Table of Content

Volume 30 Issue 8
26 August 2025

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SCD1 inhibitor CAY-10566 sensitizes cisplatin by inducing ferroptosis in oral squamous cell carcinoma cells

WANG Zhiheng¹, XING Xin¹, TAO Tao², MENG lianqin¹, WANG Jun¹, GUO Ping¹, CHAI Lin²

2025, 30(8):  1009-1016.  doi:10.12092/j.issn.1009-2501.2025.08.001

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AIM: To investigate how the stearoyl-CoA desaturase-1 (SCD1) inhibitor CAY-10566 induces ferroptosis in oral squamous cell carcinoma (OSCC) cells and enhances their sensitivity to cisplatin, with preliminary exploration of the underlying molecular mechanisms. METHODS: Bioinformatics analysis and clinical specimens were used to evaluate SCD1 expression in OSCC tissues. OSCC cell lines (Cal27 and HSC3) were treated with CAY-10566, cisplatin, the ferroptosis inhibitor Ferrostatin-1 (Fer-1), or their combinations. Cell viability was assessed using the CCK-8 assay, while reactive oxygen species (ROS) and lipid ROS levels were measured by flow cytometry. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were quantified using commercial assay kits. Western blotting was performed to analyze the protein expression of glutathione peroxidase 4 (GPX4), mechanistic target of rapamycin (mTOR), mature sterol regulatory element-binding protein 1 (m-SREBP1), SCD1, and heme oxygenase 1 (HMOX1). RESULTS: SCD1 was significantly overexpressed in OSCC tissues (P<0.01). Combined treatment with CAY-10566 and cisplatin markedly reduced OSCC cell viability (P<0.01) and increased lipid peroxidation (P<0.001), while suppressing GPX4 expression-effects that were reversed by Fer-1 (P<0.001). CAY-10566 upregulated HMOX1 expression and inhibited mTOR, m-SREBP1, and SCD1 protein levels (P<0.001). CONCLUSION: CAY-10566 promotes ferroptosis and cisplatin sensitivity in OSCC cells, potentially through HMOX1 upregulation and suppression of the mTOR/SREBP1/SCD1 axis.

LOX-1 promotes hypoxia-induced autophagy and apoptosis in endothelial cells

LI Yanfei¹, HUANG Can², LUO Ping³, HE Fang⁴, HU Changping²

2025, 30(8):  1017-1025.  doi:10.12092/j.issn.1009-2501.2025.08.002

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AIM: To investigate the role of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in hypoxia-induced autophagy and apoptosis in endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to hypoxia (1%O₂) for varying durations (0, 6, 12, 24 h) to evaluate autophagy and apoptosis levels. LOX-1 was further intervened to explore its effects on autophagy and apoptosis. GFP-LC3B adenovirus infection was observed under fluorescence microscopy to assess LC3B expression. Autophagosomes were detected by transmission electron microscopy (TEM). LOX-1 mRNA levels were measured using real-time PCR. Protein expression of LOX-1, LC3II/I, Beclin-1, Atg5, cleaved-caspase 3, Bax, and Bcl-2 was analyzed by Western blot. Reactive oxygen species (ROS) levels were quantified using the DCFH-DA fluorescent probe. Apoptosis was assessed via Hoechst staining and flow cytometry (Annexin V-PI double staining). RESULTS: Hypoxia (1%O₂, 24 h) significantly increased LC3II puncta under fluorescence microscopy, upregulated LC3II/I protein expression, and induced autophagosome formation observed by TEM. Hypoxia elevated ROS production and promoted apoptosis. LOX-1 mRNA and protein expression were upregulated in hypoxic HUVECs. LOX-1 siRNA intervention markedly reversed hypoxia-induced autophagy, downregulating autophagy-related proteins (Beclin-1, Atg5, LC3II/I). LOX-1 siRNA also suppressed ROS generation and inhibited apoptosis, as evidenced by decreased expression of cleaved-caspase 3 and Bax, and increased Bcl-2 levels. CONCLUSION: Hypoxia induced upregulation of LOX-1 expression to produce ROS, thereby promoting autophagy and apoptosis in endothelial cells.

