1.Chufeng Yisuntang Ameliorates PM2.5-induced Dry Eye via ROS/p38 MAPK Signaling Pathway
Yuan ZHONG ; Pan ZHAO ; Shi TAN ; Yu TANG ; Dongdong LI ; Lihao CHEN ; Jun PENG ; Qinghua PENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):191-200
ObjectiveTo establish a mouse model of particulate matter 2.5 (PM2.5)-induced dry eye and investigate whether Chufeng Yisuntang can ameliorate the PM2.5-induced ocular surface damage by regulating the reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. MethodsSixty 8-week-old male C57BL/6J mice were used. Ten were randomly selected as the control group. The remaining 50 mice received topical instillation of 1 drop (0.1 mL) of 5 g·L-1 PM2.5 suspension in both eyes, four times daily. Successfully modeled mice were randomized into four groups (n=10): Model, p38 MAPK inhibitor, Chufeng Yisuntang, and combination (Chufeng Yisuntang at 7.3 g·kg-1 + p38 MAPK inhibitor SB203580 at 5 mg·kg-1). Chufeng Yisuntang was administered via gavage, and the inhibitor group via intraperitoneal injection. The control and model groups received equal volumes of distilled water by gavage. All treatments lasted for 4 weeks. General conditions were dynamically observed. Tear secretion, tear film break-up time, and corneal fluorescein staining were assessed. After intervention for 4 weeks, hematoxylin and eosin (HE) staining was used to examine the histopathological changes. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure serum levels of ROS, malondialdehyde (MDA), superoxide dismutase (SOD) 1, and SOD2. Western blot and Real-time PCR were employed to determine the protein and gene levels, respectively, of p38 MAPK, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cysteinyl aspartate-specific proteinase-3 (Caspase-3) in the corneal tissue. ResultsCompared with the control group, the model group exhibited reduced tear secretion volume and tear film breakup time, along with increased corneal fluorescein staining scores (P<0.01). Compared with the model group, the Chufeng Yisuntang group, p38 MAPK inhibitor group, and combination group demonstrated increased tear secretion volume and tear film breakup time, along with decreased corneal fluorescein staining scores (P<0.01). HE staining revealed that compared with the control group, the model group exhibited marked increases in corneal epithelial cell layers and epithelial thickness, along with reduced meibomian gland acini and intensely stained, densely packed nuclei around the acini. Compared with the model group, the Chufeng Yisuntang group, p38 MAPK inhibitor group, and combination group showed intact corneal structure, improved cell morphology, and reduced damage severity. ELISA revealed elevated ROS and MDA levels (P<0.01) and decreased SOD1 and SOD2 levels (P<0.01) in the model group compared with the control group. Compared with the model group, Chufeng Yisuntang, p38 MAPK inhibitor, and the combination lowered ROS and MDA levels (P<0.01), while raising SOD1 and SOD2 levels (P<0.05, P<0.01). Western blot revealed that compared with the control group, the model group exhibited increased protein levels of p38 MAPK, Bax, and Caspase-3 (P<0.01) and reduced protein level of Bcl-2 (P<0.01). Compared with the model group, Chufeng Yisuntang, p38 MAPK inhibitor, and the combination down-regulated the protein levels of p38 MAPK, Bax, and Caspase-3 (P<0.01), while up-regulating the protein level of Bcl-2 (P<0.01). Compared with the Chufeng Yisuntang group, the combination group exhibited decreased protein levels of p38 MAPK, Bax, and Caspase-3 (P<0.01) and increased protein level of Bcl-2 (P<0.01). Real-time PCR revealed that compared with the control group, the model group exhibited upregulated mRNA levels of p38 MAPK, Bax, and Caspase-3 (P<0.01), and downregulated mRNA level of Bcl-2 (P<0.01). Compared with the model group, Chufeng Yisuntang, p38 MAPK inhibitor, and the combination down-regulated the mRNA levels of p38 MAPK, Bax, and Caspase-3 (P<0.01), while up-regulating the mRNA level of Bcl-2 (P<0.05, P<0.01). Compared with the Chufeng Yisuntang group, the combination group exhibited decreased mRNA levels of p38 MAPK, Bax, and Caspase-3 expression (P<0.05, P<0.01) and increased mRNA level of Bcl-2 (P<0.01). ConclusionChufeng Yisuntang may partially protect against PM2.5-induced corneal injury by inhibiting the ROS/p38 MAPK pathway, enhancing antioxidant defense, and reducing epithelial apoptosis.
