1.Establishment and Evaluation of Diabetic Macrovascular Atherosclerosis Model with Qi and Yin Deficiency Syndrome
Ting LUO ; Qingzhi LIANG ; Xi PENG ; Yi SU ; Hongyan XIE ; Chunguang XIE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):86-98
ObjectiveTo explore the establishment of a rat model of diabetic macrovascular atherosclerosis (DMA) with Qi and Yin deficiency syndrome induced by high-fat diet, streptozotocin (STZ), and Yin-depleting herbs, and to evaluate its biological characteristics. MethodsForty SD rats were randomly divided into a blank group (n=10) and a modeling group (n=30). Except for the blank group, rats in the model group were fed a high-fat diet for 4 weeks, followed by intraperitoneal injection of STZ (30 mg·kg-1) to establish a diabetic model. Twenty-four successfully modeled diabetic rats were randomly divided into a model group (n=7), a Qi and Yin deficiency syndrome group (n=8), and a counter-syndrome group (n=9). Except for the model group, rats received intragastric administration of Yin-depleting herbs (1.2 g·kg-1) for 8 weeks. The counter-syndrome group was further treated with Shenqi compound formula (1.69 g·kg-1) for an additional 8 weeks. General condition and body weight were recorded, and syndrome-related indicators were assessed, including precordial temperature, skin moisture content, grip strength, open-field test performance, and tongue appearance. Serum levels of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), vascular cell adhesion molecule-1 (VCAM-1), insulin-like growth factor-1 (IGF-1), and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose, blood lipids, hemorheological parameters, and coagulation function were analyzed using an automatic biochemical analyzer. Vascular ultrasound and hematoxylin-eosin (HE) staining were used to evaluate vascular lesions. ResultsIn terms of syndrome manifestations, compared with the blank group, body weight increased rapidly during the first 5 weeks in the model, Qi and Yin deficiency, and counter-syndrome groups. After STZ injection combined with Yin-depleting herbal administration at week 5, body weight decreased significantly (P<0.01) and continued to decline until the end of the experiment. Rats exhibited decreased activity, irritability, coarse and yellowish fur with obvious shedding, polydipsia, polyphagia, frequent urination, and dry stools, which were most pronounced in the Qi and Yin deficiency group. Grip strength decreased, peak activity time occurred earlier, total distance in the open-field test was reduced, and residence time was prolonged. Precordial temperature decreased (P<0.01), while paw temperature increased (P<0.05), and skin moisture and oil content were reduced (P<0.05, P<0.01). In terms of disease-related indicators, compared with the blank group, fasting blood glucose was significantly increased (>16.7 mmol·L-1) in the model and Qi and Yin deficiency groups, and blood lipid levels were significantly elevated (P<0.05). Vascular-related factors ET-1, MCP-1, VCAM-1, and VEGF were significantly increased (P<0.05,P<0.01), while IGF-1 was significantly decreased (P<0.01). Pathological examination of the aortic valve showed valvular thickening and structural disorganization. Carotid artery examination revealed discontinuity of the intima, foam cell accumulation beneath the intima, disordered smooth muscle arrangement, and widened intercellular spaces. Compared with the model group, ET-1, MCP-1, and VEGF levels were significantly decreased in both the Qi and Yin deficiency group and the counter-syndrome group. The reductions in ET-1 and MCP-1 were more pronounced in the Qi and Yin deficiency group (P<0.01), while the decrease in VCAM-1 was more significant in the counter-syndrome group (P<0.05). Compared with the blank group, the Qi and Yin deficiency group showed significantly prolonged activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) (P<0.01). The erythrocyte deformability index (TK), erythrocyte sedimentation rate, erythrocyte electrophoresis index, and whole blood low-shear viscosity all showed increasing trends. Vascular ultrasound revealed reduced arterial blood flow velocity, increased vascular resistance, and intimal thickening without plaque formation. The aortic intima showed no obvious overall thickening, with only occasional localized thickening and foam cell presence, and carotid artery injury was observed. ConclusionA rat model of DMA with Qi and Yin deficiency syndrome was successfully established using high-fat diet feeding combined with STZ injection and Yin-depleting herbal administration. Shenqi compound formula effectively alleviated Qi and Yin deficiency syndrome, regulated glucose and lipid metabolism, improved hemorheological and coagulation function, reduced vascular lesion severity, and demonstrated potential for early prevention and treatment of DMA.
