1.Carnosic acid inhibits osteoclast differentiation by inhibiting mitochondrial activity
Haishan LI ; Yuheng WU ; Zixuan LIANG ; Shiyin ZHANG ; Zhen ZHANG ; Bin MAI ; Wei DENG ; Yongxian LI ; Yongchao TANG ; Shuncong ZHANG ; Kai YUAN
Chinese Journal of Tissue Engineering Research 2025;29(2):245-253
BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.
2.Evidence-based study on postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor
Xiandan LUO ; Yanli LU ; Yihang WU ; Yanxiang GUO ; Xiaoyi YAN ; Yongchao HUO ; Hui YAN ; Zhenjiang YANG ; Hongliang ZHANG
China Pharmacy 2025;36(18):2328-2333
OBJECTIVE To systematically evaluate the methodological quality of the postoperative chemotherapy guidelines/ consensuses for ovarian epithelial tumor. METHODS A search was conducted across databases including PubMed, Embase, Web of Science, CBM, VIP, Chinese Medical Journal Data, Wanfang Data, and CNKI, as well as the official websites of GIN, NICE, Medlive, AHRQ, CSCO, ASCO, and NCCN. The search period was from the establishment of the databases/websites to March 10, 2025. The quality of the included guidelines/consensus was evaluated by using the AGREE-Ⅱ tool. RESULTS A total of 16 guidelines/consensuses were included. The domain scores of AGREE-Ⅱ evaluation were as follows: scope and purpose of 85.07%, participants of 47.92%, rigor of development of 57.49%, clarity of presentation of 88.02%, applicability of 8.20%, and independence of 53.39%. Among them, 14 were recommended at grade B and 2 were recommended at grade C. The subgroup analysis by different countries/regions and different types of studies showed that the scores for participants, rigor of development, and independence of the guidelines/consensuses in China were significantly lower than foreign countries (P<0.05); the scores for participants and rigor of development of the guidelines were significantly higher than consensuses (P<0.05). The guideline/ consensus recommendation results indicated that grade B guidelines/consensus recommend platinum-based combination chemotherapy as the preferred adjuvant chemotherapy regimen for stage Ⅰ high-grade serous carcinoma patients;platinum-based combination chemotherapy±bevacizumab was recommended as the preferred adjuvant chemotherapy regimen for stage Ⅱ-Ⅳ high- grade serous carcinoma patients and for platinum-sensitive recurrent high-grade serous carcinoma patients; non-platinum single- agent chemotherapy±bevacizumab was recommended as the preferred chemotherapy regimen for platinum-resistant recurrent high- grade serous carcinoma patients. CONCLUSIONS The overall quality of postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor is not high. The methodological quality of guidelines/consensuses in China is still lagging behind that of foreign countries. The recommendations differ from those in foreign countries. It is recommended to improve the aspects of participants, rigor of development, and independence, to recommend treatment plans based on the different stages of ovarian cancer, and develop guidelines/consensuses that align with China’s national conditions.
3.The impact of central obesity on breast cancer risk and the significance of dietary factors
Yu ZHANG ; Chunwei LI ; Yongchao WANG ; Yuanyuan BAO ; Qi LI ; Lin LI ; Yi PANG ; Chunli GUO ; Yuchen FAN ; Xiangchao MENG ; Kang YU
Chinese Journal of Clinical Nutrition 2024;32(2):65-70
Objective:To explore the influence of central obesity on the risk of breast cancer and the possible role of dietary factors in its prevention.Methods:This study is a case-control study including a total of 212 participants, of whom 63 were with breast cancer, 71 were with breast nodules, and 80 were healthy controls. We used bioelectrical impedance analysis to measure body composition,and adopted the food frequency questionnaire to investigate dietary intake of participants.Results:The visceral adipose tissue ( OR=1.03, 95% CI: 1.003 to 1.077) and trunk fat mass ( OR=1.470, 95% CI: 1.104 to 2.184) were independently associated with the increased risk of breast cancer. Dietary patterns characterized by low dietary intake of beans and dairy products ( OR=1.300, 95% CI: 1.044 to 1.619) and high intake of cereals and red meat ( OR=2.254, 95% CI: 1.705 to 2.982) will increase the risk of breast cancer. Moreover, high meat intake ( β=0.268, 95% CI: 0.034 to 0.503) would advance the accumulation of visceral fat, while high bean intake ( β=-0.485, 95% CI: -0.865 to -0.104) would inhibit. Conclusions:Central obesity is an independent risk factor for breast cancer. Insufficient intake of beans and excessive intake of red meat are identified as factors that can exacerbate central obesity in breast cancer patients.
