1.Perioperative immune dynamics and clinical outcomes in patients undergoing on-pump cardiac surgery
Zhiyuan CHENG ; Xinyi LIAO ; Juan WU ; Ping YANG ; Tingting WANG ; Qinjuan WU ; Wentong MENG ; Zongcheng TANG ; Jiayi SUN ; Jia TAN ; Jing LIN ; Dan LUO ; Hao WANG ; Chaonan LIU ; Jiyue XIONG ; Liqin LING ; Jing ZHOU ; Lei DU
Chinese Journal of Blood Transfusion 2026;39(1):31-43
Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10
/L vs preoperative 3.07×10
/L, P<0.001), with significant upregulation of CD11b (7.30×10
/L vs preoperative 3.05×10
/L, P<0.001) and CD54 (7.15×10
/L vs preoperative 2.99×10
/L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10
/L vs preoperative 1.12×10
/L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10
/L vs preoperative 1.12×10
/L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.
2.Effect of Qingfei Shenshi Decoction (清肺渗湿汤) Combined with Western Medicine on Clinical Effectiveness and Immune Function for Patients with Bronchial Asthma of Heat Wheezing Syndrome
Ying SUN ; Haibo HU ; Na LIU ; Fengchan WANG ; Jinbao ZONG ; Ping HAN ; Peng LI ; Guojing ZHAO ; Haoran WANG ; Xuechao LU
Journal of Traditional Chinese Medicine 2026;67(1):38-44
ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction (清肺渗湿汤) combined with western medicine for patients with bronchial asthma of heat wheezing syndrome, and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group, each group with 43 participants. The control group received conventional western medicine, and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group, 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness; secondary outcome measures included traditional Chinese medicine (TCM) syndrome score, asthma control test (ACT) score, pulmonary function indices such as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), serum inflammatory factor levels including interleukin-4 (IL-4), tumour necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP), and immune function indices including CD3+, CD4+, CD8+, CD4+/CD8+. All outcome measures were evaluated before and after treatment. Vital signs were monitored, and electrocardiography, blood routine, urine routine, liver function, and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% (39/40), which was significantly higher than that of the control group (85.0%, 34/40, P<0.05). After treatment, both groups showed decreased TCM syndrome scores, IL-4, TNF-α, hs-CRP, and CD8+ levels, as well as increased ACT scores, CD3+, CD4+, CD4+/CD8+, FEV1, FVC, and PEF levels (P<0.05 or P<0.01). Moreover, the improvements in these indices were more significant in the treatment group than in the control group (P<0.05 or P<0.01). No significant abnormalities in safety indicators were observed in either group, and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms, pulmonary function, and clinical effectiveness, with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.
3.Olfactory Receptors Expressed in The Intestine and Their Functions
Pei-Wen YANG ; Meng-Meng YUAN ; Ying ZHOU ; Peng LI ; Gui-Hong QI ; Ying YANG ; Zhong-Yi MAO ; Meng-Sha ZHOU ; Xiao-Shuang MAO ; Jian-Ping XIE ; Yi-Nan YANG ; Shi-Hao SUN
Progress in Biochemistry and Biophysics 2026;53(3):534-549
Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.
4.A Survey on the Perceived Experience and Acceptance of Intrapartum Ultrasound as a Novel Method for Labor Progress Assessment
Xinjuan CHEN ; Jinhui CUI ; Liping OUYANG ; Ling LI ; Jianhui FAN ; Ping LI
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):535-540
ObjectiveTo investigate the perceived experience and acceptance of intrapartum ultrasound (IPUS) as a novel method for labor progress assessment among pregnant women. MethodsFrom February 2023 to December 2024, a total of 180 pregnant women admitted to the Labor Ward of Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University, who were planned for vaginal trial of labor , were accessed for labor progress using IPUS and vaginal examination (VE) after the onset of labor and prior to the initiation n of labor analgesia. A self-designed questionnaire was used to investigate the women's perceived experiences with both examination methods and their acceptance of IPUS. The pain intensity associated with the examinations was evaluated using the visual analogue pain scale (VAS). Differences in the women's experiences and pain intensity between the two labor progress assessment methods were compared. ResultsThe acceptance rate of IPUS was 96.67% (174/180), with the remaining 6 cases undecided. Over 60% of the pregnant women reported IPUS assessment as comfortable and none of them felt discomfort, whereas 32.8% felt uncomfortable with VE (χ2=196.02, P<0.001). Nearly two-thirds of the pregnant women believed that VE would cause psychological distress, while none reported such effect with IPUS (χ2=261.52, P<0.001). Approximately 77.78% (140/180) of the pregnant women believed that IPUS could reduce their fear of vaginal delivery and enhance their confidence if it replaced VE. The VAS score for IPUS [0 (0, 2)] was significantly lower than that for VE [4 (4, 6)] (Z=-14.62, P<0.001). Further stratified analysis showed that over 90% (164/180) of the pregnant women found IPUS painless, with no moderate or severe pain reported, compared to 43.33% (78/180) experienced moderate or severe pain with VE (P<0.001). ConclusionAs a novel approach for labor progress assessment, IPUS not only alleviates the pain and discomfort associated with traditional VE and reduces the fear of childbirth but also enhances women's confidence in delivery, thereby achieving a high level of acceptance among parturient women in China.
