1.Exploration of the effects of Huayu qutan formula on atherosclerosis in ApoE-/- mice based on EETs-mediated pyroptosis
Na ZHAO ; Guoyuan SUI ; Jiawei MENG ; Meijun LYU ; Lianqun JIA
China Pharmacy 2024;35(12):1437-1442
OBJECTIVE To explore the effects and mechanism of Huayu qutan formula on atherosclerosis (AS) in ApoE-/- mice. METHODS Thirty ApoE-/- mice were randomly divided into model group, Huayu qutan formula group [20 g/(kg·d)], rosuvastatin group [1.55 mg/(kg·d)], with 10 mice in each group. Another 10 C57BL/6J mice were selected as normal control group. ApoE-/- mice were given high-lipid diet for 12 weeks to induce AS model. After modeling, each group was given relevant medicine or normal saline intragastrically, once a day, for 4 consecutive weeks. After the last administration, the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL- C), 5,6-epoxyeicosatrienoic acid (5, 6-EET), 8,9-EET, 11,12-EET, 14,15-EET, interleukin-1β (IL-1β) and IL-18 in serum were detected; mRNA expressions of inhibitor of nuclear factor κB (IκB), nuclear factor κB (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Caspase-1, IL-1β and IL-18 in the aortic tissue of mice were detected; protein expression levels of IκB, NF- κB, NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), Caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 in the aortic tissue of mice were detected. The morphological changes of the aortic tissue were observed. RESULTS Compared with model group, the serum levels of TC, TG, LDL-C, IL-1β and IL-18, the mRNA expressions of IκB, NF-κB, NLRP3, Caspase-1, IL-1β and IL-18 in aortic tissue, and the protein expressions of IκB, NF-κB, NLRP3, ASC, Caspase-1, GSDMD, IL-1β and IL-18 were all decreased significantly in Huayu qutan formula group and rosuvastatin group (P<0.05), while the serum levels of 5,6-EET, 8,9-EET, 11,12-EET and 14,15-EET were increased significantly (P<0.05). The aortic atherosclerotic plaques were alleviated significantly. CONCLUSIONS Huayu qutan formula can play role of anti-AS through EETs-mediated pyroptosis.
2.Research on the robustness of Ethos cervical cancer online fully automatic generation of adaptive plans
Bo YANG ; Zhiqun WANG ; Xiangyin MENG ; Yongguang LIANG ; Tingtian PANG ; Xingliu WANG ; Xiaoshen WANG ; Hongying LUO ; Jiawei CHEN ; Fuqiang CHEN ; Zongkai ZHOU ; Zhen ZHANG ; Jie QIU
Chinese Journal of Radiation Oncology 2024;33(2):145-151
Objective:To evaluate the robustness of fully automated adaptive planning for Ethos online adaptive radiotherapy (ART) based on the intelligent optimization engine (IOE).Methods:Clinical data of 11 stage ⅠB cervical cancer patients admitted to Peking Union Medical College Hospital between June 2021 and June 2022 were retrospectively analyzed. Original planning images and iterative cone-beam computed tomography (iCBCT) images of each radiotherapy treatment were acquired, and all patient data were imported into the Ethos simulator. IOE-based 9-field automatic plan generation was performed for 11 patients using Ethos, and the generated plans were sent to online adaptive radiotherapy simulation to obtain each online adaptive radiotherapy plan (273 fractions in total) and complete the simulated treatment. For comparison, manual plan design was performed based on the images and contoured structures used for online adaptive radiotherapy planning, and the manually plans created with evenly divided 9 fields. Dosimetric parameters, plan complexity parameters, and Mobius quality assurance (QA) pass rates were collected to compare and evaluate the robustness of the online adaptive radiotherapy plan in terms of organs at risk (OAR), target volume dosimetric parameters, and plan complexity by using paired t-test or rank sum test. Results:The online adaptive plan of cervical cancer had comparable planning target volume (PTV) coverage compared to the manual plan. For the clinical target volume (CTV) D 99%, online adaptive plan was significantly higher than the manual plan [(45.93±0.36) vs. (45.32±0.31) Gy, P<0.001]. For hot dose area, the maximum point dose (PTV D max) of adaptive plan was significantly higher than the manual plan [(49.89±1.25) vs. (48.48±0.77) Gy, P<0.001], but the PTV D 1% of adaptive plan was significantly lower than the manual plan [(47.22±0.29) vs. (47.59±0.48) Gy, P<0.001]. There was no statistical difference in the conformal index ( P=0.967). And there was significant difference in the homogeneity index, with same medians and less dispersion in adaptive plan ( P<0.001). For OAR dose, bladder D mean, rectal V 40 Gy, small intestine D mean of adaptive plan was slightly higher than that of the manual plan; the rectal D mean, small intestine D 2 cm3 of the adaptive plan was slightly lower than that of manual plan; dosimetric parameters of right and left femoral heads, spinal cord and bone marrow of the adaptive plan were better than those of manual plan. The adaptive plan had more monitor units (MU) than the manual plan, but the complexity of the adaptive plan was significantly lower than that of the manual plan (0.135±0.012 vs. 0.151±0.015, P<0.001). For Mobius γ pass rate (5%/3 mm), both adaptive and manual plans met clinical requirements. Conclusion:Ethos cervical cancer online adaptive plan, which is based on the IOE engine, demonstrates good robustness and ensures the quality of online adaptive plans generated for each treatment fraction.
