1.Molecular Crosstalk Mechanisms of Shoutai Wan and Juyuan Jian on Maternal-fetal Interface Subcellular Clusters in CBA/J×DBA/2 Recurrent Pregnancy Loss Model
Jingxin GAO ; Qiuping CHEN ; Xiaoyan ZHENG ; Pengfei ZENG ; Rui ZHOU ; Yancai TANG ; Qian ZENG ; Wenli GUO ; Jinzhu HUANG ; Weijun DING ; Linwen DENG ; Hang ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):70-87
ObjectiveTo systematically compare the differential regulation of the maternal-fetal interface cell lineages and communication networks in the CBA/J×DBA/2 mouse model of recurrent pregnancy loss (RPL) by the two classic therapeutic methods-tonifying the kidney to stabilize the fetus and invigorating the spleen to stabilize the fetus (Shoutai Wan, Juyuan Jian)-of traditional Chinese medicine (TCM) at the single-cell resolution and clarify their modern scientific connotations. MethodsFemale non-pregnant CBA/J mice were caged with male BALB/c (blank group) and DBA/2 (modeling group) mice separately. Pregnant mice in the modeling group were randomly grouped as follows: high/low-dose Shoutai Wan, high/low-dose Juyuan Jian, model (RPL), and positive control (dydrogesterone), with 10 mice in each group. Starting from the day after the detection of the vaginal plug, mice were administrated with drugs or an equal volume of normal saline by gavage for 10 consecutive days. After the intervention, the following indicators were measured. ① Macroscopic evaluation: general conditions, uterine wet weight, embryo loss rate, four coagulation parameters [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT)], and peripheral blood estradiol (E2) and progesterone (Pg) levels. The decidua with embryos was stained with hematoxylin-eosin (HE) and evaluated by transmission electron microscopy (TEM). The expression of B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor (VEGF), angiotensin Ⅱ (AngⅡ), matrix metalloproteinase-2 (MMP-2), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), CXC chemokine ligand 12 (CXCL12), and microtubule-associated protein 1 light chain 3 homolog (LC3)Ⅰ/Ⅱ was quantified by Western blot. ② Mechanism analysis at the single-cell level: The decidua with embryos from the blank, model, high-dose Shoutai Wan, and high-dose Juyuan Jian groups (6 mice per group, with 3 single-cell samples per group, totaling 24 mice) were analyzed by the BD Rhapsody™ platform, and the whole-cell atlas was drawn by uniform manifold approximation and projection (UMAP) dimensionality reduction clustering combined with the single-cell mouse cell atlas (scMCA). The differentially expressed genes (DEGs) and cell interaction networks were analyzed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and CellChat, and the protein-protein interaction (PPI) map of subtype cells was constructed. The CytoTRACE pseudo-temporal analysis was performed to explore the developmental trajectories of core immune cells (natural killer cells, NK cells) from maternal and fetal sources. Results① Pathological and Western blot results indicated that compared with the blank group, the RPL group showed an increase in the embryo loss rate (P<0.01), down-regulated expression of Bcl-2, LIF, MMP-2, and Vegf in the decidua with embryos (P<0.05), up-regulated protein levels of CXCL-12, AngⅡ, and IL-6 (P<0.05), blocked angiogenesis, apoptosis-inflammation imbalance, and coagulation dysfunction. Both prescriptions dose-dependently reduced the abortion rate and restored the angiogenesis-inflammation balance, and Shoutai pill showed superior performance in restoring the E2 level to the Pg level (P<0.05). ② Single-cell transcriptome analysis indicated that compared with the blank group, the RPL group showed differences in multiple key cell populations such as decidual cells, trophoblast cells, endothelial cells, erythroblasts, NK cells, and macrophages at the maternal-fetal interface. Immunity and angiogenesis were the key links in RPL. Compared with the RPL group, high-dose Shoutai Wan reversed the changes of NK cells in the embryonic layer (upregulating the mRNA levels of 17 genes and downregulating the mRNA levels of 29 genes) and macrophages (upregulating the mRNA levels of 117 genes and downregulating the mRNA levels of 53 genes) through the regulation of gene expression. High-dose Shoutai pill regulated the immune cells to affect unfolded proteins, cell adhesion, and programmed cell death, thereby promoting decidualization and angiogenesis and modulating embryo-membrane development. High-dose Juyuan Jian regulated the key subgroups of NK cells (up-regulating the mRNA levels of 9 genes and down-regulating the mRNA levels of 17 genes) and macrophages (up-regulating the mRNA levels of 110 genes and down-regulating the