OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

ObjectiveTo investigate the mechanisms by which Renshentang treats atherosclerosis （AS） in mice， focusing on the regulation of endothelial inflammatory responses mediated by transient receptor potential vanilloid subtype 1 （TRPV1）. MethodsAn AS model was established in apolipoprotein E knockout （ApoE^-/-） mice fed a high-fat diet. The mice were randomly divided into a simvastatin group （0.02 g·kg^-1·d^-1） and low-， medium-， and high-dose Renshentang groups （1.77， 3.54， 7.08 g·kg^-1·d^-1）， with 12 mice in each group. ApoE^-/- mice were fed a high-fat diet and treated simultaneously. C57BL/6J mice fed a normal diet served as the normal group （n=9）. After continuous administration for 12 weeks， mice were anesthetized and the aortas were collected. Oil Red O staining was used to observe lipid plaque formation in the aorta. Hematoxylin-eosin （HE） staining was performed to examine pathological changes in the aortic root. Immunohistochemistry was used to analyze the levels of pro-inflammatory factors tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， as well as the expression of TRPV1， phosphorylated phosphoinositide 3-kinase （p-PI3K）， and phosphorylated protein kinase B （p-Akt） in the aortic root. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect endothelial nitric oxide synthase （eNOS） mRNA expression in the aorta， and Western blot was used to detect TRPV1 protein expression. ResultsCompared with the normal group， the model group showed a significant increase in aortic plaque formation （P<0.01） and significantly elevated levels of TNF-α and IL-1β in the aortic root （P<0.01）. The expression levels of TRPV1， p-PI3K， and p-Akt were decreased （P<0.05， P<0.01）， and eNOS mRNA expression was reduced （P<0.05， P<0.01）. Compared with the model group， all Renshentang groups significantly reduced aortic plaque formation （P<0.01）， significantly decreased TNF-α and IL-1β levels （P<0.01）， and markedly increased the expression levels of TRPV1， p-PI3K， p-Akt， and eNOS mRNA （P<0.05， P<0.01）. ConclusionRenshentang may inhibit endothelial inflammation and suppress the formation of AS by increasing TRPV1 protein expression and up-regulating the PI3K/Akt/eNOS signaling pathway， which may be one of the molecular mechanisms underlying its therapeutic effect against AS.

Objective To explore the clinical efficacy of single-branch intraoperative stent combined with modified bilateral cerebral perfusion in type A aortic dissection. Methods A retrospective analysis was conducted on the clinical data of patients who underwent surgery for type A aortic dissection at the First Affiliated Hospital of Anhui Medical University from January 2021 to May 2024. Patients were divided into a test group (single branch stent+modified bilateral cerebral perfusion) and a control group (traditional surgical method, straight stent+unilateral cerebral perfusion) according to the surgical method. Propensity score matching analysis was used to match the two groups of patients with a ratio of 1:1, and the perioperative data and clinical efficacy after matching were compared. Results A total of 14 patients were included in the test group, including 13 males and 1 female, with an average age of (46.6±16.4) years. There were 56 patients in the control group, including 38 males and 18 females, with an average age of (52.1±11.7) years. After propensity score matching, 14 patients were included in each group. Compared with the control group, the ventilator support time [(27.4±24.3) h vs. (93.4±88.0) h, P=0.018], length of stay in the intensive care unit [(2.8±1.8) d vs. (8.7±6.5) d, P=0.009], and postoperative awakening time [(5.4±2.2) h vs. (8.8±4.8) h, P=0.047] in the test group were shorter than those in the control group, with statistically significant differences. There was no statistical difference in neurological complications between the two groups (P=1.000). Conclusion Single-branch intraoperative stent combined with modified bilateral cerebral perfusion can effectively shorten ventilator support time, length of stay in the intensive care unit, and postoperative awakening time, and is safe and effective for the treatment of type A aortic dissection, which is worth further promotion.

