t = 2.07, 5.41, both P < 0.05). The total score of Social Skills Checklist, conflict resolution ability score and relationship building ability score in the intervention group were (16.05 ± 6.85) points, (3.36 ± 1.65) points and (3.14 ± 1.83) points, respectively, which were significantly lower than (21.08 ± 8.24) points, (5.92 ± 2.35) points and (6.75 ± 2.51) points, respectively ( t = 2.87, 5.34, 7.00, all P < 0.01). Conclusion:CCRT combined with social skill training can effectively improve the negative symptoms of patients with schizophrenia.
4.Rapid analysis of chemical components of Xiaotan Tongfu formula based on UHPLC-Q-TOF/MS
Ye QIN ; Wei HUANG ; Yufang GU ; Ci’an ZHANG ; Lijuan XIU ; Jigui TANG ; Feng ZHANG ; Xuan LIU
Journal of Pharmaceutical Practice 2022;40(4):339-346
Objective To rapidly explore the chemical components of Xiaotan Tongfu formula, and to provide scientific basis for the basic research and clinical treatment of the formula. Methods Analysis was performed on an Agilent 1290 ultra-performance liquid chromatography system coupled with an Agilent 6530 accurate quality Q-TOF/MS system, by using a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm), with a gradient elution applying 0.1% aqueous formic acid solution and acetonitrile as a mobile phase. The flow rate was 0.3 ml/min. The column temperature was 30°C. The injection volume was 1 μl, and the detection wavelength was 254 nm. Mass spectrometry (MS) data were collected in both positive and negative ESI ion modes. Components in the formula were identified by using the in-house compound database, and comparing the retention time (tR), MS1 and MS2 data with the standard compounds, and the online compound MS database. Results A total of 55 compounds were identified from Coptis coptidis, Pseudomonas solani, Rhubarb, Araceae artemisiae and Pinellia chinensis. Conclusion The established UHPLC-Q-TOF/MS method could systematically and accurately identify the chemical components from Xiaotan Tongfu formula, and provided a reference for the quality marker selection and the research on the active ingredient.
5. HER2 status in gastric adenocarcinoma of Chinese: a multicenter study of 40 842 patients
Dan HUANG ; Zengshan LI ; Xiangshan FAN ; Hongmei WU ; Jianping LIU ; Wenyong SUN ; Shanshan LI ; Yinyong HOU ; Xiu NIE ; Jun LI ; Rong QIN ; Lingchuan GUO ; Jinghong XU ; Huizhong ZHANG ; Miaomiao SUN ; Qiaonan GUO ; Yinghong YANG ; Yanhui LIU ; Yu QIN ; Lijuan ZHANG ; Jinghe LI ; Zhihong ZHANG ; Peng GAO ; Yujun LI ; Weiqi SHENG
Chinese Journal of Pathology 2018;47(11):822-826
Objective:
To investigation HER2 status in gastric adenocarcinoma of Chinese and contributing factors to the HER2 expression.
Methods:
HER2 status of 40 842 gastric adenocarcinomas and clinical data were retrospectively collected from 23 hospitals dated from 2013 to 2016. The association between HER2 positivity and clinicopathologic features was analyzed.
Results:
Of the 40 842 patients the median age was 62 years, the male female ratio was 2.6∶1.0. The rate of HER2 positivity was 8.8% (3 577/40 842). HER2 expression was related to the tissue type, tumor location, Lauren classification and tumor differentiation (
6.Discussion on Academic Ideas of WEI Pin-kang in Treating Gastric Carcinoma Based on the Phlegm Theory
Ying ZHAO ; Lijuan XIU ; Xiaowei WANG ; Xuan LIU ; Ye LU ; Xiaoqiang YUE
Chinese Journal of Information on Traditional Chinese Medicine 2017;24(5):106-109
Professor WEI Pin-kang has engaged in prevention and treatment of gastrointestinal tumors through intrgrated traditional Chinese and Western medicine for more than forty years. According to the characteristics of the gastric cancer development and using the philosophy thinking of TCM comparative states, combined with the ancient theory of phlegm syndrome in TCM, Professor WEI Pin-kang put foward his original theory that is the concept of phlegm differentiation of gastric cancer theory, and built the theory of the stomach sputum pollution, which can renovate the body's environment, eradicating the cause and improving the quality of life for cancer patients.
