1.Relationship between BCR/ABL gene expression and recurrence before and after allogeneic transplantation in Ph chromosome positive acute lymphoblastic leukemia
Hui XUE ; Dongnan LI ; Yadi ZHAO ; Chao CHEN ; Zongyuan XIE
Chinese Journal of Tissue Engineering Research 2026;30(1):139-144
BACKGROUND:BCR/ABL gene is a specific gene of Ph chromosome-positive acute lymphoblastic leukemia,and its expression level has become a sensitive indicator for monitoring minimal residual disease before and after allogeneic hematopoietic stem cell transplantation.However,whether the expression level of BCR/ABL gene before transplantation affects the efficacy of transplantation and how to guide the early intervention of relapse with tyrosine kinase inhibitors after transplantation is still inconclusive.OBJECTIVE:To explore the relationship between BCR/ABL gene expression and recurrence in patients with Ph chromosome positive acute lymphoblastic leukemia before and after related and allogeneic hematopoietic stem cell transplantation.METHODS:Twenty-four patients with Ph chromosome positive acute lymphoblastic leukemia who achieved complete hematological remission and underwent allogeneic hematopoietic stem cell transplantation were selected at the Affiliated Hospital of North China University of Science and Technology between January 2015 and December 2022.Real time fluorescence quantitative polymerase chain reaction was used to dynamically detect the expression levels of BCR/ABL genes during treatment,representing minimal residual disease.Based on BCR/ABL gene expression,tyrosine kinase inhibitors combined with chemotherapy was administered before transplantation to select the timing of allogeneic hematopoietic stem cell transplantation.After transplantation,the disease status was evaluated to guide the use of tyrosine kinase inhibitors,and an early intervention plan for recurrence was developed.RESULTS AND CONCLUSION:Follow-up was until December 2023,with a median follow-up time of 49(12-82)months.There were 8 cases of hematological recurrence,with a median recurrence time of 14(8-39)months and a cumulative recurrence rate of 33%(8/24).Univariate analysis showed that recurrence after allogeneic hematopoietic stem cell transplantation was not significantly correlated with gender,age,extramedullary complications,time from diagnosis to transplantation,HLA typing,acute graft-versus-host disease,and chronic graft-versus-host disease(P>0.05).There was a significant correlation between the relief treatment course and minimal residual disease levels before transplantation.The second hematology completely resolution and positive minimal residual disease before transplantation had a higher hematological recurrence rate(P<0.05).The 3-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 27%,63%,and 74%;the 5-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 38%,57%,and 74%,respectively.It is concluded that Ph chromosome positive acute lymphoblastic leukemia patients with BCR/ABL gene positive before transplantation have a higher recurrence rate.BCR/ABL gene expression after transplantation can guide the application of tyrosine kinase inhibitors and serve as a basis for early intervention in recurrence.
2.Cerium dioxide nanoparticles regulate expression of inflammatory factors in M1 macrophages and affect fibroblast co-culture system
Peisen XIE ; Zhenpeng GUAN ; Xianjie WEI ; Keshi ZHANG ; Qingyuan KANG ; Wentao XIAO ; Xiaoshuai GUO
Chinese Journal of Tissue Engineering Research 2026;30(2):375-383