Study on the mechanism of Xiongshi Shiwei Wendan decoction promoting RCT and treat AS based on network pharmacology, molecular docking and in vitro experiment

MA Xingyu^{1, 2}, XIE Xuejiao², LI Chunqiao¹, ZHANG Zheng¹

2025, 30(8):  1026-1036.  doi:10.12092/j.issn.1009-2501.2025.08.003

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AIM: Xiongshi Shiwei Wendan decoction (SWD) comes from Xiong Jibai, a master of traditional Chinese medicine, and has been widely used in the treatment of AS. ABCA1 is an important pathway for macrophages to export cholesterol and plays a protective role in the occurrence and development of AS. The purpose of this study was to study the effects of SWD on ABCA1 expression and cholesterol efflux through network pharmacology, molecular docking and in vitro experiments, and explore the pathway mechanism of promoting reverse cholesterol transport (RCT). METHODS: The active components of SWD drugs were screened by TCMSP and HERB databases, RCT targets were predicted, the component-target network map was constructed, the PPI network was constructed and the GO and KEGG pathways were enriched and analyzed by STRING database, and the key active components of SWD were selected for molecular docking with ABCA1 protein and miR-33 by AutoDockVina. In vitro, RAW264.7 was used to establish foam cell model, oil red O staining, NBD-cholesterol staining and lentivirus overexpression cell miRNA-33 were used to study the effect of SWD on lipid accumulation and cholesterol outflow rate of RAW264.7 cells. Western blotting was used to detect the expression of ABCA1. RESULTS: According to network pharmacology, 336 active components of SWD, 267 targets of RCT and 46 targets of intersection of RCT and SWD were obtained, which involved multiple signal pathways such as lipid and atherosclerosis. Molecular docking showed that the main active components had stable conformation with ABCA1 and miR-33. In vitro experiment, it was found that the lipid content was significantly decreased (P<0.01), the cholesterol outflow rate was significantly increased (P<0.01) and the expression of ABCA1 protein was up-regulated in SWD group (P<0.01), but the expression of ABCA1 in miR-33 overexpression group was significantly decreased (P<0.01). CONCLUSION: SWD has the characteristics of multi-components and multi-targets, which can promote RCT and treat AS through miRNA-33-ABCA1 pathway.

Study on the neuroprotective effect and mechanism of Tianma Gouteng Decoction on combining rat model of Hyperactivity of Liver Yang and MCAO based on autophagic flux and CXCL12/CXCR4 axis

WANG Xiaoli, SHAO Jing, ZHANG Wei, TIAN Ping, ZHANG Xuexia, LIU Changhe, LI Kaiyan, YANG Dan, GUO Xiaoyan