mRNA levels of 81 genes), which affected decidual inflammation and apoptosis and intervened in glycolysis. ③ The pseudo-temporal analysis and communication network indicated that the communication frequency of the RPL group decreased. High-dose Shoutai Wan restored maternal-fetal tolerance through pathways such as NKG2D, CDH5, GDF, and FASLG. High-dose Juyuan Jian enhanced the IL-6/LIFR/JAK/signal transducer and activator of transcription 3 (STAT3) and desmosome/SEMA6/tumor necrosis factor-like weak inducer of apoptosis (TWEAK) signaling to improve endometrial receptivity. The RPL group showed an increased proportion of toxic dNK7, a decreased proportion of reparative dNK4, and blocked embryo fNK1. High-dose Shoutai Wan down-regulated dNK7 and up-regulated dNK4. High-dose Juyuan Jian inhibited the terminal differentiation of dNK7 and up-regulated LILRB1, thus restoring the balance of cytotoxicity and repair. ConclusionBoth the kidney-tonifying and spleen-invigorating methods are effective in treating RPL. NK and macrophages are the key immune cells in the interaction between the embryo and the membrane. The kidney-tonifying method (Shoutai Wan) has an advantage in regulating the phenotypes of unfolded protein, cell adhesion, and programmed cell death, and shows expression characteristics closer to the physiological state in the regulation of NKG2D and CDH5 signals. The spleen-invigorating method (Juyuan Jian) has an advantage in regulating epithelial-mesenchymal transition (EMT), angiogenesis, and glycolysis and shows higher communication intensity in the IL-6 and LIFR pathways.
2.Effect and Mechanism of Schisandrae Chinensis Fructus Lignans on Behavior of Schizophrenic Mice
Jiaqi LI ; Xi CHEN ; Siwei WANG ; Qi WANG ; Yiting LIU ; Ziyan GUO ; Zilong LUN ; Chengyi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):65-71
ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate (MK-801) in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank, model, positive drug, and low-, medium-, and high-dose (40, 80, 160 mg·kg-1, respectively) Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water, and the other groups were injected with 0.5 mg·kg-1 MK-801 to induce schizophrenia symptoms. Meanwhile, risperidone was injected at 0.2 mg·kg-1 in the positive drug group, and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test, open field test, forced swimming test, and water maze test. The levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) in the brain and tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in peripheral blood were quantified by enzyme-linked immunosorbent assay (ELISA). The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining, and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 (SIRT1) and forkhead box protein O3a (FoxO3a) in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group, low, medium, and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities, total distance in the open field test, immobile time in the forced swimming test, and levels of TNF-α and NF-κB in peripheral blood (P<0.05), while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue (P<0.05). Compared with the model group, risperidone and low, medium, and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region, with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus (P<0.05). ConclusionTo sum up, Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.
3.Traditional Chinese Medicine Treats Esophageal Cancer via PI3K/Akt Signaling Pathway: A Review
Wei GUO ; Chen PENG ; Yikun WANG ; Zixuan YU ; Jintao LIU ; Jing DING ; Yijing LI ; Hongxin SUN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):302-311
Esophageal cancer (EC) is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, as one of the key oncogenic pathways, can promote the cell cycle progression, proliferation, migration, and invasion, induce chemoresistance, and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine (TCM), with the advantages of targeting multiple points with multiple components to delay cancer progression, can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum, spore powder of Ganoderma lucidum without spore coat, extract of Celastrus orbiculatus, root extract of Taraxacum, and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids, terpenoids, saponins, phenols, polysaccharides, alkaloids, and other compounds. TCM compound prescriptions with such effect include Qige San, Huqi San, Xuanfu Daizhetang, Tongyoutang and its decomposed prescriptions, Liujunzi Tang, and Xishenzhi Formula. In addition, TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions, aiming to provide reference for the research and clinical application of new drugs for EC.