7.Multivariate Analysis on TCM Syndromes of Gastric Cancer
Dazhi SUN ; Lijuan XIU ; Jun SHI ; Jianpeng JIAO ; Long LIU ; Xiaoqiang YUE
Chinese Journal of Information on Traditional Chinese Medicine 2016;23(10):16-20
Objective To explore the composition and distribution law of TCM syndromes in gastric cancer. Methods Based on the multicenter and large-sample clinical epidemiological investigation, the four methods of diagnosis of and clinical materials of 767 cases of gastric cancer were collected, and the database of TCM syndromes in gastric cancer was establish. Factor analysis and clustering analysis were used to explore composition and distribution law of TCM syndromes in gastric cancer. Results Gastric cancer symptoms mainly included fatigue, weight loss, dizziness and other non-specific systemic manifestation, and epigastria discomfort, belching, fullness or eating just a little swelling, pain, acid regurgitation, loss of appetite and other local manifestations. At the same time, the red tongue, moss greasy, pulse fine or string and other traditional Chinese medicine signs were also included. Eliminating 92 cases with too little symptoms, 675 cases were under multivariate analyzed. 25 syndrome variables were selected after initial factor analysis, again through factor analysis 10 factors with eigenvalues more than 1.0 were obtained and the cumulative contribution rate was 60.5%. Through further K-means clustering analysis on 10 common factor integrals, it was found that when all the cases were clustered into 7 classes consistent with clinical practice most. The numbers of patients with the 1-7 type were 165, 82, 90, 79, 88, 95 and 76, respectively. Analysis on the main factors in the combination of professional knowledge, the 7 types were named as the syndrome of spleen and stomach qi stagnation (24.44%), the syndrome of qi and blood deficiency (12.15%), the syndrome of spleen deficiency (13.33%), the syndrome of blood stasis (11.70%), the syndrome of phlegm dampness (13.04%), the syndrome of deficiency cold of spleen and stomach (14.07%), the syndrome of incoordination between liver/gallbladder and stomach (11.41%) respectively. Conclusion The results of multivariate analysis suggests that the location of gastric cancer is in the stomach, and closely related to spleen, liver and gallbladder. The general pathogenesis is asthenia in origin and asthenia in superficiality. The deficiency lies in qi, blood and yang qi, while asthenia superficiality owes to stagnation of qi, phlegm and blood stasis.
8.Effects ofXiaotan Sanjie Decoction on Ultramicrostructure in MKN-45 Human Gastric Cancer Orthotopic Xenograft
Min YE ; Dazhi SUN ; Lijuan XIU ; Ye LU ; Pinkang WEI
Chinese Journal of Information on Traditional Chinese Medicine 2015;(9):60-62
Objective To observe the effects ofXiaotan Sanjie Decoction on ultramicrostructure in MKN-45 human gastric cancer orthotopic xenograft;To discuss its mechanism for gastric cancer. Methods MKN-45 human gastric cancer cell line was used to establish subcutaneous tumor model in nude mice as an experimental model which passed three generations of tumor source. Then OB glue was used to establish human gastric cancer orthotopic xenograft model. 40 model nude mice were divided into control group, model group (received gavage with saline),Xiaotan Sanjie Decoction group (received garage withXiaotan Sanjie Decoction) and Tegafur group (received gavage with Tegafur), 10 mice in each group. Mice in the control group were under normal diet, without medicine intervention. After 6 weeks of treatment intervention, tumor weight was detected, inhibitory rate was calculated, the ultrastructural changes of gastric cancer cells were detected through transmission electron microscopy.Results The tumor weight inXiaotan Sanjie Decoction group was significantly lower than that in control group and model group (P<0.05,P<0.01). The tumor inhibition rate was 46.2%. Under the electron microscope, MKN-45 gastric cancer cells strain changed to typical apoptosis.ConclusionXiaotan Sanjie Decoction can lead to apoptosis effects on MKN-45 human gastric cancer orthotopic xenografts. All evidences indicate that inducing apoptosis may be one of the most important mechanisms ofXiaotan Sanjie Decoction in treating gastric cancer.
9.Effects of Xiaotan Sanjie Decoction on expressions of interleukin-8 and its receptors in gastric tumor xenografts and gastric tissue adjacent to the tumor in mice.
Dawei JU ; Pinkang WEI ; Huiming LIN ; Dazhi SUN ; Shan YU ; Lijuan XIU
Journal of Integrative Medicine 2010;8(1):74-9
To explore the mechanisms of Xiaotan Sanjie Decoction (XTSJD), a compound traditional Chinese herbal medicine, in inhibiting the tumor growth and preventing recurrence by testing the protein expressions of interleukin-8 (IL-8) and its receptors chemokine receptor 1 (CXCR1) and chemokine receptor 2 (CXCR2) in gastric tumor xenografts and gastric tissue adjacent to the tumor in mice.
10.Effects of Xiaotan Jieyu Recipe on behaviors of tumor-bearing rats with chronic mild stress and the mechanism.
Lijuan XIU ; Pinkang WEI ; Huiming LIN ; Bin PANG
Journal of Integrative Medicine 2010;8(2):138-44
To investigate the effects of unpredictable chronic mild stress and Xiaotan Jieyu Recipe (XTJYR), a compound traditional Chinese herbal medicine, on the behaviors of Walker 256 tumor-bearing rats and to explore the mechanism.

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