1.Role of Ferroptosis in Bone Homeostasis and Traditional Chinese Medicine Intervention: A Review
Bo WEI ; Juan LI ; Yiwei JIANG ; Yuying ZHOU ; Chunhui LUO ; Zhongchao YU ; Pei LIU ; Yunxiang HAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):249-257
Osteoporosis (OP) is a systemic metabolic bone disease characterized by bone microstructure degeneration and bone mass loss, which has a high prevalence and disability rate. Effective prevention and treatment of OP is a major difficulty in the medical community. The nature of OP is that multiple pathological factors lead to the imbalance of human bone homeostasis maintained by osteoblasts and osteoclasts. Ferroptosis is a non-apoptotic cell death pathway, and its fundamental cause is cell damage caused by iron accumulation and lipid peroxidation. Studies have shown that ferroptosis is involved in and affects the occurrence and development of OP, which leads to OP by mediating the imbalance of bone homeostasis. Ferroptosis is an adjustable form of programmed cell death. The intervention of ferroptosis can regulate the damage degree and death process of osteoblasts and osteoclasts, which is beneficial to maintain bone homeostasis, slow down the development process of OP, improve the clinical symptoms of patients, reduce the risk of disability, and improve their quality of life. However, there are few studies on ferroptosis in OP. Traditional Chinese medicine (TCM) is a medical treasure with unique characteristics and great application value in China. It has been widely used in China and has a long history. It has the multi-target and multi-pathway advantages in the treatment of OP, with high safety, few toxic and side effects, and low treatment cost, and has a significant effect in clinical application. The intervention of TCM in ferroptosis to regulate bone homeostasis may be a new direction for the prevention and treatment of OP in the future. This article summarized the regulatory mechanisms related to ferroptosis, discussed the role of ferroptosis in bone homeostasis, and reviewed the current status and progress of active ingredients in TCM compounds and monomers in the regulation of OP through ferroptosis, so as to provide a theoretical basis for the participation of TCM in the prevention and treatment of OP in the future.
2.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
3.Protective effects of butylphthalein on nerve injury in rats with acute cerebral infarction
Li ZHOU ; Ling ZHANG ; Wei-Hai LI ; Peng LIANG ; Gui-Guo YAN ; Bai-Hai GUO
The Chinese Journal of Clinical Pharmacology 2024;40(10):1463-1467
Objective To investigate the protective effect of butyrolphthalein on nerve injury in rats with acute cerebral infarction(ACI)by regulating Toll-like receptor 4(TLR4)/nuclear transcription factor-κB(NF-κB)pathway.Methods SD rats were randomly divided into model group and experimental-L,-M,-H groups;ACI models were established in vivo except sham operation group.The experimental-L,-M,-H groups were given 20,40,80 mg·kg-1 butylphthalide,qd,for 7 days;the sham operation group and the model group were given the same amount of 0.9%NaCl,for 7 days.Neural function score,bilateral sticker removal time,balance beam crossing score,cerebral water content and cerebral infarction volume of rats in each group were measured.The expression of axonal growth inhibitory factor A(Nogo-A)and serum inflammatory factor in hippocampus were detected by enzyme-linked immunosorbent assay(ELISA).The expression of TLR4/NF-κB pathway related proteins was detected by Western blot.Results The neural function scores of sham operation group,model group,and experimental-L,-M,-H groups were 0,3.55±0.52,2.55±0.52,1.82±0.60,0.91±0.30,respectively;the Nogo-A in hippocampus were(0.93±0.23),(6.32±0.53),(5.10±0.55),(3.54±0.57),(1.58±0.30)ng·L-1,respectively;serum Nogo-A were(0.49±0.12),(5.09±0.82),(3.83±0.54),(2.23±0.64),(1.13±0.25)ng·L-1,respectively;TLR4 protein expression were 0.44±0.05,1.23±0.14,0.93±0.07,0.75±0.06,0.55±0.07,respectively;the expressions of p-p65 NF-κB protein were 0.32±0.05,0.82±0.06,0.68±0.08,0.57±0.07,0.44±0.05,respectively.There were statistically significant differences between sham operation group and model group(all P<0.05).There were significant differences in the above indexes between the model group and the experimental-L,-M,-H groups(P<0.05).Conclusion Butylphthalein can play a neuroprotective role in ACI rats by regulating TLR4/NF-κB pathway to improve nerve function and reduce inflammatory damage.
