1.Synthesis and anti-breast cancer activity of novel cyclic mono-carbonyl curcumin analogues
Xianhu FENG ; Yongjie CHEN ; Lin CHEN ; Yi HOU ; Wanjun CAO ; Qiang SU
China Pharmacy 2025;36(5):563-567
OBJECTIVE To design and synthesize mono-carbonyl curcumin analogues(MCACs) and investigate the activities of them against breast cancer. METHODS The analogues F1, F2, and F3 were obtained by aldol condensation reaction, and their antitumor activities(including the activities of human breast cancer cell MCF-7 and human lung cancer cell A549) were detected by MTT assay [evaluated with half inhibitory concentration(IC50)]. The results of MTT assay were compared with those of curcumin. Bioinformatics methods were used to collect the core targets of analogues F1, F2 and F3 acting on breast cancer, and then molecular docking verification was carried out. The cell experiments were conducted to investigate the effects of high, medium and low concentrations (16, 8, 4 μmol/L) of F1, F2 and F3 on the expression of the first core target protein as well as the effects of medium concentration of F1, F2 and F3 on the expression of cleaved-caspase-3. RESULTS Compared with curcumin, IC50 of analogues F1, F2 and F3 to A549 and MCF-7 cells(except for IC50 of analogue F2 to A549 cells) were decreased significantly(P< 0.05 or P<0.01); among them, IC50 of analogue F2 to MCF-7 cell was the lowest, being(9.67±1.27) μmol/L. Bioinformatics analysis showed that index of affinity of analogues F1, F2 and F3 with the first core target epidermal growth factor receptor (EGFR), protein kinase B (AKT) and AKT were 5.909 2, 8.402 5 and 6.486 6, respectively; high concentration of F1 could significantly reduce the phosphorylation level of EGFR protein in MCF-7 cells(P<0.01), while low, medium, and high concentrations of F2 and high concentration of F3 could significantly reduce the phosphorylation level of AKT protein in MCF-7 cells(P<0.05 or P<0.01). Medium concentration of F1, F2, and F3 could significantly increase the expression level of cleaved- caspase-3 protein in MCF-7 cells(P<0.01). CONCLUSIONS Designed and synthesized MCACs F1, F2 and F3 all have good anti- breast cancer activity, and F2 has better anti-breast cancer activity.
2.Explore the mechanism of Huangqi Jiedu decoction in the treatment of breast cancer syndrome of Zheng-deficiency and toxic-incandescence based on network pharmacology and molecular docking technology
Lingjia TIAN ; Zihao YIN ; Liang ZHOU ; Qin ZHANG ; Lixin LIANG ; Yongjie CAO ; Hua WANG ; Lifang LIU
Journal of Chinese Physician 2024;26(3):360-365
Objective:To explore the mechanism of Huangqi Jiedu Decoction (HQJD) in the treatment of breast cancer with the syndrome of Zheng deficiency and toxic incandescence by network pharmacology and molecular docking technology.Methods:The main active ingredients and targets of HQJD were screened through the traditional Chinese medicine (TCM) systematic pharmacology database and analysis platform. The relevant targets of breast cancer with the syndrome of Zheng-deficiency, toxic-incandescence were obtained using OMIM, GeneGards and Drugbank databases, and the relevant targets of HQJD for the treatment of breast cancer with the syndrome of Zheng-deficiency and toxic incandescence were obtained by intersection; The Cytoscape 3.9.1 software was used to build the protein protein interaction (PPI) network and the " drug active component target disease" network on the basis of String 11.0 database, and the core active components and core targets of HQJD in treating breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence were inferred according to the topological parameters. gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on core targets using R language; and molecular docking verification on the main active ingredients and core targets were conducted.Results:230 effective targets of active ingredients of HQJD were screened, and 15 467 active ingredients of breast cancer with syndrome of Zheng-deficiency/toxic-incandescence were obtained; 217 intersection targets; GO function enrichment analysis showed that the treatment of HQJD for breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence mainly involved oxidative stress and cytochemical stress; The enrichment analysis of KEGG pathway showed that HQJD treatment of breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence was mainly related to phosphatidylinositol 3-protein kinase B (PI3K-Akt), interleukin-17 (IL-17) and other signal pathways. The molecular docking results showed that the main active ingredients such as β-sitosterol, stigmasterol, luteolin had good binding ability with core targets.Conclusions:HQJD has the characteristics of multi-component, multi target and multi pathway in the treatment of breast cancer with syndrome of Zheng-deficiency and toxic-incandescence, and its main mechanism may be related to PI3K-Akt, IL-17, P53 and other signal pathways.
