1.Proteomic Analysis of Danlou Tablet in Improving Platelet Function for Treating Coronary Heart Disease with Phlegm-stasis Intermingling Syndrome in Minipigs
Ziyan WANG ; Ying LI ; Aoao WANG ; Hongxu MENG ; Yue SHI ; Yanlei MA ; Guoyuan ZHANG ; Lei LI ; Jianxun LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):41-53
ObjectiveThis paper aims to observe the role of Danlou tablet in treating coronary heart disease (CHD) with phlegm-stasis intermingling syndrome in minipigs by improving platelet function and explore the potential pharmacological mechanism of Danlou tablet in regulating platelet function by using proteomics technology. MethodsThirty Bama minipigs were randomly divided into a normal control group (6 pigs) and a high-fat diet group (24 pigs). After 2 weeks of high-fat diet feeding, the high-fat diet group was randomly subdivided into a model group, an atorvastatin group (1 mg·kg-1), and Danlou tablet groups (0.6 g·kg-1 and 0.3 g·kg-1). All groups continued to receive a high-fat diet for 8 weeks after the procedure. The normal control group was given a regular diet, underwent only coronary angiography, and did not receive an interventional injury procedure. The model group and each administration group were fed a high-fat diet. Two weeks later, they underwent a coronary angiography injury procedure. After the procedure, drugs were mixed into the feed every morning for 8 consecutive weeks, with the minipigs maintained on a continuous high-fat diet during this period. Quantitative proteomics technology was further used to study platelet proteins, and differential proteins were obtained by screening. Bioinformatics analysis was performed to analyze key regulatory proteins and biological pathways involved in the therapeutic effect of Danlou tablet on CHD with phlegm-stasis intermingling syndrome. ResultsCompared with the normal control group, the model group showed a significant increase in total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) of minipigs' serum (P<0.01), a significant shortening in prothrombin time of (PT) (P<0.01), a coagulation function index, and an increase in whole blood viscosity (P<0.01) and platelet aggregation rate (P<0.01). Moreover, the platelet morphology was altered, and the contents of endothelin-1 (ET-1) and nitric oxide (NO) were significantly increased (P<0.01). Hemodynamic parameters were obviously abnormal, including significantly decreased systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), and left ventricular maximal positive dp/dt (LV+dp/dtmax) (P<0.01). Left ventricular maximal negative dp/dt (LV-dp/dtmax) was significantly increased (P<0.01). Besides, there were myocardial cell hypertrophy, obvious edematous degeneration, massive interstitial inflammatory cell infiltration, high degree of fibrosis, and coronary endothelial atherosclerosis. TC and TG levels in minipigs' serum were significantly reduced in Danlou tablet groups with 0.6 g·kg-1 and 0.3 g·kg-1 (P<0.05, P<0.01), compared with those in the model group. LDL-C was decreased in the Danlou tablet group with 0.6 g·kg-1 (P<0.05). The whole blood viscosity under low and high shear conditions was significantly reduced in the Danlou tablet group with 0.6 g·kg-1 (P<0.05). In groups with all doses of Danlou tablet, maximum aggregation rate (MAR) and average aggregation rate (AAR) were significantly decreased (P<0.05, P<0.01), and platelets' morphological changes such as pseudopodia extension were reduced. ET-1 levels in the serum were significantly reduced. In the Danlou tablet group with 0.6 g·kg-1, NO level in the serum was reduced (P<0.05). In groups with all doses of Danlou tablet, DBP and MAP were significantly increased (P<0.05). In the Danlou tablet group with 0.6 g·kg-1, LVSP and LV+dp/dtmax were significantly increased (P<0.05, P<0.01), and LV-dp/dtmax was significantly decreased (P<0.05). In groups with all doses of Danlou tablet, edematous degeneration in myocardial tissue was milder, and coronary artery lesion degree was significantly alleviated. Compared with the normal control group, there were 94 differentially expressed proteins in the model group, including 81 up-regulated and 13 down-regulated proteins. Compared with the model group, the Danlou tablet group with 0.6 g·kg-1 showed 174 differentially expressed proteins, including 100 up-regulated and 74 down-regulated proteins. A total of 30 proteins were reversed after Danlou tablet intervention. Bioinformatics analysis revealed that its pharmacological mechanism may exert anti-platelet activation, aggregation, and adhesion effects through biological pathways such as regulation of actin cytoskeleton, platelet activation pathway, Fcγ receptor-mediated phagocytosis, as well as proteins such as growth factor receptor-bound protein 2 (GRB2), Ras-related C3 botulinum toxin substrate 2 (RAC2), RAC1, and heat shock protein 90 alpha family class A member 1 (HSP90AA1). ConclusionDanlou tablet can effectively reduce platelet activation and aggregation, exerting a good therapeutic effect on CHD with phlegm-stasis intermingling syndrome in minipigs. Its pharmacological mechanism may involve regulating biological pathways such as actin cytoskeleton and platelet activation pathway, as well as proteins like GRB2, RAC2, RAC1, and HSP90AA1, thereby exerting a pharmacological effect in anti-platelet activation, aggregation, and adhesion.