2025, 30(8):  1037-1048.  doi:10.12092/j.issn.1009-2501.2025.08.004

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AIM: To investigate autophagic status in ischemic stroke with Liver Yang Hyperactivity and the mechanism of Tianma Gouteng Decoction (TMGTD). METHODS: SD rats were divided into sham, model, TMGTD high/medium/low-dose (20.52/10.26/5.13 g·kg^-1·d^-1), and Nimodipine (30 mg·kg^-1·d^-1) groups. A Liver Yang Hyperactivity and cerebral ischemia-reperfusion model was established using Fuzi Decoction (2 g·kg^-1·d^-1) and thread-occlusion. After 21 days of Fuzi decoction pretreatment, rats received daily drug administration for 12 days. Syndrome indicators (irritability, 24-hour water intake, 24-hour urine volume, facial temperature) were recorded, plasma NE, E, cAMP, and cGMP were measured by ELISA, neurological function was assessed using Zea Longa and mNSS methods, brain histopathology was evaluated by HE staining, protein expression of soluble/insoluble p62 and LC3B was detected by Western blot, autophagy-related genes were analyzed by PCR array, additionally, mRNA and protein levels of CXCR4 and CXCL12 were measured by qRT-PCR and Western blot. RESULTS: Compared to the sham group, the model group showed increased irritability, 24-hours water intake, 24-hours urine volume, facial temperature, and level of NE, E, cGMP (P<0.01), neurological scores (P<0.01), LC3B-II, insoluble p62, CXCR4, CXCL12 expression (P<0.01), but decreased soluble p62 (P<0.01). TMGTD groups exhibited reduced irritability, water intake, urine volume, facial temperature, NE, E, cGMP (P<0.05, P<0.01), neurological scores (P<0.05, P<0.01), p62 expression (P<0.01), alongside increased LC3B-II (P<0.01) and improved cortical pathology. TMGD also reversed dysregulated autophagy-apoptosis genes (CXCR4, Lamp1, Tgfb1, APP, Rab24) and reduced CXCR4, CXCL12 expression (P<0.01). CONCLUSION:In the Liver Yang Hyperactivity and cerebral ischemia-reperfusion model, autophagy genes were activated but flux was impaired, and Tianma Gouteng Decoction may protect by restoring autophagic flux and inhibiting the CXCL12/CXCR4 axis.

Semaglutide alleviates hypoxia/reoxygenation-induced inflammatory injury of AC16 human cardiomyocytes by regulating autophagy through AMPK/mTOR/ULK1 pathway

JIN Lili¹, QIE Tao², LI Liqin³

2025, 30(8):  1058-1066.  doi:10.12092/j.issn.1009-2501.2025.08.005

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AIM: To investigate the effects of semaglutide on inflammation and autophagy in human AC16 cardiomyocytes under hypoxia/reoxygenation conditions. METHODS: AC16 cells were randomly divided into four groups: control (CON), hypoxia/reoxygenation (H/R), hypoxia/reoxygenation+semaglutide (H/R+SEM), and hypoxia/reoxygenation+semaglutide+3-MA (H/R+SEM+3-MA). All groups except CON underwent 8 hours of hypoxia followed by 12 hours of reoxygenation. Cell viability was measured by CCK-8. Levels of IL-1β and TNF-α were assessed by ELISA. Western blot analysis evaluated AMPK, p-AMPK, mTOR, p-mTOR, ULK1, p-ULK1, Beclin-1, and LC3. Autophagosomes were analyzed using laser confocal microscopy and transmission electron microscopy. The structure of autophagosome and autolysosome was observed by transmission electron microscopy. RESULTS: IL-1β and TNF-α levels increased significantly in the H/R group compared to CON (P<0.01) but decreased in the H/R+SEM group (P<0.01). In the H/R+SEM+3-MA group, inflammatory levels increased compared to the H/R+SEM (P<0.05). Compared with the CON group, p-AMPK/AMPK and p-ULK1/ULK1 ratios increased significantly in the H/R group (P<0.05, P<0.01). The ratios further increased in the H/R+SEM group compared to H/R (P<0.05, P<0.01). But the two ratios decreased in the H/R+SEM+3-MA group compared to H/R+SEM (P<0.01, P<0.05). The pmTOR/mTOR had the opposite trend to the two previous ratios. The expression of Beclin1 and LC3 were significantly increased in group H/R compared to CON (P<0.05), and which further increased in the H/R+SEM group compared to H/R (P<0.01). But the two indicators decreased in the H/R+SEM+3-MA group compared to H/R+SEM (P<0.01, P<0.05). Laser confocal microscopy revealed increased autophagosome numbers in H/R group compared to CON (P<0.05), and which further increased in the H/R+SEM group compared to H/R (P<0.01). While the H/R+SEM+3-MA group showed a decrease compared to H/R + SEM (P<0.05). CONCLUSION: Semaglutide may moderate regulate autophagy through AMPK/mTOR/ULK1 pathway, reduce the release of inflammatory factors, and alleviate hypoxia/reoxygenation-induced inflammatory injury.