ObjectiveTo observe the clinical efficacy and safety of Tianmeng Lingjiao Formula（天礞羚角方， TLF） as an adjunctive therapy for paroxysmal atrial fibrillation （PAF） with phlegm-heat harassing the interior syndrome. MethodsNinety patients with PAF and phlegm-heat harassing the interior syndrome were enrolled and randomly assigned in a 2∶1 ratio to test group （60 cases） and control group （30 cases）. The control group received conventional western medicine， while the test group received TLF in addition to the conventional treatment， with one dose administered daily. The treatment course for both groups was 4 weeks. The efficacy of traditional Chinese medicine （TCM） syndrome and the rate of atrial fibrillation （AF） conversion were compared between groups. Assessments included AF burden， frequency and duration of AF episodes， TCM syndrome scores， and European Heart Rhythm Association （EHRA） AF symptom classification before and after treatment. Safety indicators such as blood routine， urine routine， stool routine， liver function， kidney function， and electrolytes were also monitored. Adverse events were recorded. ResultsA total of 82 patients completed the study （54 in the test group and 28 in the control group）. After treatment， AF burden， the frequency and duration of AF episodes， and TCM syndrome scores were significantly reduced in both groups， and the test group showed lower indicators than the control group （P＜0.01 or P＜0.05）. The AF conversion rate was 25.93% （14/54） in the test group， significantly higher than 3.57% （1/28） in the control group （P＜0.05）. The total effective rate for TCM syndrome efficacy was 83.33% （45/54） in the test group， which was significantly higher than 67.86% （19/28） in the control group （P＜0.05）. After treatment， the EHRA atrial fibrillation symptom severity in the test group showed significant improvement， and the improvement in atrial fibrillation symptoms was superior to that in the control group （P＜0.01or P＜0.05）. No significant abnormalities were observed in safety indicators， and no adverse events occurred during the trial. ConclusionTLF as an adjunctive therapy can reduce AF burden， enhance the conversion rate of AF， decrease the frequency and duration of episodes， and improve clinical symptoms in patients with paroxysmal atrial fibrillation presenting with phlegm-heat harassing the interior syndrome， with a favorable safety profile.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective:To prepare decellularized extracellular matrix (dECM)-gelatin methacryloyl (GelMA) composite hydrogels and to study their effects on hepatocyte proliferation.Methods:Hepatic dECM was prepared by elution, and GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels were prepared by pepsin solubilization. The morphology of normal liver and dECM liver was observed by eyes and scanning electron microscopy using hematoxylin-eosin, Sirius red and periodate-Schiff staining, respectively. The internal structure of the dECM-GelMA composite hydrogels was observed by scanning electron microscopy, and the pore diameter was measured. Liver HL-7702 cells were co-cultured with GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels, and the cell proliferation viability was determined by cell counting kit-8. The expression of proliferating cell nuclear antigen (PCNA), Wnt family protein 5a (Wnt5a), β-catenin, extracellular-regulated protein kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting. Comparisons were made using independent sample t-test or one-factor analysis of variance. Results:After decellularization, the hepatocyte morphology showed rounded depressions, and the extracellular matrix structure was intact. The GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels showed inernally porous structures. The pore diameter increased from (3.06±1.35) μm in the GelMA hydrogel to (16.01±4.02) μm in the 50% dECM-GelMA composite hydrogel. On the 3rd, 5th and 7th day, the relative cell proliferation was higher in the 50% dECM-GelMA composite hydrogel group than that in the GelMA hydrogel group (1.89±0.04 vs 1.53±0.01, 9.36±0.04 vs 3.89±0.09, 7.15±0.27 vs 4.89±0.15, all P<0.05). The relative expression levels of PCNA, Wnt5a, β-catenin, and p-ERK1/2/ERK1/2 proteins in the 50% dECM-GelMA composite hydrogel group were higher than those in the GelMA hydrogel group (2.14±0.04 vs 1.00±0.03, 2.36±0.09 vs 1.00±0.08, 1.45±0.03 vs 1.00±0.04, 1.43±0.04 vs 1.00±0.01, all P<0.05). Conclusions:A dECM-GelMA composite hydrogel can be prepared, which may promote hepatocyte proliferation by upregulating the phosphorylation of ERK1/2 and activating Wnt/β-catenin signaling pathway.

Objective To explore the five-circuit and six-qi features of birth time and onset time of children with acute lymphoblastic leukemia(ALL).Methods A total of 877 cases of children with ALL from Children's Hospital of Soochow University from June 2021 to February 2023 were collected,and their five-circuit and six-qi features of birth time and onset time were analyzed.And then the correlation of five-circuit and six-qi features of birth time and onset time with ALL was explored preliminarily,and the pathogenic characteristics of congenital factors and acquired pathogenic factors were revealed.Results(1)The children who were born in the year with the heavenly stems being bing(the 3rd of the ten heavenly stems)and ding(the 4th of the ten heavenly stems)and with the earthly branches being shen(the 8th of the twelve earthly branches)and you(the 9th of the twelve earthly branches)are prone to suffer from ALL,and the birth year of children with ALL had the five-circuit and six-qi features of the joining of guest circuit with dominant circuit being rebellious.ALL is commonly seen in the year with the heavenly stems being geng(the 7th of the ten heavenly stems)and xin(the 8th of the ten heavenly stems)and with the earthly branches being zi(the 1st of the twelve earthly branches)and chou(the 2nd of the twelve earthly branches),and the onset year of ALL in children had the five-circuit and six-qi features of the yearly circuit being gold-circuit and water-circuit,sitian-zaiquan yearly circuit qi being shaoyin monarch-fire with yangming dryness-gold,taiyin damp-earth with taiyang cold-water,and the qi-circuit assimilation relationship being celestial correspondence,same celestial correspondence,celestial correspondence in convergent year,disharmony,mildly-rebellious,and celestial restriction.Conclusion Gold-dryness and water-cold are the congenital factors and acquired pathogenic factors of ALL.The onset of ALL in children is closely related to qi insufficiency and qi stagnation of wood and fire in five-circuit and six-qi theory.

