1.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.
2.Comparison on Rat Models of Acute Cerebral Infarction Due to Stasis Combined with Toxin Complicated with Cerebral-cardiac Syndrome
Mingjiang YAO ; Junyuan LI ; Yue LIU ; Ce CAO ; Guo YUAN ; Lei LI ; Jianxun LIU ; Yunling ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):112-119
ObjectiveTo observe and compare the electrocardiogram index, myocardial morphology, and connexin 43 (Cx43) expression of two rat models of acute cerebral infarction (ACI) due to stasis combined with toxin complicated with cerebral-cardiac syndrome (CCS), and to provide experimental evidence for the research on the occurrence mechanism of cardiac diseases induced by ACI and the clinical diagnosis and treatment of CCS. MethodSixty SPF-grade male SD rats were randomized into six groups (n=10): normal , syndrome of stasis combined with toxin induced by carrageenin combined with dry yeast (CA/Y), multi-infarct induced by micro-embolism (ME), middle cerebral artery occlusion (MCAO), CA/Y+ME, and CA/Y+MCAO groups. The model of syndrome of stasis combined with toxin was established by intraperitoneal injection with carrageenan (CA) at 10 mg·kg-1 on the first day and subcutaneous injection with dry yeast (Y) suspension (2 mg·kg-1) on the second day of modeling. Twenty-four hours after the modeling of ACI, the electrocardiograms (ECGs) of rats in each group were collected and the number/percentage (%) of abnormal ECG was calculated. The infarct area of the brain was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and myocardial injury was assessed by hematoxylin-eosin (HE) staining. Immumohistochemical staining and Western blot were employed to determine the expression of Cx43 in the myocardium. ResultA certain number of rats in each model group presented abnormal ECG. Compared with the normal group and CA/Y group, CA/Y+MCAO group had the highest rate of abnormal ECG (P<0.01). Compared with the normal, CA/Y, ME, and CA/Y+ME groups, the CA/Y+ME and CA/Y+MCAO groups showed decreased amplitudes of P-wave and T-wave, shortened P-R interval, and extended Q-T interval, which were particularly obvious in the CA/Y+MCAO group (P<0.05, P<0.01) and in accordance with the cerebral infarction area and pathological changes. The expression of Cx43 was up-regulated in both CA/Y+ME and CA/Y+MCAO groups, especially in the CA/Y+MCAO group (P<0.01). ConclusionThe two rat models of ACI due to stasis combined with toxin complicated with CCS can be used to study the mechanism of heart diseases caused by cerebrovascular diseases and the therapeutic effects of Chinese medicines with the functions of resolving stasis and detoxifying. Moreover, the CA/Y+MCAO method has higher abnormal electrocardiogram rate, severer myocardial pathological injury, and higher expression of Cx43 protein. The models can be chosen according to specific experimental purpose.
3.Analysis of the Role of Pepsin in Vocal Cord Polyp and Vocal Cord Cancer
Jingyu GAO ; Renjing LUO ; Biao RUAN ; Chaowu JIANG ; Zhuohui LIU ; Ruiqing LONG ; Qiulin LIANG ; Ce ZHANG ; Lu SU ; Peng LI
Journal of Audiology and Speech Pathology 2024;32(1):21-24
Objective To investigate the expression of pepsin in vocal cord polyps and vocal cord cancer,and to compare the difference of pepsin expression.Methods From May 2020 to December 2021,27 patients with vocal cord polyp,27 patients with vocal cord cancer and 23 healthy volunteers were selected.RSI and RFS scoring scales were used for scoring,pepsin detection kit was used for saliva pepsin detection,and immunohistochemical methods were used to detect the expression of pepsin in vocal cord tissues of patients with vocal cord polyps and vocal cord cancer.Results The RSI score,RFS score and pepsin test kit results of vocal cord polyp group and vocal cord canc-er group were higher than those of non-vocal cord disease group,and the differences of the three indexes were statis-tically significant(P<0.05).RSI score,pepsin detection kit results and pepsin immunohistochemistry results of vocal cord polyp group showed no significant difference compared with vocal cord cancer group(P>0.05).The RFS score of vocal cord polyp group was significantly different from that of vocal cord cancer group(P<0.05).Conclusion Pepsin may be an important pathogenic factor of vocal cord polyp and vocal cord cancer,and play an im-portant role in the occurrence of these two diseases.The difference of pepsin expression in vocal cord polyp and vo-cal cord cancer suggests that pepsin may have different pathogenesis.
