1.Mechanism of Buyang Huanwutang in Inhibiting Ferroptosis and Enhancing Neurological Function Recovery After Spinal Cord Injury via GPX4-ACSL4 Axis
Luchun XU ; Guozheng JIANG ; Yukun MA ; Jiawei SONG ; Yushan GAO ; Guanlong WANG ; Jiaojiao FAN ; Yongdong YANG ; Xing YU ; Xiangsheng TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):20-30
ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 (GPX4)-acyl-CoA synthetase long-chain family member 4 (ACSL4) axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury (SCI). MethodsNinety rats were randomly divided into five groups: sham operation group, model group, low-dose Buyang Huanwutang group (12.5 g·kg-1), high-dose Buyang Huanwutang group (25 g·kg-1), and Buyang Huanwutang + inhibitor group (25 g·kg-1 + 5 g·kg-1 RSL3). The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan (BBB) scale. Hematoxylin-eosin (HE), Nissl, and Luxol fast blue (LFB) staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein (MBP), GPX4, and ACSL4. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay (ELISA) was performed to measure the levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD). Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group, the model group exhibited significantly reduced BBB scores (P<0.01), severe pathological damage in spinal cord tissue, and marked mitochondrial ultrastructural disruption. In addition, the model group showed a decrease in the number of NeuN-positive cells (P<0.01), reduced fluorescence intensity of MBP and GPX4 (P<0.01), lower levels of GSH and SOD (P<0.01), and downregulated mRNA expression of GPX4 (P<0.01). Moreover, compared to the sham operation group, the model group had elevated levels of ROS, MDA, and tissue iron content (P<0.01), along with increased fluorescence intensity and mRNA expression of ACSL4 (P<0.01). Compared with the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group showed significantly improved BBB scores (P<0.05, P<0.01) and exhibited less severe spinal cord tissue damage, reduced edema and inflammatory cell infiltration, increased neuronal survival, and more intact myelin structures. Additionally, mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP (P<0.05, P<0.01). Furthermore, Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 (P<0.01) and decreased the fluorescence intensity and mRNA expression of ACSL4 (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. Finally, the Buyang Huanwutang group significantly decreased ROS, MDA, and tissue iron content (P<0.01) and significantly increased GSH and SOD levels (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis, reduces secondary neuronal and myelin injury and oxidative stress, and ultimately promotes the recovery of neurological function.
2.Process Optimization and Health Risk Assessment of Calcined Haematitum Based on QbD Concept
Yue YANG ; Jingwei ZHOU ; Jialiang ZOU ; Guorong MEI ; Yifan SHI ; Lei ZHONG ; Jiaojiao WANG ; Xuelian GAN ; Dewen ZENG ; Xin CHEN ; Lin CHEN ; Hongping CHEN ; Shilin CHEN ; Yuan HU ; Youping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):187-196
ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design(QbD) and to assess its health risk. MethodsTaking whole iron content, Fe2+ dissolution content and looseness as critical quality attributes(CQAs), and calcination temperature, calcination time, spreading thickness and particle size as critical process parameters(CPPs) determined by the failure mode and effect analysis(FMEA), the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation(AHP-CRITIC) hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry, and the health risk assessment was carried out by daily exposure(EXP), target hazard quotient(THQ) and lifetime cancer risk(LCR), and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃, calcination time of 1 h, particle size of 0.2-0.5 cm, spreading thickness of 1 cm, and vinegar quenching for 1 time[Haematitum-vinegar(10:3)]. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1, while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10-6-1×10-4, and the LCR of the rest was<1×10-6, and the LCRs of calcined Haematitum were all<1×10-6, indicating that the carcinogenic risk of calcined Haematitum was low, but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu, As, Cd, Pb and Hg were formulated as 1 014, 25, 17, 27, 7 mg·kg-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible, and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu, As, Cd, Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.
3.Process Optimization and Health Risk Assessment of Calcined Haematitum Based on QbD Concept
Yue YANG ; Jingwei ZHOU ; Jialiang ZOU ; Guorong MEI ; Yifan SHI ; Lei ZHONG ; Jiaojiao WANG ; Xuelian GAN ; Dewen ZENG ; Xin CHEN ; Lin CHEN ; Hongping CHEN ; Shilin CHEN ; Yuan HU ; Youping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):187-196
ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design(QbD) and to assess its health risk. MethodsTaking whole iron content, Fe2+ dissolution content and looseness as critical quality attributes(CQAs), and calcination temperature, calcination time, spreading thickness and particle size as critical process parameters(CPPs) determined by the failure mode and effect analysis(FMEA), the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation(AHP-CRITIC) hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry, and the health risk assessment was carried out by daily exposure(EXP), target hazard quotient(THQ) and lifetime cancer risk(LCR), and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃, calcination time of 1 h, particle size of 0.2-0.5 cm, spreading thickness of 1 cm, and vinegar quenching for 1 time[Haematitum-vinegar(10:3)]. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1, while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10-6-1×10-4, and the LCR of the rest was<1×10-6, and the LCRs of calcined Haematitum were all<1×10-6, indicating that the carcinogenic risk of calcined Haematitum was low, but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu, As, Cd, Pb and Hg were formulated as 1 014, 25, 17, 27, 7 mg·kg-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible, and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu, As, Cd, Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.