2.Action Mechanism of Huamoyan Granules in Treatment of Knee Osteoarthritis Based on TRPV1/p38 MAPK Pathway
Jin ZHANG ; Lili YANG ; Canwen ZHENG ; Jing KANG ; Yanlei MA ; Yue SHI ; Lei LI ; Hongxu MENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):79-89
ObjectiveThis paper aims to observe the protective effect of Huamoyan granules on knee osteoarthritis (KOA) and explore whether its protective effect is oriented toward an anti-inflammatory direction by regulation of macrophage polarization, which can effectively inhibit the progression of pathological inflammatory response, reduce the release of inflammatory pain mediators, and downregulate the protein expression level of transient receptor potential vanilloid 1 (TRPV1), so as to provide experimental evidence for its clinical application and investigate its action mechanism. MethodsAfter adaptive feeding, Sprague-Dawley (SD) rats were randomly divided into six groups: sham group, model group, celecoxib group, and high, medium, and low-dose synovitis granule groups (9.6, 4.8, 2.4 g·kg-1). The administration dose of celecoxib capsules was 20 mg·kg-1. There were 10 rats in the sham group and 12 rats in the model group and each administration group. A KOA animal model was established by means of intra-articular injection of sodium iodoacetate into the knee joint. From the 10th day of the experiment, each administration group was given intragastric administration at a dose of 10 mL·kg-1 for 4 weeks. General conditions of rats in each group were assessed daily. The pressure pain threshold (PPT) to mechanical stimulation and joint diameter were recorded. X-ray examination was performed on the right knee joints of rats for imaging analysis. Enzyme linked immunosorbent assay (ELISA) was performed to detect the tumor necrosis factor-α (TNF-α), serum interleukin-1β (IL-1β), and other pro-inflammatory cytokines in rat serum samples, as well as the expression levels of neurogenic inflammatory mediators such as nerve growth factor (NGF) and calcitonin gene-related peptide (CGRP). Histopathological changes in the knee joint synovial tissues were examined by hematoxylineosin (HE) staining. Safranin O-fast green staining was performed to observe and evaluate the degree of knee cartilage lesions. Western blot was employed to quantitatively analyze TRPV1, p38 mitogen-activated protein kinase (p38 MAPK), and phosphorylated (p)-p38 MAPK in rat knee synovial tissues. Immunofluorescence (IF) was used to measure and assess M1/M2 macrophage polarization. ResultsCompared with those in the sham group, the circumference and joint diameter of the right knee were markedly enlarged in the model group (P<0.01), while PPTs of rats showed a significant reduction (P<0.01). The contents of IL-1β, TNF-α, CGRP, and NGF in rats' serum were significantly elevated (P<0.01), and the synovial Krenn score was increased (P<0.01). The Mankin score of cartilage tissue was increased (P<0.01), and the protein expressions of TRPV1 and p-p38 MAPK/p38 MAPK were significantly upregulated (P<0.01). The experimental intervention significantly reduced the proportion of pro-inflammatory M1 macrophages in the total macrophage population (P<0.01), and the percentage of M2 macrophages was decreased (P<0.01). The M1/M2 macrophage ratio was significantly elevated (P<0.01). Knee joint diameters of all dose groups of Huamoyan granules and the celecoxib group were reduced (P<0.01) compared with those of the model group, and the PPT recovery speeds in the high and medium-dose groups of Huamoyan granules were more obvious (P<0.05). The contents of IL-1β, CGRP, and NGF in the rats' serum in all administration groups were significantly reduced (P<0.05, P<0.01), and the content of TNF-α in rats' serum was significantly reduced (P<0.01). All dose groups of Huamoyan granules demonstrated significant reductions in both synovial Krenn score (P<0.05, P<0.01) and protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in rats' synovial tissues (P<0.01). The percentage of M1 macrophages in the synovial tissues of the celecoxib group and all dose groups of Huamoyan granules was decreased (P<0.01). The percentage of M2 macrophages was increased (P<0.05), and the M1/M2 ratio was decreased (P<0.01). ConclusionHuamoyan granules can alleviate the inflammatory response of KOA, reduce the release of inflammatory pain mediators, and downregulate TRPV1 protein expression by regulating macrophage polarization. Its mechanism may be related to the TRPV1/p38 MAPK signaling pathway, thereby achieving the effect of improving peripheral pain hypersensitivity in KOA.
