This paper analyzed the traditional Chinese medicine （TCM） and western medical understanding of coronary microvascular disease （CMVD） from the three dimensions of "disease-syndrome-symptom". In western medicine， by summarizing the suspected diagnosis and understanding of CMVD， it is believed that inflammatory responses and vascular endothelial damage are the key mechanisms of the pathogenesis. From the perspective of TCM， the disease location is at blood， vessels and heart， and the fundamental cause is spleen and kidney depletion， closely realted to phlegm， stasis， toxin， wind and qi. Integrating the understanding of both TCM and western medicine， clinical treatment advocates taking the CMVD pathology as the base， and the TCM understanding of pathogenesis as the main focus. The properties of Chinese herbal medicinals is used as the guidance for medication， and the pharmacological understanding as the assisstance of treatment， with the medical history and the severity of the condition are additionally considered. It is finally proposed that during the acute phase， the methods of nourishing yin and resolving toxins， softening hardness and dissipating masses， dispelling wind and unblocking collaterals should be applied to alleviate the emergency. In the subacute phase， the focus should be on raising and lifting qi promote its movement， with flexible use of medicinals that can unblock yang. In the remission phase， the method of tonifying spleen and fortifying kidney should be used to maintain the stability of the condition.

Zhizichi Tang （栀子豉汤）， first recorded in Treatise on Febrile and Miscellaneous Diseases （《伤寒杂病论》） by ZHANG Zhongjing， a medical sage during the Han dynasty， is one of the classical prescriptions in traditional Chinese medicine （TCM）. It plays an important role in the clinical practice of TCM because of its dispersing and transparent characteristics. It is one of the representative parts of “dispersing fire stagnation” and is used mainly for the treatment of various symptoms caused by heat depression in the chest and diaphragm. Pharmacological research has found that it has multiple effects， such as sedative hypnosis and anti-depression， inhibiting oxidative stress and inflammatory responses， regulating the intestinal flora， improving insulin resistance and endocrine metabolism disorders， reducing liver toxicity， and protecting the nerve and heart. Clinical studies have confirmed that its treatment of anxiety， depression， insomnia， and other diseases has few side effects and high safety. Combined with the analysis of TCM syndrome and pharmacological effects， Zhizichi Tang also shows potential in treating other diseases such as heart， lung system， spleen and stomach， liver system， endocrine， and metabolic system diseases. Therefore， the authors， by searching Chinese and foreign literature， especially in recent five years， systematically reviewed and summarized the research progress on Zhizichi Tang in six aspects of TCM syndrome， dosage and administration， chemical composition， pharmacological effects， clinical application， and adverse reactions， aiming to provide a reference for further research and clinical application of Zhizichi Tang.