Individualized dosage study of vitamin D3 based on physiologically-based pharmacokinetic modeling

WEI Yuanyuan¹, MA Tao¹, TANG Yuezhou¹, LI Hubo^{1, 2}, TIAN Xiaoyu^{1, 2}, DANG Yunjie¹, ZHOU Xu¹

2025, 30(8):  1067-1075.  doi:10.12092/j.issn.1009-2501.2025.08.007

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AIM: To establish a physiologically-based pharmacokinetic (PBPK) model for vitamin D in adults, aiming to provide guidance for the rational clinical use of vitamin D in individuals with vitamin D deficiency. METHODS: Relevant literature and databases were reviewed to obtain the physicochemical properties and pharmacokinetic parameters of vitamin D3. The PBPK model for adult whole-body vitamin D was constructed, optimized, and predicted using PK-Sim^® software. The model's predictive performance was evaluated using confidence intervals, goodness of fit, and fold error (FE). The effectiveness of commonly used clinical dosing regimens was assessed based on the final optimized model, and personalized dosing recommendations were provided. RESULTS: The established adult whole-body PBPK model for vitamin D had a goodness of fit R² of 0.961, approaching 1, and the FE values for AUC_0-∞ and C_max were both within the range of 0.5 and 2, indicating that the constructed PBPK model possesses good data predictive capability. CONCLUSION: A successful PBPK model for oral vitamin D3 in adults has been established, showing good predictive performance for single oral doses of vitamin D3. Single oral doses of vitamin D3 (7 500 μg and 15 000 μg) are safe and effective dosing regimens for improving vitamin D insufficiency or deficiency in Asian adults. Regular monitoring of vitamin D levels before and during treatment is recommended to achieve the optimal outcomes of personalized therapy.

Myeloid-derived suppressor cells in predicting the efficacy and prognosis of PD-1 inhibitor combined with chemotherapy in non-small cell lung cancer patients

GENG Biao, SUN Zhengui, ZHAO Chunyang, CHEN Xingwu

2025, 30(8):  1076-1083.  doi:10.12092/j.issn.1009-2501.2025.08.008

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AIM: To explore the relationship between the level of myeloid-derived suppressor cell (MDSC) infiltration in tumor tissues and the clinical efficacy and prognosis of combined PD-1 inhibitor and chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: A retrospective analysis was conducted on 92 NSCLC patients who received PD-1 inhibitor combined with chemotherapy at the First Affiliated Hospital of Anhui Medical University from June 2019 to June 2024. Tumor tissue samples were examined using immunohistochemistry to detect the level of MDSC infiltration, dividing the patients into high-infiltration group (MDSC≥2) and low-infiltration group (MDSC<2). The objective response rate (iORR), disease control rate (iDCR), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Kaplan-Meier survival analysis and Log-rank test were used to plot PFS and OS survival curves, and Cox regression analysis was applied to identify factors influencing prognosis. RESULTS: Among the 92 patients, 53 were in the low MDSC infiltration group, and 39 were in the high MDSC infiltration group. The low MDSC infiltration group showed significantly better treatment responses compared to the high MDSC infiltration group. The objective response rate (iORR) was 77.3% in the low MDSC infiltration group, higher than the 56.4% in the high MDSC infiltration group (P=0.033). The disease control rate (iDCR) was 94.3%, also significantly higher than the 66.7% in the high MDSC infiltration group (P=0.001). Moreover, the median progression-free survival (PFS) and overall survival (OS) in the low MDSC infiltration group were 16.9 months and 27.6 months, respectively, which were significantly longer than those in the high MDSC infiltration group (PFS 12.6 months, OS 22.3 months). Kaplan-Meier analysis revealed that both PFS and OS in the low MDSC infiltration group were significantly longer than those in the high MDSC infiltration group. Cox univariate analysis showed that smoking, PD-L1 expression levels, tumor stage, and MDSC infiltration level were closely associated with PFS and OS. Multivariate Cox regression analysis further indicated that high MDSC infiltration was an independent risk factor for both PFS (HR=2.678, P=0.013) and OS (HR=2.254, P=0.022). CONCLUSION: The level of MDSC infiltration in tumor tissues is closely related to the efficacy and prognosis of PD-1 inhibitor combined with chemotherapy in NSCLC patients. High MDSC infiltration suggests reduced treatment sensitivity and poor prognosis. MDSC infiltration level may serve as a predictive biomarker for the efficacy and prognosis of PD-1 inhibitor combined with chemotherapy in advanced NSCLC.

