1.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.
2.Analysis of red blood cell transfusion reactions in China from 2018 to 2023
Bo PAN ; Xiaoyu GUAN ; Jue WANG ; Yunlong PAN ; Liu HE ; Haixia XU ; Xin JI ; Li TIAN ; Ling LI ; Zhong LIU
Chinese Journal of Blood Transfusion 2025;38(5):704-710
Objective: To analyze the demographic characteristics of patients with red blood cell transfusion reactions, the usage of red blood cell preparations, and the differences in the composition ratio of adverse reactions based on multi-center data from the Haemovigilance Network, in order to reveal the clinical characteristics of red blood cell transfusion and its underlying issues. Methods: Clinical data of patients who experienced transfusion reactions after red blood cell transfusion in the Haemovigilance Network from 2018 to 2023 were collected. The demographic characteristics of patients who experienced transfusion reactions with different types of red blood cell preparations, the utilization of these preparations, and the differences of the composition ratios of transfusion reactions were analyzed. Count data were expressed as numbers (n) or percentages (%), and comparisons between groups were performed using the Chi-square test. Results: Red blood cell transfusion reactions were more common in females (53.56%), with the majority of patients aged 50-69 years (35.54%). The Han polulation accounted for the vast majority of patients (92.77%), and patients in the hematology and obstetrics/gynecology departments had a relatively high proportion of transfusion reactions (13.26% and 14.26%, respectively). Leukocyte-reduced red blood cells and suspended red blood cells were the most common types of transfusion reactions reported among red blood cell preparations. Allergic reactions and non-hemolytic febrile reactions were the most common transfusion reactions, and there were significant differences in the composition ratios of allergic reactions (χ
=869.89, P<0.05) and non-hemolytic febrile reactions (χ
=812.75, P<0.05) across various types of red blood cell preparations. Conclusion: There are differences in the demographic characteristics and composition ratio of transfusion reactions among different red blood cell preparations. The management of red blood cell transfusion reactions should be tailored to patient characteristics and conditions, and the selection and use of blood products should be optimized to reduce or avoid the occurrence of transfusion reactions, such as considering the use of washed red blood cells for patients with a history of transfusion allergies or those prone to allergies.
3.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.
4.Mechanism Study on Chaihuang Qingyi Huoxue Granules Reduce Inflammatory Damage in Severe Acute Pancreatitis Rats by Suppressing NLRP3 Inflammasome Activation
Jia YANG ; Xiaoyu LI ; Chaoli JIANG ; Xin ZHOU ; Zhi LI
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(1):17-25
Objective To investigate the protective effect and mechanism of Chaihuang Qingyi Huoxue Granules on pancreatic tissue of rats with severe acute pancreatitis,and to observe its regulation on NLRP3 inflammasome activation.Methods Sixty-four SD rats were randomly divided into sham-surgery(SO)group,severe acute pancreatitis model(SAP)group,Chaihuang Qingyi Huoxue Granules(CH)group,and MCC950(NLRP3 inhibitor)group.Each group was further divided into 12-hour and 24-hour subgroups,with rats in each group.The SAP group,CH group,and MCC950 group were retrogradely injected with 3.5%sodium taurocholate(2 mL·kg-1)into the pancreatic ducts to establish SAP model.The MCC950 group was immediately intraperitoneally injected with MCC950(1 mg·mL-1)after model preparation.After awakening from anesthesia,the CH group was administrated by gavage with Chaihuang Qingyi Huoxue Granules solution(0.35 g·mL-1)once every 6 hours.Ascites,abdominal aortic blood,and pancreatic tissue were collected at 12 hours and 24 hours after SAP model construction.The serum amylase and lipase activities were detected using an automated biochemical analyzer.HE staining was used to observe pancreatic injury.Serum levels of IL-18 and IL-1β were detected by ELISA.The expressions of gene and proteins related to the activation of NLRP3 inflammasome were analyzed by IHC,qRT-PCR and Western Blot.Results Compared with the SAP group,the pathological damage of pancreatic tissues in the CH and MCC950 groups was significantly reduced,and the pathological score was significantly reduced(P<0.05).The levels of serum lipase,amylase,IL-18,and IL-1β were also significantly decreased(P<0.05).After treatment with Chaihuang Qingyi Huoxue Granules or intraperitoneal injection of NLRP3 inhibitor,the positive expressions of NLRP3,ASC and Caspase-1 in pancreatic tissues,as well as the mRNA levels of NLRP3,ASC and Caspase-1,the protein levels of NLRP3,ASC,Pro-Caspase-1 and Caspase-1 were significantly reduced compared to the SAP group(P<0.05).Conclusion Chaihuang Qingyi Huoxue Granules can inhibit the activation of NLRP3 inflammasome,reduce the mRNA and protein expressions of NLRP3,ASC and Caspase-1 in pancreatic tissues,and suppress the release of the downstream inflammatory factors IL-18 and IL-1β and alleviate pancreatitis damage in SAP model rats.