BACKGROUND:Macrophage polarization plays a key role in chronic inflammatory joint diseases such as rheumatoid arthritis.Cerium dioxide(CeO2)nanoparticles have a wide range of biomedical applications such as modulating the local inflammatory microenvironment of tissues.OBJECTIVE:To investigate the role of CeO2 nanoparticles on macrophage polarization and inflammatory factor expression,as well as inflammatory modulation in a co-culture system of macrophages and fibroblasts.METHODS:(1)CeO2 nanoparticles were dispersed and observed morphologically by transmission electron microscopy.(2)Human leukemia monocytes(THP-1)were induced to differentiate and establish the M1 macrophage pro-inflammatory cell model of rheumatoid arthritis.The cells were divided into M0 group(undifferentiated macrophages),M1 group(successful macrophage modeling),CeO2 nanoparticle treatment group(M1 group with CeO2 nanoparticle treatment),and dexamethasone control group(M1 group with dexamethasone treatment)and incubated for 48 hours.The effects of CeO2 nanoparticles on the expression of inflammatory factors(endogenous nitric oxide synthase,CD86,CD80)in M1 macrophages and M1 macrophage phenotype(CD80,CD206)were detected by RT-qPCR,western blot assay,and flow cytometry.(3)A co-culture system of macrophages and fibroblasts was established,and CeO2 nanoparticles acted on the upper macrophages.The regulation of CeO2 nanoparticles on the expression of inflammatory factors(interleukin-6,tumor necrosis factor-α,cyclooxygenase-2,and endogenous nitric oxide synthase)of fibroblasts in the co-culture system was observed at the mRNA and protein levels.RESULTS AND CONCLUSION:(1)Transmission electron microscopy showed that the diameter of CeO2 nanoparticles was(19.5±2.0)nm.(2)Compared with the M0 group,the mRNA of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the M1 group were upregulated.Compared with the M1 group,the mRNA expression of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the CeO2 nanoparticle treatment group were downregulated.Flow cytometry showed that 20 nm CeO2 nanoparticles downregulated the number of M1 macrophages.(3)Compared with the M1 group,20 nm CeO2 nanoparticles downregulated the mRNA and protein expression of inflammatory factors(tumor necrosis factor α,interleukin 6,cyclooxygenase 2,and endogenous nitric oxide synthase)in the co-culture system HFL1 cells.(4)The results showed that 20 nm CeO2 nanoparticles can alleviate inflammation in the co-culture system by inhibiting the expression of pro-inflammatory factors in M1 macrophages,providing a new idea for the treatment of inflammatory diseases such as rheumatoid arthritis.
3.Effect and mechanism of collagen combined with microneedles in treatment of skin photoaging
Fengyi TAN ; Jiamin XIE ; Zhenfeng PAN ; Xinxu ZHANG ; Zetai ZHENG ; Zhiying ZENG ; Yanfang ZHOU
Chinese Journal of Tissue Engineering Research 2026;30(2):451-458
BACKGROUND:Collagen combined with microneedling therapy has gradually become an important means of improving skin photoaging.OBJECTIVE:To summarize and explore the main mechanism and clinical application status of collagen combined with microneedle therapy.METHODS:PubMed,China National Knowledge Infrastructure,and ScienceDirect databases were searched for Chinese and English literature published before August 2024.Chinese and English search terms were"ultraviolet radiation,photoaging,collagen,microneedling,clinical applications."Finally,74 articles were included for summary.RESULTS AND CONCLUSION:Collagen treats skin photoaging through mechanisms such as inhibiting matrix metalloproteinase expression,retaining skin moisture,and reducing melanin formation.Microneedles can better promote the penetration of collagen into deep layers of the skin,breaking down the skin's barrier and increasing the absorption rate.Collagen combined with microneedles has various beneficial effects for treating skin photoaging,such as whitening,anti-wrinkle,improving skin elasticity,shrinking pores,and repairing skin barriers.It also has the advantages of easy operation,significant effects,and high safety.Currently,the research on collagen combined with microneedling therapy is still in its early stages,and achieving clinical application may become a key research direction in the future.The clinical application of collagen combined with microneedles for the treatment of photoaging still faces many challenges,such as exploring the optimal mechanical structure and materials of microneedles,selecting appropriate microneedle types,and insufficient clinical evidence that collagen combined with microneedles can further delay the treatment of skin photoaging.