Changes of intestinal flora in patients with type 2 diabetes mellitus complicated with coronary heart disease after liraglutide treatment and its correlation with glucose and lipid metabolism indexes

XING Ying, ZHENG Rongjiong, JIANG Chunhui, Mayila·kahaer, Muhuyati·wulasihan

2025, 30(8):  1084-1091.  doi:10.12092/j.issn.1009-2501.2025.08.009

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AIM: To explore the changes of intestinal flora in patients with type 2 diabetes mellitus complicated with coronary heart disease after liraglutide treatment and its correlation with glucose and lipid metabolism indexes. METHODS: Twenty-six patients with type 2 diabetes mellitus complicated with coronary heart disease were selected to compare the changes of glucose and lipid metabolism indexes and intestinal flora (high-throughput sequencing technique) before and after liraglutide treatment, and to analyze the correlation between glucose and lipid metabolism indexes and intestinal flora. RESULTS: Compared with those before treatment, the indexes of glucose metabolism and lipid metabolism in the patients were significantly decreased (P<0.01). Liraglutide had no significant effect on the diversity of intestinal flora (P>0.05), but can significantly change the composition of intestinal flora (P<0.05). While beneficial bacteria such as Lachnospiraceae increased significantly, it significantly reduced the abundance of pathogenic bacteria such as Escherichia_Shigella (P<0.05), and promoted the production of short-chain fatty acids and body metabolism. CONCLUSION: Lilalutide can affect the composition of intestinal flora in type 2 diabetes patients with coronary heart disease, and then participate in the regulation of glucose and lipid metabolism.

The median effective dose of ciprofol combined with sufentanil to inhibit tracheal intubation reaction in patients undergoing intracranial aneurysm embolization