3.The efficacy of trabecular metal Cones in reconstructing metaphyseal bone defects during revision total knee arthroplasty
Yongjie CHEN ; Guoqing LI ; Yang WANG ; Baochao JI ; Li CAO
Chinese Journal of Orthopaedics 2024;44(4):233-242
Objective:To investigate the clinical outcomes and efficacy of trabecular metal (TM) cones for the reconstruction of metaphyseal bone defects in revision total knee arthroplasty.Methods:A retrospective analysis was conducted on 46 patients (47 knees), who underwent revision total knee arthroplasty with TM cones for metaphyseal defect reconstruction from July 2015 to August 2023. The cohort comprised 12 males and 34 females, ranging from 41 to 83 years of age, with a mean of 68.65 ± 9.09 years. Body mass index (BMI) ranged from 19.5 to 36.0 kg/m 2, averaging 27.20±4.50 kg/m 2. Bone defects were stratified according to the Anderson Orthopedic Research Institute (AORI) classification, including 64 sides (AORI T2B type 20 sides, T3 type 16 sides, F2B type 11 sides, F3 type 17 sides) which were addressed with 67 cones. Evaluations during follow-up included range of motion (ROM), visual analogue scale (VAS) for pain, and the American Knee Society Score (KSS). Long leg radiographs and knee X-rays were reassessed for femorotibial angle (FTA) and joint alignment, osseointegration of the TM cones, and any complications were documented. Results:The average follow-up duration was 46.22±26.55 months (range 16-103 months). The KSS knee score significantly improved from 29.22±19.79 preoperatively to 88.22±6.01 at the final follow-up ( F=258.118, P<0.001). Similarly, the KSS function score saw a marked increase from a preoperative average of 7.65±8.21 to 56.30±6.10 at the final follow-up ( F=354.711, P<0.001). VAS scores significantly decreased from 5.35±1.50 preoperatively to 0.28±0.50 at the final follow-up ( F=300.934, P<0.001). ROM improved from 67.72°±34.62° preoperatively to 85.33°±9.15° at the final follow-up ( F=7.798, P<0.001), and the FTA improved from 179.24°±10.30° preoperatively to 174.39°±1.69° at the final follow-up, a statistically significant enhancement ( F=9.123, P<0.001). Osseointegration was observed in 95.5% of the cases (64/67 cones). There were no instances of osteolysis or aseptic loosening observed, indicating stable prosthetic fixation. Complications were minimal, with one reported case of a femoral shaft fracture, which was successfully treated with internal fixation, resulting in satisfactory healing at 6 months. At the last follow-up (3 years after operation), the patient could walk at home with a walker and the other patients had no complications such as periprosthetic joint infection, dislocation and periprosthetic fracture. Conclusion:The application of trabecular metal cones in revision total knee arthroplasty provides an effective solution for the reconstruction of severe metaphyseal bone defects, enhancing prosthetic stability and restoring the knee joint's mechanical alignment. The trend towards successful osseointegration in the TM cones is promising, and a significant improvement in knee joint function has been observed.
