1.Mechanism of Ferroptosis in Cerebral Ischemia-reperfusion and Interventional Mechanism of Huoxue Huayu Jiedu Prescription Based on "Blood Stasis and Toxin" Pathogenesis
Jiayue HAN ; Danyi PAN ; Jiaxuan XIAO ; Yuchen LIU ; Jiyong LIU ; Yidi ZENG ; Jinxia LI ; Caixing ZHENG ; Hua LI ; Wanghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):51-60
ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury, as well as the protective role of Huoxue Huayu Jiedu prescription (HXHYJDF) against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups: sham group, model group, deferoxamine (DFO) group (100 mg·kg-1), low-dose HXHYJDF group (4.52 g·kg-1), medium-dose HXHYJDF group (9.04 g·kg-1), and high-dose HXHYJDF group (18.07 g·kg-1), with ten rats in each group. Except for the sham group, the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1st, 3rd, 5th, and 7th days post-reperfusion using the modified neurological severity scores (m-NSS). Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin (HE) staining and transmission electron microscopy. The contents of malondialdehyde (MDA), glutathione (GSH), divalent iron ions (Fe2+), and reactive oxygen species (ROS) in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry and Western blot (WB) were used to detect the expression of iron death marker proteins glutathione peroxidase 4 (GPX4), ferroportin-1 (FPN1), transferrin receptor protein 1 (TfR1), and ferritin mitochondrial (FtMt) in brain tissue. ResultsCompared with the sham group, the mNSS score of the model group was significantly increased (P<0.01). HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced, and the intercellular space was widened. The nucleus was fragmented, and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded, and the mitochondrial cristae decreased. The matrix was lost and vacuolated, and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS increased significantly (P<0.01). The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased (P<0.01), and the expression of FtMt and TfR1 proteins was significantly increased (P<0.01). Compared with those of the model group, the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3rd and 5th days, respectively (P<0.05, P<0.01). The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS decreased significantly (P<0.05, P<0.01). The content of GSH in the low-dose HXHYJDF group increased significantly (P<0.01), and the contents of MDA and ROS decreased significantly (P<0.01). The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly (P<0.01), and the expression of FtMt and TfR1 decreased significantly (P<0.01). The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly (P<0.05), and the expression of TfR1 decreased significantly (P<0.01). WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose, medium-dose, and low-dose HXHYJDF groups were significantly up-regulated (P<0.01), and the expression levels of FtMt and TfR1 proteins were significantly down-regulated (P<0.01). ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury, improve the pathological morphology of the infarcted brain tissue, and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury, with increased levels of MDA, Fe2+, ROS, and TfR1 and decreased levels of FtMt, FPN1, GPX4, and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins, promoting the discharge of free iron, reducing brain iron deposition, alleviating oxidative stress, and inhibiting ferroptosis.
2.Application and comparison of three occupational health risk assessment methods in an automobile manufacturing industry
Qiang ZENG ; Tao LIU ; Xiaoxiao GUO ; Cheng HAN ; Jing LIU ; Hui TAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(4):271-276
Objective:Three occupational health risk assessment methods were used to assess the occupational health risk of noise exposed posts in an automobile manufacturing enterprise. According to the results, the selection of risk assessment methods and risk management of such occupational noise enterprises were provided.Methods:Form April to November 2021, The occupational health field survey was carried out in an automobile manufacturing industry in Tianjin. The occupational health MES risk assessment method, occupational health risk index risk assessment method and Australian occupational hazard risk assessment method were used to evaluate the occupational health risk of noise-exposed posts in this enterprise, and the evaluation results of different methods were analyzed and compared.Results:The average value of LAeq, 8 h in the four workshops of automobile manufacturing industry was 82.95 dB (A) , and the noise detection exceeding rate was 22.41% (26/116) . The LAeq, 8h and exceeding rate noise of welding workshop were higher than those of other workshops (χ 2=23.56, 32.94, P<0.01) . The three occupational health risk assessment methods have the same risk assessment results for the four major workshops. The assembly and painting workshops are level 4 risk (possible risk) , and the stamping and welding workshops are level 3 risk (significant risk) . Conclusion:Occupational noise has certain potential hazards to workers in automobile manufacturing enterprises. Therefore, in the future work, corresponding organizational management measures should be taken to improve the working environment and reduce the actual exposure level of workers in order to protect the health of occupational workers.