2.Effect of Folic Acid-modified Crebanine Polyethylene Glycol-polylactic Acid Hydroxyacetic Acid Copolymer Nanoparticles Combined with Ultrasonic Irradiation on Subcutaneous Tumor Growth of Liver Cancer in Mice
Rui PAN ; Junze TANG ; Hailiang ZHANG ; Kun YU ; Xiaoyu ZHAO ; Xin CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):217-225
ObjectiveTo investigate the effect of folic acid-modified crebanine polyethylene glycol-polylactic acid hydroxyacetic acid copolymer(PEG-PLGA) nanoparticles(FA-Cre@PEG-PLGA NPs, hereinafter referred to as NPs) combined with ultrasonic irradiation on subcutaneous tumor of liver cancer in Kunming(KM) mice. MethodsEighty-four healthy male KM mice were utilized to establish a subcutaneous tumor model of mouse hepatocellular carcinoma with H22 cells, then mice were randomly divided into model group, placebo group, hydroxycamptothecin group(8 mg∙kg-1), low, medium and high dose crebanine raw material groups(2, 2.5, 3 mg∙kg-1, hereinafter referred to as the low, medium and high dose crebanine groups, respectively), low, medium and high dose NPs groups(2, 2.5, 3 mg∙kg-1), and low, medium and high dose NPs combined with ultrasonic irradiation groups(2, 2.5, 3 mg∙kg-1, hereinafter referred to as the low, medium and high dose combination groups, respectively). The corresponding doses of drugs were administered via tail vein injection, the model group received no treatment, while the placebo group was injected with an equivalent amount of normal saline. Dosing was conducted for a total of 10 times on alternate days. The body mass of the mice was monitored, and parameters such as body mass change rate, thymus index, spleen index, tumor volume, tumor weight, relative tumor growth rate(T/C), and tumor inhibition rate(TGI) were calculated. Pathological changes in liver and kidney tissues as well as the tumor were observed by hematoxylin-eosin(HE) staining. Additionally, the levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), blood urea nitrogen(BUN) and creatinine(CREA) in serum of mice were detected by biochemical method. Furthermore, the effect of ultrasound on the distribution of NPs in subcutaneous tumors of mouse hepatocellular carcinoma was observed by in vivo imaging technique. ResultsAmong different treatment methods, the combination of NPs and ultrasound irradiation had the best therapeutic effect. Compared with the model group, the body mass growth rates of mice in the medium and high combination groups decreased, while the thymus index and spleen index increased, but there was no statistically significant difference in serum AST, ALT, BUN and CREA levels, indicating that NPs combined with ultrasound irradiation had little effect on the normal physiological state of the body, oth groups had TGI>40% and T/C<60%, indicating a clear anti-tumor effect. Pathological analysis showed that compared with the NPs groups, the combination groups exhibited varying degrees of necrosis in tumor cells, accompanied by less damage to the liver and kidneys. In vivo imaging of small animals showed that compared with the high dose NPs group, the high dose combination group had stronger tumor targeting ability(P<0.01). ConclusionNPs combined with ultrasonic irradiation can not only effectively targeted the drug to the tumor site, inhibit the subcutaneous tumor growth of mouse liver cancer, but also decrease damage to liver and kidney tissues.