3.Performance evaluation of Ethos intelligent optimization engine in automatic plan generation
Zhiqun WANG ; Bo YANG ; Xiangyin MENG ; Yongguang LIANG ; Tingtian PANG ; Xingliu WANG ; Xiaoshen WANG ; Hongying LUO ; Jiawei CHEN ; Fuqiang CHEN ; Zongkai ZHOU ; Zhen ZHANG ; Jie QIU
Chinese Journal of Radiation Oncology 2024;33(4):339-345
Objective:To evaluate the automatic optimization performance and clinical feasibility of the intelligent optimization engine (IOE) in the Ethos online adaptive radiotherapy platform.Methods:Clinical data of 11 patients with postoperative cervical cancer treated with Halcyon accelerator were retrospectively analyzed. Manual planning was performed for all patients using the 4 full arc volumetric modulated arc therapy (VMAT) (Manual-4Arc) in Eclipse, with a prescription dose of 45 Gy/25F. Patient images and structures were imported into the Ethos simulator, and appropriate clinical goals were added based on clinical requirements. The target coverage was normalized to 95%. Automatic plan generation was conducted using IOE, resulting in 7, 9, and 12 field intensity modulated radiotherapy (IMRT) plans (IMRT-7F、IMRT-9F、IMRT-12F), as well as 2 and 3 arc VMAT plans (VMAT-2Arc、VMAT-3Arc). Dosimetric index comparisons were made between the Manual-4Arc plans and the 5 groups of IOE-generated plans through one-way analysis of variance. Based on the analysis results, Turky post hoc multiple comparisons were performed to evaluate the automatic optimization performance of IOE.Results:In terms of the high dose area, the IMRT-12F plans showed the lowest D 1% for the planning target volume (PTV), and there were significant differences compared to the Manual-4Arc plans ( P=0.004). Regarding target coverage, all groups produced clinical target volume (CTV) plans that met the clinical requirements. Although the Ethos online adaptive plans were normalized during planning, the PTV coverage was slightly insufficient. For organs at risk (OAR) close to the target, such as the bladder, there were significant differences in V 30 Gy, V 40 Gy, and D mean among the 6 groups of plans. The dose ranking for the bladder was generally as follows: IMRT-12F
4.Advances in studies of Th17/Treg cells in prostatic disease
Jiawei LI ; Jialin MENG ; Chaozhao LIANG
Chinese Journal of Immunology 2024;40(9):1981-1985
N?ive CD4+T cells play a key role in the initiation and maintenance of immune response.In the effect of cytokines and costimulatory molecules,they differentiate into Th1,Th2,Treg and Th17.Increasing evidences indicated that Th17 and Treg cells produce a significant effect on immune stability,autoimmune disease and cancer.Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is the most common type of prostatitis,accounting for 90%~95%,which is closely correlated with the progression of be-nign prostatic hyperplasia and prostate cancer.Benign and malignant diseases of the prostate share much similarity in immune microen-vironment.Thus,this review summarizs the latest research progress on the mechanism of Th17/Treg cells in prostatic disease.