5.Kaixuan Jiedu Compatibility Alleviates Skin Lesions and Inflammatory Reactions in Psoriasis-like Mice
Ningxin ZHANG ; Jiaqi LI ; Xinqian LIU ; Tianbo ZHANG ; Meiqi SUN ; Mingjing LI ; Bin YANG ; Ping SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):79-88
ObjectiveTo investigate the efficacy and safety of Kaixuan Jiedu compatibility and the decomposed prescriptions in the treatment of psoriasis. MethodsThirty Balb/c mice were randomly grouped as follows (n=6): normal, model, Kaixuan Jiedu (KXJD, 15.21 g·kg-1), Kaixuan (KX, 3.08 g·kg-1), and Jiedu (JD, 12.13 g·kg-1). Except the normal group, the rest groups were modeled for psoriasis-like skin lesions by topical application of imiquimod, and samples were collected after 7 days of continuous intervention. Mice were photographed at the lesion site during modeling and before sampling and the psoriasis area and severity index (PASI) was calculated. Hematoxylin-eosin (HE) staining was used to observe pathological changes in the lesions and measure the epidermal thickness. Mice were photographed and observed for the tortuous dilation of dermal capillaries. The expression of vascular endothelial growth factor (VEGF), platelet-endothelial cell adhesion molecule (CD31), proliferating cell nuclear antigen (Ki67), and cytokeratin 10 (CK10) in the epidermal tissue was detected by immunohistochemistry. Immunofluorescence assay was employed to determine the expression of Claudin-1 and Occludin. Real-time PCR was employed to determine the mRNA levels of interleukin-17A (IL-17A) and interleukin-23 (IL-23). The spleen and thymus were photographed and weighed, and the spleen and thymus indices were calculated. The safety of the treatment was assessed by automatic biochemistry testing of the serum, liver, and kidney functions and by HE staining of the liver, kidney and spleen. ResultsCompared with that of the normal group, the skin of the model group showed erythema, infiltration, and typical psoriasis-like changes, tortuous dilation of dermal capillaries, hyperkeratosis in epidermal cells, acanthosis, massive lymphocytic infiltration in the dermis, impaired barrier function, increased expression of VEGF, CD31, Ki67, and CK10 (P<0.01), reduced expression of Claudin-1 and Occludin (P<0.01) in the epidermis, and up-regulated mRNA levels of IL-17A and IL-23 (P<0.01). In addition, the mice in the model group showed spleen enlargement, thymus atrophy, increased spleen index, and decreased thymus index (P<0.01). Compared with the model group, KXJD and JD reduced psoriasis-like skin lesions, inhibited the tortuous dilation of dermal capillaries, reduced the expression of VEGF, CD31, Ki67, and CK10 (P<0.01), increased the expression of claudin-1 (P<0.01), and down-regulated the mRNA levels of inflammatory factors (P<0.01). Moreover, the KXJD group outperformed the JD group. The JD group showed no significant difference from the model group regarding the spleen index, thymus index, and Occludin expression. The psoriasis indicators in the KX group were not significantly different from those in the model group. ConclusionKXJD and JD can reduce the symptoms of local skin lesions of psoriasis, which is manifested as different inhibition degrees of the proliferation and differentiation of keratin-forming cells, tortuous dilation of dermal capillaries, and inflammatory reactions, as well as the protection of the skin barrier. Moreover, KXJD outperformed JD. KX alone did not significantly reduce psoriasis lesions in mice. KXJD and the decomposed prescriptions are safe and effective, causing no obvious liver and kidney injuries.