LU Fangzhou¹, LIU Meijuan¹, ZENG Qiong¹, ZHANG Wenbin², LU Jun¹

2025, 30(8):  1092-1098.  doi:10.12092/j.issn.1009-2501.2025.08.010

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AIM: To investigate the median effective dose of ciprofol combined with sufentanil to inhibit tracheal intubation reaction in patients undergoing intracranial aneurysm embolization. METHODS: Forty-five patients who underwent embolization for intracranial aneurysms were divided into two groups according to age: non-elderly group (aged 18-64 years) and elderly group (aged > 65 years). Patients in the two groups were first given intravenous ciprofol, of which the initial dose of ciprofol was 0.4 mg/kg and sufentanil 0.3 μg/kg and rocuronium 0.6 mg/kg were respectively injected according to BIS value and modified observer's assessment of alertness and sedation (MOAA/S) score. Then, endotracheal intubation was defined as 3 minutes after the induction of the study drug. Dixon sequential method was adopted, and the dose of ciprofol for the next patient was determined according to whether the tracheal intubation reaction was positive (Positive reaction of tracheal intubation was defined as the patient's kinomotor reaction such as coughing during tracheal intubation or the increase of MAP or HR within 2 minutes after intubation was greater than 20% of the basic value). When the tracheal intubation indicated a positive response, the next patient was raised by one gradient, otherwise, it was lowered by one gradient until the study ended at 7 crosses. The common dose ratio of adjacent patients was 1:1.1. The Probit probability method was used to calculate the 50% effective dose (ED₅₀), 95% effective dose (ED₉₅) and the corresponding 95% confidence interval (CI) of ciprofol. Perioperative adverse reactions were recorded in both groups. RESULTS: In the non-elderly group, the ED₅₀ of ciprofol inhibiting positive tracheal intubation reaction was 0.472 mg/kg (95%CI 0.419-0.565 mg/kg), and the ED₉₅ was 0.567 mg/kg (95%CI 0.513-1.293 mg/kg). In the elderly group, the ED₅₀ of ciprofol inhibiting tracheal intubation reaction was 0.409 mg/kg (95%CI 0.383-0.434 mg/kg) and the ED₉₅ was 0.452 mg/kg (95%CI 0.430-0.591 mg/kg). CONCLUSION: The ED₅₀ of ciprofol combined with sufentanil inhibiting positive tracheal intubation reaction was 0.472 mg/kg in non-elderly patients and 0.409 mg/kg in elderly patients.

Effect of high-dose methotrexate on alkaline phosphatase in children with acute lymphoblastic leukemia

LI Xingui¹, XU Daliang², YU Biao¹, GU Yun¹, DENG Yan¹, ZHANG Shihai³

2025, 30(8):  1099-1104.  doi:10.12092/j.issn.1009-2501.2025.08.011

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AIM: To investigate the effects of high-dose methotrexate (MTX) on alkaline phosphatase (ALP) and the effects of ALP changes on bone metabolism, bone marrow granulogram function, liver function and excretion. METHODS: Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and albumin (ALB) were used as liver function indicators, serum calcium (Ca) and phosphorus (P) were used as bone metabolism indicators, neutrophil (ANC) and white blood cell count (WBC) were used as bone marrow granuloline function indicators, and methotrexate C_48h concentration ≥1 μmol/L was used as the excretion delay. One-way ANOVA analysis was performed on the ALP levels before and after the first chemotherapy and the second chemotherapy, and the children were divided into normal group and low group according to the ALP level, and the seven indexes before and after chemotherapy were quantitatively and qualitatively analyzed, and univariate and multivariate Logistic regression analysis was performed on the concentration of methotrexate C_48h and the above indexes in the children treated with the second chemotherapy. RESULTS: After the first chemotherapy and the second chemotherapy, ALP was significantly decreased [(204.0±83.6) U/L vs.(172.8±67.3) U/L, (179.4±59.3) U/L vs. (169.6±57.1) U/L, all P<0.05], and the serum Ca, P, ANC, WBC, and ALB were significantly decreased (P<0.05), and AST and ALT were increased (P<0.05), and ALT was an independent risk factor for delayed excretion (OR=1.049, 95%CI 1.023-1.077, P<0.001), ALB was an independent protective factor for delayed excretion (OR=0.551, 95% CI 0.460-0.660, P<0.001), and ALP was not a significant contributor to MTX excretion delay. CONCLUSION: ALP is not a good predictor of liver function and bone marrow granulopathy function due to a significant decrease in ALP caused by high-dose MTX, and ALP together with serum calcium and phosphorus levels can constitute an early warning indicator of bone metabolism disorders.