3.Clinical Research Progress in Acupuncture for the Treatment of Tourette Syndrome
Mingyuan HAN ; Xiaolin LYU ; Zhongren SUN ; Shaopeng LIU ; Xinyuan CAO ; Yuxin WANG ; Ying FAN ; Xiangxin ZENG ; Hongna YIN
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(2):181-185
Tourette syndrome(TS)is a chronic neurodevelopmental disorder.Acupuncture can effectively improve the clinical symptoms of TS patients.This article systematically summarized the clinical research status of acupuncture for the treatment of TS in recent years from the aspects of characteristic acupuncture methods,characteristic needles and comprehensive therapies,and put forward suggestions and prospects for systematically elaborating the peripheral-central mechanism of acupuncture for TS around the intestinal immunity and brain network mechanism in the future,so as to provide reference for optimizing clinical research and treatment.
4.Effect Evaluation of Responsible Segmental Decompression Combined with Orthopedic Fixation of Short-Segment Fusion Surgery for Treating Degenerative Lumbar Scoliosis
Hui ZENG ; Gangqiang WU ; Can HUANG ; Xiaojun HAN ; Bo LIU ; Cheng CHEN ; Long MA ; Bowen ZHANG ; Honghai WANG
Journal of Medical Biomechanics 2024;39(5):896-902
Objective To investigate the therapeutic effect of segmental decompression combined with corrective short-segment fusion surgery for the treatment of degenerative lumbar scoliosis.Methods In total,124 patients with degenerative lumbar scoliosis were selected and divided into short-and long-segment fusion groups using the random number table method,with 62 patients in each group.Posterior short-segment decompression,fixation,and fusion were performed in the short-segment fusion group;the fusion segment was the adjacent lumbar vertebra.Posterior long-segment decompression,fixation,and fusion were performed in the long-segment fusion group;the fusion segments included multiple adjacent lumbar vertebrae.At the 6th month after surgery,the coronal Cobb angle of lumbar convexity,sagittal Cobb angle of lumbar lordosis,intervertebral foramen height,intervertebral space height,intervertebral foramen area,spinal canal area,spinal canal diameter,Japanese Orthopedic Association(JOA)score,Oswestry Disability Index(ODI),degree of pain in the lower back and lower limbs,and postoperative complications were compared between the groups.Results The Cobb angle of the coronal lumbar scoliosis in the short-and long-segment fusion groups was significantly higher than that before surgery(P<0.05).At the 6th month after surgery,the intervertebral foramen height,intervertebral space height,intervertebral foramen area,spinal canal area,and spinal canal diameter in both groups increased,and those in the short-segment fusion group were higher than those in the long-segment fusion group(P<0.05);at the 6th month after the operation,the JOA scores of the short-segment and long-segment fusion groups were higher than those before surgery,and the JOA score of the short-segment fusion group was higher than that of the long-segment fusion group(P<0.05).The ODI score was lower than that before surgery in the short-and long-segment fusion groups,and the ODI score in the short-segment fusion group was lower than that in the long-segment fusion group(P<0.05).At the 6th month after surgery,the pain scores of the lower back and lower limbs in the short-and long-segment fusion groups were significantly higher than those before surgery(P<0.05).There were two cases of dural tears during decompression caused by lamina dura adhesion in the long-segment fusion group,and no serious complications were observed in the short-segment fusion group.Conclusions Both short-and long-segment decompression fixation fusion using a posterior approach can achieve good therapeutic effects for treating degenerative lumbar scoliosis.However,compared to the long-segment fusion group,the short-segment fusion group undergoing short-segment decompression fixation fusion through a posterior approach had a shorter surgical period,lower intraoperative blood loss,better recovery of lumbar function,and a lower risk of postoperative complications.