OBJECTIVES: To investigate the role of the BNIP3-PI3K/Akt signaling pathway in mediating the inhibitory effect of Buyang Huanwu Decoction (BYHWT) on mitochondrial autophagy in human synovial fibroblasts from rheumatoid arthritis patients (FLS-RA) cultured under a hypoxic condition. METHODS: Forty normal Wistar rats were randomized into two groups (n=20) for daily gavage of BYHWT or distilled water for 7 days to prepare BYHWT-medicated or control sera. FLS-RA were cultured in routine condition or exposed to hypoxia (10% O₂) for 24 h wigh subsequent treatment with IL-1β, followed by treatment with diluted BYHWT-medicated serum (5%, 10% and 20%) or control serum. AnnexinV-APC/7-AAD double staining and T-AOC kit were used for detecting apoptosis and total antioxidant capacity of the cells, and the changes in ROS, ATP level, mitochondrial membrane potential and Ca²⁺ homeostasis were analyzed. The changes in mRNA and protein expressions of BNIP3, PI3K and AKT and mRNA expressions of LC3, Beclin-1 and P62 were detected using RT-qPCR and Western blotting. RESULTS: Treatment with BYHWT-medicated serum dose-dependently lowered apoptosis rate of IL-1β-induced FLS-RA with hypoxic exposure. The treatment significantly decreased T-AOC concentration, increased ROS production, autophagosome formation and ATPase levels, and lowered mitochondrial membrane potential and Ca²⁺ level in the cells. In IL-1β-induced FLS-RA with hypoxic exposure, treatment with BYHWT-medicated serum significantly increased BNIP3 protein expression, decreased the protein expressions of PI3K and AKT, increased the mRNA expressions of BNIP3 and P62, and lowered the mRNA expressions of PI3K, AKT, LC3 and Beclin-1 without significantly affecting Beclin-1 protein expression. The cells treated with 5% and 10% BYHWT-medicated serum showed no significant changes in LC3 expression. CONCLUSIONS BYHWT inhibits mitochondrial autophagy in IL-1β-induced FLS-RA with hypoxic exposure possibly by inhibiting BNIP3-mediated PI3K/AKT signaling pathway.
Drugs, Chinese Herbal/pharmacology* ; Arthritis, Rheumatoid/pathology* ; Animals ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Autophagy/drug effects* ; Humans ; Fibroblasts/cytology* ; Rats, Wistar ; Membrane Proteins/metabolism* ; Rats ; Phosphatidylinositol 3-Kinases/metabolism* ; Mitochondria/metabolism* ; Cells, Cultured ; Proto-Oncogene Proteins/metabolism* ; Apoptosis/drug effects* ; Cell Hypoxia ; Synovial Membrane/cytology* ; Male ; Mitochondrial Proteins

In clinical practice, TCM external treatment is used to treat cancer pain, malignant pleural effusion, cancer-related fatigue and other related diseases of non-small cell lung cancer (NSCLC). TCM external treatment can also prevent and treat adverse reactions related to NSCLC treatment measures, such as postoperative cough, radiation-induced lung injury, nausea and vomiting after chemotherapy, bone marrow suppression after chemotherapy, immune and targeted drug-related rash, etc. It mainly uses external use of Chinese materia medica, acupuncture, moxibustion, scraping, acupoint pressing and other methods. Different TCM external treatment method are often used in combination to improve the curative effect. External therapy has been widely used in the treatment of NSCLC related diseases. By balancing yin and yang of viscera, promoting the recovery of body function, it can achieve the role of cancer prevention, improvement of quality of life, control of clinical symptoms, attenuation and effect enhancement.

Objective To investigate biological markers associated with psychotic symptoms in patients with bipolar disorder(BD)based on electronic medical records of patients,and to develop an interpretable risk prediction model that supports the identification of high-risk individuals and that facilitates decision-making for providing clinical intervention in a timely manner.Methods A total of 2 352 patients diagnosed with BD and admitted to West China Hospital,Sichuan University were enrolled using the electronic medical records system of the hospital.The participants were divided into two subgroups,the bipolar disorder depression(BDD)group and the bipolar disorder mania(BDM)group.The logistic regression algorithm was used to train and validate the prediction model,and interpretability methods were used to analyze the contribution of each feature to individuals and the effect of the features on specific target prediction decisions.Results The logistic regression model demonstrated robust predictive performance across the BD,BDD,and BDM cohorts,with areas under the curve(AUC)of the receiver operating characteristic curves always exceeding 81.6%.The core predictive features included platelet distribution width(PDW),fibrinogen(FIB),platelet large cell ratio(P-LCR),activated partial thromboplastin time(APTT),prothrombin time(PT),and triglyceride(TG).The logistic regression model exhibited strong interpretability and was combined with nomograms for intuitive risk quantification and individualized prediction.Conclusion The logistic regression model enables rapid and simple screening of BD patients with psychotic symptoms.Distinct patterns of changes observed in blood biomarkers of BDD and BDM subgroups enrich the understanding of the underlying pathophysiological mechanisms and highlight the importance of considering subtypes in the intervention and management of patients.