4.Empirical study of input, output, outcome and impact of community-based rehabilitation stations
Xiayao CHEN ; Ying DONG ; Xue DONG ; Zhongxiang MI ; Jun CHENG ; Aimin ZHANG ; Didi LU ; Jun WANG ; Jude LIU ; Qianmo AN ; Hui GUO ; Xiaochen LIU ; Zefeng YU
Chinese Journal of Rehabilitation Theory and Practice 2026;32(1):83-89
ObjectiveTo investigate the present situation of input, output, outcome and impact of all registered community-based rehabilitation stations in Inner Mongolia in China, and analyze how the input predict the output, outcome and impact. MethodsFrom March 1st to April 30th, 2025, a questionnaire survey was conducted on all registered community-based rehabilitation stations in Inner Mongolia, covering four dimensions: input, output, outcome and impact. A total of 1 365 questionnaires were distributed. The input included four items: laws and policies, human resources, equipment and facilities, and rehabilitation information management. The output included two items: technical paths and benefits/effectiveness. The outcome included three items: coverage rates, rehabilitation interventions and functional results. The impact included two items: health and sustainability. Each item contained several questions, all of which were described in a positive way. Each question was scored from one to five. A lower score indicated that the situation of the community-based rehabilitation station was more in line with the content described in the question. Regression analysis was performed using the total score of each item of input dimension as independent variables, and the total scores of the output, outcome and impact dimensions as dependent variables. ResultsA total of 1 262 valid questionnaires were collected. The mean values of input, output, outcome and impact of community-based rehabilitation stations were 1.827 to 1.904, with coefficient of variation of 45.892% to 49.239%. The regression analysis showed that, rehabilitation information management, human resources, and laws and policies significantly predicted the output dimension (R² = 0.910, P < 0.001). Meanwhile, all four items in the input dimension predicted both the outcome (R² = 0.850, P < 0.001) and impact dimensions (R² = 0.833, P < 0.001). ConclusionInput, output, outcome and impact of the community-based rehabilitation stations in Inner Mongolia were generally in line with the content of the questions, although some imbalances were observed. Additionally, the input of community-based rehabilitation stations could significantly predict their output, outcome and impact.
5.Mechanisms of Antidepressant Effect of Zhizi Houpotang and Its Herbal Pairs Based on NLRP3/GSDMD Signaling Pathway
Chang CHEN ; Ziwen GUO ; Tingyu SONG ; Yan WANG ; Baomei XIA ; Weiwei TAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):72-80
ObjectiveTaking classical herbal pair compatibility research as the entry point, this study aimed to deeply investigate the material basis and compatibility rules underlying the antidepressant effects of the traditional Chinese medicine (TCM) formula Zhizi Houpotang, and to elucidate its antidepressant mechanism, with a particular focus on its regulation of neuroinflammatory responses mediated by the NOD-like receptor protein 3 (NLRP3)/gasdermin D (GSDMD) signaling pathway and the consequent improvement of neuronal synaptic plasticity. MethodsC57BL/6J mice were randomly divided into a blank control group, a chronic unpredictable mild stress (CUMS) depression model group, a Zhizi Houpotang full-formula group (6 g·kg-1·d-1), a Magnoliae Officinalis Cortex (MOC)-Aurantii Fructus Immaturus (AFI) herbal pair group (4.2 g·kg-1·d-1), a Gardeniae Fructus (GF)-MOC herbal pair group (4.2 g·kg-1·d-1), a GF-AFI herbal pair group (3.6 g·kg-1·d-1), and a positive drug group (fluoxetine, 12 mg·kg-1·d-1). Depressive-like behaviors in mice were evaluated using behavioral tests. Immunofluorescence staining was used to label and quantify the expression of the microglial marker ionized calcium-binding adaptor molecule 1 (Ibal) and the purinergic receptor P2X ligand-gated ion channel 7 (P2RX7) in the prefrontal cortex (PFC). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) in serum and PFC tissues. Western blot was employed to determine the expression of pannexin 1 (Panx1), P2RX7, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, GSDMD, postsynaptic density protein 95 (PSD95), and the presynaptic protein Synapsin 1 in PFC tissues. Golgi staining was used to assess dendritic spine density of neurons in the PFC. ResultsCompared with the blank control group, the depression model group exhibited significant depressive-like behaviors. In addition, the immunofluorescence areas of Ibal and P2RX7 in the PFC were significantly increased (P<0.01), the levels of IL-1β and IL-18 in serum and the PFC were significantly elevated (P<0.01), and the protein expression levels of Panx1, P2RX7, NLRP3, ASC, Caspase-1, and GSDMD in the PFC were significantly upregulated (P<0.01). In contrast, the protein expression levels of PSD95 and Synapsin 1 were significantly downregulated (P<0.01), and neuronal dendritic spine density was significantly reduced (P<0.01). Compared with the model group, the Zhizi Houpotang full-formula group and the GF-MOC herbal pair group showed significant improvement in all the above indicators (P<0.01). The GF-AFI herbal pair group improved all the above indicators except P2RX7, Caspase-1, GSDMD, and PSD95 (P<0.05, P<0.01). In contrast, the MOC-AFI herbal pair group showed no statistically significant improvement in any of the above indicators compared with the model group. ConclusionZhizi Houpotang and its key herbal pair, GF-MOC, can effectively ameliorate CUMS-induced depressive-like behaviors in mice. Its core antidepressant mechanism may involve inhibition of P2RX7/Panx1 signaling, thereby blocking the NLRP3/GSDMD-mediated pyroptosis pathway and significantly reducing the release of inflammatory cytokines IL-1β and IL-18. Simultaneously, it upregulates the expression of synapse-related proteins PSD95 and Synapsin 1 and increases dendritic spine density, promoting the recovery of synaptic plasticity. These results suggest that GF plays a key role in the antidepressant effects of this formula, and that the compatibility of GF with MOC may represent the principal herbal pair combination responsible for its core therapeutic action.
6.TCM Treatment of Sarcopenia Based on PI3K/Akt Signaling Pathway: A Review
Yan CHEN ; Ting DAI ; Changsheng GUO ; Zhihai FENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):316-326
Sarcopenia is a systemic skeletal muscle disease characterized by the gradual decline of muscle mass,strength,and function,and its occurrence and development are related to multiple factors,involving several signaling pathways. Among them,the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway,as a key pathway regulating cellular growth,survival,and metabolism,plays an important role in the formation and development of sarcopenia. Its abnormal activation or deactivation may lead to an imbalance in muscle protein metabolism,resulting in muscle atrophy and reduction. Modern medicine is still in the exploratory stage of treatment for sarcopenia. Traditional Chinese medicine (TCM),with its multi-pathway and multi-target characteristics,has shown increasing advantages in the prevention and treatment of sarcopenia. In recent years,various monomers, extracts,and compound formulas of TCM have been proven to effectively prevent and treat sarcopenia by promoting muscle cell protein synthesis,reducing protein degradation,inhibiting cell apoptosis and inflammatory response,and improving mitochondrial function. This paper reviewed the improvement effects of TCM on sarcopenia based on the PI3K/Akt pathway and explored its specific action mechanisms, aiming to provide new insights for the treatment of sarcopenia with TCM.