3.Surveillance and evaluation of vector control in Fuyang District, Hangzhou for the 19th Asian Games
Jie XU ; Wenjin PAN ; Renyu TANG ; Liqun DU
Shanghai Journal of Preventive Medicine 2025;37(2):114-119
ObjectiveTo assess the risk of vector-born infectious diseases by monitoring the major vectors in the relevant venues of the 19th Hangzhou Asian Games in Fuyang competition area, so as to provide references for the prevention and control of vector in similar large-scale events or activities in the future. MethodsFrom April to October 2023, monitoring and evaluation of rodent, mosquito, fly and cockroach density levels were carried out in various venues and reception hotels in Fuyang competition area (venues and hotels were the 1st circle area, and various environments and places in the surrounding 500 meters were the 2nd circle area). SPSS 25.0 software was used to analyze the data, and chi-square test or Fisher’s precision probability test were used to calculate the qualified rate and positive rate. Moreover, the path index, landing index and Bretrau index were analyzed by Kruskal-Wallis H test. ResultsThe control effect of vector density in the 1st circle was significantly better than that in the 2nd circle. Since September, the monitoring indices of the venues in the two circles had reached the national A-level and B-level standard, respectively. The positive rate of rodent traces generally showed a trend of first increasing and then decreasing, and the peak was shown to occur in July and August, with the highest rate of 5.38%. The qualified rate of rodent prevention facilities continued to rise, and facilities in the 1st and 2nd circles had reached national A-level and B-level standard respectively in late August. The landing index and path index of mosquitoes basically showed a changing trend from high to low, with the highest landing index of 4.56 individuals·person-time-1 and the highest path index of 2.44 places·km-1.The adult fly infestation rate remained at a low level, with the highest rate of 4.17%, and the minimum qualified rate of fly prevention facilities was 28.57%, which reached the national standard after July. The positive detection rates of adult flies and cockroach traces showed no significant pattern, with the highest rate of 7.00% and 8.33%, respectively. The detection rate of live ootheca was always at a low level. ConclusionThe relevant venues in the Fuyang competition area of the 19th Asian Games in Hangzhou meet national standards in terms of vector control indicators such as rodents, mosquitoes, flies, cockroaches and other vectors. By means of environmental improvement, facilities for preventing rodents and flies, and deepening biological and chemical prevention and control methods, it can be ensured that there will be no vector-borne diseases and infestation incidents during the event.
4.Spicy food consumption and risk of vascular disease: Evidence from a large-scale Chinese prospective cohort of 0.5 million people.
Dongfang YOU ; Dianjianyi SUN ; Ziyu ZHAO ; Mingyu SONG ; Lulu PAN ; Yaqian WU ; Yingdan TANG ; Mengyi LU ; Fang SHAO ; Sipeng SHEN ; Jianling BAI ; Honggang YI ; Ruyang ZHANG ; Yongyue WEI ; Hongxia MA ; Hongyang XU ; Canqing YU ; Jun LV ; Pei PEI ; Ling YANG ; Yiping CHEN ; Zhengming CHEN ; Hongbing SHEN ; Feng CHEN ; Yang ZHAO ; Liming LI
Chinese Medical Journal 2025;138(14):1696-1704
BACKGROUND:
Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association.
METHODS:
This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results.
RESULTS:
During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037).
CONCLUSIONS
Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans
;
Male
;
Female
;
Prospective Studies
;
Middle Aged
;
Aged
;
Vascular Diseases/etiology*
;
Risk Factors
;
China/epidemiology*
;
Adult
;
Proportional Hazards Models
;
Cerebrovascular Disorders/epidemiology*
;
East Asian People
5.Efficacy and safety of avatrombopag in the treatment of thrombocytopenia after umbilical cord blood transplantation.
Aijie HUANG ; Guangyu SUN ; Baolin TANG ; Yongsheng HAN ; Xiang WAN ; Wen YAO ; Kaidi SONG ; Yaxin CHENG ; Weiwei WU ; Meijuan TU ; Yue WU ; Tianzhong PAN ; Xiaoyu ZHU
Chinese Medical Journal 2025;138(9):1072-1083
BACKGROUND:
Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
METHODS:
We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation.
RESULTS:
Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z = 2.095, P = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P = 0.003).
CONCLUSION
Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans
;
Female
;
Male
;
Thrombocytopenia/etiology*
;
Adult
;
Retrospective Studies
;
Cord Blood Stem Cell Transplantation/adverse effects*
;
Middle Aged
;
Adolescent
;
Young Adult
;
Thiazoles/adverse effects*
;
Platelet Count
;
Receptors, Thrombopoietin/agonists*
;
Child
;
Thiophenes
6.Prognostic value of ultrasound carotid plaque length in patients with coronary artery disease.