5.Research on medical service satisfaction evaluation based on ECSI model——taking the S city public hospital as an example
Limin CHEN ; Chunling LIU ; Xintong XIE ; Lizhu ZENG ; Jieyi HAN ; Chengxiao ZHU ; Zhaoyi XIE ; Weizhen WU
Modern Hospital 2024;24(6):831-835,839
Objective To deeply analyze the problems of public hospitals in medical service satisfaction,construct a more applicable and explanatory service satisfaction evaluation model,and provide reference for the improvement path of patients'medical service satisfaction.Methods Based on the ESCI model,this paper puts forward a research hypothesis,compiles the"Medical Service Satisfaction Evaluation Scale of Public Hospitals in S City",selects S public hospitals as the research object,and evaluates medical service satisfaction from the perspective of patients.Results At present,the main problems affecting the improvement of patients'satisfaction with medical service management in public hospitals in S city are as follows:it is urgent to improve the diagnosis and treatment technology in terms of hardware quality and optimize the environmental hygiene of public hos-pitals,and it is an urgent task to shorten the waiting time for medical treatment in software quality.The score of medical service satisfaction evaluation of S public hospitals was 3.76,and the satisfaction of patients in S public hospitals with their medical serv-ices was at a moderately low level.Conclusion In view of the above problems,it is recommended to strengthen the construction of key specialties,strengthen the construction of talent team,optimize the medical process,open digital linkage services,and strengthen service management,so as to promote the improvement of patients'satisfaction with medical services.
6.Traditional Chinese Medicine Intervention in Sepsis Based on TLR4 Signaling Pathway: A Review
Jing YAN ; Sheng XIE ; Laian GE ; Guangyao WANG ; Zhu LIU ; Bingjie HAN ; Yaoxuan ZENG ; Jinchan PENG ; Jincheng QIAN ; Liqun LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):282-291
Sepsis is one of the common severe diseases caused by the dysregulated host response to infection, which seriously threatens the life and health of human beings all over the world. The incidence and mortality of the disease are extremely high, and it has always been an urgent problem to be solved in the field of acute and critical diseases. At present, anti-infection, fluid resuscitation, mechanical ventilation and other programs are most used in clinic to treat sepsis, but their poor prognosis and high cost and other issues remain to be resolved. Therefore, it is necessary to explore a new, efficient, safe and inexpensive drug and treatment model at this stage. The treatment of traditional Chinese medicine (TCM) is based on syndrome differentiation and holistic concept. It can effectively regulate the progression of sepsis, maintain the homeostasis of the body, and has fewer adverse reactions. It has achieved good clinical results. In recent years, a large number of studies have shown that TCM can reduce the inflammatory response by regulating the Toll-like receptor 4(TLR4) signaling pathway, thereby reducing the severity and mortality of sepsis patients. However, there is still a lack of systematic exposition of TCM regulating TLR4 signaling pathway in the treatment of sepsis. Therefore, this article summarizes the relationship between TLR4 signaling pathway and sepsis and the mechanism of TCM in the disease by searching and consulting relevant literature in recent years. It is found that some Chinese medicine monomers and active ingredients, Chinese medicine compounds and Chinese medicine preparations can effectively reduce systemic inflammatory response, repair organ damage and improve the prognosis of sepsis by inhibiting the activation of TLR4 signaling pathway. However, due to various limitations, some studies have directly focused on the differential expression and function of TLR4, ignoring the downstream molecular expression and phenotypic effects of TLR4. The alternative mechanism, relationship and specific molecular mechanism of the pathway are still unclear. There are problems such as unclear pharmacokinetics and unclear mechanism in the pro- and anti-inflammatory balance, which need to be further studied and explored in order to provide new ideas for the potential treatment and drug development for sepsis.