4.The Application of Lipid Nanoparticle-delivered mRNA in Disease Prevention and Treatment
Wei-Lun SUN ; Ti-Qiang ZHOU ; Hai-Yin YANG ; Lu-Wei LI ; Yu-Hua WENG ; Jin-Chao ZHANG ; Yuan-Yu HUANG ; Xing-Jie LIANG
Progress in Biochemistry and Biophysics 2024;51(10):2677-2693
In recent years, nucleic acid therapy, as a revolutionary therapeutic tool, has shown great potential in the treatment of genetic diseases, infectious diseases and cancer. Lipid nanoparticles (LNPs) are currently the most advanced mRNA delivery carriers, and their emergence is an important reason for the rapid approval and use of COVID-19 mRNA vaccines and the development of mRNA therapy. Currently, mRNA therapeutics using LNP as a carrier have been widely used in protein replacement therapy, vaccines and gene editing. Conventional LNP is composed of four components: ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, which can effectively load mRNA to improve the stability of mRNA and promote the delivery of mRNA to the cytoplasm. However, in the face of the complexity and diversity of clinical diseases, the structure, properties and functions of existing LNPs are too homogeneous, and the lack of targeted delivery capability may result in the risk of off-targeting. LNPs are flexibly designed and structurally stable vectors, and the adjustment of the types or proportions of their components can give them additional functions without affecting the ability of LNPs to deliver mRNAs. For example, by replacing and optimizing the basic components of LNP, introducing a fifth component, and modifying its surface, LNP can be made to have more precise targeting ability to reduce the side effects caused by treatment, or be given additional functions to synergistically enhance the efficacy of mRNA therapy to respond to the clinical demand for nucleic acid therapy. It is also possible to further improve the efficiency of LNP delivery of mRNA through machine learning-assisted LNP iteration. This review can provide a reference method for the rational design of engineered lipid nanoparticles delivering mRNA to treat diseases.
5.The value of high-throughput sequencing data reanalysis in identifying ERBB2 amplification in colorectal cancer patients
Min-Na SHEN ; Li ZHANG ; Xin-Ning CHEN ; Fei HUANG ; Chao-Gang BAI ; Li-Meng CHEN ; Hai-Xiang PENG ; Yan ZHOU ; Bei-Li WANG ; Bai-Shen PAN ; Wei GUO
Fudan University Journal of Medical Sciences 2024;51(2):166-171
Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.
6.Raman Spectroscopy Analysis of The Temporal Heterogeneity in Lung Cell Carcinogenesis Induced by Benzo(a)pyrene
Hai-Tao ZHOU ; Wei YAO ; Cao-Zhe CUI ; Xiao-Tong ZHOU ; Xi-Long LIANG ; Cheng-Bing QIN ; Lian-Tuan XIAO ; Zhi-Fang WU ; Si-Jin LI
Progress in Biochemistry and Biophysics 2024;51(6):1458-1470
ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.
7.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
8.Feasibility of monitoring the baseline of motor evoked potentials immediately after tracheal intubation with-out muscle relaxants in lumbar spine surgery
Wei ZHENG ; Na LI ; Lei LIU ; Songtao LIU ; Hai ZHOU ; Jie LIU ; Zhengquan HU ; Liwei WANG
The Journal of Practical Medicine 2024;40(16):2298-2304
Objective To investigate the feasibility of monitoring the baseline of motor evoked potentials immediately following tracheal intubation without the administration of muscle relaxants in lumbar spine surgery.Methods A prospective study was conducted at Xuzhou Central Hospital,involving a total of 156 patients who were scheduled for Transforaminal Lumbar Interbody Fusion.These patients were randomly divided into two groups:a control group consisting of 72 cases(33 males and 39 females)and an observation group consisting of 75 cases(37 males and 38 females).The control group underwent monitoring of motor evoked potentials(TceMEP)baseline after spinal exposure during the operation,while the observation group had immediate monitoring of TceMEP baseline after tracheal intubation without muscle relaxants.Hemodynamic changes,intubation satisfaction,and operation time during tracheal intubation were compared between the two patient groups.Additionally,the baseline success rate,stimulation threshold,sensitivity,and specificity of TceMEP were compared between the two groups.Results There were no significant differences in hemodynamic changes and intubation satisfaction between the two patient groups during tracheal intubation(P>0.05).The control group had an intubation time of(6.52±1.22)min,while the observation group had a significantly longer intubation time of(9.44±0.84)min(P<0.05).The baseline success rate of TceMEP in the observation group was 100%,with an average stimulation threshold of(225.00±22.13).In contrast,the control group had a baseline success rate of 84.72%and an average stimulation threshold of(342.01±31.07)V for TceMEP monitoring prior to nailing procedures.The success rate of monitoring TceMEP after nailing in the control group was 93.06%,whereas it reached 100%in the observation group,demonstrating a statistically significant difference between the two groups(P<0.05).There were no statistically significant differences in sensitiv-ity and specificity between the two groups for TceMEP monitoring results(P>0.05).Conclusions The success rate of monitoring TceMEP baseline immediately after tracheal intubation without muscle relaxation is higher,with a smaller stimulation threshold.There were no differences in sensitivity and specificity compared to the baseline moni-toring of TceMEP after spinal exposure during the operation.