2.Pinelliae Rhizoma and Its Prescription Compatibility for Depression Treatment: A Review
Zhe XIE ; Yifan SHI ; Linzhe SU ; Ming BAI ; Yucheng LI ; Baoying WANG ; Erping XU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):284-293
Depression is a common mental disorder that falls under the category of "stagnation syndrome" in traditional Chinese medicine (TCM). Its complex pathogenesis poses challenges for the development of novel therapeutic agents. Currently, clinically used antidepressants are often accompanied by significant side effects, and statistics show that about one-third of patients do not respond to these medications. TCM demonstrates advantages in the treatment of depression through multi-target, multi-pathway and multi-mechanistic approaches. Pinelliae Rhizoma, a phlegm-resolving herb, exhibits effects such as drying dampness and resolving phlegm, as well as eliminating stuffiness and reducing masses. The characteristics of harmonizing Yin and Yang and resolving stagnation in the middle energizer align precisely with the pathogenesis of depression syndrome, demonstrating therapeutic efficacy in affected patients. Literature studies have found that the active ingredients of Pinelliae Rhizoma, such as cavidine, baicalein, β-sitosterol, as well as Pinelliae Rhizoma herb pairs, such as Pinelliae Rhizoma-Magnoliae Officinalis Cortex, Pinelliae Rhizoma-husked sorghum, Pinelliae Rhizoma-Prunellae Spica, exhibit significant antidepressant effects. Furthermore, TCM formulas containing Pinelliae Rhizoma as the principal therapeutic agent, such as Banxia Xiexin Tang, Banxia Houpo Tang, and Wendan Tang, as well as formulas incorporating Pinelliae Rhizoma like compound Xiaochaihu Tang, Chaihu Jia Longgu Muli Tang, and Erchen Tang, have also demonstrated favorable antidepressant efficacy. The antidepressant mechanism of these agents may involve modulation of 5-hydroxytryptamine (5-HT) and dopamine (DA) levels, up-regulation of brain-derived neurotrophic factor (BDNF) expression, regulation of the hypothalamus-pituitary-adrenal (HPA) axis, reduction of oxidative stress, modulation of nuclear transcription factor-κB (NF-κB) signaling pathway, and inhibition of microglia-mediated inflammatory responses. This review summarized the antidepressant mechanisms and clinical applications of the active components, herb pairs, and TCM formulas containing Pinelliae Rhizoma, aiming to provide a reference for modern research on the use of Pinelliae Rhizoma in antidepressant therapy.