4.In vitro biocompatibility of graded glass infiltrated ultra-translucent zirconia
Qiya ZHANG ; Yixiang TONG ; Shijiao YANG ; Yumeng ZHANG ; Ling DENG ; Wei WU ; Yao XIE ; Jian LIAO ; Ling MAO
Chinese Journal of Tissue Engineering Research 2026;30(2):443-450
BACKGROUND:In previous studies,glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by a double sintering method to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials that can maintain high transparency and high flexural strength.OBJECTIVE:To evaluate the in vitro biocompatibility of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials.METHODS:(1)Glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by double sintering to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia(or 5Y-PSZ ultra-translucent zirconia,3Y-TZP transparent zirconia)was placed in DMEM culture medium containing 10%fetal bovine serum for 12,24 and 72 hours,and the surface area ratio of culture medium to sample was 3 mL/cm2,and the 12-,24-and 72-hour material extracts were obtained.(2)After culturing mouse fibroblast L929 for 24 hours,the original culture medium was discarded and divided into 7 groups for culture:the control group was replaced with DMEM culture medium containing 10%fetal bovine serum by volume,and the other 6 groups were replaced with 24-hour extract of 3Y-TZP transparent zirconia,24-hour extract of 5Y-PSZ ultra-translucent zirconia,24-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,72-hour extract of 3Y-TZP transparent zirconia,72-hour extract of 5Y-PSZ ultra-translucent zirconia,and 72-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.After 1,3,and 5 days of culture,cell growth was observed under a microscope,and the cell proliferation rate was obtained by CCK-8 assay to determine cytotoxicity.(3)Human anticoagulated blood was mixed with 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,5Y-PSZ ultra-translucent zirconia,and 3Y-TZP transparent zirconia,and the hemolysis rate was detected after 0.5 hours.Human anticoagulated blood was mixed with 12-hour extract of 3Y-TZP transparent zirconia,12-hour extract of 5Y-PSZ ultra-translucent zirconia,and 12-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,and the hemolysis rate was detected after 0.5 hours.RESULTS AND CONCLUSION:(1)Under the microscope,it could be seen that the number of cells in each group increased with the extension of culture time,and the cell morphology of each experimental group was basically the same as that of the control group.The cytotoxicity grade of the 24-hour extract of 3Y-TZP transparent zirconia group on the first day of culture was grade 0,and the cytotoxicity grade of the other experimental groups at each time period was grade 1.(2)Neither the material nor the material extract caused obvious hemolytic reaction,and the hemolytic rate was less than 5%.(3)The results showed that 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia had no significant effect on the growth and proliferation of mouse fibroblasts L929,and did not cause hemolytic reaction with human blood,and had good in vitro biocompatibility.
5.Autophagy regulates early embryonic development in mice via affecting H3K4me3 modification
Jing HU ; Ling ZHU ; Juan XIE ; Deying KONG ; Doudou LIU
Chinese Journal of Tissue Engineering Research 2026;30(5):1147-1155
BACKGROUND:Autophagy,as a key regulatory mechanism of cell development,plays an important role in different stages of embryonic development.The mechanism of how autophagy regulates embryonic development through histone modifications is currently unclear.OBJECTIVE:To investigate the effect of autophagy on trimethylation of lysine 4 on histone H3(H3K4me3)modification in embryos and its effect on embryonic development.METHODS:Mouse fertilized eggs were divided into control and autophagy inhibitor-treated groups(chloroquine phosphate-treated group and 3-methyladenine-treated group),and cultured in vitro to different periods of time,and were then classified as early 2-cell embryos,middle 2-cell embryos,late 2-cell embryos,4-cell embryos,8-cell embryos,morula stage,and blastocyst stage.Levels of reactive oxygen species,autophagy marker proteins LC3B and P62,DNA loss marker γH2AX,and H3K4me3 were analyzed by immunofluorescence assay in late 2-cell embryos of each group.Changes in H3K4me3 modification in late 2-cell embryos of each group were detected by CUT&Tag.RESULTS AND CONCLUSION:(1)Autophagy inhibition caused embryo development arrest.(2)There was no significant difference in reactive oxygen species and γH2AX between the autophagy inhibitor-treated groups and control group.(3)H3K4me3 levels were significantly elevated in the autophagy inhibitor-treated group compared with the control group.(4)CUT&Tag results showed a significantly increased H3K4me3 peaks on the proximal promoter region of the genes after autophagy inhibition and an increase of H3K4me3-specific modification genes.These findings suggest that autophagy may affect embryonic development by regulating the level of H3K4me3 modification.