5.The application value of spectral CT venography in the display and staging of deep venous thrombosis in the lower extremity
Shigeng WANG ; Yijun LIU ; Xin FANG ; Beibei LI ; Xu WANG ; Zhiming MA ; Xiaoyu TONG ; Yong FAN ; Wei WEI ; Anliang CHEN
Journal of Practical Radiology 2024;40(3):478-482
Objective To investigate the application value of spectral computed tomography venography(CTV)in the display and staging of deep venous thrombosis(DVT)in the lower extremity.Methods Eighty-two patients with CTV were selected and ran-domly divided into group A(42 patients)and group B(40 patients).Group A:tube voltage 120 kVp.Group B:gemstone spectral ima-ging(GSI)mode,reconstruction of 50 keV and iodine(water)maps.The CT and standard deviation(SD)values of the veins were measured,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated in 120 kVp images of group A and in 50 keV images of group B.Two observers scored the image quality of the 2 groups subjectively,and Kappa test was used to examine the con-sistency.Based on the duration from the occurrence of clinical symptoms,the DVTs were classified.The CT values and iodine con-centration(IC)of DVT were measured in the 120 kVp images of group A and in the iodine(water)maps of group B,respectively.The receiver operating characteristic(ROC)curve was drawn to compare the effectiveness of CT values and IC in diagnosing DVT staging.Results CT values,SNR,and CNR of veins in group B were higher than those in group A(P<0.05).The subjective scores of the two groups were consistent(Kappa=0.926-0.955,P<0.05).The score for the display of veins and thrombus clarity in group B was 5(4,5),which was better than the score of 4(3,4)in group A(P<0.05).The efficiency of IC in diagnosing DVT staging[area under the curve(AUC)=0.973]was better than that of CT values(AUC=0.891).Conclusion The spectral CTV can improve the contrast of lower extremity deep veins and the clarity of thrombus,and can provide more objective indicators for the diagnosis of thrombus staging,which is conducive to accurate clinical diagnosis and treatment.
6.CBCT analysis of the relative position between maxillary central incisors and alveolar bone in Southern Chi-nese adults
Ziling DING ; Xin LIU ; Xiaoyu YANG ; Chufeng LIU
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(2):116-122
Objective Exploring the position and bone wall thickness characteristics of the maxillary central inci-sors in Southern Chinese adults to provide a clinical reference for the design of immediate maxillary central incisor im-plantation surgery.Methods The hospital ethics committee approved the study,and the patients provided informed consent.CBCT images of 990 adult patients(aged 20-79 years)from the Stomatology Hospital(January 2018 to Decem-ber 2021)were categorized based on the dental arch form and age-sex groups.Sagittal CBCT images of the maxillary central incisors were used to measure the labial and palatal bone thickness wall at 4 mm the CEJ to apical,the middle of the root,and the angle between the tooth long axis and the long axis of the alveolar process,to compare the thickness of the labial and palatal bone walls in samples of male and female patients,and to explore the relationship between the angle between the tooth long axis and the alveolar process long axis in samples of male and female patients in different age groups(20-39 years;40-59 years;60-79 years).Results Significant differences were found in the labiopalatine side of the alveolar bone of the maxillary incisor root position.A total of 95.8%(948/990)of the maxillary incisors were positioned more buccally,4.1%(41/990)were positioned more midway,and 0.1%(1/990)were positioned more palatal-ly.The thicknesses of the bone wall at the CEJ of 4 mm below the palatal side,the middle of the root,and at the apex were greater(1.82±0.56 mm,3.20±1.10 mm,and 7.70±2.00 mm,respectively)than those at the labial side(1.21± 0.32 mm,0.89±0.35 mm,and 1.86±0.82 mm,respectively),with statistical significance(P<0.05).Male bone wall thickness was generally greater than female bone wall thickness(P<0.05).The angle between the long axis of male teeth and the alveolar bone was 14.77°±5.66°,while that of female teeth was 12.80°±5.70°,with a statistically signifi-cant difference(P<0.05).The angle between the long axis of teeth and the alveolar bone in the 40-59-year-old group and the 60-79-year-old group was greater than that in the 20-39-year-old group,and the difference was statistically sig-nificant(P<0.05).Conclusion A total of 95.8%of adults in South China have maxillary central incisors with root de-viation toward the labial bone cortex.The thickness of the labial bone wall is much thinner than that of the labial bone wall,which is the middle of the thickness of the root.In Southern Chinese adults,the angle between the upper central incisor and the long axis of the alveolar bone in males is greater than that in females,and the degree of the angle in-creases with age.It is recommended to pay attention to the thickness of the bone wall around the root and the angle be-tween the teeth before immediate implantation surgery to choose a reasonable implantation plan.