3.Expert Consensus on Clinical Application of Qidong Yixin Oral Liquid
Changkuan FU ; Xiaochang MA ; Mingjun ZHU ; Yue DENG ; Hongxu LIU ; Mingxue ZHANG ; Ying CHEN ; Yan ZHOU ; Ling ZHANG ; Jianhua FU ; Wei YANG ; Yu'er HU ; Ming CHEN ; Yanming XIE ; Yuanyuan LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):147-158
The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis (VMC). It has the functions of tonifying Qi, nourishing the heart,calming the mind, and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However,the understanding of its efficacy evidence, advantageous aspects, dosage and administration, and medication safety remains insufficient in clinical practice. Therefore,the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid (hereinafter referred to as consensus) was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine,successively completing multiple tasks such as the consensus project initiation,determination of clinical problems,evidence search and evaluation,formation of recommendation opinions and consensus suggestions,solicitation of opinions,peer review, submission for review and release, and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions,clarifying the clinical positioning,efficacy advantages,syndrome differentiation,dosage and administration,combination therapy,timing of medication,adverse reactions,contraindications, and precautions of Qidong Yixin oral liquid,indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease,providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23, 2024. Standard number:GSCACM-376-2024.
4.Meta-analysis and Grade Evidence Evaluation of Qi-reinforcing and Blood-activating/ Stasis-expelling Chinese Patent Medicines in Treatment of Coronary Microvascular Disease
Jiaping CHEN ; Juju SHANG ; Hongxu LIU ; Xiang LI ; Xiaolei LAI ; Huiwen ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):157-166
ObjectiveTo systematically evaluate the efficacy and safety of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines in the treatment of coronary microvascular disease (CMD). MethodsPubMed, Cochrane Library, CNKI, Wanfang Data, and VIP were searched for the randomized controlled trials (RCTs) on the treatment of CMD with Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis with the time interval from inception to December 31, 2023. The primary outcome indicators included the index of microcirculatory resistance (IMR), coronary flow reserve (CFR), and corrected TIMI flow frame count (cTFC). The secondary outcome indicators included symptomatic efficacy, left ventricular ejection fraction (LVEF), hypersensitive C-reactive protein (hs-CRP), nitric oxide (NO), and adverse events. Cochrane risk-of-bias assessment tool 2.0 (RoB 2.0) and Stata 17.0 were used for literature quality evaluation and meta-analysis of the included RCTs. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to evaluate the quality of evidence. ResultsA total of 36 RCTs were included in this study, involving 3 029 patients. Compared with conventional Western medicine alone, the combined use of Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis and Western medicine reduced the IMR [mean difference (MD)=-5.93, 95% confidence interval (95%CI) [-8.73,-3.14], n=382, P<0.01], cTFC (MD=-9.35, 95%CI [-13.94,-4.76], n=618, P<0.01), and hs-CRP [standard mean difference (SMD)=-1.50, 95%CI [-1.90,-1.11], n=1 483, P<0.01], improved the CFR (SMD=1.14, 95%CI [0.08,2.19], n=304, P=0.03), symptomatic efficacy [relative risk (RR)=1.36, 95%CI [1.21,1.53], n=756, P<0.01], LVEF (MD=4.39, 95%CI [2.31,6.47], n=533, P<0.01), and NO (SMD=3.16, 95%CI [2.07,4.25], n=946, P<0.01) of CMD patients. In terms of safety, the combined therapy reduced the occurrence of adverse events in CMD patients (RR=0.49, 95%CI [0.29,0.82], n=591, P=0.01). GRADE showed moderate quality evidence for adverse events, low quality evidence for cTFC, symptomatic efficacy, LVEF, and NO, and very low quality evidence for IMR, CFR, and hs-CRP. ConclusionBased on microcirculatory function indicators, the combined use of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines and Western medicine may further improve the coronary microvascular function in CMD patients with good safety. The above conclusions remain to be verified with high-quality clinical trials.