6.Establishment and validation of a prediction model for mineral and bone disorder in maintenance hemodialysis patients
Yanling HUANG ; Jiping SHEN ; Kai CAO ; Ping XIE ; Jinyuan ZHAO ; Rulian LIANG
Chinese Journal of Clinical Medicine 2026;33(1):58-64
Objective To explore the risk factors for mineral and bone disorder in maintenance hemodialysis patients, and to construct and validate a nomogram prediction model. Methods A total of 306 patients undergoing maintenance hemodialysis at Shanghai Eighth People’s Hospital from January 2021 to May 2025 were selected as study subjects and randomly divided into a training set (n=214) and a validation set (n=92) in a 7∶3 ratio. In the training set, patients were divided into a normal bone mineral metabolism group and an abnormal bone mineral metabolism group, and related factors were compared between the two groups. The multivariate logistic regression analysis was used to identify the influencing factors of mineral and bone disorder in maintenance hemodialysis patients in the training set, and a nomogram prediction model was constructed. ROC curves were drawn to evaluate the ability of the nomogram model for predicting mineral and bone disorder in these patients. Calibration curves and Hosmer-Lemeshow goodness-of-fit test were used to analyze the consistency of the predictive probability of nomogram model and actual probability of mineral and bone disorder in these patients. The decision curve was used to assess the clinical benefit using nomogram prediction model. Results Among the 306 hemodialysis patients, 254 patients had mineral and bone disorder, accounting for 83.01%. Among the 214 patients in the training set, 177 had mineral and bone disorder, accounting for 82.71%. In the training set, age, gender, body mass index (BMI), hypertension rate, dialysis age, blood urea nitrogen (BUN), hemoglobin (Hb), albumin (ALB), alkaline phosphatase (ALP), serum creatinine (SCr), uric acid (UA), estimated glomerular filtration rate (eGFR), and rate of taking phosphate binders were statistically significant different between the two groups (P<0.05). The multivariate logistic regression analysis showed higher age, female, hypertension, longer dialysis duration, decreased eGFR, and not taking phosphate binders were identified as risk factors for mineral and bone disorder in maintenance hemodialysis patients (P<0.01). The nomogram prediction model was constructed. The area under the ROC curve of the model for mineral and bone disorder in the training set and validation set was 0.895 (95%CI 0.850-0.941) and 0.881 (95%CI 0.830-0.932), respectively, with maximum Youden indice of 0.650 and 0.600, sensitivity of 0.856 and 0.849, and specificity of 0.794 and 0.751. The Hosmer-Lemeshow test showed the nomogram prediction model had good consistency in predictive probabilities with actual probabilities in training set and validation set. The decision curve showed the nomogram model could bring clinical net benefits when the threshold probabilities in the training set and validation set were less than 0.96 and 0.91. Conclusions The nomogram prediction model constructed based on six independent risk factors including age, gender, hypertension, dialysis duration, eGFR, and using phosphate binders or not, shows good discrimination and calibration, with good clinical predictive ability, which could provide guidance for the management of maintenance hemodialysis patients.
7.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.
8.Ameliorative effect and mechanism of Forsythia suspensa-Lonicera japonica herb pair on acute lung injury via regulating serum exosomal miRNA
Zhaohua CHEN ; Shumin XIE ; Wanshun CHANG ; Yuqing HAN ; Yanwen CHEN ; Yanhui ZHU ; Mingzhuo CAO ; Haiying HUANG
China Pharmacy 2026;37(3):305-310
OBJECTIVE To study the ameliorative effect and mechanism of Forsythia suspensa-Lonicera japonica herb pair on acute lung injury (ALI) based on serum exosomal microRNA (miRNA). METHODS The rats were randomly divided into a blank group (normal saline), model group (nomal saline), and F. suspensa-L. japonica herb pair group (2.55 g/kg), with 10 rats in each group. Except for the blank group, the other groups were used to establish an ALI model by intratracheal dripping of 5 mg/ mL lipopolysaccharides. After modeling, each group was given relevant medicine/normal saline intragastrically, once a day, for 3 consecutive days. After the last medication, the pathological status of lung tissue was observed; lung wet-to-dry weight ratio and leukocyte counts in bronchoalveolar lavage fluid (BALF) were determined. The levels of inflammatory factors [tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), IL-10] in BALF were determined. Exosomes were isolated from rat serum, and high- throughput sequencing technology was employed to screen differentially expressed miRNA within the exosomes, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Based on the screened differentially expressed miRNA and the enriched KEGG pathways, in vitro cellular experiments were conducted for validation. RESULTS The animal experimental results demonstrated that after intervention with the F. suspensa-L. japonica herb pair, the wet-to-dry weight ratio, the number of leukocytes in BALF, as well as the levels of TNF-α and IL-1β in BALF of ALI rats were all significantly reduced (P<0.01), while the level of IL-10 was significantly increased (P<0.01). The results of high-throughput sequencing experiments revealed that the F. suspensa-L. japonica herb pair could significantly up-regulate the expressions of miR-345-3p, miR-194-5p, miR-653-5p, and others in exosomes. Among them, the KEGG pathways involved in the target genes of differentially expressed miRNA included the hypoxia-inducible factor-1(HIF-1) signaling pathway, among others. The results of cellular E-mail:huang.haiying@126.com validation experiments showed that overexpressed miR-345-3p could significantly elevate the level of IL-10 in the cell supernatant (P<0.01), while significantly reducing the levels of TNF-α and IL-1β in the cell supernatant, as well as the mRNA and protein expression levels of protein kinase B1, phosphatidylinositol 3- kinase, and HIF-1α (P<0.01). CONCLUSIONS F. suspensa-L. japonica herb pair can alleviate inflammatory responses and thereby exert a therapeutic effect in improving ALI by up-regulating the expression of miR-345-3p in serum exosomes and inhibiting the activity of the HIF-1 signaling pathway.