4.Antibacterial effects in vitro of low-intensity pulsed ultrasound combined with 3.5 g/L povidone-iodine on the biofilm of methicillin-resistant staphylococcus aureus
Tianxing WANG ; Guoqing LI ; Yang WANG ; Baochao JI ; Yongjie CHEN ; Haikang ZHOU ; Li CAO
Chinese Journal of Orthopaedic Trauma 2024;26(9):818-823
Objective:To explore the in vitro antibacterial effects of low-intensity pulsed ultrasound (LIPUS) combined with 3.5 g/L povidone iodine solution on the biofilm of methicillin-resistant staphylococcus aureus (MRSA). Methods:Immature (cultured for 24 hours) and mature (cultured for 72 hours) MRSA biofilms were established on the surfaces of glass slides or confocal dishes. They were randomly divided into 4 groups ( n=9) according to different intervention methods. In the control group, glass slides or confocal dishes were placed in 500 mL of physiological saline for 3 minutes; in the PI group, glass slides or confocal dishes were placed in 500 mL of 3.5 g/L povidone iodine solution for 3 minutes; in the LIPUS group, glass slides or confocal dishes were placed in 500 mL of physiological saline and simultaneously intervened with LIPUS for 3 minutes; in the LIPUS & PI group, glass slides or confocal dishes were placed into 500 mL of 3.5 g/L povidone iodine solution and simultaneously intervened with LIPUS for 3 minutes. After intervention, confocal microscopy (CLSM) and scanning electron microscopy (SEM) were used to observe and compare the structure, morphology, bacterial survival, and viable cell count of the MRSA biofilms among the 4 groups. Results:On the MRSA biofilms cultured for 24 and 72 hours, CLSM and SEM observed sparse biofilms in the LIPUS group and LIPUS & PI group, and also a large number of dead bacteria in the LIPUS & PI group. On the MRSA biofilms cultured for 24 hours, the bacterial colony counts in the control group, PI group, LIPUS group, and LIPUS & PI group were (1.21±0.45)×10 6 CFU/mL, (3.38±2.81)×10 3 CFU/mL, (1.82±0.37)×10 3 CFU/mL, and (69.67±27.93) CFU/mL, respectively. Except for the comparison between PI group and LIPUS group, which showed no statistically significant difference ( P>0.05), there were statistically significant differences between the other groups when compared pairwise ( P<0.05). On the MRSA biofilms cultured for 72 hours, the bacterial colony counts in the control group, PI group, LIPUS group, and LIPUS & PI group were (3.01±0.70)×10 6 CFU/mL, (1.80±1.52)×10 5 CFU/mL, (2.10±0.52)×10 3 CFU/mL, and (68.67±19.55) CFU/mL, respectively. There were statistically significant differences between the 4 groups when compared pairwise ( P<0.05). Conclusions:Application of LIPUS or 3.5 g/L povidone iodine alone for 3 minutes on the immature or mature MRSA biofilms in vitro only leads to partial antibacterial activity. However, LIPUS can enhance the in vitro antibacterial effect of 3.5 g/L povidone iodine on the MRSA biofilms at different maturity levels.
5.Survey of hepatitis B virus infection for liver cancer screening in China: A population-based, cross-sectional study
Yongjie XU ; Changfa XIA ; He LI ; Maomao CAO ; Fan YANG ; Qianru LI ; Mengdi CAO ; Wanqing CHEN
Chinese Medical Journal 2024;137(12):1414-1420
Background::Hepatitis B virus (HBV) infection is the primary cause of hepatocellular carcinoma (HCC) in China. The target population for HCC screening comprises individuals who test positive for hepatitis B surface antigen (HBsAg). However, current data on the prevalence of HBV infection among individuals who are eligible for HCC screening in China are lacking. We aimed to assess the seroepidemiology of HBV infection among Chinese individuals eligible for HCC screening to provide the latest evidence for appropriate HCC screening strategies in China.Methods::Questionnaires including information of sex, age, ethnicity, marital status, educational level, source of drinking water, as well as smoking and alcohol consumption history and serum samples were collected from females aged 45–64 years and males aged 35–64 years in 21 counties from 4 provinces in eastern and central China between 2015 and 2023. Enzyme-linked immunosorbent assay methods were used to detect the serum HBV marker HBsAg.Results::A total of 603,082 individuals were enrolled, and serum samples were collected for analysis from January 1, 2015 to December 31, 2023. The prevalence of HBsAg positive in the study population was 5.23% (31,528/603,082). The prevalence of HBsAg positive was greater in males than in females (5.60% [17,660/315,183] vs 4.82% [13,868/287,899], χ 2 = 187.52, P <0.0001). The elderly participants exhibited a greater prevalence of HBV infection than younger participants (χ 2 = 41.73, P <0.0001). Birth cohort analysis revealed an overall downward trend in HBV prevalence for both males and females. Individuals born in more recent cohorts exhibited a lower prevalence of HBV infection as compared to those born earlier. Conclusions::The current prevalence of HBV infection remains above 5% in populations eligible for HCC screening in China.
