1.Mechanism of Shenmai Injection to Improve Cisplatin Resistance in NSCLC Based on Endoplasmic Reticulum Stress Through PERK/ATF4/CHOP Signaling Pathway
Shengnan GUO ; Hao CAO ; Dan WANG ; Wenjun LIU ; Jianguang WANG ; Jialu LYU ; Chun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):70-78
ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer (NSCLC) based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase (PERK)/activated transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line (A549/cisplatin) were randomly divided into four groups: Blank control group (0.9% sodium chloride), cisplatin group (5 µg·g-1cisplatin), Shenmai injection group (5.2 mg·g-1 Shenmai injection), and combination therapy group (5.2 mg·g-1 Shenmai injection +5 µg·g-1cisplatin). The drug intervention lasted for 4 weeks, and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin (HE) staining was performed to observe tumor tissue pathology. Transmission electron microscopy (TEM) was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK, ATF4, and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein (BIP), PERK, phosphorylated PERK (p-PERK), eukaryotic translation initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), ATF4, CHOP, B-cell lymphoma -2 (Bcl-2), and Bcl-2 Associated X protein (Bax). A549/cis cells were divided into blank group: Blank control group (normal culture medium), cisplatin group (23.3 µmol·L-1 cisplatin), Shenmai Injection group (20 g·L-1 Shenmai injection), and combination therapy group (20 g·L-1 Shenmai injection+23.3 µmol·L-1 cisplatin). Cell counting kit-8 (CCK-8) method was used to detect cell viability, TEM was used to observe the morphology of endoplasmic reticulum, and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group, the combination therapy group showed increased body weight (P<0.05), decreased tumor volume (P<0.05), and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK, ATF4, and CHOP increased (P<0.05). Western blot revealed elevated protein expression levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, and Bax (P<0.05), while Bcl-2 expression decreased (P<0.05). As shown in the in vitro experiment, compared with the cisplatin group, the combination therapy group exhibited a reduced cell survival rate (P<0.05). TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP and Bax (P<0.05), with decreased Bcl-2 expression (P<0.05). ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC, which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.
2.Mechanism of Sangpi Zhike Prescription in Treating Cough After Respiratory Syncytial Virus Infection Based on "Lung-intestine Co-treatment" Theory
Chuang SUO ; Xiaohong BAI ; Zhitong YU ; Xue GONG ; Chan XIU ; Qihui LYU ; Zhihui LIU ; Kelin LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):126-137
ObjectiveTo explore the mechanism of Sangpi Zhike prescription in treating cough after respiratory syncytial virus (RSV) infection through the "lung-intestine co-treatment" approach using network pharmacology and animal experimental validation. MethodsActive ingredients and targets of Sangpi Zhike prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease targets were obtained from GeneCards and Online Mendelian Inheritance in Man(OMIM) databases. Protein-protein interaction (PPI) networks and drug-component-target networks were constructed using overlapping targets between drugs and diseases to identify core targets. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analyses were performed on the overlapping targets. Sixty mouse models were established: 10 as the normal group, and the remaining mice were infected with RSV via slow nasal drip of RSV suspension, with cough induced using capsaicin solution. After modeling, mice were divided into a model group, a Montelukast Sodium group (1 mg·kg-1·d-1), and low, medium, and high dose groups of Sangpi Zhike prescription (4.875,9.75,and 19.5 g·kg-1·d-1), with 10 mice per group. From day 14 after RSV infection, the normal and model groups received saline via gavage, while other groups received corresponding drug treatments once daily for 5 d. Hematoxylin-eosin(HE) staining was used to observe pathological changes in lung and intestinal tissue. The protein content of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated (p)-ERK1/2 in the lung and colon tissue of mice was detected by Western blot. Real-time polymerase chain reaction(Real-time PCR) detected ERK1/2 mRNA expression in lung and intestinal tissue. Immunohistochemistry assessed p-MEK1/2, p-ERK1/2, p-c-Fos protein levels, and inflammatory cytokines interleukin(IL)-4 and (TNF)-α in lung and colon tissue. ResultsNetwork pharmacology identified 184 active ingredients and 684 targets in Sangpi Zhike prescription, with 1 344 RSV-related disease targets and 209 overlapping targets. Core targets included TNF, Fos, and Jun. KEGG enrichment revealed 179 pathways, primarily mitogen-activated protein kinase(MAPK), cancer, TNF, and IL-17 signaling pathways. Animal experiments showed that, compared to those of the normal group, the lung tissue sections of the model group showed typical inflammatory damage, infiltration of inflammatory cells, rupture of alveolar septa, extensive alveolar fusion, and disruption of tight junctions between single-layer columnar epithelial cells in the intestinal tissue. The values of p-ERK1/2 and ERK1/2 in lung and intestinal tissue were significantly increased (P<0.01), and the expression level of ERK1/2 mRNA was significantly elevated (P<0.01). The levels of ERK1/2, p-MEK1/2, p-ERK1/2, p-c-Fos, IL-4, and TNF-α along the ERK pathway were significantly increased (P<0.05, P<0.01). Compared to the model group, Sangpi Zhike prescription groups showed reduced lung and intestinal inflammation, decreased p-ERK1/2/ERK1/2 ratios (P<0.05,P<0.01), lower ERK1/2 mRNA levels, and downregulated ERK pathway proteins (P<0.05,P<0.01). ConclusionSangpi Zhike prescription alleviates cough and intestinal symptoms after RSV infection via the "lung-intestine co-treatment" mechanism by suppressing expression levels of ERK1/2, p-MEK1/2, p-ERK1/2, p-c-Fos, IL-4, and TNF-α on ERK pathway components, thereby mitigating lung and intestinal pathological damage.