ObjectiveTo observe the clinical efficacy and relative mechanism of the Modified Wenshen Yixin Formula （温肾益心方加减， MWYF） as an auxiliary treatment of coronary heart disease （CHD） complicated with hypothyroidism of spleen-kidney yang deficiency. MethodsA total of 135 CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency were included and divided into control group （67 cases） and experimental group （68 cases） according to the patients' wishes of herbal medicine administration. The control group was given conventional western medicine， while the treatment group was additionally given MWYF， 1 dose per day； both groups were treated for 8 weeks. The traditional Chinese medicine （TCM） syndrome scores， angina scores， SF-36 scores， thyroid function indicators including thyroid stimulating hormone （TSH）， thyroxine （T4） and triiodothyronine （T3）， as well as serum cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， monocyte chemoattractant ligand 2 （CCL2）， and tumor necrosis factor-related activator protein （CD40L） levels before and after treatment were compared between the two groups. The dosage and reduction and discontinuation rate of thyroid hormone preparations after treatment were compared between the two groups. The effectiveness regarding TCM syndrome and angina pectoris was evaluated， and the safety was assessed. ResultsBias was adjusted by matching on propensity score， and 102 cases were finally included in the statistical analysis， with 51 cases in each group. The total effective rate regarding TCM syndrome ［94.12% （48/51） versus 64.71% （33/51）］， the total effective rate regarding angina pectoris ［80.39% （41/51） versus 62.75% （32/51）］， and the reduction and discontinuation rate of thyroid hormone preparation ［39.21% （20/51） versus 5.88% （3/51）］ were significantly higher in the experimental group than those in the control group （P＜0.05 or P＜0.01）. After treatment， the total TCM syndrome score， individual scores of major symptoms ， the major symptoms score， the secondary symptoms score， angina pectoris score， and TSH level were significantly reduced （P＜0.01）， while all dimensions of SF-36 scores， T4， T3， and cAMP levels significantly increased in both groups （P＜0.05 or P＜0.01）. The dosage of thyroid hormone preparations and the levels of cGMP， CCL2， and CD40L in the experimental group significantly decreased after treatment （P＜0.01）. When compared between the two groups after treatment， the total TCM syndrome score， the major symptoms score， the scores of individual major symptom （chest tightness， chest pain， fear of cold， cold limbs， waist and kness soreness and weakness）， the secondary symptoms score， angina pectoris score， TSH， cGMP， CCL2， and CD40L levels of the experimental group were significantly lower than those of the control group （P＜0.05 or P＜0.01）， while all dimension scores of SF-36， T4， T3， and cAMP levels were significantly higher （P＜0.01）. A total of three adverse events occurred during treatment， none of which were judged to be related to the interventions of this study. ConclusionMWYF can significantly ameliorate the TCM syndrome， angina pectoris， quality of life and thyroid function in CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency， and can promote the reduction and disconti-nuation of thyroid hormone preparations. The mechanism may be related to the regulation of cAMP/cGMP balance， the regulation of hypothalamic-pituitary-thyroid metabolic axis and the reduction of immune inflammation.