6.Clinical analysis of one-stage THA combined with intra-articular injection of antibiotics in the treatment of infection after internal fixation of hip fracture
Haiyao ZHANG ; Guoqing LI ; Yang WANG ; Baochao JI ; Haikang ZHOU ; Yongjie CHEN ; Li CAO
Chinese Journal of Orthopaedics 2024;44(16):1085-1092
Objective:To evaluate the clinical efficacy of single-stage total hip arthroplasty (THA) combined with intra-articular antibiotic injection in managing postoperative infections following internal fixation of hip fractures.Methods:A retrospective analysis was conducted on 25 patients who underwent single-stage THA for infection following internal fixation of hip fractures from January 2013 to January 2021 at the Department of Joint Surgery, First Affiliated Hospital of Xinjiang Medical University. The cohort comprised 15 males and 10 females, with an average age of 61.52±13.06 years (range, 32-89 years) and an average body mass index of 24.04±3.84 kg/m 2 (range, 18-34 kg/m 2). The fractures included 13 femoral neck fractures, 6 intertrochanteric fractures, 4 acetabular fractures, 1 proximal femoral fracture, and 1 combined acetabular and intertrochanteric fracture. Preoperative joint cavity puncture or intraoperative joint fluid extraction, biochemical analysis, microbial culture, and drug sensitivity tests were performed. During surgery, infected internal fixation devices were removed, and hip prostheses were implanted following thorough debridement. Postoperatively, patients received intravenous and intra-articular sensitive antibiotics based on bacterial culture and drug sensitivity results. Joint stability was evaluated according to the Engh standard, and hip function was assessed using the Harris score. Results:Microbial cultures were positive in 12 cases, identifying Staphylococcus epidermidis (4 cases), Staphylococcus aureus (2 cases), Escherichia coli (2 cases), Enterobacter cloacae (1 case), Pseudomonas aeruginosa (1 case), Corynebacterium striatum (1 case), and a mixed infection of Staphylococcus epidermidis and Enterococcus faecalis (1 case). All 25 patients were followed for an average of 56.64±26.38 months (range, 24-123 months). Intravenous and intra-articular antibiotic treatment was administered to all patients. One case experienced sinus tract formation and pus discharge on the 20th postoperative day, diagnosed as periprosthetic infection, resulting in treatment failure, yielding an infection control rate of 96% (24/25). All patients demonstrated stable prosthesis fixation with no subsidence, loosening, or osteolysis. At the final follow-up, the Harris hip score improved significantly from a preoperative score of 26.69±13.47 to 92.30±5.60 ( t=22.882, P<0.001). Complications included 2 cases of hip dislocation, 2 cases of deep venous thrombosis in the lower extremities, 1 case of poor wound healing, and 1 case of periprosthetic fracture. Conclusion:Single-stage THA combined with intra-articular antibiotic injection is effective in controlling infections following internal fixation of hip fractures. This approach not only achieves a high infection control rate but also reconstructs hip joint function, resulting in satisfactory postoperative outcomes.