9.Effect of Changji'an Formula (肠激安方) on the miR-29b-3p/TRAF3/NF-κB/MLCK Axis in Colonic Tissues in Diarrhea-predominant Irritable Bowel Syndrome Model Rat with Liver Depression and Spleen Deficiency Syndrome
Yongfu WANG ; Wei KE ; Xiangyu XIE ; Hongmei TANG ; Liuze SI ; Yuna CHAI
Journal of Traditional Chinese Medicine 2026;67(4):439-446
ObjectiveTo explore the potential mechanism of Changji'an Formula (肠激安方) on intestinal permeability for rats with diarrhea-predominant irritable bowel syndrome (IBS-D) of liver depression and spleen deficiency syndrome by the microRNA-29b-3p (miR-29b-3p)/tumor necrosis factor receptor-associated factor 3 (TRAF3)/nuclear factor-κB (NF-κB)/myosin light chain kinase (MLCK) axis. MethodsTwenty-four 1-day-old male Sprague-Dawley (SD) suckling rats were selected, and the IBS-D rat model of liver depression and spleen deficiency syndrome was established via a three-factor method,i.e. maternal separation plus acetic acid stimulation and restraint stress, for 6 consecutive weeks. After successful modeling, the rats were randomly divided into a model group, pinaverium bromide group, low-dose and high-dose Changji'an Formula groups, with 6 rats in each group. Another 6 age-matched non-modeled SD rats were included as the control group. The low-dose and high-dose Changji'an Formula groups were given intragastric administration of Changji'an Formula solution at doses of 16.74 g/(kg·d) and 33.48 g/(kg·d), respectively; the pinaverium bromide group received intragastric administration of pinaverium bromide tablets at 0.018 g/(kg·d); and the control group was given distilled water at 10 ml/(kg·d) via intragastric gavage. The intervention was conducted once daily for 14 consecutive days. After the gavage treatment, the fecal water content of rats in each group was measured. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of intestinal permeability indicators, including D-lactic acid (D-LA), diamine oxidase (DAO), and lipopolysaccharide (LPS). Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the mRNA expression levels of miR-29b-3p, TRAF3, tumor necrosis factor-α (TNF-α), p65, p50, and MLCK in colonic tissues. Western Blot analysis was employed to detect the protein expression levels of TRAF3, TNF-α, p65, phosphorylated p65 (p-p65), MLCK, myosin light chain (MLC), phosphorylated MLC (p-MLC), and tight junction proteins including junctional adhesion molecule-A (JAM-A), Occludin, and Claudin-1 in colonic tissues. ResultsCompared with the control group, the model group exhibited significantly increased fecal water content and serum levels of D-LA, DAO, and LPS, along with decreased protein expression levels of JAM-A, Occludin, and Claudin-1 in colonic tissues (P<0.05 or P<0.01). Additionally, in the model group, the mRNA expression levels of miR-29b-3p, TNF-α, p65, p50, and MLCK in colonic tissues were up-regulated, while the mRNA and protein expression levels of TRAF3 were down-regulated; the protein levels of TNF-α and MLCK, as well as the ratios of p-p65/p65 and p-MLC/MLC, significantly elevated (P<0.01). Compared with the model group, all treatment groups showed reduced fecal water content and serum levels of D-LA, DAO, and LPS, along with down-regulated mRNA expression levels of miR-29b-3p, TNF-α, p65, p50, and MLCK, and up-regulated TRAF3 mRNA expression in colonic tissues. Moreover, the pinaverium bromide group and high-dose Changji'an Formula group presented increased protein levels of Occludin, Claudin-1, and TRAF3, as well as decreased protein levels of TNF-α and MLCK, and reduced ratios of p-p65/p65 and p-MLC/MLC in colonic tissues (P<0.05 or P<0.01). Compared with the low-dose Changji'an Formula group, the high-dose group had lower fecal water content and serum levels of DAO and LPS (P<0.01). In comparison with the pinaverium bromide group, the high-dose Changji'an Formula group showed a significant decrease in serum DAO level (P<0.01). ConclusionsChangji'an Formula can reduce intestinal permeability and restore intestinal barrier function in IBS-D rats of liver depression and spleen deficiency syndrome by regulating the miR-29b-3p/TRAF3/NF-κB/MLCK axis.