7.Establishment of a new predictive model for esophagogastric variceal rebleeding in liver cirrhosis based on clinical features
Wen GUO ; Xuyulin YANG ; Run GAO ; Yaxin CHEN ; Kun YIN ; Qian LI ; Manli CUI ; Mingxin ZHANG
Journal of Clinical Hepatology 2026;42(1):101-110
ObjectiveTo establish a new noninvasive, simple, and convenient clinical predictive model by identifying independent predictive factors for rebleeding after endoscopic therapy in cirrhotic patients with esophagogastric variceal bleeding (EGVB), and to provide a basis for individualized risk assessment and development of clinical intervention strategies. MethodsCirrhotic patients with EGVB who were diagnosed and treated in The First Affiliated Hospital of Xi’an Medical University from September 2018 to October 2023 were enrolled as subjects, and according to whether the patient experienced rebleeding within 1 year after endoscopic therapy, they were divided into rebleeding group with 93 patients and non-rebleeding group with 84 patients. Clinical data were collected and analyzed. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Logistic model was established based on the results of the univariate and multivariate analyses, and the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to assess the accuracy of the model. R software was used to visualize the model by plotting a nomogram, and the Bootstrap method was used for internal validation of the model. ResultsThe multivariate analysis showed that red blood cell count (RBC), cholinesterase (ChE), alkaline phosphatase (ALP), albumin (Alb), thrombin time (TT), portal vein trunk diameter, sequential therapy, and primary prevention were independent predictive factors for rebleeding. Based on the results of the multivariate analysis, a logistic model was established as logit(P)=-0.805-1.978×(RBC)+0.001×(ChE)-0.020×(ALP)-0.314×(Alb)+0.567×(TT)+0.428×(portal vein trunk diameter)-2.303×[sequential therapy (yes=1, no=0)]-2.368×[primary prevention (yes=1, no=0)]. The logistic model (AUC=0.928, 95% confidence interval [CI]: 0.893—0.964, P<0.001) had a better performance in predicting rebleeding than MELD score (AUC=0.603, 95%CI: 0.520—0.687, P=0.003), Child-Pugh class (AUC=0.650, 95%CI: 0.578—0.722, P=0.001), and FIB-4 index (AUC=0.587, 95%CI: 0.503—0.671, P=0.045). The model had an optimal cut-off value of 0.607, a sensitivity of 0.817, and a specificity of 0.817. Internal validation confirmed that the model had good predictive performance and accuracy. ConclusionSequential therapy, implementation of primary prevention, an increase in RBC, and an increase in Alb are protective factors against rebleeding, while prolonged TT and widened main portal vein diameter are risk factors. The logistic model based on these independent predictive factors can predict rebleeding and thus holds promise for clinical application.
8.Analysis of a child with Osteo-oto-hepato-enteric syndrome and a literature review.
Dandan WANG ; Qianqian LI ; Hongxiang GUO ; Yongning CHEN ; Qingfei HAO ; Yanlei XU ; Xiuyong CHENG
Chinese Journal of Medical Genetics 2026;43(3):204-212
OBJECTIVE:
To analyze the phenotype and genotype of a neonate with Osteo-oto-hepato-enteric syndrome (O2HE) and review the literature.
METHODS:
A female neonate diagnosed with O2HE syndrome on December 13, 2024 at the First Affiliated Hospital of Zhengzhou University was selected as the study subject, and her clinical characteristics were analyzed, and pathogenic variants were explored by whole exome sequencing (WES). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2025-KY-1038).
RESULTS:
The proband, a female infant, was delivered by Cesarean section at 36+1 weeks of gestation. Five days after birth, she had developed severe diarrhea, mild cholestasis, sensorineural hearing loss, and growth retardation. WES revealed that she has harbored novel compound heterozygous variants c.512delA (p.Lys171Serfs*64) and c.698C>A (p.Thr233Asn) of the UNC45A gene, which were inherited from her mother and father, respectively. A total of 8 English papers were retrieved, which involved 16 patients from 14 families. Combined with our case, the 17 patients included 13 (76.5%) females and 4 (23.5%) males. Four patients (23.5%) had consanguineous parents. One case was excluded from further genetic analysis due to co-morbidity with other genetic variants. The primary clinical features included diarrhea (87.5%), cholestasis (81.3%), sensorineural hearing loss (31.3%), bone fragility (37.5%), and developmental delay (50.0%). Bi-allelic compound heterozygous mutations were identified in 12 patients (75.0%), and homozygous variants in 4 (25.0%). These included missense, nonsense, frameshift and deletional variants. The c.710T>C (p.Leu237Pro) variant was identified for 5 times, 3 of which were in homozygote forms.