3.Current Research Status,Challenges,Differentiation and Treatment Strategies of Traditional Chinese Medicine for Gastroesophageal Reflux Disease
Fengyun WANG ; Mi LYU ; Bingduo ZHOU ; Beihua ZHANG ; Yi WANG ; Tingting XU ; Cong HE ; Xiaokang WANG ; Xin LIU ; Yang WANG ; Kaiyue HUANG ; Lusi XU ; Xudong TANG
Journal of Traditional Chinese Medicine 2026;67(4):392-396
This article systematically reviews the current research status as well as diagnosis and treatment strategies of traditional Chinese medicine (TCM) for gastroesophageal reflux disease (GERD). Studies demonstrate that TCM, based on the "disease-syndrome combination" approach, exhibits multi-target advantages in alleviating symptoms of various GERD subtypes, promoting mucosal repair, regulating emotions, and facilitating the reduction of western medication. To address clinical challenges such as symptom overlap and limited therapeutic efficacy, strategies have been proposed including "treating different diseases with the same method" and integrated regulation based on viscera correlation. Future efforts should focus on elucidating the mechanisms of compound prescriptions, promoting TCM drug development under the "three-combination" evaluation framework that integrates TCM theory, human experience and clinical trial evidence, and optimizing integrated traditional and western medicine models to enhance GERD management.
4.Exploring Anti-inflammatory Synergistic Mechanism of Atractylodis Macrocephalae Rhizoma Processed with Aurantii Fructus Immaturus Juice Based on Differential Component Tracking Strategy
Hongda XUAN ; Shengnan SHEN ; Linlin LI ; Jingjing LIAO ; Xianyu XU ; Xiaoxia LIU ; Haining LYU ; Fang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):228-237
ObjectiveTaking Aurantii Fructus Immaturus juice(AFI)-processed Atractylodis Macrocephalae Rhizoma(AMR) as an example, this study aims to systematically compare the volatile and non-volatile components of AMR and its processed products, investigate the key differential components, evaluate their anti-inflammatory activities, and elucidate the synergistic mechanism of processing. MethodsThe chemical compositions of volatile and non-volatile components in AMR and AFI-processed AMR were systematically characterized using gas chromatography-mass spectrometry(GC-MS) and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), with relative mass fractions and response values determined separately. Volatile components were identified through searches in the National Institute of Standards and Technology(NIST)17 database, comparison with retention index(RI) and fragmentation pattern matching. Non-volatile components were identified by searching Waters Traditional Chinese Medicine (TCM) spectral library, in conjunction with PubChem and MassBank, characteristic fragmentation patterns and response values were also used to support identification. Differential components were screened using principal component analysis(PCA), orthogonal partial least squares-discriminant analysis(OPLS-DA), with variable importance in the projection(VIP) value >1. Components with high log2fold change(FC) among major differential groups were selected as those exhibiting significant changes before and after processing. The anti-inflammatory activity of the differential compounds was evaluated by assessing their effects on nitric oxide(NO) production in a lipopolysaccharide(LPS)-induced RAW264.7 macrophage model. Enzyme-linked immunosorbent assay(ELISA) was used to detect the effects of the differential components on tumor necrosis factor(TNF)-α, interleukin(IL)-1β, IL-6, and monocyte chemotactic protein(MCP)-1 levels, and immunofluorescence(IF) was employed to assess their effects on nuclear transcription factor(NF)-κB p65 translocation, thereby elucidating the underlying molecular mechanisms. ResultsA total of 36 compounds were identified in the volatile components of AMR and AFI-processed AMR, among which, sesquiterpenes and monoterpenes were significantly increased after processing. In the non-volatile components, 36 compounds were identified, and the main differential