10.Effect of Shenqi Jianxin Formula(参芪健心方)on Mitochondrial Autophagy and the PINK1/Parkin Signaling Pathway in Cardiac Tissues in Chronic Heart Failure
Peichi XIE ; Pan LIU ; Zitong DING ; Jingyi BAI ; Deqi PANG ; Xiaohua DAI
Journal of Traditional Chinese Medicine 2026;67(4):447-455
ObjectiveTo explore the potential mechanism of Shenqi Jianxin Formula (参芪健心方) in the treatment of chronic heart failure (CHF) from the perspective of regulating mitochondrial autophagy via the PTEN-induced kinase 1 (PINK1)/E3 ubiquitin ligase (Parkin) pathway. MethodsMale SD rats were subjected to abdominal aortic constriction to establish the CHF model. Twenty-four successfully modeled rats were randomly divided into the model group, sacubitril/valsartan group, and low- and high-dose Shenqi Jianxin Formula groups, with 6 rats in each group. Six other rats were set as the sham surgery group, which were only separated the abdominal aorta and then closed the abdomen. Rats in the low-dose and high-dose Shenqi Jianxin Formula groups were given intragastric administration of Shenqi Jianxin Formula suspension at doses of 4.41 g/(kg·d) and 17.64 g/(kg·d), respectively; the sacubitril/valsartan group received intragastric administration of sacubitril/valsartan sodium tablet suspension at 10 mg/(kg·d); the sham surgery group and the model group were given normal saline at 10 ml/(kg·d) via intragastric gavage. The intervention lasted for 4 consecutive weeks. Cardiac function indices including left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were detected, and serum brain natriuretic peptide (BNP) content was measured. HE staining and Masson staining were used to observe myocardial histopathological changes. Transmission electron microscopy was employed to examine the ultrastructure of cardiac tissues. Quantitative real-time polymerase chain reaction (Rt-qPCR) was performed to determine the mRNA expressions of PINK1/Parkin pathway-related factors and autophagy-associated proteins including Beclin-1, p62, and microtubule-associated protein 1 light chain 3 (LC3) in myocardial tissues. ResultsCompared with the sham surgery group, the model group showed significant decreases in LVEF and LVFS levels, an increase in serum BNP content, down-regulated mRNA and protein expressions of PINK1, Parkin and Beclin-1 in cardiac tissues, up-regulated mRNA and protein expressions of p62, as well as significant reductions in LC3B mRNA expression, phosphorylated PTEN-induced kinase 1 (p-PINK1) and phosphorylated E3 ubiquitin ligase (p-Parkin) protein levels, and the ratio of microtubule-associated protein 1 light chain 3-Ⅱ to microtubule-associated protein 1 light chain 3-Ⅰ (LC3Ⅱ/LC3Ⅰ) (P<0.05). Pathological results revealed obvious myocardial cell edema, necrosis and degeneration, increased disorder of myocardial fiber arrangement, extensive inflammatory cell infiltration, moderate to severe mitochondrial swelling, a few mitochondrial vacuolar changes, and no obvious autophagy in the field of vision in the model group. Compared with the model group, all the above indicators were significantly improved in the high-dose Shenqi Jianxin Formula group and the sacubitril/valsartan group (P<0.05). Moreover, the improvement of each index in the high-dose Shenqi Jianxin Formula group was superior to that in the low-dose group (P<0.05). In the high-dose Shenqi Jianxin Formula group, myocardial myofibrils were arranged regularly with orderly orientation, the striated structure was clear, and necrotic cells significantly reduced. ConclusionShenqi Jianxin Formula can activate the PINK1/Parkin signaling pathway in myocardial tissues, enhance mitochondrial autophagy, and clear dysfunctional mitochondria, thereby improving cardiac function and delaying the progression of CHF.

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