3.Zishen Huoxue Prescription Alleviates Endoplasmic Reticulum Stress in Hippocampal Neurons of 2-VO Rats via GRP78/PERK/ATF4 Signaling Pathway
Yao SU ; Feng QIU ; Tao YI ; Hanquan LI ; Le XIE ; Xiuli ZHANG ; Dahua WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):93-102
ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription (ZSHXP) ameliorates cognitive dysfunction in rats with vascular dementia (VD) induced by the bilateral common carotid artery ligation (2-VO model rats) through regulating the glucose-regulated protein 78 (GRP78)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley (SD) rats were randomly divided into six groups: Sham group, Model group, donepezil hydrochloride group (0.45 mg·kg-1), and ZSHXP groups at low (8.90 g·kg-1), medium (17.80 g·kg-1), and high (35.60 g·kg-1) doses,with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats, and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin (HE) and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy (TEM) was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen (NeuN) with GRP78 and βⅢ Tubulin with gasdermin D (GSDMD) in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress (ERS)-related proteins including GRP78, PERK, ATF4, phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), C/EBP homologous protein (CHOP), NOD-like receptor protein 3 (NLRP3), Caspase-1 and GSDMD. ResultsCompared with the sham operation group, the model group showed a significantly prolonged escape latency (P<0.01), a significant decrease in the number of platform crossings and the residence time in the target quadrant (P<0.01), and a markedly reduced recognition index (P<0.01). Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity, deformed and shrunken cell bodies, and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously, accompanied by abnormal dilation and swelling, and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78, p-PERK/PERK, ATF4, CHOP, NLRP3, GSDMD and Caspase-1 in the model group were significantly elevated (P<0.01). Compared with the model group, the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency (P<0.01) and an increased number of platform crossings (P<0.05, P<0.01). The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups (P<0.05, P<0.01), with a significantly improved recognition index (P<0.01). In the donepezil hydrochloride group and all ZSHXP groups, the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group, the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group, the protein expressions of GRP78, ATF4 and CHOP were increased (P<0.01), while the expression of p-PERK/PERK was decreased (P<0.05). In the ZSHXP low-dose group, the expressions of GRP78, p-PERK/PERK and CHOP were elevated (P<0.05, P<0.01). The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK, ATF4 and CHOP (P<0.01), and the high-dose group had a markedly reduced GRP78 protein expression (P<0.01). In the donepezil hydrochloride group, the Caspase-1 protein expression was increased (P<0.01) and the NLRP3 protein expression was decreased (P<0.01). In the ZSHXP low-dose group, the GSDMD expression was elevated (P<0.01) while the NLRP3 protein expression was reduced (P<0.01). After treatment with medium and high doses of ZSHXP, the protein expression levels of NLRP3, GSDMD and Caspase-1 were significantly decreased (P<0.01). ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway, which ameliorates ERS and inhibits neuronal pyroptosis.
4.Zishen Huoxue Prescription Alleviates Endoplasmic Reticulum Stress in Hippocampal Neurons of 2-VO Rats via GRP78/PERK/ATF4 Signaling Pathway
Yao SU ; Feng QIU ; Tao YI ; Hanquan LI ; Le XIE ; Xiuli ZHANG ; Dahua WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):93-102
ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription (ZSHXP) ameliorates cognitive dysfunction in rats with vascular dementia (VD) induced by the bilateral common carotid artery ligation (2-VO model rats) through regulating the glucose-regulated protein 78 (GRP78)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley (SD) rats were randomly divided into six groups: Sham group, Model group, donepezil hydrochloride group (0.45 mg·kg-1), and ZSHXP groups at low (8.90 g·kg-1), medium (17.80 g·kg-1), and high (35.60 g·kg-1) doses,with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats, and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin (HE) and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy (TEM) was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen (NeuN) with GRP78 and βⅢ Tubulin with gasdermin D (GSDMD) in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress (ERS)-related proteins including GRP78, PERK, ATF4, phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), C/EBP homologous protein (CHOP), NOD-like receptor protein 3 (NLRP3), Caspase-1 and GSDMD. ResultsCompared with the sham operation group, the model group showed a significantly prolonged escape latency (P<0.01), a significant decrease in the number of platform crossings and the residence time in the target quadrant (P<0.01), and a markedly reduced recognition index (P<0.01). Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity, deformed and shrunken cell bodies, and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously, accompanied by abnormal dilation and swelling, and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78, p-PERK/PERK, ATF4, CHOP, NLRP3, GSDMD and Caspase-1 in the model group were significantly elevated (P<0.01). Compared with the model group, the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency (P<0.01) and an increased number of platform crossings (P<0.05, P<0.01). The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups (P<0.05, P<0.01), with a significantly improved recognition index (P<0.01). In the donepezil hydrochloride group and all ZSHXP groups, the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group, the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group, the protein expressions of GRP78, ATF4 and CHOP were increased (P<0.01), while the expression of p-PERK/PERK was decreased (P<0.05). In the ZSHXP low-dose group, the expressions of GRP78, p-PERK/PERK and CHOP were elevated (P<0.05, P<0.01). The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK, ATF4 and CHOP (P<0.01), and the high-dose group had a markedly reduced GRP78 protein expression (P<0.01). In the donepezil hydrochloride group, the Caspase-1 protein expression was increased (P<0.01) and the NLRP3 protein expression was decreased (P<0.01). In the ZSHXP low-dose group, the GSDMD expression was elevated (P<0.01) while the NLRP3 protein expression was reduced (P<0.01). After treatment with medium and high doses of ZSHXP, the protein expression levels of NLRP3, GSDMD and Caspase-1 were significantly decreased (P<0.01). ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway, which ameliorates ERS and inhibits neuronal pyroptosis.