Appropriate dose of dexmedetomidine assisted sedation in minimally invasive breast surgery

CHEN Jianxiao^{1, 2}, LV Hao², GUO Xiaowen³

2025, 30(8):  1105-1111.  doi:10.12092/j.issn.1009-2501.2025.08.012

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AIM: To investigate the appropriate dose of intravenous dexmedetomidine (Dex) for sedation in minimally invasive breast surgery under regional block. METHODS: A total of 120 patients with multiple breast masses were selected and divided into Dex 0.5 μg/kg group (group D₁), Dex 0.75 μg/kg group (group D₂), Dex 1.0 μg/kg group (group D₃) and normal saline group (group C) according to the random number table method. After intravenous injection of test drugs, minimally invasive rotary cutting under retromammary space anesthesia was performed. The optimal sedation rate during operation, the optimal sedation rate after operation, Ramsay sedation scores were recorded before anesthesia, at the end of intravenous administration, at the retromammary space anesthesia, at the beginning of surgery, 5 min after surgery, at the end of surgery, 30 min after administration, and 60 min after administration, visual analogue scale (VAS), vital signs (SBP, DBP, HR, SpO₂), the incidence of moderate and above pain (VAS>3) and adverse reactions were observed. The optimal sedation was defined as intraoperative Ramsay score 2-4 points and postoperative Ramsay score 2-3 points. RESULTS: Dex had a dose-dependent sedative and analgesic effect. The optimal sedation rate during operation in group D₂ and D₃ was significantly higher than that in group C and D₁, and the optimal sedation rate after operation in group D₂ was the highest. The rate of VAS score greater than 3 points in group D₂ and group D₃ was significantly lower than that in group C and group D₁, and there was no statistical difference between group D₂ and group D₃. The incidence of dizziness in group D₂ and group D₃ was higher than that in group C and group D₁. There was no significant difference in the incidence of hypotension, hypertension, severe bradycardia, hypoxemia and nausea among the groups. CONCLUSION: Preoperative single intravenous application of 0.75 μg/kg dexmedetomidine has a definite sedative and analgesic effect, and the optimal sedation rate during and after operation is high. It is an appropriate dose for sedation assisted by minimally invasive breast surgery under regional block.

Research progress on antitumor effects of Hedysari radix and active components

WEI Xiaocheng, LI Xinrong, HE Jungang, LI Xu, QIANG Zhengze, WANG Yan, WANG Mingwei, LI Chengyi

2025, 30(8):  1112-1121.  doi:10.12092/j.issn.1009-2501.2025.08.013

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Hedysari radix is the characteristic chinese medicine of Gansu Province, with "MiCang Hedysari radix" as the best. Modern pharmacological research has shown that it has polysaccharides and flavonoids, which have good anti-tumor effects and can inhibit the occurrence and development of various cancers, such as lung cancer, liver cancer, and breast cancer. Cancer is ranked as the second leading cause of death in the world, and the morbidity and mortality rates are increasing year by year, seriously affecting the quality of life. At present, with the modernization of Traditional Chinese Medicine (TCM), there has been a significant breakthrough in the treatment of malignant tumors with TCM. Based on this, by collating the relevant literature at home and abroad in recent years, the anti-tumor effects and mechanisms of Hedysari radix and its active ingredients are summarized to provide a scientific basis for the study of elucidating the material basis of the anti-tumor effects of Hedysari radix and to promote the development of the Hedysari radix industry.

Research progress on the mechanism of IL-33/ST2 signaling pathway in kidney diseases

WANG Qian^{1, 2, 3}, LIANG Changchang^{1, 2, 3}, SHEN Shipeng^{1, 2, 3}, LIU Maodong^{1, 2, 3}, BAI Lu^{1, 2, 3}

2025, 30(8):  1122-1126.  doi:10.12092/j.issn.1009-2501.2025.08.014

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Interleukin-33 (IL-33) is a member of the interleukin-1 superfamily and a "warning factor" for inflammation in the body. When cells die or tissues are damaged, IL-33 is released in large quantities and binds to its receptor ST2 to form a complex, exerting various biological effects. IL-33/ST2 signaling pathway is activated in many kidney diseases, such as acute renal injury, obstructive nephropathy, diabetes nephropathy, IgA nephropathy, lupus nephritis, and kidney transplantation. It plays an important role in inflammation and renal fibrosis by regulating the intrinsic and adaptive immune responses of the kidney. This article reviews the research progress of IL-33/ST2 signaling in common kidney diseases, hoping to provide new targets and ideas for the treatment of kidney diseases.