Wendong TANG ; Zhichao XU ; Tingfang ZHU ; Yawei YANG ; Jian NA ; Wei ZHANG ; Liang CHEN ; Zongjun LIU ; Ming FAN ; Zhifu GUO ; Xianxian ZHAO ; Yuan BAI ; Bili ZHANG ; Hailing ZHANG ; Pan LI
Chinese Medical Journal 2025;138(14):1755-1757
7.Characteristic ion Identification of Different Original Haliotidis Concha and Its Counterfeits
Xiaojie LIANG ; Guowei LI ; Lin ZHOU ; Qiping HU ; Muxiang LUO ; Jiehao TANG ; Xiangdong CHEN ; Liye PAN ; Dongmei SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):263-269
ObjectiveTo establish a method for the identification of Haliotidis Concha and its counterfeits, and to improve its quality evaluation method. MethodsA total of 17 batches of Haliotis discus hannai, 4 batches of H. ruber, 3 batches of H. laevigata, 3 batches of H. ovina, 3 batches of H. diversicolor, 3 batches of H. asinina, 3 batches of H. iris were collected. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive-Orbitrap-MS/MS) was used to analyze the hydrolysates of different original Haliotidis Concha and its counterfeits, and the potential characteristic ions of each species were screened by Venn diagram. UPLC-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS) was used to validate the characteristic ions, and the specific detection method of the characteristic ions was established. ResultsA total of 1 182, 167, 47, 89, 104, 203, 424 potential characteristic ions were screened from H. discus hannai, H. ruber, H. laevigata, H. ovina, H. diversicolor, H. asinina and H. iris, respectively. And 9 characteristic ions were selected. The precision, stability and repeatability of the 9 characteristic ions in the established identification method met the requirements. Different original Haliotidis Concha and its counterfeits could detect their own characteristic ions, including m/z 631.83-886.48(double charge) and m/z 631.83-443.74(double charge) of H. discus hannai, m/z 699.28-232.11(double charge) and m/z 699.28-544.27(double charge) of H. ruber, m/z 535.76-752.37(double charge) and m/z 535.76-548.28(double charge) of H. laevigata, m/z 708.35-442.28(double charge) and m/z 708.35-215.14(double charge) of H. ovina, m/z 561.33-614.86(triple charge), m/z 561.33-468.28(triple charge), m/z 608.29-618.32(double charge) and m/z 608.29-390.21(double charge) of H. diversicolor, m/z 769.85-274.10(double charge), m/z 769.85-532.75(double charge), m/z 827.43-646.36(single charge), m/z 827.43-257.12(single charge) of H. asinina, and m/z 468.24-576.29(double charge) and m/z 468.24-505.26(double charge) of H. iris. ConclusionIn this study, a total of 9 characteristic ions are screened from 6 kinds of original Haliotidis Concha and its counterfeits, and a specific identification method is established, which is helpful to solve the limitations of the existing quality evaluation methods of Haliotidis Concha, and provide a basis for the production, circulation and medication quality.
8.Characteristic ion Identification of Different Original Haliotidis Concha and Its Counterfeits
Xiaojie LIANG ; Guowei LI ; Lin ZHOU ; Qiping HU ; Muxiang LUO ; Jiehao TANG ; Xiangdong CHEN ; Liye PAN ; Dongmei SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):263-269
ObjectiveTo establish a method for the identification of Haliotidis Concha and its counterfeits, and to improve its quality evaluation method. MethodsA total of 17 batches of Haliotis discus hannai, 4 batches of H. ruber, 3 batches of H. laevigata, 3 batches of H. ovina, 3 batches of H. diversicolor, 3 batches of H. asinina, 3 batches of H. iris were collected. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive-Orbitrap-MS/MS) was used to analyze the hydrolysates of different original Haliotidis Concha and its counterfeits, and the potential characteristic ions of each species were screened by Venn diagram. UPLC-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS) was used to validate the characteristic ions, and the specific detection method of the characteristic ions was established. ResultsA total of 1 182, 167, 47, 89, 104, 203, 424 potential characteristic ions were screened from H. discus hannai, H. ruber, H. laevigata, H. ovina, H. diversicolor, H. asinina and H. iris, respectively. And 9 characteristic ions were selected. The precision, stability and repeatability of the 9 characteristic ions in the established identification method met the requirements. Different original Haliotidis Concha and its counterfeits could detect their own characteristic ions, including m/z 631.83-886.48(double charge) and m/z 631.83-443.74(double charge) of H. discus hannai, m/z 699.28-232.11(double charge) and m/z 699.28-544.27(double charge) of H. ruber, m/z 535.76-752.37(double charge) and m/z 535.76-548.28(double charge) of H. laevigata, m/z 708.35-442.28(double charge) and m/z 708.35-215.14(double charge) of H. ovina, m/z 561.33-614.86(triple charge), m/z 561.33-468.28(triple charge), m/z 608.29-618.32(double charge) and m/z 608.29-390.21(double charge) of H. diversicolor, m/z 769.85-274.10(double charge), m/z 769.85-532.75(double charge), m/z 827.43-646.36(single charge), m/z 827.43-257.12(single charge) of H. asinina, and m/z 468.24-576.29(double charge) and m/z 468.24-505.26(double charge) of H. iris. ConclusionIn this study, a total of 9 characteristic ions are screened from 6 kinds of original Haliotidis Concha and its counterfeits, and a specific identification method is established, which is helpful to solve the limitations of the existing quality evaluation methods of Haliotidis Concha, and provide a basis for the production, circulation and medication quality.