5.Development of a Diagnostic Scale for Qi-Yin Deficiency with Blood Stasis Syndrome in Diabetic Macrovascular Disease
Qingzhi LIANG ; Ting LUO ; Yi SU ; Xiaoqin LIU ; Hong GAO ; Hongyan XIE ; Chunguang XIE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):225-234
ObjectiveTo construct a standardized diagnostic scale for Qi-Yin deficiency with blood stasis syndrome in diabetic macrovascular disease. MethodsLiterature related to Qi-Yin deficiency with blood stasis syndrome in diabetic macrovascular disease was retrieved from CNKI, VIP, and Wanfang databases. Diagnostic information from four diagnostic methods was extracted and standardized, with items having a frequency of ≥15 included in the item pool. A three-round Delphi expert consultation was conducted, screening items using support degree, mean score, rank sum, and coefficient of variation. Item weights were determined using analytic hierarchy process (AHP), gactor analysis (FA), and combined weighting method (CWM). The optimal weighting method was selected by comparing the area under the receiver operating characteristic (ROC) curve (AUC). The Youden index was calculated to establish the diagnostic cutoff value, which was proportionally scaled. ResultsA total of 102 studies were included. Thirty-five items were incorporated into the item pool. The authority coefficients for the three Delphi rounds were 0.82, 0.85, and 0.86, with coordination coefficients of 0.648, 0.538, and 0.506, respectively. Fifteen items were retained after screening. ROC curve analysis showed the AUC ranking as FA > CWM > AHP. The maximum Youden index was 0.814, corresponding to a diagnostic cutoff of 8.361 (scaled to 40 points). The final scale adopted a structured diagnostic framework: the symptom dimension requires at least 2 items, and the tongue or pulse dimension requires at least 1 category. ConclusionThis study developed a standardized diagnostic scale for Qi-Yin deficiency with blood stasis syndrome in diabetic macrovascular disease. Core items were screened via the Delphi method, with factor analysis identified as the optimal weighting method through AUC comparison. The diagnostic threshold (40 points) and structured diagnostic framework provide a quantitatively clear, clinically practical tool.
6.Application Characteristics and Patterns of Marketed Traditional Chinese Patent Medicines for Treating Abortion
Changyue SONG ; Shuangfei DENG ; Siyu LI ; Daiyue DING ; Jinghong XIE ; Xiaohui SU ; Xiangying KONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):244-251
ObjectiveThis paper aims to analyze the variety characteristics and prescription patterns of marketed traditional Chinese patent medicines for treating abortion and provide references for new medicine development and clinical application. MethodsRelevant information of traditional Chinese patent medicines for treating abortion was systematically retrieved and collected. Microsoft Excel 2021 software was used to sort and statistically analyze the medicine syndrome types, quantity, market situation, and status of package inserts. Based on the Ancient and Modern Medical Case Cloud Platform (V2.3.9), the medicine properties, flavors, meridian tropism, and medication characteristics of standardized prescriptions were analyzed. ResultsA total of 39 marketed traditional Chinese patent medicines for treating abortion in China were included. According to disease type, these medicines were categorized as therapeutic medicines for threatened abortion and recurrent spontaneous abortion. According to clinical function, they were categorized into three groups: fetus stabilization, blood nourishment, and adjunctive conditioning. They were also categorized into pre-pregnancy conditioning and post-pregnancy fetal maintenance by clinical intervention stage. Post-marketing research showed that only three products had undergone safety evaluations and one involved pharmacoeconomic research, indicating a general lack of standardized evidence-based data. Dosage forms were mainly pills and granules. Package insert analysis revealed that 15 products listed "contraindications", while 28 included "precautions". Based on prescription inclusion and exclusion criteria, 25 products were selected for further analysis. Their therapeutic effects were mainly concentrated on "tonifying the kidney and spleen, replenishing Qi, and nourishing blood", with core medicines including Paeoniae Radix Alba, Angelicae Sinensis Radix, and Atractylodis Macrocephalae Rhizoma. Most medicines were warm or neutral in nature, predominantly sweet and pungent in flavor, and mainly entered the spleen, liver, and kidney meridians. ConclusionTraditional Chinese patent medicines for treating abortion demonstrate clear clinical value. However, shortcomings remain, including insufficient post-marketing research, prescription homogeneity, and incomplete package inserts. Future efforts should establish a clinically value-oriented modern development pathway, strengthen safety surveillance and evidence evaluation, improve package inserts, and promote precision use to further enhance clinical value.