components were flavonoids, sesquiterpenoids, and triterpenoids. Flavonoids were the primary differential components distinguishing AMR from its processed products, representing compounds directly introduced during processing. Five compounds, including atractylenolide Ⅲ, tangeritin, nobiletin, hesperidin and narirutin, were selected as representatives of three classes based on their most prominent differential expression among different compound types for subsequent anti-inflammatory activity studies. The results showed that 100 μmol·L-1 tangerine and narirutin could significantly inhibit LPS-induced NO production(P<0.01) in a concentration-dependent manner. Tangeritin was able to significantly inhibit the levels of TNF-α and MCP-1 secreted by RAW264.7(P<0.05), while narirutin significantly inhibited the levels of TNF-α, IL-1β, MCP-1 and IL-6(P<0.01). IF revealed that both tangeritin and narirutin significantly blocked the translocation of NF-κB p65 from the cytoplasm to the nucleus. ConclusionAFI-processed AMR significantly alters the chemical composition profile of AMR, and the newly introduced flavonoid components during processing may be key to its enhanced anti-inflammatory effects.
5.Key Information Research and Modern Clinical Application of Xiaofengsan
Weilu NIU ; Mengjie YANG ; Chengqi LYU ; Cuicui SHEN ; Ningli WANG ; Huangchao JIA ; Liyun WANG ; Xuewei LIU ; Mingsan MIAO ; Xiaomeng WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):238-249
Employing bibliometric methods and adhering to principles of textual research, this study systematically investigated prescription source, formula name, composition evolution, dose evolution, origin, processing, ancient and modern applications of Xiaofengsan. Xiaofengsan, also known as Renshen Xiaofengsan and Chantui Xiaofengsan, was first recorded in the Taiping Huimin Hejijufang(hereafter referred to as Jufang) of the Southern Song dynasty. The formula composition included Schizonepetae Spica, Glycyrrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Notoptery Rhizoma et Radix, Bombyx Batryticatus, Saposhnikoviae Radix, Poria, Cicadae Periostracum, Pogostemonis Herba, Ginseng Radix et Rhizoma, Magnoliae Officinalis Cortex and Citri Reticulatae Pericarpium, a total of 12 medicinal materials. In terms of the evolution of formula composition, formulas across dynasties largely aligned with those recorded in Jufang, with only minor variations in application. The results of the formula dosage research indicated that one dose of medication in Jufang corresponded to the following modern dosages:Schizonepetae Spica of 82.6 g, Glycyrrhizae Radix et Rhizoma of 82.6 g, Chuanxiong Rhizoma of 82.6 g, Notoptery Rhizoma et Radix of 82.6 g, Bombyx Batryticatus of 82.6 g, Saposhnikoviae Radix of 82.6 g, Poria of 82.6 g, Cicadae Periostracum of 82.6 g, Pogostemonis Herba of 82.6 g, Ginseng Radix et Rhizoma of 82.6 g, Magnoliae Officinalis Cortex of 20.65 g and Citri Reticulatae Pericarpium of 20.65 g, the origins of all the constituent drugs were consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The results of the investigation into the decoction method indicated that the aforementioned drugs should be finely ground into powder(pass through the No.5 sieve), and 8.26 g was taken for each dose, which was taken with the clear liquid obtained by steeping tea leaves in boiling water for several minutes. This mixture was administered three times daily, 30 min after meals. The ancient functional indications of this formula mainly involved dispelling wind-heat, eliminating pathogenic factors and regulating the middle Jiao. It primarily treated all wind-heat syndromes manifesting as skin diseases, predominantly affecting the upper body, especially the head and face. The diseases involved in modern applications were mostly dermatological diseases, including urticaria, eczema, atopic dermatitis and others. In this paper, by combing the relevant ancient literature, the key information of Xiaofengsan was textual researched, in order to provide reference for the modern application and development of this formula.