9.Variation Tendency and Prediction of Colorectal Cancer Burden Among Chinese Population from 1990 to 2021
Tongzhou WANG ; Juanfang ZHU ; Jin ZHOU ; Pan ZHANG ; Qin TANG
Cancer Research on Prevention and Treatment 2025;52(4):319-323
Objective To examine the current status and trends of colorectal cancer (CRC) burden among Chinese residents from 1990 to 2021. Methods Data on CRC burden in China, Asia, and the global population from 1990 to 2021 were retrieved from the Global Burden of Disease database for descriptive analysis. An age-period-cohort model was employed to estimate the effects of age, period, and cohort on CRC mortality and to forecast changes in disease burden. Results In 2021, China’s age-standardized mortality rate, prevalence rate, and DALY rate for CRC were higher than global and Asian averages. The estimated annual percentage changes (EAPC) from 1990 to 2021 were −0.49% (95%CI: −0.55% to −0.43%) for mortality, 3.17% (95%CI: 3.03%−3.31%) for prevalence, and −0.62% (95%CI: −0.71% to −0.54%) for DALYs. Areas with high and medium-high sociodemographic indexes (SDIs) showed significant decreases in standardized mortality and DALY rates, but these rates remained higher compared with other regions. CRC mortality increased with age in the Chinese population, more prominently in males than in females. Using the 2002–2006 period as a reference (RR=1), the period effect on CRC mortality risk for women was higher than that for men until 2004, after which it declined considerably. With the 1957 birth cohort as a reference (RR=1), CRC mortality risk generally decreased across subsequent birth cohorts. Predictions indicate that by 2035, the standardized prevalence rate will be 267.21 per 100 000, and the standardized mortality rate will be 12.29 per 100 000. Conclusion From 1990 to 2021, China’s age-standardized CRC mortality and DALY rates have decreased, while the standardized prevalence rate has increased. These findings suggest the government to establish a comprehensive multi-level CRC prevention network.
10.Targeting effect and anti-tumor mechanism of folic acid-modified crebanine nanoparticles combined with ultra-sound irradiation on M109 cells in vitro and in vivo
Hailiang ZHANG ; Xiaoyu ZHAO ; Jiahua MEI ; Rui PAN ; Junze TANG ; Kun YU ; Rui XUE ; Xiaofei LI ; Xin CHENG
China Pharmacy 2025;36(14):1730-1736
OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles (FA-Cre@PEG- PLGA NPs, hereinafter referred to as “NPs”) combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration, and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells, and the best ultrasound time was selected. Using human lung cancer A549 cells as a control, the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration, invasion, apoptosis, cell cycle and reactive oxygen species (ROS) levels of M109 cells were detected by cell scratch test, Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration; the changes of mitochondrial membrane potential (MMP) were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed, and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells, and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells, and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells, the uptake rate of NPs in M109 cells was significantly higher (P<0.01), and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group, the apoptosis rate of M109 cells and ROS level were increased significantly (P<0.01), while the MMP decreased significantly (P<0.01) in the different concentration (100, 200, 300 μg/mL) groups of M109 cells. Compared with the mice in non-ultrasound group, the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced (P<0.05 or P<0.01). CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo, the anti-tumor mechanism includes inhibiting cell migration and invasion, blocking cell cycle, and inducing apoptosis.

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