7.Fluid Suppression Techniques Combined With Amide Proton Transfer-Weighted Imaging for the Evaluation of Adult-Type Diffuse Gliomas
Hongquan ZHU ; Yuanhao LI ; Yujie DING ; Yufei LIU ; Nanxi SHEN ; Yan XIE ; Su YAN ; Dong LIU ; Xiaoxiao ZHANG ; Li LI ; Wenzhen ZHU
Korean Journal of Radiology 2026;27(3):252-263
Objective:
To evaluate the diagnostic potential of fluid suppression (FS) techniques combined with amide proton transferweighted imaging (APTw) for assessment of isocitrate dehydrogenase (IDH) mutation status, glioma subtypes, and tumor proliferation.
Materials and Methods:
This retrospective study included 117 patients with adult-type diffuse gliomas. Conventional APTw, FSAPTw, and spillover-corrected FS-APTw (SCFS-APTw) metrics were calculated from 3T MRI data in tumor parenchyma, necrotic or cystic regions, and contralateral normal-appearing white matter. APTw signals were compared across the three techniques within each region, between IDH-mutant and IDH-wildtype gliomas, and among astrocytoma, oligodendroglioma, and glioblastoma subtypes. Diagnostic performance for distinguishing IDH mutation status and glioma subtypes was assessed using receiver operating characteristic (ROC) analysis. Correlations between APTw metrics and Ki-67 expression were also analyzed.
Results:
Both FS-APTw and SCFS-APTw significantly reduced signal intensity in tumor parenchyma and necrotic or cystic regions, with SCFS-APTw demonstrating a stronger suppression effect. IDH-wildtype gliomas showed significantly higher APTw metrics than IDH-mutant gliomas (all P < 0.001). Glioblastomas exhibited significantly higher metrics than oligodendrogliomas (all corrected P ≤ 0.015) and astrocytomas (all corrected P < 0.001). SCFS-APTw achieved the highest area under the ROC curve (AUC) of 0.846 for identification of IDH mutation status. For differentiation between astrocytomas and glioblastomas, the 90th percentile of APTw yielded the highest AUC (0.860), followed by SCFS-APTw (0.849). For discrimination between oligodendrogliomas and glioblastomas, the highest AUC (0.832) was obtained using the 90th percentile of SCFS-APTw. None of these metrics successfully differentiated oligodendrogliomas from astrocytomas. SCFS-APTw demonstrated the strongest correlation with Ki-67 expression (r = 0.451).
Conclusion
FS techniques effectively reduce elevated APTw signals originating from fluid compartments. Their combination with APTw imaging enables evaluation of IDH mutation status, glioma subtypes, and tumor proliferative activity in adulttype diffuse gliomas.