6.Prediction and verification of the mechanism of Chaiqi yigan granules improving hepatocellular carcinoma
Guiping MA ; Yuanjie ZHANG ; Yichi ZHOU ; Jinzhen LYU ; Conghui WANG ; Fenping LU ; Bowen LIU ; Yun RAN ; Shiping HU
China Pharmacy 2026;37(5):620-625
OBJECTIVE To predict and validate the mechanisms of Chaiqi yigan granules (CQYG) improving hepatocellular carcinoma (HCC). METHODS The signaling pathways of CQYG intervention in HCC were predicted using network pharmacology. A mice model of transplanted hepatocellular carcinoma was established by injecting H22 hepatoma cells into the axilla. Successfully modeled mice were randomly divided into model group (normal saline), sorafenib group (positive control, 50 mg/kg), and CQYG low-, medium- and high-dose groups (24.83, 49.66, 99.32 g/kg), with 10 mice in each group. Mice in each group were administered the corresponding drug solution or normal saline intragastrically, once a day, for 14 consecutive days. After last administration, pathological morphological changes in the tumor tissues of mice were observed in each group. Immunohistochemical staining was performed to detect the expression of the nuclear proliferation antigen Ki-67 in tumor tissues of mice. Western blot assay was used to measure the expression of proteins related to epithelial-mesenchymal transition (EMT) [N-cadherin, E-cadherin, Vimentin, matrix metalloproteinase 7 (MMP7)] and the mitogen-activated protein kinase (MAPK) signaling pathway [p38 MAPK, phosphorylated p38 MAPK, c-Jun N-terminal kinase (JNK), phosphorylated JNK, extracellular regulated protein kinase 1/2 (ERK1/2), phosphorylated ERK1/2] in tumor tissue of mice. RESULTS Network pharmacology analysis revealed that metabolic pathways, pathways in cancer, and the MAPK signaling pathway were key signaling pathways through which CQYG exert their anti-hepatocellular carcinoma effects. In animal experiments, the tumor tissues of mice in the model group exhibited dense tumor cells and vigorous growth. Compared with model group, CQYG high-dose group showed a decreased density of tumor cells in the tumor tissues of mice. Moreover, the expression levels of Ki-67, N-cadherin, MMP7 and Vimentin proteins, along with the phosphorylation levels of ERK1/2 and JNK proteins, were all significantly reduced ( P <0.05). The expression level of E-cadherin protein was significantly increased ( P <0.05), the phosphorylation level of p38 MAPK protein was increased, the difference was not statistically significant ( P >0.05). CONCLUSIONS CQYG can inhibit EMT by regulating the MAPK signaling pathway, thereby suppressing tumor cell invasion and metastasis and ultimately exerting a therapeutic effect in improving HCC.
7.Serum nitric oxide synthase 4 and matrix metalloproteinase-2 expression in patients with diabetic neovascular glaucoma and their clinical significance
Xiaomin LIU ; Jingfei BAN ; Jing LYU ; Wenwen LI ; Jingke LI ; Shunling YANG
International Eye Science 2026;26(1):103-108
AIM: To investigate and analyze serum nitric oxide synthase 4(NOX4)and matrix metalloproteinase(MMP)-2 expressions in patients with diabetes mellitus(DM)complicated with neovascular glaucoma(NVG)and their clinical significance.METHODS: A prospective study was conducted on 161 patients with DM complicated with NVG admitted to Handan City Eye Hospital(The Third Hospital of Handan)from June 2020 to June 2023. Based on whether complications occurred 1 a after trabeculectomy in the study group patients, they were divided into a group with good prognosis(n=90)and a group with poor prognosis(n=71). During the same period, 161 patients with chronic angle-closure glaucoma without iris neovascularization were selected as the control group. ELISA method was applied to detect the expression levels of serum NOX4 and MMP-2. ROC curve was plotted to evaluate the diagnostic value and postoperative complication prediction value of NOX4 and MMP-2 in patients with DM complicated with NVG. Pearson method was applied to analyze the correlation of NOX4 and MMP-2 with vascular endothelial growth factor(VEGF)and interleukin-6(IL-6). Multivariate Logistic regression was applied to analyze the influencing factors of postoperative complications in the study group.RESULTS:The general information of the study group and control group of patients is comparable. Compared with the control group, the expression levels of serum NOX4, MMP-2, VEGF, and IL-6 in the study group were significantly increased(P<0.001). According to Pearson analysis, serum NOX4 and MMP-2 levels significantly positively correlated with VEGF and IL-6 levels, respectively(P<0.001). According to ROC curve, the AUC of NOX4 combined with MMP-2 in the diagnosis of DM complicated with NVG was better than that of individual diagnosis of NOX4(Z=3.341, P<0.05)and MMP-2(Z=2.788, P<0.05). The duration of DM, the proportion of people with intraocular pressure >21 mmHg, and the expression levels of NOX4, MMP-2, VEGF, and IL-6 in the poor prognosis group were all higher than those in the good prognosis group(P<0.001). The duration of DM, intraocular pressure >21 mmHg, the levels of NOX4, MMP-2, VEGF, and IL-6 were all risk factors for poor prognosis in DM patients with NVG(P<0.001). According to ROC curve, the combined prediction of NOX4 and MMP-2 for postoperative complications in patients with DM complicated by NVG was superior to the AUC predicted by NOX4(Z=3.727, P<0.05)and MMP-2(Z=2.219, P<0.05), respectively.CONCLUSION:NOX4 and MMP-2 are upregulated in the serum of patients with DM complicated by NVG. Combined detection of these two markers holds significant clinical value for the early diagnosis and prognosis of patients with DM complicated by NVG.