Progress in basic and clinical research of pitolisant in treating narcolepsy

ZHANG Huimin, ZHAN Shuqin

2025, 30(8):  1127-1132.  doi:10.12092/j.issn.1009-2501.2025.08.015

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Pitolisant, a selective histamine H3 receptor inverse agonist, promotes wakefulness by blocking H3 autoreceptor-mediated feedback inhibition to elevate central histamine levels. It is clinically indicated for wake promotion in narcolepsy. The development journey of pitolisant spans over two decades, encompassing extensive preclinical and clinical research. These studies have demonstrated both sustained efficacy in managing narcolepsy and a favorable long-term safety profile. Notably, pitolisant received formal marketing authorization from China's National Medical Products Administration (NMPA) for treating excessive daytime sleepiness or cataplexy in adult narcolepsy patients. This approval addresses an unmet medical need in China's therapeutic landscape, providing patients with a safe, effective, and well-tolerated novel therapeutic option. This article will summarize the basic and clinical research progress of pitolisant from the aspects of development history, preclinical studies and pharmacological effects, clinical research and indications, medication guidelines, and safety, aiming to provide a scientific basis for the clinical treatment of narcolepsy.

Advances in immunogenetic mechanisms of drug-induced liver injury

ZENG Xiangchang^{1, 2, 3, 4, 5, 7}, RAO Tai^{1, 3, 4, 5}, CHEN Lulu², LI Chaopeng², ZENG Guirong⁶, CHEN Jun⁷, OUYANG Dongsheng^{1, 2, 3, 4, 5}

2025, 30(8):  1133-1146.  doi:10.12092/j.issn.1009-2501.2025.08.016

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Drug-induced liver injury (DILI) is one of the major challenges in drug development and clinical practice, and effective prevention and control measures remain lacking. Research has shown that DILI is primarily mediated by immune responses. Human leukocyte antigen (HLA) alleles are currently the strongest genetic factors reported to be associated with DILI. Due to the low positive predictive value of HLA alleles, preemptive HLA genetic screening has limited clinical utility in preventing DILI. However, its high negative predictive value makes it valuable for DILI diagnosis and causality assessment. In recent years, polymorphisms in immune-related genes-such as those involved in antigen processing and presentation pathways, T-cell receptors, immunostimulatory molecules, and cytokines-have been found to be associated with DILI. Future studies combining these genes with HLA analysis may provide deeper mechanistic insights into DILI and facilitate their translational application in clinical practice, ultimately improving drug safety.

Application of inhaled levosimendan in pulmonary hypertension complicated with right heart failure

LIU Wanyu, SUN Tongwen, MAO Zhengrong

2025, 30(8):  1147-1152.  doi:10.12092/j.issn.1009-2501.2025.08.017

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Pulmonary hypertension (PH) is a serious disease characterized by abnormally high pulmonary arterial pressure (PAP), which leads to increased cardiac burden and may eventually lead to right heart failure. Levosimendan, as a calcium sensitizer, has the dual role of enhancing cardiac constriction force and promoting vascular dilation. It shows a good prospect in the treatment of PH combined with right heart failure by reducing PAP, increasing RV contractile force and reducing anterior and posterior cardiac load without increasing myocardial oxygen consumption. Since it does not increase the intracellular Ca²⁺ concentration, it avoids the arrhythmia-inducing, reduced coronary perfusion and other side effects of other positive inotropic drugs. At present, levosimandan is mainly transfused intravenically, which may lead to systemic hypotension, arrhythmia and other side effects, while inhalation administration can reduce the occurrence of adverse reactions, but its effectiveness and safety in the treatment of PH combined with right heart failure remains to be studied. The purpose of this review was to investigate the role of inhaled levosimendan in PH combined with right heart failure.