8.Professor YANG Chunbo's Experience in Treating Refractory Constipation Complicated with Melanosis Coli from the Perspective of Damp-Heat Theory
Zhiqiang SU ; Yu LIN ; Zhengning YANG ; Baojie XIE ; Jintuan CHEN ; Yunfeng LUO ;
Journal of Traditional Chinese Medicine 2026;67(16):1713-1716
This paper summarizes professor YANG Chunbo's clinical experience in treating refractory constipation (RC) complicated with melanosis coli (MC) from the perspective of damp-heat theory. Internal accumulation of damp-heat is considered as the core pathogenesis of this condition, and the therapeutic principles should focus on clearing, transforming, tonifying, and resolving. Self-formulated Qinghua Beverage (清化饮) is developed to clear and transform damp-heat, regulate qi, and soothe collaterals. In clinical practice, RC complicated with MC is classified into damp-heat with qi stagnation syndrome and damp-heat with stasis obstruction syndrome. Qinghua Beverage is used as the base prescription with modifications according to syndrome differentiation. For damp-heat with qi stagnation syndrome, medicinals that promote qi movement and unblock the bowels, activate blood and clear collaterals are added, while for damp-heat with stasis obstruction syndrome, herbs that resolve stasis and unblock collaterals are incorporated, with simultaneous consideration of nourishing blood and supporting collaterals.
9.Mechanism of Xuefu Zhuyutang in Intervening in Ferroptosis in Rats with Coronary Heart Disease with Blood Stasis Syndrome Based on ACSL4 Signalling Pathway
Yi LIU ; Yang YANG ; Chang SU ; Peng TIAN ; Mingyun WANG ; Ruqian ZHONG ; Xuejiao XIE ; Qing YAN ; Qinghua PENG ; Qiuyan ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):27-38
ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 (ACSL4) signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group, sham-operation group, model group, trimetazidine group (5.4 mg·kg-1), low-, medium-, and high-dose group (3.51, 7.02,14.04 g·kg-1) of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome, and continuous treatment for 7 d was conducted, while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed, and indicators such as electrocardiogram, echocardiography, and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin (HE) staining, and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe2+, lipid peroxidation (LPO), glutathione (GSH), and T-GSH/glutathione disulfide (GSSG) in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species (ROS). Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), ACSL4, and ly-sophosphatidylcholine acyltransferase3 (LPCAT3) in myocardial tissue. ResultsCompared with those in the normal group, the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage, bow-back elevation of the ST segments, elevated T waves, J-point elevation, and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01). Blood rheology showed that the viscosity of the whole blood (low, medium, and high rate of shear) was significantly increased (P<0.01). HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken, and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles, and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased (P<0.01). The content of Fe2+, LPO, and ROS in myocardial tissue was significantly increased (P<0.01). The content of GSH was significantly decreased (P<0.01), and T-GSH/GSSG was decreased (P<0.01). The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased (P<0.05, P<0.01), while those of ACSL4 and LPCAT3 increased significantly (P<0.01). Compared with the model group, the general macroscopic symptoms and electrocardiogram results of rats in low-, medium- and high-dose groups of Xuefu Zhuyutang were alleviated, and the differences in LVEF/LVFS ratios were all significantly increased (P<0.05, P<0.01). The differences in whole-blood viscosity (low, medium, and high rate of shear) were all significantly decreased (P<0.01). The results of HE staining and transmission electron microscopy showed that the morphology, structure, and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-, medium-, and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01). The content of Fe2+, LPO, and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01), and the content of GSH and T-GSH/GSSG was significantly increased (P<0.05, P<0.01). The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01), and ACSL4 and LPCAT3 were decreased to different degrees in the low-, medium-, and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01). ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway, thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.
10.Changing antimicrobial resistance profiles of Burkholderia cepacia in hospitals across China:results from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Chunyue GE ; Yunjian HU ; Xiaoman AI ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Hui LI ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(5):557-562
Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1%(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5%,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3%(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1%)were isolated from sputum and respiratory secretions,followed by urine(10.7%)and blood samples(8.1%).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1%.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4%in the patients<18 years old to 20.6%in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

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