4.Efficacy of Alteplase in repairing T-lymphocyte mediated brain tissue immunoinflammatory damage after acute ischemic stroke
Jianyu WANG ; Li ZHANG ; Yongchao WANG ; Yan WEI
Chinese Journal of Immunology 2024;40(7):1484-1489
Objective:To study the efficacy of Alteplase in repairing T-lymphocyte mediated brain tissue immunoinflammatory damage after acute ischemic stroke(AIS).Methods:A total of 100 patients with AIS admitted to Hengshui People's Hospital from June 2022 to June 2023 were selected,and divided into regular group and Alteplase group,with 50 cases in each group,after enroll-ment,the regular group received routine intervention treatment,while the Ateplase group received thrombolytic therapy with Ateplase.Compared changes in neurological function,cerebrovascular reserve function,cerebral hemodynamics,T lymphocytes mediated brain tissue immunoinflammatory damage indicators CD4+T cell subsets[pro-inflammatory cells(Th1,Th17),anti-inflammatory cells(Th2,Treg cells)]and related cytokines levels between two groups of patients,and evaluated clinical efficacy and prognosis.Results:After treatment,NIHSS score of Alteplase group was lower than that of regular group[(6.57±0.79)points vs(9.34±1.23)points,t=13.400,P<0.05].CVR and BHI of cerebral vascular reserve in Alteplase group were higher than those in regular group[(34.54±4.35)%vs(29.89±2.31)%,1.00±0.23 vs 0.92±0.08,t=6.676,2.323,P<0.05],PI was lower than that of regular group(0.60±0.07 vs 0.72±0.08,t=7.982,P<0.05).Cerebral hemodynamic CBF of Alteplase group was higher than that of regular group[(49.89±9.76)ml/(100 g/min)vs(40.34±7.86)ml/(100 g/min),t=5.389,P<0.05].MTT and TTP were shorter than those in regular group[(6.45±0.78)s vs(9.78±1.02)s,(24.45±2.16)s vs(26.78±3.25)s,t=18.340,4.222,P<0.05].Proportion of Th1 and Th17 cells and levels of IFN-γ and IL-17 in Ateplase group were lower than those in regular group[(3.27±0.59)%vs(5.64±0.52)%,(2.34±0.25)%vs(4.35±0.38)%,(3.24±0.45)pg/ml vs(4.90±0.65)pg/ml,(10.23±1.43)pg/ml vs(14.35±2.14)pg/ml,t=21.310,31.250,14.850,11.320,P<0.05),proportion of Th2 and Treg cells and levels of IL-4 and TGF-β were higher than those in regular group[(8.75±0.54)%vs(7.02±0.37)%,(7.24±2.13)%vs(5.88±1.67)%,(13.24±2.16)pg/ml vs(10.26±1.29)pg/ml,(90.32±9.02)pg/ml vs(81.45±8.97)pg/ml,t=18.690,3.553,8.375,4.930,P<0.05].Total effective rate and good prognosis rate of Alteplase group were higher than those of regular group(94.00%vs 80.00%,80.00%vs 62.00%,χ2=4.332,3.934,P<0.05).Conclu-sion:In treatment of AIS,Alteplase has effect of repairing the immune inflammation injury of brain tissue mediated by T lymphocytes,alleviating brain injury,improving cerebrovascular reserve function and nerve function,and the prognosis is good.
5.Application of Microsatellite Instability in Endometrial Cancer via A Prediction Model Based on Diffusion Weighted Imaging Deep Learning Features
Yongchao NIU ; Fang ZHOU ; Dandan ZHAO ; Mengyan HOU ; Shujian LI ; Yong ZHANG
Chinese Journal of Medical Imaging 2024;32(9):922-927
Purpose To explore the value of a prediction model based on diffusion weighted imaging(DWI)deep learning features in endometrial cancer microsatellite instability status assessment.Materials and Methods DWI data of 32 microsatellite instability and 55 microsatellite stability endometrial cancer patients were analysed from June 2020 to April 2023 in Xinxiang Central Hospital,retrospectively.Apparent diffusion coefficient(ADC)values of the primary lesions were measured,and deep learning features and imaging histological features of the primary lesions were extracted using multilayer convolutional neural networks and PyRadiomics,respectively.The least absolute shrinkage and selection operator and random forest were used for feature screening and model building,respectively.The area under the receiver operating characteristic curve(AUC)and net reclassification improvement were used to evaluate model performance.Bootstrap based on 1 000 resamples was used for internal validation of the model.Results For the deep learning model,a total of 6 features were included,the 7th,57th,77th,82nd,97th and 108th features,with an AUC of 0.905(95%CI 0.823-0.957);for the radiomics model,a total of 6 features were included,1 neighborhood grey level difference matrix,4 grey level region size matrices and 1 grey level tour length matrix feature,with an AUC was 0.844(95%CI 0.751-0.913);for ADC values,the microsatellite instability group had smaller ADC values than the microsatellite stability group(t=-4.123,P<0.001),with an AUC of 0.810(95%CI 0.712-0.886).Compared with the radiomics model and ADC values,the deep learning model showed improved risk prediction,with net reclassification improvements of 0.856 and 0.486(P<0.01,P=0.024),respectively.In Bootstrap-based internal validation,the deep learning model also demonstrated higher performance than the radiomics model,with AUCs of 0.897(95%CI0.889-0.905)and 0.829(95%CI0.812-0.839),respectively.Conclusion A prediction model based on deep learning features of DWI images can provide a better assessment of microsatellite instability status in endometrial cancer patients than radiomics model and ADC values.
