1.Material basis and action mechanism of drug-containing serum of Modified Erxian Pill inhibiting macrophage pyroptosis
Siyuan LI ; Yuru WANG ; Ye XU ; Di GUO ; Nan NAN ; Yang LIU ; Jie ZHAO ; Huiqin HAO
Chinese Journal of Tissue Engineering Research 2025;29(19):4029-4037
BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.
2.Preparation,characterization and tissue distribution of polyethylene glycol-modified Curcumin solid lipid nanoparticle inhalable micropowder
Nan LI ; Zi WANG ; Di HAO ; Lingyu KONG ; Xu LI
China Pharmacy 2025;36(19):2387-2392
OBJECTIVE To prepare polyethylene glycol (PEG)-modified flower lactose (FL) loaded Curcumin (Cur) solid lipid nanoparticle (SLN) inhalable micropowder (referred to as “PEG-Cur-FL”). METHODS PEG-Cur-FL was prepared by the solvent emulsification diffusion low-temperature solidification method, and its encapsulation efficiency, drug loading capacity, powder properties, aerodynamic particle size, in vitro deposition properties, and in vitro release characteristics were characterized. The mice were divided into Cur-SLN-FL (unmodified with PEG) group and PEG-Cur-FL group, with 55 mice in each group. Both groups of mice were given a single inhalation of 5 mg/kg (calculated as Cur) of the corresponding drug micropowder through an air tube. At 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours after administration, eyeballs were removed to collect blood and tracheal, lung, liver and kidney tissues were separated. The mass concentration of Cur in mouse plasma and various tissue samples was measured, and the tissue distribution and retention of the drug were analyzed. RESULTS The encapsulation efficiency and drug loading capacity of PEG-Cur-FL were (86.2±1.8)% and (4.2±0.2)%, respectively; the bulk density and tap density were (0.24±0.01) g/cm3 and (0.30±0.01) g/cm3, respectively; the aerodynamic particle size was (2.74±0.64) μm; the in vitro effective site deposition rate (secondary drug deposition rate) was (45.07±2.79)%. Compared with Cur raw materials, Cur-SLN- FL and PEG-Cur-FL had sustained release effects under both leakage and non-leakage conditions, and PEG-Cur-FL had a smoother sustained release in artificial lung fluid, with release characteristics consistent with the Weibull model. The results of in vivo distribution showed that the drug concentration in the lung tissue of PEG-Cur-FL group was significantly lower than that of Cur- SLN-FL group during the same period after 1 hour of administration, while the drug concentration in the lung tissue at 4 to 48 hours was significantly higher than that of Cur-SLN-FL group during the same period (P<0.05); the plasma drug concentrations of the PEG-Cur-FL group at all time points from 0.25 to 12 hours were significantly lower than those of the Cur-SLN-FL group during the same period (P<0.05), and the drug concentrations in liver and kidney tissues were also lower than those of the Cur-SLN-FL group during the same period (P<0.05). CONCLUSIONS PEG-Cur-FL is prepared successfully; the inhalable micropowder has good inhalability and release performance; after administration through the trachea, the effective concentration of Cur in lung tissue can be increased, while reducing its plasma drug concentration and drug distribution concentration in non-target organs.