CONCLUSION
O2HE syndrome should be suspected in cases with diarrhea, cholestasis, and hearing abnormalities during early postnatal period. Genetic testing facilitate early identification, genetic diagnosis and treatment.
Humans
;
Female
;
Infant, Newborn
;
Male
;
Mutation
;
Hearing Loss, Sensorineural/genetics*
;
Diarrhea, Infantile/genetics*
;
Exome Sequencing
;
Phenotype
;
Fetal Growth Retardation
;
Hair Diseases
;
Facies
9.Effects of Modified Buyang Huanwu Tang on Mice with Cerebral Ischemia-reperfusion Injury by Regulating PINK1/Parkin Signaling Pathway-mediated Mitochondrial Autophagy
Li GUO ; Hengwen CHEN ; Cun ZHAN ; Zhenzhen YING ; Zuomin WU ; Shaoju JIN ; Shangmei CAO ; Shengming HUANG ; Jin WANG ; Xiaotao YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):34-43
ObjectiveTo investigate the effects of modified Buyang Huanwu Tang on cerebral ischemia-reperfusion injury (CI/RI) in mice via the PTEN-induced putative kinase 1/E3 ubiquitin ligase (PINK1/Parkin) signaling pathway-mediated mitophagy, and to explore the underlying mechanism by which modified Buyang Huanwu Tang improves CI/RI. MethodsSeventy-two male C57BL/6J mice were randomly divided into six groups (n = 12 per group): Sham-operated group, middle cerebral artery occlusion/reperfusion (MCAO/R) model group, low-, medium-, and high-dose modified Buyang Huanwu Tang groups (8.84, 17.68, 35.36 g·kg-1·d-1), and an aspirin group (13.00 mg·kg-1·d-1). Neurological deficit scores were assessed using the Zea-Longa method. Cerebral infarct volume ratio was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Histopathological changes and neuronal injury in brain tissues were observed using hematoxylin-eosin (HE) staining and Nissl staining. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Mitochondrial ultrastructure in brain tissue was observed by transmission electron microscopy (TEM). Serum levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression levels of PINK1, Parkin, microtubule-associated protein 1 light chain 3B (LC3B, LC3Ⅱ/Ⅰ), and p62 in brain tissues were detected by real-time quantitative reverse transcription PCR (Real-time PCR) and Western blot, respectively. ResultsCompared with the sham-operated group, the MCAO/R model group showed significantly increased neurological deficit scores and cerebral infarct volume ratios (P<0.01). Severe cortical injury on the infarct side was observed, characterized by decreased neuronal density, cytoplasmic vacuolation, nuclear pyknosis, a marked reduction in Nissl bodies, dissolution of Nissl bodies in the cytoplasm of some pyramidal neurons, and blurred cellular boundaries. The number of TUNEL-positive cells increased significantly (P<0.01). Mitochondria exhibited cristae membrane rupture and matrix vacuolation, with rupture of the outer mitochondrial membrane and formation of autophagosomes, the number of which increased significantly. Serum SOD activity decreased significantly (P<0.01), while MDA content increased significantly (P<0.01). In infarcted brain tissues of model mice, the relative mRNA expression and protein levels of PINK1, Parkin and LC3B were significantly increased (P<0.05, P<0.01), whereas p62 mRNA and protein expression were significantly decreased (P<0.05, P<0.01), showing statistical significance. Compared with the model group, all treatment groups showed significantly decreased neurological deficit scores and cerebral infarct volume ratios (P<0.01). Neuronal density increased significantly, cytoplasmic vacuolation was alleviated, nuclear morphology tended to be more regular and clearer, Nissl body density increased significantly with reduced dissolution and improved contour clarity. The mitochondrial cristae structure was partially restored, with some mitochondria showing autophagosome encapsulation, and the degree of mitochondrial damage was alleviated. Serum SOD activity increased significantly (P<0.01), while MDA content decreased significantly. The mRNA and protein expression levels of PINK1, Parkin, and LC3Ⅱ/Ⅰ were significantly increased (P<0.05, P<0.01), while p62 mRNA and protein expression in the low- and medium-dose modified Buyang Huanwu Tang groups were significantly decreased (P<0.05, P<0.01), showing statistical significance. ConclusionModified Buyang Huanwu Tang can upregulate the protein expression levels of PINK1, Parkin, and LC3Ⅱ/Ⅰ and downregulate p62 protein expression, suggesting that it may improve CI/RI by regulating the expression of proteins related to the PINK1/Parkin signaling pathway. Regulation of the mitophagy pathway may be one of the mechanisms by which modified Buyang Huanwu Tang alleviates CI/RI in mice.