6.Kaixuan Jiedu Compatibility Alleviates Skin Lesions and Inflammatory Reactions in Psoriasis-like Mice
Ningxin ZHANG ; Jiaqi LI ; Xinqian LIU ; Tianbo ZHANG ; Meiqi SUN ; Mingjing LI ; Bin YANG ; Ping SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):79-88
ObjectiveTo investigate the efficacy and safety of Kaixuan Jiedu compatibility and the decomposed prescriptions in the treatment of psoriasis. MethodsThirty Balb/c mice were randomly grouped as follows (n=6): normal, model, Kaixuan Jiedu (KXJD, 15.21 g·kg-1), Kaixuan (KX, 3.08 g·kg-1), and Jiedu (JD, 12.13 g·kg-1). Except the normal group, the rest groups were modeled for psoriasis-like skin lesions by topical application of imiquimod, and samples were collected after 7 days of continuous intervention. Mice were photographed at the lesion site during modeling and before sampling and the psoriasis area and severity index (PASI) was calculated. Hematoxylin-eosin (HE) staining was used to observe pathological changes in the lesions and measure the epidermal thickness. Mice were photographed and observed for the tortuous dilation of dermal capillaries. The expression of vascular endothelial growth factor (VEGF), platelet-endothelial cell adhesion molecule (CD31), proliferating cell nuclear antigen (Ki67), and cytokeratin 10 (CK10) in the epidermal tissue was detected by immunohistochemistry. Immunofluorescence assay was employed to determine the expression of Claudin-1 and Occludin. Real-time PCR was employed to determine the mRNA levels of interleukin-17A (IL-17A) and interleukin-23 (IL-23). The spleen and thymus were photographed and weighed, and the spleen and thymus indices were calculated. The safety of the treatment was assessed by automatic biochemistry testing of the serum, liver, and kidney functions and by HE staining of the liver, kidney and spleen. ResultsCompared with that of the normal group, the skin of the model group showed erythema, infiltration, and typical psoriasis-like changes, tortuous dilation of dermal capillaries, hyperkeratosis in epidermal cells, acanthosis, massive lymphocytic infiltration in the dermis, impaired barrier function, increased expression of VEGF, CD31, Ki67, and CK10 (P<0.01), reduced expression of Claudin-1 and Occludin (P<0.01) in the epidermis, and up-regulated mRNA levels of IL-17A and IL-23 (P<0.01). In addition, the mice in the model group showed spleen enlargement, thymus atrophy, increased spleen index, and decreased thymus index (P<0.01). Compared with the model group, KXJD and JD reduced psoriasis-like skin lesions, inhibited the tortuous dilation of dermal capillaries, reduced the expression of VEGF, CD31, Ki67, and CK10 (P<0.01), increased the expression of claudin-1 (P<0.01), and down-regulated the mRNA levels of inflammatory factors (P<0.01). Moreover, the KXJD group outperformed the JD group. The JD group showed no significant difference from the model group regarding the spleen index, thymus index, and Occludin expression. The psoriasis indicators in the KX group were not significantly different from those in the model group. ConclusionKXJD and JD can reduce the symptoms of local skin lesions of psoriasis, which is manifested as different inhibition degrees of the proliferation and differentiation of keratin-forming cells, tortuous dilation of dermal capillaries, and inflammatory reactions, as well as the protection of the skin barrier. Moreover, KXJD outperformed JD. KX alone did not significantly reduce psoriasis lesions in mice. KXJD and the decomposed prescriptions are safe and effective, causing no obvious liver and kidney injuries.
7.Pharmacoeconomic evaluation of durvalumab combined with chemotherapy as first-line therapy for advanced biliary tract cancer
Liman HUO ; Yangyang DUAN ; Ping LIANG ; Bin SHAN ; Xiaoli SUN ; Rui FENG
China Pharmacy 2025;36(17):2141-2147
OBJECTIVE To assess the cost-effectiveness of durvalumab combined with chemotherapy as a first-line treatment for advanced biliary tract cancer from the perspective of the Chinese healthcare system. METHODS Using data from the TOPAZ-1 clinical trial, a three-state Markov model comprising progression-free survival (PFS), progressive disease (PD) and death was developed, with a cycle length of 21 days and a 10-year time horizon. Patients in the observation group received durvalumab in combination with gemcitabine and cisplatin, whereas those in the control group received placebo plus the same chemotherapy regimen. The evaluation indexes were quality-adjusted life year (QALY) and the incremental cost-effectiveness ratio (ICER). The willingness-to-pay (WTP) threshold was set at three times the 2024 Chinese per capita gross domestic product (GDP) (287 247 yuan/QALY). The sensitivity analyses, along with scenario analyses, were performed. RESULTS In the base-case analysis, the ICER of observation group compared to control group was 1 166 344.46 yuan/QALY, far exceeding the WTP threshold, indicating that the regimen was not cost-effective. One-way sensitivity analysis identified the PD state utility, discount rate, cost of durvalumab, and PFS state utility as the main drivers of ICER variation. Probabilistic sensitivity analysis showed that, at the above WTP threshold, the probability of the acceeptance of this regimen was 0, further supporting the robustness of the base-case findings. In the scenario analysis, inclusion of a patient assistance program reduced the ICER to 235 885.16 yuan/ QALY, below the above WTP threshold, suggesting cost-effectiveness under this assistance program. However, when applying a regional WTP threshold set at three times the per capita GDP (158 475 yuan/QALY) of Gansu Province (the province with the lowest GDP in China in 2024), the ICER remained above the threshold, indicating that the regimen was not cost-effective at the regional level. CONCLUSIONS At current pricing, durvalumab plus chemotherapy as a first-line treatment for advanced biliary tract cancer is not cost-effective in China. Although the introduction of a patient assistance program can substantially reduce the ICER and achieve cost-effectiveness at a WTP threshold set at three times the 2024 per capita GDP of China, due to limited affordability in low-income areas, the program remains not cost-effective.