5.Biomechanical and Lateralized Lower Limb Kinematics of Males with Unilateral Functional Ankle Instability During Continuous Vertical Jump Landing
Zilong WANG ; Zhiqi ZHANG ; Lingyue MENG ; Mengya LU ; Jiawei BAO ; Qiuxia ZHANG ; Lingyu KONG
Journal of Medical Biomechanics 2024;39(5):931-938
Objective This study investigated lower limb biomechanics and lateral asymmetry during the continuous vertical jump(CVJ)landing process in individuals with unilateral functional ankle instability(FAI)and compared these characteristics with those of healthy individuals.Methods Fourteen males with unilateral FAI were selected as the experimental group,and 14 males without ankle joint injury were matched to the control group.Both the groups performed 30 CVJ landing tasks.Lower limb kinematic and kinetic characteristics during the 1st,15th,and 30th CVJ landings were synchronously collected using Vicon and Kistler equipment,and a 2×3 mixed analysis of variance was adopted for the data.Results In the execution of CVJ landing tasks,patients with FAI demonstrated no significant differences in the kinematic and kinetic characteristics of the affected limbs compared with healthy controls.However,a greater degree of lateral asymmetry was observed in the FAI group,particularly in the symmetry index(SI)of the vGRF peak.Despite the increase in the number of jump landings and consequent increase in fatigue levels,which led to adjustments in lower limb movement patterns,these adjustments did not appear to have a significant impact on the biomechanical characteristics and asymmetry of the affected limb in patients with FAI.Conclusions This study provides a theoretical basis for the prevention of recurrent ankle sprains in patients with FAI,as well as rehabilitation training prior to their return to sports.These findings underscore the importance of addressing lower limb asymmetry in the rehabilitation training of patients with FAI to reduce the risk of potential long-term injuries.When formulating rehabilitation plans for patients with FAI,particular attention should be paid to the correction of lower limb asymmetry with consideration of biomechanical adaptability under different states to achieve a more comprehensive rehabilitation outcome.
6.Analyzing the social health status of older adults in urban communities and its associated factors
Jiawei LI ; Xiaoqing MENG ; Chao GAO ; Baiyu ZHOU ; Shangxin LIU ; Jiahui YAN ; Qiyu PAN ; Yan CEN ; Juqiang CHEN ; Pulin YU
Chinese Journal of Geriatrics 2024;43(10):1321-1325
Objective:To examines the social health status and influencing factors affecting the elderly population in urban communities of Beijing, based on the "the Standard for Healthy Chinese Older Adults(2022)" .Methods:Using the stratified sampling method, a total of 159 elderly individuals aged 60 and above from the Lanyuan community in the Malianwa street jurisdiction of Haidian district, Beijing, were selected as research subjects.The average age of the participants was(70.7±7.9)years, comprising 74 males and 85 females.Household face-to-face interviews were conducted, utilizing self-compiled questionnaires to perform a comprehensive assessment and analysis of the social health status of the elderly.Results:In the study involving community-based elderly participants, 32.1%(51 cases)were classified as healthy.The analysis revealed statistically significant differences in the social health status among various age groups of the elderly( χ2=11.802, P=0.019), with a notable downward trend in social health status as age increases( χ2=9.626, P=0.002).Furthermore, the results of multivariate Logistic regression analysis indicated that educational level( OR=2.119, 95% CI: 1.044-4.031, P=0.038)and chronic disease status( OR=5.007, 95% CI: 1.083-23.140, P=0.039)are significant influencing factors on the social health status of older adults. Conclusions:The social health status of the elderly in urban communities in Beijing is generally low and deteriorates progressively with age.Both educational attainment and chronic disease prevalence significantly influence the social health of this demographic.For elderly individuals with lower educational levels and poor chronic disease management, it is essential to conduct social health assessments and implement targeted intervention strategies to enhance their overall social health.
7.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
Objective:
To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value.
Methods:
A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL).
Results:
A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%).
Conclusion
The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.
8.Genome-wide CRISPR screening identifies critical role of phosphatase and tensin homologous(PTEN)in sensitivity of acute myeloid leukemia to chemotherapy
LIN LIMING ; TAO JINGJING ; MENG YING ; GAN YICHAO ; HE XIN ; LI SHU ; ZHANG JIAWEI ; GAO FEIQIONG ; XIN DIJIA ; WANG LUYAO ; FAN YILI ; CHEN BOXIAO ; LU ZHIMIN ; XU YANG
Journal of Zhejiang University. Science. B 2024;25(8):700-710,中插5-中插6
Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.
9.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
Objective:
To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value.
Methods:
A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL).
Results:
A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%).
Conclusion
The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.
10.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
Objective:
To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value.
Methods:
A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL).
Results:
A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%).
Conclusion
The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.

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