7.Active Components in Chinese Medicinal Herbs Regulate Osteogenic Signaling Pathway in Treatment of Steroid-induced Osteonecrosis of Femoral Head: A Review
Zhengya SHANG ; Linzhong CAO ; Yi ZHANG ; Chengxiang MA ; Kangyi HU ; Haodong YANG ; Jinning SUN ; Yongjie ZHANG ; Xiaorui YANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(18):229-240
As a threat to human health, steroid-induced osteonecrosis of femur head is a common refractory orthopedic disease mainly caused by glucocorticoids, with poor prognosis and unclear pathogenesis. Osteogenesis-associated signaling pathways play an important role in bone formation. Glucocorticoid-induced abnormal activation and transport of these signaling pathways lead to abnormal differentiation of bone marrow mesenchymal stem cells, dysfunction of bone metabolism, and osteogenesis disorders, which may be the main reasons for the occurrence and development of steroid-induced osteonecrosis of femur head. Bone formation and remodeling need the participation of bone marrow mesenchymal stem cells, which are stem cells characterized by continuous self-renewal and differentiation. The key to strengthening bone remodeling is to improve the osteogenic differentiation capacity, which is the key point to inhibit bone resorption and prevent bone marrow mesenchymal stem cells from differentiating into osteoclasts. Traditional Chinese medicine (TCM) has been used in the treatment of osteonecrosis in ancient times. It is recorded in the Treasury of Words on Materia Medica (《本草汇编》) that "The deficiency in the lower energizer cannot be tonified without Eucommiae Cortexz.The soreness in lower legs cannot be alleviated without Eucommiae Cortex...The pain in the waist and knee cannot be relieved without Eucommiae Cortex...Tonifying liver and invigorating kidney, Eucommiae Cortex is an essential medicine." This indicates that ancient physicians have already begun to use the liver-tonifying, kidney-invigorating, and sinew-bone-strengthening effects of Eucommiae Cortex for the treatment of osteonecrosis. As the national support for the development of TCM strengthens, increasing studies have been conducted on the TCM prevention and treatment of steroid-induced osteonecrosis of femur head. Studies have suggested that Chinese medicinal herbs can exert a positive effect on the differentiation of bone marrow mesenchymal stem cells by affecting targeted signaling molecules, and promote osteogenesis and bone defect repair, thus combating the occurrence and development of steroid-induced osteonecrosis of femur head. The regulation of osteogenic signaling pathway by Chinese medicines to prevent steroid-induced osteonecrosis of femoral head has become a hot research topic. This article reviews the studies about the prevention and treatment of steroid-induced osteonecrosis of femur head with the active components in Chinese medicinal herbs by regulating osteogenic signaling pathways. We then explore the mechanism of the active components in promoting the differentiation of bone marrow mesenchymal stem cells into osteoblasts and inhibiting their differentiation into osteoclasts to facilitate bone formation, aiming to provide a reference for the further study of treating steroid-induced osteonecrosis of femoral head with Chinese medicinal herbs.
8.Exploration on teaching reform of cancer epidemiology course
Yongjie XU ; Xueyan LI ; Xuesi DONG ; Wei CAO ; Chao QIN ; Jiang LI ; Liang ZHAO ; Fei WANG ; Changfa XIA ; Wanqing CHEN ; Ni LI
Chinese Journal of Preventive Medicine 2022;56(7):1027-1030
This study aims to explore optimized teaching mode of cancer epidemiology for undergraduates, and provide scientific ideas and basis for improving teaching quality. Non-randomized concurrent control study was used. Undergraduates, enrolled in 2018, from the department of preventive medicine in A and B medical universities were selected as research objects. Traditional teaching mode was used for cancer epidemiology course in A medical university, and innovative teaching mode named "one core, four dimensions" was adopted in B medical university. After the course, questionnaire method was used to investigate self-cognition of students, teaching satisfaction and class preparation time of teachers in B Medical University. The post-class test method was used to compare the students′ grades of cancer epidemiology in the two universities. The results indicated that among the 58 students of B medical university, 94.83% (55/58) students were familiar with common types of epidemiological studies and 86.21% (50/58) mastered the evaluation indicators of screening research. Among the nine teaching faculties from B medical university, seven reported that the new teaching plan helped students to learn frontier knowledge of cancer epidemiology, and eight reported the new teaching model was conducive to the interaction between teachers and students. The text score of students in B medical university was 50.34±4.90, significantly higher than that in A medical university (46.21±4.91, t=5.20, P<0.001). The optimized teaching mode of cancer epidemiology is highly praised by students and teachers, which has the potential to improve students′ grasp of cancer epidemiology, the ability to combine theory with practice, and the teaching effect of cancer epidemiology.