5.Prevention and Treatment of Post-Percutaneous Coronary Intervention Coronary Microvascular Dysfunction from the Perspective of "Deficiency Qi Retention and Stagnation"
Yunze LI ; Huiqi ZONG ; Hongxu LIU ; Mingxuan LI ; Xiang LI
Journal of Traditional Chinese Medicine 2025;66(12):1273-1276
It is believed that "deficiency qi retention and stagnation" is the fundamental pathogenesis of coronary microvascular dysfunction (CMD) after percutaneous coronary intervention (PCI). Patients often have severe coronary vessel congestion before PCI, leading to emptiness in the heart's collaterals, which results in deficiency of healthy qi, poor movement of blood and body fluids, so the heart collaterals are susceptible to stagnation and stasis,then phlegm and stasis generate; after PCI, it is easy to damage the healthy qi then lead to qi deficiency, causing qi, blood, and body fluids fail to transport, thereby leading to blood stasis and phlegm turbidity retention, generating heat and wind to damage the heart and body. It is proposed that the prevention before PCI should replenish qi and collaterals, expel blood stasis and resolve phlegm, to support "deficient qi" in heart collaterals and prevent "stagnation" after PCI. Postoperative management should focus on replenishing qi and protecting the collaterals, eliminating pathogen and controlling development, so as to avoid exacerbating deficiency and stagnation by damaging healthy qi, and eliminate pathogen and unblock the collaterals to interrupt the pathogenesis, which prevent "retention and stagnation" from changes.
6.Effect of electroacupuncture on learning and memory abilities in vascular dementia rats via the NCOA4/FTH1 signaling pathway-mediated ferritinophagy.
Wei SUN ; Yinghua CHEN ; Tong WU ; Hongxu ZHAO ; Haoyu WANG ; Ruiqi QIN ; Xiaoqing SU ; Junfeng LI ; Yuanyu SONG ; Yue MIAO ; Xinran LI ; Yusheng HAN
Chinese Acupuncture & Moxibustion 2025;45(9):1271-1280
OBJECTIVE:
To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD.
METHODS:
A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot.
RESULTS:
Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01).
CONCLUSION
Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals
;
Electroacupuncture
;
Dementia, Vascular/genetics*
;
Male
;
Rats
;
Signal Transduction
;
Humans
;
Memory
;
Rats, Sprague-Dawley
;
Nuclear Receptor Coactivators/genetics*
;
Ferritins/genetics*
;
Learning
;
Hippocampus/metabolism*
;
Acupuncture Points
7.Clinical study of double-channel core decompression combined with medullary cavity irrigation for non-traumatic osteonecrosis of femoral head.
Jinhui MA ; Hongxu LI ; Haoyang LIU ; Bailiang WANG ; Weiguo WANG ; Fuqiang GAO ; Wei SUN ; Liming CHENG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(4):399-405
OBJECTIVE:
To compare the effects of double-channel core decompression (CD) combined with medullary cavity irrigation with those of simple CD on progression of collapse and clinical outcomes in non-traumatic osteonecrosis of the femoral head (ONFH).
METHODS:
A retrospective analysis was conducted on the clinical data of 19 patients (30 hips) with non-traumatic ONFH who underwent double-channel CD combined with medullary cavity irrigation and admitted between January 2024 and October 2024 (CD+irrigation group). According to a 1: 2 ratio, 54 patients (60 hips) who underwent simple CD and were matched in terms of age, gender, and body mass index (BMI) were included as the control (CD group). There was no significant difference in baseline data such as age, gender, BMI, affected side, ONFH type, preoperative Association Research Circulation Osseous (ARCO) stage, bone marrow edema stage, visual analogue scale (VAS) score for pain, and Harris score between the two groups ( P>0.05). The postoperative discharge time and occurrence of complications were recorded for both groups. The VAS scores before operation and at discharge after operation were compared, and the differences between pre- and post-operation (change values) were calculated for intergroup comparison. The Harris scores before operation and at discharge and 3 months after operation were also compared. During follow-up, X-ray film, CT, and MRI were performed for reexamination. The ARCO stage and bone marrow edema stage were evaluated at 3 months after operation and compared with those before operation to determine whether there was radiological progression or relief.