4.Potential value of canonical and non-canonical roles of connexin 43 in disease treatment
Xiaoxuan ZHUGE ; Ce LI ; Guangjie BAO ; Hong KANG
Chinese Journal of Tissue Engineering Research 2024;28(7):1130-1136
BACKGROUND:Connexin 43(Cx43),which is thought to be engaged in the gap junction process and build the structural groundwork for the development of direct material signaling channels between cells,is crucial for maintaining the homeostatic balance of tissue metabolism.Recent research,however,has revealed fresh information about its distinct hemichannel function and highlighted the significance of its subcellular localization and self-fragmentation for cellular physiological activities and pathological processes. OBJECTIVE:To systematically summarize the molecular characteristics and expression of Cx43 in a variety of cells,concentrate on the pathological and physiological roles of channel-dependent Cx43 and channel-independent Cx43,and investigate the potential value in disease treatment by reviewing the pertinent literature in the database. METHODS:The Chinese and English keywords were"gap junction,connexin 43(Cx43),hemichannel,channel-dependent Cx43,channel-independent Cx43,extracellular vesicles(EVs),mitochondria,GJA1-20k",which were searched in PubMed and CNKI.Finally,81 articles were selected for review. RESULTS AND CONCLUSION:(1)The canonical role of Cx43 is to form a gap junction channel.Channel-dependent Cx43 has primarily involved in disease physiopathological processes by directly constituting gap junction channels,but full attention should be paid to the issue of its structural and functional integrity.Adhesion is a crucial characteristic of gap junctions,which are strongly associated with barrier-like diseases.(2)The non-canonical role of Cx43 is non-gap junction channel-dependent effect.In addition to being localized at the plasma membrane,inner mitochondrial membrane,extracellular vesicle surface,and other structures,Cx43 hexamer has also been found to play a role in positive pro-inflammatory mechanisms,mitochondrial functional metabolism,and targeted uptake of extracellular vesicles in inflammatory diseases.Selective shortened segments control mitochondrial homeostasis by encouraging the polymerization of peri-mitochondrial actin and are involved in the targeted translocation of full-length Cx43 to intracellular structural domains.(3)The development of targeted medicines and the solving of issues like the mechanism of seed cell transformation in tissue engineering-based therapies are both made possible by these two categories of impacts.The interactions of various types of Cx43,however,are frequently not fully taken into account in some of the existing original studies,which confuses the overall characteristics and skews the results.(4)It is necessary to systematically frame the physiological characteristics of Cx43 in different forms and its potential mechanisms in various diseases,so as to provide a reference for the exploration of the Cx43 integrity mechanism and the diagnosis and treatment of multiple diseases.
5.Mechanism of Ferroptosis in Myocardial Cells and Protective Effect of Traditional Chinese Medicine
Haoran LI ; Ce CAO ; Lei LI ; Jianxun LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):260-270
Ferroptosis is a new type of programmed cell death, characterized by iron overload and lipid peroxidation. Cardiovascular disease (CVD) is an ischemic or hemorrhagic disease of the heart caused by various factors, mainly including myocardial infarction, heart failure, etc. Ferroptosis is involved in the process of myocardial cell damage and plays a driving role in the progression of various CVDs. Its main mechanisms include the destruction of iron homeostasis, the production of reactive oxygen species, the disorder of the antioxidant system, mitochondrial membrane damage, endoplasmic reticulum stress, tumor suppressor gene p53, transcription factor Nrf2 pathway, etc. Myocardial injury is one of the causes of death in many patients with heart disease. Monomers or compounds of traditional Chinese medicine have shown good effects in the treatment of myocardial cell injury caused by ferroptosis, including baicalin protecting cardiac microvascular endothelial cells of myocardial ischemia-reperfusion (I/R) rats through intracellular phosphatidylinositol kinase/phosphokinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) pathway, Aralia elata saponin inhibiting myocardial cell ferroptosis through glucocorticoid receptor/p53/solute carrier family 7 members 11 (NR3C1/p53/SLC7A11) pathway, Xinyang tablets improving oxidative stress by regulating phosphorylated serine/threonine protein kinase/stress-activated protein kinase/p53 (MLK3/JNK/p53) signaling pathway. It is of great significance to explore the mechanism of ferroptosis and the protective effect of related traditional Chinese medicine after myocardial cell injury. This article reviews the mechanism of ferroptosis and its relationship with myocardial cells, as well as traditional Chinese medicine monomers and formulas for treating CVDs through the ferroptosis pathway. The article focuses on the pathways and effects of traditional Chinese medicine treatment, so as to provide a reference for the treatment of CVDs with traditional Chinese medicine.