Atherosclerosis(AS)is the important pathological foundation of cardiovascular and cerebrovascular diseases.There is a high degree of consistency between AS and yin-nature carbuncles in terms of etiology,disease-location,severity of illness,pathogenesis,therapies and progression of disease.Based on the theory of yin-nature carbuncles and after the analysis of the characteristics of zang-fu organs mainly involved in AS and the intricate pathogenesis of AS,this paper put forward the use of warming-eliminating,warming-expulsing and warming-tonifying therapies together for treating AS,and established Chiqilin Powder,the experienced prescription including triplet medicinals,i.e.,Notoginseng Radix et Rhizoma,Draconis Sanguis,and Fermentum Rubrum.In the prescription,Notoginseng Radix et Rhizoma mainly has the warming-tonifying and warming-expulsing actions,and also exerts the warming-eliminating actions;Draconis Sanguis exerts eliminating,expulsing and tonifying actions simultaneously;Fermentum Rubrum mainly has the warming-tonifying and warming-eliminating actions,and also exerts the warming-expulsing actions.In clinical practice,the application of Chiqilin Powder in the treatment of AS patients with yang deficiency and phlegm blended with blood stasis syndrome has achieved remarkable therapeutic effects,which will provide reference for the clinical use of Chinese herbal medicine in the treatment of AS.

Background: Bushen Zhuanggu Formula (BZF), derived from the classic Yougui Pills, has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head (NONFH), particularly by promoting bone repair. However, its underlying mechanisms remain unclear. Objective: This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH. Materials and methods: A total of 518 potential BZF targets were identified from the ETCM v2.0 database. Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls. A drug target-disease gene interaction network was constructed to identify candidate BZF targets involved in NONFH pathogenesis. In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH. Results: Network analysis identified key pathways associated with blood circulation obstruction, immune-inflammatory imbalance, and abnormal bone metabolism. Protein kinase C alpha (PKCA), Ras proto-oncogene (RAS), mitogen-activated protein kinase 3(ERK), ETS proto-oncogene 1 (ETS1), and receptor activator of nuclear factor-κB ligand (RANKL) formed a signaling axis implicated in NONFH pathogenesis. BZF treatment alleviated joint inflammation, preserved trabecular bone morphology, reduced bone loss, and promoted bone repair. Mechanistically, BZF significantly downregulated the expression of PKCA, RAS, ERK, ETS1, and RANKL, improved blood circulation, and inhibited osteoclast activation while promoting osteoblast activation. Conclusion: BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis, thereby reversing dysregulated bone metabolism.

OBJECTIVE To observe the clinical efficacy of Yijinjing in the treatment of elderly sarcopenia and its effect on chro-nic inflammatory response in patients,and to explore the Yijinjing exercise prescription suitable for elderly patients with sarcopenia.METHODS A total of 120 elderly patients with sarcopenia admitted to the Department of Rehabilitation Medicine,Suzhou Hospital of Traditional Chinese Medicine from September 2022 to September 2024 were selected and randomly divided into a control group and a Yijinjing group,with 60 cases in each group.The control group received health education and dietary guidance,and the Yijinjing group received Yijinjing exercises on the basis of the intervention of the control group.The changes in skeletal muscle mass,upper and lower limb muscle strength,muscle thickness,muscle cross-sectional area,physical fitness and chronic inflammation level were observed in the two groups before and after the intervention.RESULTS After intervention,the skeletal muscle mass,grip strength,30 s sit-stand test times,rectus femoris thickness and cross-sectional area,vastus intermedius thickness,and physical fit-ness assessment of the patients in the Yijinjing group were significantly increased compared with those before treatment(P<0.05),and the indicators after intervention were higher than those in the control group(P<0.05);the serum TNF-α and IL-18 levels in the Yi-jinjing group were significantly decreased compared with those before treatment(P<0.05),and the indicators after intervention were lower than those in the control group(P<0.05);there was no statistically significant change in the biceps brachii thickness and serum IL-6 level in the Yijinjing group compared with those before treatment(P>0.05);there was no significant correlation between the bi-ceps brachii thickness and grip strength after Yijinjing intervention,r=0.139 8,P>0.05;there was a significant negative correlation between the TNF-α level and grip strength after Yijinjing intervention,r=-0.313 8,P<0.05.CONCLUSION Yijinjing exercises can improve muscle mass and strength in elderly patients with sarcopenia,and improve the physical fitness of patients,which may be related to improving the chronic inflammatory state of the body.