6.Application effect of accelerated rehabilitation surgical care in patients with early cancer of digestive tract undergoing endoscopic submucosal dissection under the diagnosis-intervention packet
Haiyan ZHANG ; Lingnan ZHU ; Wenni JIANG ; Yue WU ; Yongchao DUAN ; Songjia CHEN
Chinese Journal of Practical Nursing 2024;40(5):338-343
Objective:To evaluate the effect of accelerated rehabilitation surgery (ERAS) under diagnosis-intervention packet (DIP) in patients with early cancer of digestive tract undergoing endoscopic submucosal dissection (ESD).Methods:The 64 patients with early cancer of digestive tract treated with ESD in the Gastroenterology Department of the Second People′s Hospital of Jiaozuo were selected by randomized controlled trial and convenient sampling method. According to random number table method, they were divided into routine group and observation group, 32 patients in each group. All patients in the 2 groups paid their medical expenses by DIP method, the routine group was treated with traditional perioperative nursing, and the observation group was treated with ERAS perioperative management mode. The postoperative complication rate, length of hospital stay, DIP allocation ratio, and patient satisfaction with nursing were compared between the two groups.Results:There were 16 men and women in the routine group, 14 men and 18 women in the observation group.After intervention, the incidence of postoperative complications was 21.88% (7/32) in the routine group and 3.12% (1/32) in the observation group, and the difference between the two groups was statistically significant ( χ2=5.14, P<0.05). The length of stay was (10.93 ± 2.87) d in the routine group and (9.01 ± 1.53) d in the observation group, and the difference between the two groups was statistically significant ( t=4.13, P<0.05). The average hospitalization expenses per case was (20 108.23 ± 6 495.49) yuan in the routine group and (18 589.03 ± 4 439.46) yuan in the observation group, and the difference between the two groups was statistically significant ( t=20.57, P<0.05). The DIP allocation ratio of the observation group was 87.98% (303 419.26/344 872.99), and that of the routine group was 69.33% (244 864.99/353 187.65), and the difference between the two groups was statistically significant ( χ2=4.81, P<0.05). The satisfaction of the observation group was 96.88% (31/32) and the routine group was 78.13% (25/32), and the difference between the two groups was statistically significant ( χ2=5.14, P<0.05). Conclusions:The accelerated rehabilitation surgical nursing can effectively reduce the postoperative complications, the average length of stay, the average hospitalization expenses per case under DIP in patients with early cancer of digestive tract treated by ESD, improve the DIP allocation ratio of ESD diseases and the patient′s nursing satisfaction, which reflects the value of nursing work and can be applied to the nursing management of other surgical diseases.
7.Value of CT value in differentiating benign and malignant thyroid calcification
Yongchao SHEN ; Jiahao ZHENG ; Lexing ZHANG ; Shuhui LIANG
China Modern Doctor 2024;62(5):47-50
Objective To investigate the value of CT value in differential diagnosis of benign and malignant thyroid calcification.Methods The CT plain scan data of 48 cases of thyroid benign calcification and 26 cases of thyroid malignant calcification confirmed by pathology were analyzed retrospectively,and the CT values of 74 cases of thyroid calcification were measured.The best threshold and the maximum area under the receiver operator characteristic(ROC)curve for differentiating benign and malignant thyroid calcification were determined by plotting ROC curve,and the corresponding specificity,sensitivity,positive predictive value,negative predictive value,false positive rate,false negative rate,accuracy and Jordan index were calculated.Then the optimal threshold value was used as a parameter for differential diagnosis of benign and malignant thyroid calcification,and we adoptted χ2 analyze the statistical difference between benign and malignant thyroid calcification in CT gray value.Results The area under the ROC curve was 0.814,and the 95%confidence interval(CI)was 0.712-0.915.When the CT value was 869.5HU(for the convenience of 870HU),the specificity was 69.2%,the sensitivity was 81.3%,the positive predictive value was 64.3%,the negative predictive value was 82.6%,the false positive rate was 20.8%,and the false negative rate was 30.8%,the accuracy was 75.7%and the maximum of the Youden index was 0.505.When 870HU was taken as the differential diagnosis parameter of thyroid benign and malignant calcification(χ2=16.795,P<0.001).Conclusion When the CT value is 870HU,it has important value in differential diagnosis of benign and malignant thyroid calcification.