RESULTS:
All incisions in both groups healed by first intention after operation, with no infection, femoral neck fracture, or other operation-related complications. All patients were followed up, and the follow-up time of the CD+irrigation group was (146.8±27.7) days, and that of the CD group was (164.3±48.2) days; there was no significant difference between the two groups ( t=1.840, P=0.069). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). At discharge after operation, the VAS score of the CD+irrigation group was significantly lower than that of the CD group ( P<0.05), and the change value was significantly higher than that of the CD group ( P<0.05). The Harris scores at discharge and 3 months after operation in the CD+irrigation group were significantly higher than those in the CD group ( P<0.05). The Harris score gradually increased with time, and the differences between different time points were significant ( P<0.05). Radiological reexamination showed that there was no significant difference in the ARCO stage and the incidence of radiological progression between the two groups at 3 months after operation ( P>0.05); however, the bone marrow edema stage and the degree of bone marrow edema relief in the CD+irrigation group were better than those in the CD group, with significant differences ( P<0.05).
CONCLUSION
Double-channel CD combined with medullary cavity irrigation can significantly alleviate hip joint pain and improve joint function in patients with non-traumatic ONFH, reduce the degree of bone marrow edema in the femoral head, and delay the progression of ONFH.
Humans
;
Femur Head Necrosis/therapy*
;
Retrospective Studies
;
Male
;
Female
;
Decompression, Surgical/methods*
;
Therapeutic Irrigation/methods*
;
Adult
;
Treatment Outcome
;
Middle Aged
;
Femur Head/surgery*
8.Shuangshen Ningxin Capsules Regulates Mitochondrial Fission and Fusion to Alleviate Myocardial Ischemia-reperfusion Injury in Rats
Gaojie XIN ; Yuanyuan CHEN ; Zixin LIU ; Yue YOU ; Ce CAO ; Aoao WANG ; Hongxu MENG ; Xiao HAN ; Jianxun LIU ; Lei LI ; Jianhua FU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):87-94
ObjectiveTo explore whether the mechanism of Shuangshen Ningxin capsules (SSNX) in alleviating myocardial ischemia-reperfusion injury (MIRI) in rats is related to the regulation of mitochondrial fission and fusion. MethodThis study focused on Sprague Dawley (SD) rats and ligated the left anterior descending branch of the coronary artery to construct a rat model of MIRI. The rats were divided into the sham operation group, model group, SSNX group (90 mg·kg-1) and trimetazidine group (5.4 mg·kg-1). The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were detected by micro method. Changes in mitochondrial membrane potential (△Ψm) and the degree of mitochondrial permeability transition pore (mPTP) opening were detected by the chemical fluorescence method. The intracellular adenosine triphosphate (ATP) level was detected by the luciferase assay. The messenger ribonucleic acid (mRNA) and protein expression levels of mitochondrial fission and fusion related factors dynamin-related protein 1 (DRP1), mitochondrial fission 1 protein (FIS1), optic atrophy protein 1 (OPA1), mitochondrial outer membrane fusion protein 1 (MFN1), and MFN2 were detected by real-time polymerase chain reaction (real-time PCR) and Western blot. ResultCompared with the sham operation group, the model group showed a decrease in serum SOD activity and an increase in MDA content. The opening level of mPTP, the level of △Ψm and ATP content decreased, the protein expressions of mitochondrial fission factors DRP1 and FIS1 increased, and the protein expressions and mRNA transcription levels of fusion related factors OPA1 and MFN1 decreased. Compared with the model group,SSNX significantly increased serum SOD activity, reduced MDA content, increased intracellular ATP level and △Ψm, reduced the opening level of mPTP, downregulated the protein expressions of mitochondrial fission factors DRP1 and FIS1, and increased the mRNA transcription levels and protein expressions of fusion related factors OPA1 and MFN1. ConclusionSSNX inhibits the expressions of mitochondrial fission factors DRP1 and FIS1, and increases the expressions of fusion related factors OPA1 and MFN1, inhibiting mitochondrial fission and increasing mitochondrial fusion, thereby alleviating MIRI.
9.The ninth edition of TNM staging for lung cancer: precise staging for precise diagnosis and treatment
Hanyue LI ; Yiyang WANG ; Hui LIU ; Hongxu LIU ; Liyan JIANG ; Yuchen HAN ; Wenyong ZHOU ; Teng MAO ; Wentao FANG
Chinese Journal of Surgery 2024;62(6):537-542
The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.
10.Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson’s disease
Yuwen ZHAO ; Lixia QIN ; Hongxu PAN ; Tingwei SONG ; Yige WANG ; Xiaoxia ZHOU ; Yaqin XIANG ; Jinchen LI ; Zhenhua LIU ; Qiying SUN ; Jifeng GUO ; Xinxiang YAN ; Beisha TANG ; Qian XU
Chinese Medical Journal 2024;137(4):450-456
Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

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