OBJECTIVE To investigate the mechanism of Cichorium glandulosum in the treatment of liver fibrosis by using network pharmacology and experimental validation. METHODS A "component-target-pathway" network was constructed with the help of TCMSP, Pubchem, SwissTargetPrediction and Genecards databases, and the STRING database was used to predict the targets of Cichorium glandulosum against liver fibrosis. KEGG and GO enrichment analysis was performed in the DAVID database, and molecular docking of active ingredients and key targets was docked in AUTODOCK. PDGF-BB was used to induce activation of cells and verify the effects of six compounds, including quercetin, quercetin, chicoric acid, caffeic acid, chlorogenic acid, and isochlorogenic acid, on the proliferation, apoptosis, and liver fibrosis indicators of HSC-T6 cells. Western blotting was used to detect the expression of Ras, ERK1, ERK2, C-fos, and JNK proteins in HSC-T6 cells. RESULTS Network pharmacology screened 239 common targets between the components and liver fibrosis, PPI analysis showed that SRC, STAT3, HSP90AA1 and other targets were key targets, KEGG analysis showed that the pathways affected by Cichorium glandulosum included cancer pathways, metabolic pathways, etc. GO analysis predicted that Cichorium glandulosum mainly affected processes such as signal transduction. The molecular docking results showed that the target that could bind well with the components MAPK1, and the components that could bind well with the target aesculetin, caffeic acid and chlorogenic acid. Compared with the model group, the inhibition effect of the six compounds on PDGF-BB-induced HSC-T6 cell activation was stronger, and all 6 compounds had the effects to reverse the index of liver fibrosis, in which aesculetin had the strongest activity(P<0.01). The expression of Ras, ERK1, ERK2, C-fos, and JNK in HSC-T6 cells decreased after the interventions of 6 compounds. CONCLUSION Each component of Cichorium glandulosum has different anti liver fibrosis effects, which are related to the inhibition of ERK/RAS pathway activation.

Objective To investigate the serum levels of semaphorin 3E(Sema3E)in patients with intracranial aneurysms,revealing the correlation between Sema3E and 1-month poor prognosis after interventional embolization.Methods This study was a prospective single-center cohort study,recruiting 102 consecutive patients with intracranial aneurysms who underwent interventional surgery from June 2020 to January 2022 in our hospital.Among them,11 patients were excluded.Clinical and radiological profiles were collected.Peripheral blood was collected after admission,and serum Sema3E levels were determined by enzyme-linked immunosorbent assay.All the aneurysms were treated with endovascular coil embolization or stent-assisted coil embolization.The primary outcome was evaluated with the Glasgow Outcome Scale(GOS)1 month after interventional therapy.The favorable outcome was defined as a GOS score of 4-5,and a poor outcome was defined as a GOS score of 1-3(severe disability,vegetative state,or death).Univariate and multivariate logistic regression analyses were used to identify potential prognostic factors after interventional therapy.Results The average age of 91 patients with intracranial aneurysm was 59.9±11.0 years old,including 70 cases(76.9%)with favorable prognosis and 21 cases(23.1%)with poor prognosis.The mean preoperative Glasgow Coma Scale(GCS)score of the poor prognosis group(9.4±4.5)was significantly lower than that of the favorable prognosis group(13.3±2.5;P<0.001).In the poor prognosis group,the Hunt-Hess grade(3.6±0.6 vs.2.0±1.3,P<0.001)and the serum Sema3E levels[(6.21±1.58)μg/L vs.(4.38±1.77)μg/L,P<0.001]were significantly higher than those in the favorable prognosis group.Logistic regression analysis showed the Hunt-Hess grade(OR =7.150,P =0.003),stent-assisted coil embolization(OR =15.777,P =0.010),and the serum Sema3E level(OR =1.756,P =0.027)were independent prognostic factors for intracranial aneurysms after interventional therapy.Conclusions The serum Sema3E level is closely correlated with the severity of intracranial aneurysms.The serum Sema3E level is a prognostic factor for interventional treatment,which can be used as a biomarker for predicting poor outcomes.