8.Effects of volatile oil from Acorus tatarinowii on CX3CL1/CX3CR1 signal axis and neuroinflammation in a rat model of tic disorders
Yan-qin DING ; Peng FENG ; Ming-lu WANG ; Yu-tong WANG ; Ke-xin SUN ; Xing WEI ; Yong-yan TIAN ; Xing-ping TANG ; Ping LI ; Ruo-lan LU ; Ling LI
Chinese Traditional Patent Medicine 2025;47(6):1825-1833
AIM To investigate the effects of volatile oil from Acorus tatarinowii Schott(A.tatarinowii)on neuroinflammation in a rat model of tic disorders.METHODS The SD rats were randomly divided into the blank group(8 rats)and the model group(40 rats).The rat models of tic disorders established successfully by intraperitoneal injection of iminodiapropionitrile(IDPN)were further divided into the model group,the tiapride group and the high-dose,moderate-dose and low-dose A.tatarinowii volatile oil groups,with 8 rats in each group.The 4-week intragastric treatment of respective drug was initiated the next day after the completion of modeling,and normal saline was dosed upon the blank group and the model group,during which the rats' behavioral changes were assessed by stereotyped behavior and motor behavior score every week.After the administration,the rats had their morphological changes of striatal neurons observed by Nissl staining;their levels of TGF-β,IL-10,TNF-αand IL-1β in serum and striatum detected by ELISA;their striatal protein expressions of CX3CL1 and CX3CR1 detected by Western blot and immunohistochemistry;and their striatal expressions of M1,M2 microglia marker proteins CD86,CD206,SYN and PSD-95 detected by immunofluorescence co-staining.RESULTS Compared with the model group,the A.tatarinowii volatile oil groups demonstrated improved twitch-like behavior;decreased scores of motor behavior and rigid behavior(P<0.01);alleviated damage of Nissl bodies in neurons;increased serum and striatum levels of TGF-β and IL-10(P<0.05,P<0.01);decreased levels of TNF-α and IL-1β(P<0.01);decreased striatal protein expressions of CX3CL1 and CX3CR1(P<0.01);increased protein expressions of PSD95 and SYN(P<0.05,P<0.01);and decreased CD86/Iba1(P<0.01)and increased CD206/Iba1(P<0.01)in terms of the fluorescence intensity.CONCLUSION A.tatarinowii volatile oil contributes an anti-tic effect and improves the neuroinflammation in the brain of the rat model of tic disorders by promoting the transformation of microglia into M2 type via CX3CL1/CX3CR1 signal axis.
9.Application of cognitive interview in cultural adaptation of the prenatal physical activity dual screening questionnaire
Fang-ping XU ; Zhi-zhen LI ; Hua TAO ; Li-ping SUN ; Xiao-jiao WANG ; Xin-li ZHU ; Chun-yi GU
Fudan University Journal of Medical Sciences 2025;52(2):297-300,304
To explore the understanding of the target population regarding the Get Active Questionnaire for Pregnancy(GAQ-P)and the Companion Health Care Provider Consultation Form for Prenatal Physical Activity(cHCP-CF-PPA)in the Chinese context,and to verify the consistency of the Chinese version of the prenatal physical activity dual screening questionnaire with the original version in terms of language expression,27 pregnant women and 12 healthcare providers were selected from Obstetrics and Gynecology Hospital,Fudan University during Aug and Oct 2023,and were interviewed using purposive sampling.Two rounds of cognitive interviews were conducted.The first round revealed that some respondents experienced ambiguities in understanding the meanings of 5 items in the questionnaire.Following modifications,the second round indicated that the revised items were consistent in meaning with the original questionnaire.Cognitive interviews can facilitate the adaptation of the prenatal physical activity dual screening questionnaire to the Chinese cultural context,improve the understanding of the questionnaire items among the target population,and promote the localization of the screening tool.
10.Mechanism of baicalin combined with heat stimulation in treating acute lymphoblastic leukemia based on network pharmacology and in vitro experimental verification
Zi-ru LIU ; Zhu-yun SUN ; Ping-liang GE ; Ran SHI ; Xiao-yun LIU ; Dong-xue YE ; Guo-ying ZHANG ; Rong RONG ; Yong YANG
Chinese Pharmacological Bulletin 2025;41(6):1167-1176
Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

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