10.Effect of Jianpi Qinghua Granules on Blood Glucose Fluctuations and Skeletal Muscle Mass and Function in Newly Diagnosed Overweight/Obese Type 2 Diabetes Patients with Qi-Yin Deficiency Syndrome
Yuan CHEN ; Qiuyue GUO ; Yanyan XIAO ; Hao LU ; Chi CHEN ; Junfei XU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):218-224
ObjectiveTo investigate the effects of Jianpi Qinghua granules on blood glucose fluctuations in patients with newly diagnosed overweight/obese type 2 diabetes mellitus (T2DM) and Qi-Yin deficiency syndrome from the perspective of skeletal muscle mass and function, while providing new insights for the treatment of diabetes. MethodsThis study employed a randomized, double-blind, placebo-controlled design. A total of 110 newly diagnosed overweight/obese T2DM patients meeting the inclusion criteria were randomly assigned to either the traditional Chinese medicine (TCM) group (54 cases) or the control group (56 cases). Patients in the TCM group received Jianpi Qinghua Granules, while those in the control group received a placebo. Both groups underwent dietary and exercise guidance. After 12 weeks of intervention, blood glucose fluctuations were assessed using the following parameters: time in the target blood glucose range (TIR), mean daily blood glucose (MBG), standard deviation of mean daily blood glucose (SDBG), mean amplitude of glycemic excursions (MAGE), coefficient of variation of blood glucose (CV), glycated hemoglobin (HbA1c) achievement rate, fasting plasma glucose (FPG), and 2 hour postprandial glucose (2 hPG). Skeletal muscle mass was measured by dual-energy X-ray absorptiometry (DXA), while skeletal muscle function was evaluated using a handheld dynamometer for distal muscle strength and a 5-time sit-to-stand test for lower limb function. Additionally, pancreatic islet function and TCM syndrome scores were analyzed. ResultsNo significant differences were observed in baseline data between the two groups before intervention, ensuring comparability. After treatment, compared to the control group, the TCM group showed a significant increase in TIR (P<0.01). While the SDBG and CV decreased, and MBG and MAGE increased in the TCM group, these differences were not statistically significant. Notably, the TCM group exhibited significant reductions in 2 hPG (P<0.01) and HbA1c (P<0.05), though the decrease in FPG was not statistically significant. The HbA1c achievement rate in the TCM group was significantly higher than that in the control group (χ2=45.498, P<0.01). In terms of skeletal muscle mass and function, the TCM group demonstrated a significant increase in handgrip strength (P<0.01) and a significant reduction in the 5-time sit-to-stand duration (P<0.05). However, although body fat percentage increased, leading to a decrease in skeletal muscle mass and the ratio of skeletal muscle to fat, these changes were not statistically significant. For pancreatic islet function, the TCM group showed significant reductions in fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) (P<0.01). Additionally, the TCM syndrome score in the TCM group was significantly reduced (P<0.01). ConclusionJianpi Qinghua granules may reduce blood glucose fluctuations in newly diagnosed overweight/obese T2DM patients with Qi-Yin deficiency syndrome by enhancing skeletal muscle function, improving pancreatic islet function, and ameliorating related TCM syndromes.

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