6.Staged Treatment with Chinese Herbal Medicine in a Controlled Ovarian Hyperstimulation of In Vitro Fertilization-Embryo Transfer Programme
Journal of Traditional Chinese Medicine 2024;65(2):219-223
It is believed that kidney deficiency is the fundamental pathogenesis while liver constraint and spleen deficiency, and disharmony of chong (thorough vessel, 冲脉)and ren (conception vessel, 任脉) is the key pathogenesis of infertility patients who adopted controlled ovarian hyperstimulation of in vitro fertilization-embryo transfer (IVF-ET) programme. Therefore, the method of tonifying the kidneys dominantly and treating the liver and spleen simultaneously is proposed, and Chinese herbal medicine is suggested to be used in adjuvant treatment of staged IVF-ET controlled ovrian hyperstimulation. In the regulation stage, modified Liuwei Dihuang Pill (六味地黄丸) can be used to tonify kidney and supplement essence, fortify spleen and nourish liver; in the ovulation promotion stage, modified Wenjing Decoction (温经汤) should be used to warm kidney and assist yang, dispel stasis and nourish blood; in the pre-transplantation endothelial preparation stage, modified Shenling Baizhu Powder (参苓白术散) is suggested to fortify spleen and replenish qi, invigorate blood and resolve stasis; after the transplantation stage, modified Shoutai Pill (寿胎丸) or Taiyuan Decoction (胎元饮) can be taken to fortify spleen and tonify kidney, benefit qi and nourish blood.
7.Arthroscopic all-inside reconstruction of isolated posterior cruciate ligament injury
Jian XIAO ; Hao LI ; Jun YAN ; Fan HU ; Ce WANG ; Gengyan XING
Chinese Journal of Orthopaedics 2024;44(3):139-145
Objective:To investigate the indications and effects of arthroscopic all-inside reconstruction in the treatment of isolated posterior cruciate ligament (PCL) injury.Methods:A retrospective analysis was performed on 47 patients with isolated PCL injury, who underwent arthroscopic all-inside reconstruction in the Third Medical Center of the PLA General Hospital from January 2016 to January 2020. There were 39 males and 8 females, aged 27.14±7.70 years old (range 16-40 years old). The preoperative kneeling-position stress X-ray showed that the degree of tibial posterior displacement was 8-10 mm, which was a complete and isolated Grade II PCL injury. The tibial and femoral tunnels were created through posterior-medial, anteromedial, and anterolateral portals, while the lateral portal to the medial femoral condyle was enlarged to position the tibial tunnel and protect the anterior cruciate ligament. The autologous graft tendon was pulled through the femoral and tibial tunnels secured with an adjustable loop plate. The efficacy was evaluated by evaluating and comparing preoperative and postoperative Lachman test, posterior drawer test, knee range of motion and relaxation, pain visual analogue scale (VAS) and Lysholm score.Results:43 patients were followed up for 35.21±3.88 months (range 12-40 months). The symptoms of knee instability all improved after surgery. At the follow-up of 1 year after surgery, 41 (95%) and 40 (93%) patients showed normal or I-degree laxity in Lachman test and posterior drawer test, respectively. The active range of motion and passive flexion of the knee joint were increased to 90°-110° and 110°-130°, respectively. The Lysholm score was 86.44±4.08 at the first year of follow-up and 90.12±3.33 at the last follow-up with significant difference compared with pre-operations ( P<0.05). The VAS score was 2.07±0.94 at the first year of follow-up and 1.28±0.83 at the last follow-up with significant difference compared with pre-operations ( P<0.05). The Lysholm score and VAS were 90.12±3.33 and 1.28±0.83, which were significantly improved compared to 1-year-follow-up ( P<0.05). Conclusion:Routine kneeling stress X-rays can evaluate the degree of tibial posterior displacement in isolated PCL injuries. With tibial posterior displacement equal to or greater than 10 mm, surgical reconstruction was required. All-inside reconstruction of isolated PCL injury was a safe and minimally invasive surgery to improve symptoms and restore knee functions.