8.Impact of DRG payment on length of stay and medical costs in COPD patients from Kashgar region
Jiale YANG ; Ningning WANG ; Aierken AIZEZIJIANG ; Lingkai LIAN ; Xinyi LYU ; Pengcheng LIU ; Wenbing YAO
China Pharmacy 2026;37(8):991-997
OBJECTIVE To analyze the impact of the diagnosis-related groups (DRG) payment reform on the length of stay and medical costs in patients with chronic obstructive pulmonary disease (COPD) in Kashgar region, aiming to provide localized empirical evidence for the optimization of regional medical insurance payment methods. METHODS Based on the inpatient settlement database of the Xinjiang Uygur Autonomous Region Healthcare Security Administration, settlement data of COPD inpatients from 17 medical institutions in Kashgar region between January 1, 2022, and December 31, 2024, were extracted. The overall changes in patients’ length of stay and costs were compared before and after the reform. Subsequently, interrupted time series analysis (ITSA) was employed to explore the impact of the DRG payment reform on these variables. RESULTS Following the reform, both the average length of stay and various cost decreased significantly compared to the pre-reform period ( P <0.001). At the overall sample level, the average length of stay, average total cost, average drug cost, average medical service cost, and average examination cost per admission all demonstrated significant long-term downward trends after the reform ( P <0.05). However, the decrease in average out-of-pocket costs and the increase in average consumable costs per admission were not statistically significant ( P >0.05). In tertiary medical institutions, the average length of stay and all categories of costs (except average consumable costs per admission) exhibited significant long-term upward trends after the reform ( P <0.05); conversely, in secondary and lower-level medical institutions, the average length of stay, average total cost, average drug cost, average medical service cost, and average examination cost per admission showed significant long-term downward trends ( P <0.05). CONCLUSIONS The DRG payment reform has achieved an overall effect of reducing the length of stay and controlling costs in COPD patients from Kashgar region. However, the effects vary across different levels of medical institutions: secondary and lower-level institutions show a long-term downward trend in length of stay and costs, whereas tertiary institutions exhibit a long-term upward trend. Furthermore, patients’ out-of-pocket financial burden does not show significant improvement.