7.Full-field Anterior Chamber Angle Measurement Based on Optical Reflection Tomography
Bi-Wang LIU ; Jun-Ping ZHONG ; Hai-Na LIN ; Ya-Guang ZENG ; You-Ping YU ; Hong-Yi LI ; Ding-An HAN ; Jin-Ying CHEN
Progress in Biochemistry and Biophysics 2024;51(9):2240-2248
ObjectiveAngle-closure glaucoma (ACG) is one of the major eye-blinding diseases. To diagnose ACG, it is crucial to examine the anterior chamber angle. Current diagnostic tools include slit lamp gonioscopy, water gonioscopy, ultrasound biomicroscopy (UBM), and anterior segment optical coherence tomography (AS-OCT). Slit lamp and water gonioscopy allow convenient observation of the anterior chamber angle, but pose risks of invasive operation and eye infections. UBM can accurately measure the structure of the anterior chamber angle. However, it is complex to operate and unsuitable for patients, who have undergone trauma or ocular surgery. Although AS-OCT provides detailed images, it is costly. The aim of this study is to explore a non-invasive, non-destructive optical reflection tomography (ORT) technique. This technique can achieve low-cost three-dimensional imaging and full-field anterior chamber angle measurement of the porcine eye. MethodsThe experiment involved assembling an optical reflection tomography system, which included a complementary metal oxide semiconductor (CMOS) camera, a telecentric system, a stepper motor, and a white light source, achieving a spatial resolution of approximately 8.5 μm. The process required positioning the porcine eye at the center of the field of the imaging system and rotating it around its central axis using a stepper motor. Reflection projection images were captured at each angle with an exposure time of 1.0 ms and an interval of 2°. The collected reflection-projection data were processed using a filtered reflection tomography algorithm, generating a series of two-dimensional slice data. These slices essentially represented cross-sectional views of the three-dimensional structural image, and were reconstructed into a complete three-dimensional structural image. Based on the reconstructed three-dimensional structural image of the porcine eye, the anterior chamber angles at different positions were measured, and a distribution map of these angles was drawn. Simultaneously, the ORT measurements were compared with the standard results obtained from optical coherence tomography (OCT) to assess the accuracy of ORT measurements. ResultsIn this study, we successfully obtained the reflection projection data of a porcine eye using ORT technology, reconstructed its three-dimensional structural image, and measured the anterior chamber angle, generating the corresponding distribution map. To better distinguish the different structural parts of porcine eye, the three-dimensional structural image was marked with blue, green, and yellow dashed lines from the outer to the inner layers. The area between the blue and green dashed lines corresponded to the sclera. The area between the green and yellow dashed lines corresponded to the iris. The area inside the yellow dashed line corresponded to the pupil. The three-dimensional structural image clearly revealed the key anatomical features of the porcine eye. It was able to measure the anterior chamber angle at different positions. Additionally, the anterior chamber angle measurements of the porcine eye using ORT were compared with the measurements obtained using a TEL320C1 type OCT system, showing an average deviation of 0.51° and a mean square error
8.Research progress in regulation and mechanism of transcription factors on tanshinones
Yan-hong BAI ; Lin-lin XIN ; Ting ZENG ; Feng-xia HAN ; Yong-qing ZHANG ; Gao-bin PU ; Xue CHEN ; Qian LIU
Acta Pharmaceutica Sinica 2024;59(5):1218-1228
italic>Salvia miltiorrhiza, a commonly used traditional Chinese medicine, has been widely recognized for its blood-activating and stasis-removing properties in the clinical treatment of cardiovascular and cerebrovascular diseases. The synthesis and regulatory mechanism of tanshinones, the key active constituents of
9.Advances in crystal nucleation for amorphous drugs
Jie ZHANG ; Kang LI ; Zi-qing YANG ; Zi-han DING ; Sai-jun XIAO ; Zhi-ming YUE ; Li-mei CAI ; Jia-wen LI ; Ding KUANG ; Min-zhuo LIU ; Zhi-hong ZENG
Acta Pharmaceutica Sinica 2024;59(7):1962-1969
Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.
10.Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study
Xiaoshuai ZHANG ; Bingcheng LIU ; Xin DU ; Yanli ZHANG ; Na XU ; Xiaoli LIU ; Weiming LI ; Hai LIN ; Rong LIANG ; Chunyan CHEN ; Jian HUANG ; Yunfan YANG ; Huanling ZHU ; Ling PAN ; Xiaodong WANG ; Guohui LI ; Zhuogang LIU ; Yanqing ZHANG ; Zhenfang LIU ; Jianda HU ; Chunshui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yanqiu HAN ; Li'e LIN ; Zhenyu ZHAO ; Chuanqing TU ; Caifeng ZHENG ; Yanliang BAI ; Zeping ZHOU ; Suning CHEN ; Huiying QIU ; Lijie YANG ; Xiuli SUN ; Hui SUN ; Li ZHOU ; Zelin LIU ; Danyu WANG ; Jianxin GUO ; Liping PANG ; Qingshu ZENG ; Xiaohui SUO ; Weihua ZHANG ; Yuanjun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2024;45(3):215-224
Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

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