3.Early gait analysis after total knee arthroplasty based on artificial intelligence dynamic image recognition
Ming ZHANG ; Ya-Nan SUI ; Cheng WANG ; Hao-Chong ZHANG ; Zhi-Wei CAI ; Quan-Lei ZHANG ; Yu ZHANG ; Tian-Tian XIA ; Xiao-Ran ZU ; Yi-Jian HUANG ; Cong-Shu HUANG ; Xiang LI
China Journal of Orthopaedics and Traumatology 2024;37(9):855-861
Objective To explore early postoperative gait characteristics and clinical outcomes after total knee arthroplasty(TKA).Methods From February 2023 to July 2023,26 patients with unilateral knee osteoarthritis(KOA)were treated with TKA,including 4 males and 22 females,aged from 57 to 85 years old with an average of(67.58±6.49)years old;body mass in-dex(BMI)ranged from 18.83 to 38.28 kg·m-2 with an average of(26.43±4.15)kg·m-2;14 patients on the left side,12 pa-tients on the right side;according to Kellgren-Lawrence(K-L)classification,6 patients with grade Ⅲ and 20 patients with grade Ⅳ;the courses of disease ranged from 1 to 14 years with an average of(5.54±3.29)years.Images and videos of standing up and walking,walking side shot,squatting and supine kneeling were taken with smart phones before operation and 6 weeks after operation.The human posture estimation framework OpenPose were used to analyze stride frequency,step length,step length,step speed,active knee knee bending angle,stride length,double support phase time,as well as maximum hip flexion angle and maximum knee bending angle on squatting position.Western Ontario and McMaster Universities(WOMAC)arthritis index and Knee Society Score(KSS)were used to evaluate clinical efficacy of knee joint.Results All patients were followed up for 5 to 7 weeks with an average of(6.00±0.57)weeks.The total score of WOMAC decreased from(64.85±11.54)before op-eration to(45.81±7.91)at 6 weeks after operation(P<0.001).The total KSS was increased from(101.19±9.58)before opera-tion to(125.50±10.32)at 6 weeks after operation(P<0.001).The gait speed,stride frequency and stride length of the affected side before operation were(0.32±0.10)m·s-1,(96.35±24.18)steps·min-1,(0.72±0.14)m,respectively;and increased to(0.48±0.11)m·s 1,(104.20±22.53)steps·min-1,(0.79±0.10)m at 6 weeks after operation(P<0.05).The lower limb support time and active knee bending angle decreased from(0.31±0.38)sand(125.21±11.64)° before operation to(0.11±0.04)s and(120.01±13.35)° at 6 weeks after operation(P<0.05).Eleven patients could able to complete squat before operation,13 patients could able to complete at 6 weeks after operation,and 9 patients could able to complete both before operation and 6 weeks after operation.In 9 patients,the maximum bending angle of crouching position was increased from 76.29° to 124.11° before operation to 91.35° to 134.12° at 6 weeks after operation,and the maximum bending angle of hip was increased from 103.70° to 147.25° before operation to 118.61° to 149.48° at 6 weeks after operation.Conclusion Gait analysis technology based on artificial intelligence image recognition is a safe and effective method to quantitatively identify the changes of pa-tients'gait.Knee pain of KOA was relieved and the function was improved,the supporting ability of the affected limb was im-proved after TKA,and the patient's stride frequency,stride length and stride speed were improved,and the overall movement rhythm of both lower limbs are more coordinated.
4.Application of the Glisson hepatic pedicle priority approach marked by APR triangle in laparoscopic anatomic right hemihepatectomy
Hao-Nan LI ; Jing WANG ; Run-Hua LI ; Jing-Jing ZHENG ; Jiang-Lun SHEN
Journal of Regional Anatomy and Operative Surgery 2024;33(10):854-858
Objective To study the application effect of Glisson hepatic pedicle priority approach marked by APR triangle in laparoscopic anatomic right hemihepatectomy(LARH).Methods The clinical data of 66 patients underwent LARH in the Affiliated Hospital of Tangshan Vocational and Technical College were retrospectively analyzed.According to the surgical approaches,the patients were divided into the extrathecal group and the APR group.The 35 patients of the extrathecal group underwent LARH via Glisson hepatic pedicle extrathecal approach.The 31 patients of the APR group were treated with LARH through the Glisson hepatic pedicle priority approach marked by APR triangle.The clinical data including perioperative indexes,postoperative complications,oxidative stress and liver function indexes of patients in the two groups were statistically analyzed,and the differences between the two groups were compared.Results The operative time and intraoperative blood loss of patients in the APR group were significantly shorter/less than those in the extrathecal group,with statistically significant differences(P<0.05).There was no significant differences in the intraoperative blood transfusion ratio,drainage tube indwelling time,first exhaust time,postoperative hospitalization time or postoperative complications of patients between the two groups(P>0.05).The levels of malondialdehyde(MDA),cortisol(Cor)and superoxide dismutase(SOD)at each time point after surgery of patients in the two groups were significantly different from those before surgery(P<0.05),and the levels of MDA,Cor and SOD at each time point after surgery of patients in the APR group were significantly better than those in the extrathecal group(P<0.05).The levels of albumin(ALB),total bilirubin(TBil),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)at each time point after surgery of patients in the two groups were significantly different from those before surgery(P<0.05).Moreover,the levels of ALB,TBil,AST and ALT at each time point after surgery of patients in the APR group were significantly better than those in the extrathecal group(P<0.05).Conclusion Compared with the Glisson hepatic pedicle extrathecal approach,the Glisson hepatic pedicle priority approach marked by APR triangle in LARH has shorter operation time,less bleeding and less oxidative stress reaction,which is beneficial to the recovery of liver function after surgery.