7.Measurement of the relationship between maxillary premolar roots and the maxillary sinus floor using cone beam CT and analysis of the impact on immediate implantation
Xin LIU ; Ziling DING ; Xiaoyu YANG ; Chufeng LIU ; Zhonglang LIANG ; Leyi HUANG
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(6):444-450
Objective To analyze the spatial relationship between the roots of maxillary anterior premolars and the maxillary sinus,thus providing an anatomical basis for timing,planning,surgical approaches,and implant selection at this site.Methods Cone beam CT(CBCT)images were collected from 264 patients(aged 20-65 years)who visited the Ruihua Dental Clinic between January 2017 and March 2023.The minimum distance from the apex of the maxillary an-terior premolar roots to the lower wall of the maxillary sinus was measured on the coronal plane.The classification of the vertical relationship between the tooth root and the lower wall of the maxillary sinus was performed,and comparisons were made bilaterally,between genders,and among different age groups.Results The minimum distance(Q50)from the apex of the first maxillary premolar root to the lower wall of the maxillary sinus was 7.34 mm for the single-root type,7.80 mm for the buccal root of the double-root type,and 7.36 mm for the palatal root.For the second maxillary premo-lar,the median distance was 2.56 mm for the single root type,1.73 mm for the buccal root type,and 1.23 mm for the palatal root type.There was a significant difference in the shortest distance from the apex of the right second maxillary premolar single root to the lower wall of the maxillary sinus among the different age groups(P<0.05),with the 20-29-year-old group having the smallest median distance(1.52 mm)and the≥40-year-old group having the largest(4.44 mm).There was no significant difference in the effect of sex or laterality on distance(P>0.05).The most common vertical relationship between the apex of the maxillary anterior premolar roots and the lower wall of the maxillary sinus was non-contact.There was no significant difference in the vertical relationship classification between the single-root and dou-ble-root types(P>0.05).Conclusion Most maxillary first premolar roots can provide sufficient bone height,which makes it easy to achieve immediate implantation.The maxillary second premolar root frequently involves insufficient bone,which is necessary to make full use of the bone wall of the extraction socket or the sinus floor cortical bone to achieve initial stability.The vertical relationship between the premolar root and maxillary sinus was influenced by age and dental position.Younger age groups often exhibit inadequate bone height,and the indication for immediate implan-tation should be carefully considered.The number of roots does not significantly affect the relationship between the sinus and root;however,double-rooted premolars offer more support for immediate implantation and socket healing due to the small root diameter and bony separation between the roots.
8.Low energy targeted reconstruction combined with adaptive statistical iterative reconstruction-Veo in venography of lower extremity
Shigeng WANG ; Xin FANG ; Yijun LIU ; Beibei LI ; Xu WANG ; Yong FAN ; Xiaoyu TONG ; Wei WEI
Journal of Practical Radiology 2024;40(5):809-813
Objective To investigate the application value of energy spectral CT low energy(keV)targeted reconstruction tech-niques combined with adaptive statistical iterative reconstruction-Veo(ASIR-V)algorithm in lower extremity computed tomography venography(CTV).Methods Forty patients with lower extremity CTV examination were retrospectively selected.Gemstone spec-tral imaging(GSI)mode was used with a transient tube voltage of 80 kVp/140 kVp and tube current in GSI Assist mode.Group A(conventional group):70 keV combined with 40%ASIR-V mono-energy images,conventional display field of view(DFOV)inclu-ding both lower extremity.Group B(low keV group):50 keV combined with 50%ASIR-V mono-energy images,DFOV as in group A.Group C(low keV targeted reconstruction group):50 keV combined with 50%to 80%ASIR-V mono-energy images(10%interval,called as groups C1-C4),targeted reconstruction(small DFOV,covered one lower extremity with left and right femurs as the center).The CT and standard deviation(SD)values of the bilateral lower extremity veins were measured on each axial image and the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated.Two observers scored the venous images and the sharpness of embolus display subjectively using a 5-point scale and Kappa test was used to examine the consistency.Results In terms of vein dis-play,the score of groups B and C was better than that of group A(P<0.05).In terms of embolus display sharpness,the scores of large and small embolus in group C increased with the increase of ASIR-V percentage initially and then gradually decreased(P<0.05).The scores in group C2 were the highest which were superior to the scores of group B and group A(P<0.05).The CT values of each venous segment in groups B and C were higher than those in group A(P<0.05).In groups C1 to C4,with the increasing weight of ASIR-V,the SNR and CNR increased gradually(P<0.05),but slightly lower than those in group B(P<0.05).Conclusion 50 keV targeted reconstruction techniques combined with 60%ASIR-V algorithm significantly improves the contrast of lower extremity veins and the embolus display sharpness,providing more accurate clinical imaging information.