9.Sex disparity of lung cancer risk in non-smokers: a multicenter population-based prospective study based on China National Lung Cancer Screening Program
Zheng WU ; Fengwei TAN ; Zhuoyu YANG ; Fei WANG ; Wei CAO ; Chao QIN ; Xuesi DONG ; Yadi ZHENG ; Zilin LUO ; Liang ZHAO ; Yiwen YU ; Yongjie XU ; Jiansong REN ; Jufang SHI ; Hongda CHEN ; Jiang LI ; Wei TANG ; Sipeng SHEN ; Ning WU ; Wanqing CHEN ; Ni LI ; Jie HE
Chinese Medical Journal 2022;135(11):1331-1339
Background::Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer incidence distinct from the females—even after excluding the influence of smoking; but the knowledge regarding the factors causing the difference is sparse. Based on a large multicenter prospective cancer screening cohort in China, we aimed to elucidate the interpretable sex differences caused by known factors and provide clues for primary and secondary prevention.Methods::Risk factors including demographic characteristics, lifestyle factors, family history of cancer, and baseline comorbidity were obtained from 796,283 Chinese non-smoking participants by the baseline risk assessment completed in 2013 to 2018. Cox regression analysis was performed to assess the sex difference in the risk of lung cancer, and the hazard ratios (HRs) that were adjusted for different known factors were calculated and compared to determine the proportion of excess risk and to explain the existing risk factors.Results::With a median follow-up of 4.80 years, 3351 subjects who were diagnosed with lung cancer were selected in the analysis. The lung cancer risk of males was significantly higher than that of females; the HRs in all male non-smokers were 1.29 (95% confidence interval [CI]: 1.20-1.38) after adjusting for the age and 1.38 (95% CI: 1.28-1.50) after adjusting for all factors, which suggested that known factors could not explain the sex difference in the risk of lung cancer in non-smokers. Known factors were 7% (|1.29-1.38|/1.29) more harmful in women than in men. For adenocarcinoma, women showed excess risk higher than men, contrary to squamous cell carcinoma; after adjusting for all factors, 47% ([1.30-1.16]/[1.30-1]) and 4% ([7.02-6.75]/[7.02-1])) of the excess risk was explainable in adenocarcinoma and squamous cell carcinoma. The main causes of gender differences in lung cancer risk were lifestyle factors, baseline comorbidity, and family history.Conclusions::Significant gender differences in the risk of lung cancer were discovered in China non-smokers. Existing risk factors did not explain the excess lung cancer risk of all non-smoking men, and the internal causes for the excess risk still need to be explored; most known risk factors were more harmful to non-smoking women; further exploring the causes of the sex difference would help to improve the prevention and screening programs and protect the non-smoking males from lung cancers.
10.Exploration on teaching reform of cancer epidemiology course
Yongjie XU ; Xueyan LI ; Xuesi DONG ; Wei CAO ; Chao QIN ; Jiang LI ; Liang ZHAO ; Fei WANG ; Changfa XIA ; Wanqing CHEN ; Ni LI
Chinese Journal of Preventive Medicine 2022;56(7):1027-1030
This study aims to explore optimized teaching mode of cancer epidemiology for undergraduates, and provide scientific ideas and basis for improving teaching quality. Non-randomized concurrent control study was used. Undergraduates, enrolled in 2018, from the department of preventive medicine in A and B medical universities were selected as research objects. Traditional teaching mode was used for cancer epidemiology course in A medical university, and innovative teaching mode named "one core, four dimensions" was adopted in B medical university. After the course, questionnaire method was used to investigate self-cognition of students, teaching satisfaction and class preparation time of teachers in B Medical University. The post-class test method was used to compare the students′ grades of cancer epidemiology in the two universities. The results indicated that among the 58 students of B medical university, 94.83% (55/58) students were familiar with common types of epidemiological studies and 86.21% (50/58) mastered the evaluation indicators of screening research. Among the nine teaching faculties from B medical university, seven reported that the new teaching plan helped students to learn frontier knowledge of cancer epidemiology, and eight reported the new teaching model was conducive to the interaction between teachers and students. The text score of students in B medical university was 50.34±4.90, significantly higher than that in A medical university (46.21±4.91, t=5.20, P<0.001). The optimized teaching mode of cancer epidemiology is highly praised by students and teachers, which has the potential to improve students′ grasp of cancer epidemiology, the ability to combine theory with practice, and the teaching effect of cancer epidemiology.

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