5.Prognostic Value of IGF2BP3 Gene Expression Levels in Patients with Acute Myeloid Leukemia
Ning LE ; Jing-Jing YANG ; Yu-Chen LIU ; Xia-Wei ZHANG ; Hao WANG ; Ya-Nan WEN ; Yi-Fan JIAO ; Li-Li WANG ; Li-Ping DOU
Journal of Experimental Hematology 2024;32(2):355-364
Objective:To investigate the relationship between IGF2BP3 gene expression and prognosis in patients with acute myeloid leukemia(AML).Methods:High throughput transcriptome sequencing was performed on bone marrow primary leukemia cells from 27 patients with AML in our center,the relationship between IGF2BP3 expression levels and clinical characteristics were analyzed and verify the samples from patients with newly treated AML and refractory AML.The expression level of IGF2BP3 gene were analyzed in 20 healthy subjects and 26 patients with AML.The expression of IGF2BP3 in two anthracycline-resistant cell lines(HL60/ADR,K562/ADR)was detected by RT-qPCR and Western blot,and the expression difference of IGF2BP3 was compared with that in sensitive cells(HL60,K562).The relationship between the expression level of IGF2BP3 in patients with AML and prognostic were analyzed through data analysis of 746 patients with AML,and the prognostic value of IGF2BP3 in AML was analyzed by multivariate Cox regression analysis.Results:In the bone marrow primary leukemia cells of 27 AML patients in our center,the expression level of IGF2BP3 in patients with refractory AML was significantly higher than that in chemotherapy sensitive patients(P=0.0343).The expression of IGF2BP3 in leukemia patients with extramedullary infiltration(EMI)was significantly higher than that in AML patients without extramedullary infiltration(P=0.0049).Compared with healthy subjects(n=20),IGF2BP3 expression in AML patients(n=26)was higher(P=0.0009).The expression of IGF2BP3 mRNA in the anthracycline resistant cell lines(HL60/ADR,K562/ADR)was significantly higher than that in the sensitive cell lines(K562/ADR vs K562,P=0.0430;HL60/ADR vs HL60,P=0.7369).Western blot results showed that the expression of IGF2BP3 protein in mycin resistant cells was significantly higher than that in sensitive cells(P<0.001).qPCR results showed that the expression level of IGF2BP3 mRNA in refractory AML patients was significantly higher than that in patients with chemotherapy sensitive(P=0.002).High expression of IGF2BP3 was associated with poor prognosis in AML(P<0.05)in 3 large sample cohorts of AML patients.Univariate and multivariate prognostic analyses demonstrated that high expression of IGF2BP3 was significantly associated with shorter event-free survival(EFS,HR=1.887,P=0.024)and overall survival(OS,HR=1.619,P=0.016).Conclusion:The high expression of IGF2BP3 gene may be an important factor in the poor prognosis of AML,suggesting that IGF2BP3 gene may be a new molecular marker for the clinical prognosis evaluation and treatment strategy of AML.