9.Analysis of Traditional Chinese Medicine Constitution Types of Nonspecific Low Back Pain and the Influencing Factors for the Thickness of Ligamentum Flavum
Zhou-Hang ZHENG ; Yu ZHANG ; Long CHEN ; Dong-Chun YOU ; Wei-Feng GUO ; Xing-Ming LIU ; Huan CHEN ; Rong-Hai WU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(5):1103-1108
Objective To investigate the distribution of the traditional Chinese medicine(TCM)constitution types in the patients with nonspecific low back pain(NLBP)and to explore the correlation of the thickness of ligamentum flavum with the age,body mass index(BMI),gender,the presence of diabetes mellitus,and the grading of hypertension.Methods Sixty patients with NLBP admitted to Guangdong Second Traditional Chinese Medicine Hospital from January 2023 to June 2023 were selected as the study subjects.The TCM constitution types of the patients were identified,the thickness of the ligamentum flavum at lumbar vertebrae 4/5 segment(L4/5)disc level was measured by computerized tomography(CT)scanning,and the patients'age,genders,TCM constitution types,BMI,the presence or absence of diabetes mellitus,and hypertension grading were recorded.Correlation analysis and linear regression analysis were used for the exploration of the relevant influencing factors for the thickness of the ligamentum flavum of patients with NLBP.Results(1)The average thickness of ligamentum flavum in the 60 patients with NLBP was(2.60±0.72)mm.(2)The TCM constitutions of NLBP patients were classified into four types,of which blood stasis constitution was the most common,accounting for 21 cases(35.0%),followed by 19 cases(31.7%)of damp-heat constitution,12 cases(20.0%)of phlegm-damp constitution,and 8 cases(13.3%)of qi deficiency constitution.(3)The results of correlation analysis showed that BMI,gender,TCM constitution type and the presence or absence of diabetes mellitus had no influence on the thickness of ligamentum flavum in NLBP patients(P>0.05),while the age and hypertension grading had an influence on the thickness of ligamentum flavum(P<0.01).(4)The results of linear regression analysis showed that the age had an influence on the thickness of the ligamentum flavum(b = 0.034,t = 6.282,P<0.01),while the influence of the hypertension grading had no influence on the thickness of the ligamentum flavum(P>0.05).Conclusion The TCM constitution type of NLBP patients is predominated by blood stasis constitution,the thickness of ligamentum flavum is significantly affected by the age,and hypertension may be a potential factor affecting the thickness of ligamentum flavum.
10.Clinical Efficacy of"Triple-posture Positive Bone-setting"Chiropractic Manipulation Combined with Tongluo Huoxue Formula for the Treatment of Lumbar Spinal Stenosis of Qi Deficiency and Blood Stasis Type
Long CHEN ; Zhou-Hang ZHENG ; Yu ZHANG ; Meng-Shu WANG ; Zhao-Yuan ZHANG ; Wei-Feng GUO ; Huan CHEN ; Xing-Ming LIU ; Dong-Chun YOU ; Rong-Hai WU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1450-1456
Objective To observe the clinical efficacy of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula for the treatment of lumbar spinal stenosis(LSS)with qi deficiency and blood stasis syndrome.Methods Sixty patients with LSS of qi deficiency and blood stasis type were randomly divided into trial group and control group,with 30 cases in each group.The trial group was treated with"triple-posture positive bone-setting"chiropractic manipulation(a chiropractic manipulation performed under the positive cooperation of the patients at three postures)combined with Tongluo Huoxue Formula,while the control group was treated with"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medicine.The course of treatment for the two groups covered 4 weeks.Before and after treatment,the patients of the two groups were observed in the changes of pain visual analogue scale(VAS)score,Japanese Orthopedic Association(JOA)score of lumbar function,Oswestry Disability Index(ODI)score,straight-leg raising test results and serum interleukin 6(IL-6)and C-reactive protein(CRP)levels.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the trial group was 96.67%(29/30)and that of the control group was 63.33%(19/30).The intergroup comparison(tested by Fisher's exact test)showed that the clinical efficacy of the trial group was significantly superior to that of the control group(P<0.05).(2)After treatment,the lumbar function indicators of pain VAS scores and ODI scores in the trial group were significantly lower(P<0.05),and the JOA scores were significantly higher than those before treatment(P<0.05),while in the control group,only the ODI scores were significantly lower than those before treatment(P<0.05).The intergroup comparison showed that the decrease of VAS and ODI scores and the increase of JOA scores in the trial group were significantly superior to those in the control group(P<0.05 or P<0.01).(3)After treatment,the Laseque s sign of the trial group was significantly improved compared with that before treatment(P<0.05),while no significant improvement was presented in the control group(P>0.05).The intergroup comparison showed that the improvement of Laseque's sign in the trial group was significantly superior to that in the control group(P<0.01).(4)After treatment,the levels of serum inflammatory factors of IL-6 and CRP in the two groups were lower than those before treatment(P<0.05),and the decrease of serum IL-6 level in the trial group was significantly superior to that in the control group(P<0.05),but CRP level in the two groups after treatment did not differ from that before treatment,no statistically significant difference was shown between the two groups after treatment,either(P>0.05).(5)The incidence of adverse reactions in the trial group was 6.67%(2/30)and that in the control group was 13.33%(4/30),and the intergroup comparison(by Fisher's exact test)showed that there was no significant difference between the two groups(P>0.05).Conclusion The therapeutic effect of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula exert certain effect for the treatment of LSS patients with qi deficiency and blood stasis syndrome,and it has more obvious advantages in improving the lumbar function,promoting the rehabilitation of the patients,and lowering the level of serum inflammatory factors than"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medication.

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