BACKGROUND:Studies have shown that cardiomyocyte apoptosis is closely related to cardiac decompensation and the cardiac aging process.Appropriate exercise can alter heart pump function in patients with heart failure as well as attenuate aging-induced cardiomyocyte apoptosis,hypertrophy,and fibrotic damage. OBJECTIVE:To investigate the effects of long-term aerobic exercise on cardiomyocyte apoptosis and the thioredoxin system in aging rats. METHODS:Thirty-six male Sprague-Dawley rats were selected and divided into three age groups:3-month-old young group,9-month-old middle-aged group,and 18-month-old elderly group,with 12 rats in each group.Within each age group,rats were randomly assigned to sedentary and exercise subgroups(n=6 per group).The sedentary groups did not undergo any exercise intervention.The exercise groups were acclimated to a treadmill environment and subsequently subjected to treadmill exercise for 45 minutes per day,at a speed of 15 m/min,5 days per week for 10 weeks in total.At 24 hours after the final intervention,ELISA was employed to measure serum levels of cardiac troponin I and creatine kinase-MB in rats.TUNEL assay was utilized to detect cardiomyocyte apoptosis,while western blot assay was employed to assess the protein expression of Bax,Bcl-2,Caspase 3,thioredoxin-1,thioredoxin-2,thioredoxin reductase-1,thioredoxin reductase-2,thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardial tissue. RESULTS AND CONCLUSION:Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged sedentary groups and elderly exercise group(P<0.01).Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged exercise groups and elderly exercise group(P<0.01).Positive apoptotic cells in rat myocardial tissue,along with increased protein expression of Bax and Caspase 3,exhibited an age-related upward trend,while Bcl-2 protein expression showed a declining trend.In comparison with the sedentary groups within each age category,the number of apoptotic cardiomyocytes and the expression of Bax and Caspase 3 proteins were reduced to different degrees,and the expression of Bcl-2 protein was increased to different degrees in the corresponding exercise groups.Compared with the young sedentary group,middle-aged sedentary group and elderly exercise group,elderly sedentary rats showed a significant decrease in the expression of myocardial thioredoxin 1,thioredoxin 2,thioredoxin reductase 1,and thioredoxin reductase 2 proteins(P<0.05,P<0.01).The expression of myocardial thioredoxin 1,thioredoxin 2,and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the young exercise group(P<0.05,P<0.01),while the expression of thioredoxin reductase 1 and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the middle-aged exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly sedentary group than the young sedentary group,middle-aged sedentary group and elderly exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly exercise group than the young exercise group and middle-aged exercise group(P<0.01).To conclude,aerobic exercise may enhance the anti-apoptotic effects of thioredoxin by down-regulating the expression of thioredoxin-interacting protein in aging rat hearts,leading to the downregulation of apoptosis signal-regulated kinase 1 and P38 mitogen-activated kinase protein,thereby alleviating myocardial cell apoptosis in aging rat hearts.

Objective:To investigate the inhibitory effect of lycium barbarum polysaccharide(LBP)on apoptosis of Schwann cells(SCs)and its related mechanisms.Methods:The autophagy model was prepared by starvation treatment of RSC96 cells for 12 h,and the expressions of autophagy related proteins LC3 and p62 were detected by Western Blot.Cell Counting Kit-8(CCK-8)kits were used to detect the optimal concentration of LBP.RSC96 cells were randomly divided into Control group,Starvation group and Starvation+LBP group.The expressions of autophagy associated pro-teins(LC3,p62)and myelin associated proteins(p75NTR,PMP22,S100β)were detected by Western Blot or immu-nofluorescence staining.Annexin V/PI fluorescence staining was used to detect apoptosis of the cells.The cell cycle was analyzed by flow cytometry.Western Blot analysis of phosphorylation levels of pathway proteins Erk1/2 and Akt.Results:CCK8 results showed that the viability of damaged RSC96 cells was the best when LBP was 300 μg/ml.Com-pared with Control group,LC3-Ⅱ/LC3-I levels in Starvation group were significantly increased(P＜0.05).Compared with Starvation group,the proportion of apoptotic and necrotic cells in Starvation+LBP group was significantly de-creased,and the proportion of cells in S and G2/M stages was increased.The expression levels of LC3-Ⅱ,p75NTR,PMP22 and S100β were increased,while the expression levels of autophagy substrate protein p62 were decreased.In-creased expression of pathway protein p-Erk1/2(P＜0.05),while the expression of p-Akt protein decreased slightly.Conclusion:LBP can inhibit the apoptosis of SCs and promote the expression of myelin-related proteins by enhancing autophagy,which is related to the activation of Erk1/2 and/or the inhibition of Akt.