6.The impact of DRGs payment on Traditional Chinese Medicine hospitals:Based on difference-in-difference analysis
Hui-Jun GUO ; Jing LIU ; Guang-Yu HU ; Yi-Wei HAO ; Xin-Mei HAO ; Ya-Nan WANG ; Hui-Dong ZHU ; Qiu-Yan LI
Chinese Journal of Health Policy 2024;17(6):47-55
Objective:This study aims to evaluate the impact of Diagnosis-Related-Groups(DRGs)payment on the average total cost,length of stay,service volume,effectiveness,and characteristics of traditional Chinese medicine(TCM)hospitals.Methods:A national medical center specializing in TCM was selected as the research subject.The Difference-in-Difference Model(DID)was utilized to analyze the differences in various indicators between insured patients(intervention group)and uninsured patients(control group)before and after the implementation of the payment reform policy.The reliability and stability of the model were verified through parallel trend tests and placebo tests.Results:The coefficients of DID interaction terms for eleven indicators including average total hospitalization cost,number of cases,length of stay,proportion of medical service revenue,and proportion of herbal medicine revenue were significant(P<0.05).The DID interaction term coefficients for four indicators including herbal medicine usage rate and proportion of non-pharmacological TCM therapy revenue were not significant(P>0.05).Conclusion:DRG payment significantly reduced the per-admission cost,with significant decreases in consumables and medical technology expenses,optimizing cost structure,and a slight decrease in the proportion of herbal medicine costs.It is necessary to further expand the sample size,track policy impacts,and comprehensively evaluate the effects of DRG payment on TCM hospitals in China.
7.Research on the capacity and improvement path of home-and community-based integrated health and social care:A fuzzy-set qualitative comparative analysis based on 39 cases
Si-Qi LIU ; Jun ZHAO ; Nan LIU ; Hao-Yan DENG ; Qi CHEN ; Fang WANG
Chinese Journal of Health Policy 2024;17(9):28-35
Objective:Empirical analysis of the multiple driving paths of service capabilities of home-and community-based integrated health and social care in China,for providing useful reference for promoting the system improvement.Methods:Based on the World Health Organization's Integrated Care for Older People(ICOPE)implementation framework,an analysis framework for service capabilities of home-and community-based integrated health and social care was constructed.39 districts(counties)in Wuxi,Jiaozuo,Changsha,Chengdu,and Chongqing were included.The fuzzy-set qualitative comparative analysis(fsQCA)method was used to analyze the configuration paths of high or non-high-level service capabilities of home-and community-based integrated health and social care.Results:The service capabilities of home-and community-based integrated health and social care is improved by the configuration of various factors.Four path configurations might contribute to the development of service capabilities of home-and community-based integrated health and social care,and three path configurations might hinder the development.Institutional support,financing mechanism and the demand level of regional aging population are the key factors.Conclusions:Service capabilities of home-and community-based integrated health and social care are affected by the interaction and interrelation between multiple factors.Strategies should be jointly implemented from different aspects to improve service capabilities.
8.Accuracy of Echocardiographic Diagnosis and the Short-term Post-operative Outcome of Pediatric Cardiac Tumors
Tingting ZHANG ; Nan XU ; Jiayi XING ; Jiaqi ZHANG ; Li ZHANG ; Bing ZHANG ; Hao WANG ; Kunjing PANG
Chinese Circulation Journal 2024;39(10):1003-1008
Objectives:To summarize the experience of echocardiographic diagnosis and the short-term post-operative outcome of children with cardiac tumors. Methods:A total of 27 infants and children,who underwent echocardiography examination and were preliminarily diagnosed with cardiac tumors in Fuwai Hospital from January 2018 to June 2023,were retrospectively included in this study.Clinical symptoms,echocardiographic results,surgical and perioperative results and early outcomes were analyzed. Results:Among the 27 patients,16 were males.The age ranged from 1 month to 11 years(mean age:[3.2±2.5]years)and the body weight ranged from 5.7 to 40.0 kg(mean body weight:[17.2±11.2]kg).Cardiac tumors were pathologically confirmed in 25 cases,including 14 cases of fibroma,5 cases of rhabdomyoma,3 cases of myxoma,2 cases of lipoma,1 case of hemangioma.Preoperative echocardiographic diagnosis was consistent with postoperative pathologic diagnosis in 14 cases.Nontumor lesions were misdiagnosed as tumors by echocardiography in 2 cases.All the patients underwent surgery,complications occurred in 2 cases early post surgery and underwent reoperations and recovered well.There were no deaths during a median follow-up of 29.8(6.5,72.0)months,recurrence occurred in one child with myxoma. Conclusions:Pediatric patients with cardiac tumors have specific echocardiographic manifestations.It is necessary to sum up related experience constantly to improve the diagnostic accuracy.Short-term outcome post-surgery is satisfactory for the treatment of benign pediatric cardiac tumors.