9.Mechanism of Bushen Kaixuan Tongluo Prescription in Improving Diabetic Nephropathy Based on cAMP Signaling Pathway
Miao XU ; Baosheng ZHAO ; You WANG ; Yuzhuo CHANG ; Zehao LIU ; Lingling QIN ; Haiyan WANG ; Ming GAO ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):87-96
ObjectiveTo investigate the molecular mechanism by which the Bushen Kaixuan Tongluo prescription exerts a renal protective effect in mice with diabetic kidney disease (DKD) by regulating the cyclic adenosine monophosphate (cAMP) signaling pathway. MethodsThirty specific pathogen-free (SPF) male db/db mice were adaptively fed for three weeks. Mice with a random tail vein blood glucose level ≥ 11.1 mmol·L-1 and urinary albumin-creatinine ratio (ACR) ≥ 30 mg·g-1 were considered successfully modeled. The successfully modeled mice were randomly divided into five groups with six mice in each group: the model group, the low-, medium-, and high-dose Bushen Kaixuan Tongluo prescription groups (administered at doses of 7, 14, 28 g·kg-1·d-1 respectively), and the positive drug irbesartan group (administered at a dose of 20 mg·kg-1·d-1). Additionally, six db/m mice were selected as the blank group. Mice in each group were given intragastric administration of the Bushen Kaixuan Tongluo prescription at the corresponding concentrations, irbesartan, or an equal volume of pure water, and the intervention lasted for 12 weeks. During the experiment, the general conditions, body weight changes, and renal function indicators of the mice were dynamically monitored. After the intervention, a blood glucose meter was used to measure the fasting blood glucose (FBG) of the mice. An automatic biochemical analyzer was employed to detect the levels of serum creatinine (SCr), blood urea nitrogen (BUN), urinary microalbumin (uALB), ACR, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglycerides (TG), leptin (LEP), glycosylated serum protein (GSP), and insulin (INS) in the mice. Renal tissues were collected for hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and Masson's trichrome staining to observe the histopathological changes. Immunohistochemistry (IHC) was used to detect the expressions of protein kinase A (PKA) and cAMP response element-binding protein (CREB) in the mice. Western blot analysis was performed to determine the expression levels of PKA, phosphorylated protein kinase A (p-PKA), CREB, phosphorylated cAMP response element-binding protein (p-CREB), and B-cell lymphoma-2 (Bcl-2) proteins in the renal tissues of the mice. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of PKA, CREB, and Bcl-2 in the renal tissues of the mice. ResultsCompared with the blank group, the mice in the model group showed listlessness, decreased activity, and a significant increase in body weight (P<0.01). Biochemical indicators revealed that the levels of BUN, uALB, ACR, AST, ALT, TC, TG, FBG, LEP, GSP, and INS were significantly increased (P<0.01), while SCr showed an increasing trend with no statistically significant difference. Compared with the model group, the mice in the Bushen Kaixuan Tongluo prescription intervention groups had improved general conditions and a decreasing trend in body weight. Biochemical indicators showed that the levels of BUN, uALB, ACR, TC, GSP, and INS were significantly decreased (P<0.05), while SCr, AST, ALT, TG, and LEP showed a decreasing trend with no statistically significant difference. Renal histopathological analysis showed that the model group exhibited typical DKD pathological features such as thickening of the glomerular basement membrane, expansion of the mesangial matrix, and deposition of collagen fibers in the renal tubulointerstitium, and all treatment groups could alleviate the above pathological damages. The IHC results showed that compared with the blank group, the expression levels of p-PKA and p-CREB in the renal tissues of the model group were significantly decreased (P<0.01). Compared with the model group, the expression level of p-PKA in the medium-dose Bushen Kaixuan Tongluo prescription group was significantly increased (P<0.01), while the expression level of p-CREB showed an increasing trend with no statistically significant difference. Western blot results showed that compared with the blank group, the expression levels of p-PKA/PKA, p-CREB/CREB, and Bcl-2 in the model group were significantly decreased (P<0.05). Compared with the model group, the expression levels of these proteins in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly increased (P<0.01). Real-time PCR results showed that compared with the blank group, the mRNA expressions of PKA, CREB, and Bcl-2 in the model group were significantly down-regulated (P<0.05). Compared with the model group, the mRNA expressions of these genes in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly up-regulated (P<0.05). ConclusionThe Bushen Kaixuan Tongluo prescription can improve the liver and kidney functions of db/db mice, correct lipid metabolism disorders and glucose metabolism imbalance. Its renal protective effect is associated with up-regulating the cAMP signaling pathway to improve renal fibrosis and reduce the level of oxidative stress, thereby protecting renal function.
10.Regulatory effect of histone lactylation modification in hepatic fibrosis
Weichu ZENG ; Xing LYU ; Fengfan LI ; Zhenni LIU ; Jungang LI ; Weilin ZHANG ; Peiting LIU ; Bingchu LI ; Ruohong CHEN ; Zhiyang CHEN ; Min HU
Journal of Clinical Hepatology 2026;42(3):704-710
Hepatic fibrosis is a reversible pathological process in various chronic liver diseases and is closely associated with the development and progression of severe liver diseases such as liver cirrhosis and hepatocellular carcinoma, and it has emerged as a significant global health challenge. In recent years, studies have shown that histone lactylation, a newly discovered epigenetic modification, actively participates in regulating the progression of hepatic fibrosis. This article systematically reviews the core regulatory effect of histone lactylation modification in the interaction between inflammatory microenvironment and hepatic fibrosis, in order to clarify the cascade regulatory mechanism of “inflammation-hepatic fibrosis” and provide new insights for early diagnosis, targeted intervention, and prevention of malignant transformation in hepatic fibrosis.

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