8.Comparison of accuracy and postoperative efficacy of robot and navigation technology assisted placement of pedicle screws
Houkun LI ; Liang YAN ; Lequn SHAN ; Yongchao DUAN ; Kai SUN ; Xuefang ZHANG ; Yadong ZHANG ; Dingjun HAO
Chinese Journal of Orthopaedics 2024;44(13):851-857
Objective:To compare the accuracy and efficacy of robot assisted and navigation assisted pedicle screw fixation.Methods:Retrospective analysis of 764 patients with lumbar spine disorders who underwent internal fixation treatment at the Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, from June 2017 to April 2023 were performed. They were divided into the Renaissance group (212 cases), the Tinavi group (301 cases), and the S8 navigation group (251 cases), according to the method of assisted placement of pedicle screws. The operation time, fluoroscopy time, X-ray radiation dose, intra-operative blood loss, accuracy of screw placement, screw revision rate, pain visual analogue scale (VAS), Oswestry disability index (ODI) and postoperative infection rate were compared among the three groups.Results:922 screws were placed in the Renaissance group, 1,260 screws in the Tinavi group, and 1,044 screws in the S8 navigation group. The accuracy of clinically acceptable pedicle screw placement was 92.08% (849/922), 99.68% (1,256/1,260), and 99.43% (1,038/1,044) in the three groups, respectively, with the Renaissance group being smaller than the Tinavi group and the S8 group (χ 2=90.334, P<0.001; χ 2=68.446, P<0.001), and the Tinavi group and the S8 group had no statistically significant difference (χ 2=0.380, P=0.537). The operation time of the three groups was 173.64±62.23 min, 177.11±60.85 min, 176.02±60.93 min, and the intraoperative blood loss was 118.16±58.26 ml, 121.84±55.91 ml, 123.62±59.84 ml, respectively, and the differences between the groups were not statistically significant ( P>0.05). The fluoroscopy time of the three groups was 8.73±2.92 s, 10.67±2.85 s, and 11.31±2.89 s, and the X-ray radiation doses were 18.83±7.41 μSv, 20.40±7.60 μSv, and 22.88±7.47 μSv, respectively, with statistically significant differences between the groups and the two comparisons ( P<0.05). All patients were given follow-up for 3-30 months. Three cases in the postoperative Renaissance group underwent screw revision for nerve root irritation due to screw penetration of the pedicle cortex, and none of the other two groups underwent screw revision. Postoperatively, one case in the Renaissance group and one case in the Tinavi group had superficial infections, which were cured after prolonged antibiotic use. At 3 months postoperatively, the VAS scores for leg pain in the Renaissance group, the Tinavi group, and the S8 navigation group were 3.52±1.14, 3.59±1.12, and 3.39±1.16, and the VAS scores for back pain were 3.54±1.14, 3.57±1.12, and 3.51±1.15, respectively; the ODI scores were 12.48%±4.53%, 12.01%±4.57%, and 12.28%±4.60%, and none of the differences between the groups were statistically significant ( P>0.05). Conclusion:The accuracy of screw placement by the Tinavi robot was comparable to that of the S8 navigation, and both were superior to that of the Renaissance robot; the fluoroscopy time and radiation dose of the Renaissance robot were smaller than those of the Tinavi robot, which was smaller than that of the S8 navigation. The early efficacy of robotics and navigation-assisted pedicle screw internal fixation for lumbar spine disorders is similar.
9.A neutrophil-biomimic platform for eradicating metastatic breast cancer stem-like cells by redox microenvironment modulation and hypoxia-triggered differentiation therapy.
Yongchao CHU ; Yifan LUO ; Boyu SU ; Chao LI ; Qin GUO ; Yiwen ZHANG ; Peixin LIU ; Hongyi CHEN ; Zhenhao ZHAO ; Zheng ZHOU ; Yu WANG ; Chen JIANG ; Tao SUN
Acta Pharmaceutica Sinica B 2023;13(1):298-314
Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.
10.ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy.
Zheng ZHOU ; Keying LI ; Yongchao CHU ; Chao LI ; Tongyu ZHANG ; Peixin LIU ; Tao SUN ; Chen JIANG
Acta Pharmaceutica Sinica B 2023;13(3):1246-1261
As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.

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