9.Synthesis of 18F-labeled glucagon-like peptide-1 receptor agonist targeting probe and its preliminary evaluation in diagnosis of insulinoma with PET/CT
Yunfei XIE ; Nan LIU ; Zhaohui LIU ; Limeng HE ; Huan MA ; Hao LIU ; Hao WANG ; Haiyan GAO ; Weiwei ZHANG ; Wei ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(11):673-677
Objective:To explore the automated synthesis of glucagon-like peptide-1 receptor agonist 18F-AlF-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-maleimide (Mal)-cysteine (Cys) 39-exendin-4 ( 18F-exendin-4), and verify its diagnostic efficacy on insulinoma with PET/CT. Methods:Using NOTA-Mal-Cys 39-exendin-4 as the labeled precursor, 18F-exendin-4 was obtained by constructing Al 18F one-step reaction sequence and using All in one multifunctional chemical synthesizer for radiolabelling, purification and preparation. After the quality control, 18F-exendin-4 PET/CT imaging was performed on 1 patient (female, 55 years old) with clinical suspicion of insulinoma. Results:Radiolabelling of 18F-exendin-4 took about 40 min, with the non-decay corrected radiochemical yield of (18.03±2.67)% ( n=3), the molar activity>39.74 GBq/μmol, and the radioactivity concentration>390.00 MBq/ml. The injection was a colorless transparent liquid with pH value of 6.5, and the radiochemical purity>96%. Results of bacteria and endotoxins testing met the standards of Pharmacopoeia of the People′ s Republic of China (2020). PET/CT image analysis showed a nodular high uptake of 18F-exendin-4 in the pancreatic body. The pathological and immunohistochemical results were consistent with the characteristics of neuroendocrine neoplasm (G2). Conclusions:The automatic radiolabelling of 18F-exendin-4 is successfully realized by All in one multifunctional chemical synthesizer. 18F-exendin-4 has been proved to be of clinical value in diagnosis of insulinoma, and is suitable for promotion in medical institutions equipped with medical cyclotrons.
10.Relationship between occipitocervical angle and difficult airway after occipitocervical fusion surgery
Nan WU ; Linzhong ZHANG ; Wenhui SONG ; Yujing ZHANG ; Lili WANG ; Kaiheng LIANG ; Hao YIN
Chinese Journal of Anesthesiology 2024;44(6):718-722
Objective:To evaluate the relationship between the occipitocervical angle(basilar vertebral angle [O-C 2 angle], mento-pharyngeal angle [M-P angle], and cervical range of motion [CROM]) and difficult airway after occipitocervical fusion surgery in the patients. Methods:This was a retrospective study. The clinical data from patients who underwent occipitocervical fusion surgery at our hospital from March 2018 to March 2023 were retrospectively collected. Preoperative and last follow-up airway assessment data and cervical lateral X-rays were collected to measure the O-C 2 angle, M-P angle and CROM. Patients were divided into negative group (Mallampati grade Ⅰ or Ⅱ, suggesting no difficulty in intubation) and positive group (Mallampati grade Ⅲ or Ⅳ, suggesting possible difficulty in intubation) based on the last follow-up modified Mallampati classification. Results:A total of 53 patients were finally included, with 18 cases in positive group and 35 in negative group. There were no statistically significant differences in the O-C 2 angle and CROM between preoperative and last follow-up in the 53 patients ( P>0.05), and the M-P angle was significantly decreased at the last follow-up compared with that before operation ( P<0.05). Compared with negative group, O-C 2 angle and M-P angle were significantly decreased at the last follow-up ( P<0.05), and no significant change was found in CROM in positive group ( P<0.05). Compared with that before operation, the M-P angle was significantly decreased at the last follow-up in both groups, and the O-C 2 angle was significantly decreased at the last follow-up in positive group ( P<0.05). The areas under the receiver operating characteristic curves of O-C 2 angle, M-P angle and CROM in predicting difficult airway were 0.895, 0.888 and 0.519 respectively. Conclusions:The decrease in the O-C 2 angle and M-P angle after occipitocervical fusion surgery can increase the risk of difficult airway, and both can be used for airway assessment in the patients undergoing this kind of surgery.

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