9.One case of severe cardiac arrhythmias caused by Huoxiang Zhengqi liquid
Yinping ZHAO ; Xiaoyu XIN ; Guibo XIE ; Huayan LI ; Yuan YAN
Chinese Journal of Pharmacoepidemiology 2024;33(4):476-480
A 22-year-old male self-administered Huoxiang Zhengqi liquid(10 mL,bid)orally due to abdominal pain and diarrhea.The symptoms improved significantly on the same day.Palpitations occurred about 30 minutes after 10 mL Huoxiang Zhengqi Liuquid administration in the morning and afternoon of the next day and in the morning of the third day,respectively,which was spontaneously relieved.Electrocardiogram showed that multiple arrhythmias alternated,including disordered atrial rhythm,paroxysmal atrial fibrillation,paroxysmal supraventricular tachycardia,frequent premature ventricular contractions,junctional premature contractions,atrioventricular block,and sinus bradycardia.After admission,the patient was given electrocardiography monitoring,polarizing fluid,verapamil injection,and other treatment methods to relieve symptoms,after 12 days of treatment,the patient's condition improved,and the electrocardiogram showed sinus rhythm.This case suggests that as an over-the-counter drug,the safety of Huoxiang Zhengqi liquid should be paid more attention by clinic and public.If patients manifest palpitation symptoms while using Huoxiang Zhengqi liquid,it is imperative to consider the potential for drug-induced serious arrhythmia and get medical treatment promptly.
10.Different transplantation models of hepatocellular carcinoma in mice
Rui PAN ; Kun YU ; Hailiang ZHANG ; Yongren ZHENG ; Xiaoyu ZHAO ; Junze TANG ; Jianming WU ; Xin CHENG
Acta Laboratorium Animalis Scientia Sinica 2024;32(3):329-336
Objective To explore the otherness of orthotopic injection of cell suspensions and transplantation of tumor tissue blocks to establish orthotopic implantation models of hepatocellular carcinoma in mice,and to provide a technical reference for the establishment of an orthotopic implantation model.Methods Healthy KM mice were divided into four groups:group A,direct injection of H22 cells;group B,direct injection of H22 ascitic cells;group C,transplantation of tissues;and group D,direct injection of saline.Activity and weight changes were observed regularly in each group and survival times were recorded.Liver tumor formation,tumor size,abdominal organ adhesion degree,and metastasis were observed in all groups.B-ultrasound imaging was performed,concentrations of alpha fetoprotein(AFP)and abnormal prothrombin(DCP)were detected,and liver histopathological changes were detected by hematoxylin and eosin staining.Results Mice molding operation time in groups A,B,and C were(3.36±0.44)min,(3.30±0.41)min,and(5.68±0.65)min,respectively.After modeling for 25 days,the rates of model formation in groups A,B,and C were all 100.0%.Severe abdominal adhesions occurred in 40.0%of mice in group A and 60.0%in group B,but in no mice in group C or D.Ascites occurred in 40.0%,100.0%,and 0.0%and abdominal wall tumors in 30.0%,60.0%,and 0.0%of mice in groups A,B,and C,respectively,while 40.0%of mice in group B also had liver metastasis.B-ultrasound imaging,detection of serum AFP and DCP levels,and histopathological result showed smooth liver margins,uneven echo and slightly lower echo mass,maintained high AFP and DCP secretion,and large numbers of inflammatory cells and tumor cells in mice in groups A,B,and C.Conclusions At day 25,all three methods can thus be used to establish orthotopic transplantation models of HCC.Among these,inj ection of cell suspensions demonstrated the advantage of simplicity in operation and the presence of multiple metastatic nodules within the liver,compared to transplantation of tumor tissue.Conversely,transplantation of tumor tissue showed the advantage of causing less impact on the abdomen and other organs when compared to inj ection of cell suspensions.


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