8.Mechanism of Prevention and Treatment of Myocardial Ischemia-reperfusion Injury by Qi-replenishing and Blood-activating Chinese Medicines Based on Theory of Qi and Blood Interacting in Vessels
Han PENG ; Gaojie XIN ; Ce CAO ; Fan GUO ; Lingmei LI ; Jianhua FU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):27-34
Myocardial ischemia-reperfusion injury (MIRI) is a common injury in the treatment of ischemic heart diseases. MIRI can be categorized as chest impediment and palpitation in traditional Chinese medicine, with the pathogenesis related to Qi and blood disharmony. The simultaneous disorders of Qi and blood are the key mechanism of MIRI, and thus the differentiation of Qi and blood syndromes is the prerequisite for the treatment. The theory of Qi and blood interacting in vessels is proposed by our team based on Qi being the commander of blood and blood being the mother of Qi as well as previous pharmacological studies. Specifically, Qi marshals blood by vessels, and the blood carries Qi by vessels. Accordingly, Qi and blood interact in the vessels. MIRI is accompanied by mitochondrial dysfunction, platelet function abnormality, and vascular endothelial damage, which are correlated with Qi deficiency, blood stasis, and vessel damage, respectively. Mitochondrial, platelet, and vascular endothelial structural and functional changes triggered by their interactions are one of the mechanisms by which Qi deficiency, blood stasis, and vessel damage lead to the occurrence and development of MIRI. By exploring the correlations between Qi and mitochondria, between blood and platelets, and between vessels and blood vessels, we can explain the modern scientific content of the theory of Qi and blood interacting in vessels in traditional Chinese medicine. According to the pathogenesis of Qi and blood disharmony in vessels, we discussed the pharmacological mechanisms of Qi-replenishing medicines, blood-activating medicines, and their combinations in the prevention and treatment of MIRI. On the basis of the research achievements in the prevention and treatment of MIRI by Qi-replenishing and blood-activating Chinese medicines based on the theory of Qi and blood interacting in vessels, we analyzed the effects of these medicines on Qi, blood, and vessels. According to the theory of Qi and blood, this article reveals the theoretical basis and scientific connotations of the prevention and treatment of cardiovascular diseases, with the aim of providing new ideas and references for the clinical application of traditional Chinese medicine in the prevention and treatment of cardiovascular diseases.
9.Technical Analysis of Patentee of Domestic Clinical Intelligent Decision Support System
Dongyun ZHANG ; Chencheng LI ; Ce YIN ; Yunqiu ZHANG
Journal of Medical Informatics 2024;45(5):53-58
Purpose/Significance To analyze the technical situation of patent owners in the field of clinical decision support system(CDSS)in China as a whole,so as to provide references for CDSS related technical research.Method/Process Firstly,the CDSS patent data are analyzed from the aspects of application trend,patent disclosure,technology field distribution,etc.,then the patentees are di-vided into different categories,and their technical concerns are analyzed by word frequency and interword vector.Finally,the technology correlation and patent exclusives are analyzed based on the active patentees.Result/Conclusion The number of CDSS patent disclosure shows an overall increasing trend.This field has not formed a technological monopoly in China.Government departments and research in-stitutions should pay attention to the possible financial risks.
10.Implications of left atrial volume index in patients with three-vessel coronary disease: A 6.6-year follow-up cohort study
Ru LIU ; Lei SONG ; Ce ZHANG ; Lin JIANG ; Jian TIAN ; Lianjun XU ; Xinxing FENG ; Linyuan WAN ; Xueyan ZHAO ; Ou XU ; Chongjian LI ; Runlin GAO ; Rutai HUI ; Wei ZHAO ; Jinqing YUAN
Chinese Medical Journal 2024;137(4):441-449
Background::Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD.Methods::This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. Results::During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001). Conclusions::LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.

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