4.Research progress on active components of traditional Chinese medicine inhibiting esophageal carcinoma by targeting mitochondrial apoptosis pathway
Junke XIAO ; Xiaoyan MU ; Jiaojiao GUO ; Shangzhi YANG ; Xuewei CAO ; Zhizhong GUO
China Pharmacy 2025;36(10):1283-1288
Esophageal carcinoma is a malignant disease with a high incidence rate and poor prognosis. The mitochondrial apoptosis pathway plays a pivotal role in the regulation of cell death and has become a focal point in current cancer therapeutics research. Various active components from traditional Chinese medicine (TCM) can target the mitochondrial apoptosis pathway to inhibit esophageal carcinoma, presenting as potential therapeutic agents for this disease. This paper summarizes relevant research on the inhibition of esophageal carcinoma by active components in TCM via targeting the mitochondrial apoptosis pathway. It has been found that flavonoids (casticin, icariin, luteolin, kaempferol, hesperetin, deguelin, etc.), terpenoids (oridonin, Jaridonin, artesunate, ethyl acetate fraction of pleurotus ferulatus triterpenoid, etc.), alkaloids (matrine, swainsonine, etc.), polyphenols (curcumin, epigallocatechin-3-gallate, corilagin, etc.), steroids (α-hederin, polyphyllin Ⅵ, etc.), phenols (optimized scorpion venom peptide CT-K3K7, gecko active polypeptide, etc.), volatile oils (cinnamaldehyde, α -asarone, etc.) and other active components from TCM can target the intrinsic mitochondrial apoptosis pathway, induce apoptosis in esophageal carcinoma cells, and inhibit their proliferation, invasion and migration by regulating oxidative stress, blocking the cell cycle, regulating signaling pathways such as PI3K/Akt and MAPK.
5.Triglyceride-glucose index and homocysteine in association with the risk of stroke in middle-aged and elderly diabetic populations
Xiaolin LIU ; Jin ZHANG ; Zhitao LI ; Xiaonan WANG ; Juzhong KE ; Kang WU ; Hua QIU ; Qingping LIU ; Jiahui SONG ; Jiaojiao GAO ; Yang LIU ; Qian XU ; Yi ZHOU ; Xiaonan RUAN
Shanghai Journal of Preventive Medicine 2025;37(6):515-520
ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹
6.Evaluation of the effect of meteorological risk forecasting service intervention on acute onset and medical expenses of patients with COPD in Pudong New Area of Shanghai
Zhitao LI ; Xiaonan WANG ; Xiaolin LIU ; Juzhong KE ; Yang LIU ; Chaowei FU ; Qingping LIU ; Jiaojiao GAO ; Jiahui SONG ; Kang WU ; Li PENG ; Xiaofang YE ; Xiaonan RUAN
Shanghai Journal of Preventive Medicine 2024;36(2):197-202
ObjectiveTo evaluate the intervention effect of meteorological risk forecasting service on acute onset and medical expenses of chronic obstructive pulmonary disease(COPD) patients, and to provide scientific basis for the establishment of health management model for chronic obstructive pulmonary disease(COPD) patients. MethodsStudy subjects were recruited from chronic obstructive pulmonary patients aged ≥40 in Pudong New Area. Propensity score matching method was used to determine the intervention group and the control group. The control group received regular health education and follow-up management, and the intervention group was provided with meteorological and environmental risk forecasting services through WeChat, mobile phone short message service(SMS)and telephone. Finally, a total of2 589 subjects were included in the analysis, including 1 300 in the intervention group and 1 289 in the control group. General demographic data, past medical history and family history of COPD, COPD related knowledge and practice survey, COPD related symptom assessment, acute onset, health service utilization and medical expenses before and after intervention were collected through questionnaire survey. The differences of acute attack, health service utilization and related medical expenses between the two groups before and after intervention were compared to evaluate the intervention effect. ResultsIn terms of acute attacks, after intervention, the incidence of acute attacks in the intervention group was lower than that before intervention(χ2=52.901, P<0.001), and the incidence of acute attacks in the groups with different intervention methods was lower than that before intervention (P<0.001). WeChat had the best effect, decreasing the incidence by 14.4%, followed by mobile phone SMS SMS decreasing by 12.3%. In terms of utilization of health services, the outpatient rate due to acute attack was lower in the intervention group after intervention than that before intervention (χ2=7.129, P=0.008), and the outpatient rate due to acute attack was lower in the subjects who received the forecast service through mobile phone SMS than that before intervention (χ2=4.675, P<0.001). In terms of medical expenses, there was no significant difference between control group and intervention group with different intervention methods before intervention (P>0.05). After intervention, the difference between the control group and the intervention group with different intervention methods was statistically significant (H=11.864, P<0.05). The results of multiple comparisons showed that compared with the control group, the average annual medical expenses of patients receiving mobile phone SMS and telephone forecasting services after intervention were lower than those of the control group, and the difference was statistically significant (P<0.05). ConclusionMeteorological risk forecasting service can reduce the acute onset of COPD, reduce the rate of consultation and medical expenses due to acute onset, and provide scientific basis for the basic COPD health management model.
7.Association between dietary rhythm and depressive symptoms in adolescents
ZHANG Yadi, XIE Yang, WANG Jiaojiao, ZHANG Xinyu, WAN Yuhui, TAO Fangbiao
Chinese Journal of School Health 2024;45(4):483-487
Objective:
To describe the prevalence and association of dietary rhythm and depressive symptoms among adolescents, so as to provide a basis for improving unhealthy behavioral habits,and to promote adolescent physical and mental health.
Methods:
From October to December 2021, a total of 22 868 students were selected from one middle school and high school in urban and rural areas of eight cities, namely, Shenyang, Xuzhou, Shenzhen, Taiyuan, Nanchang, Zhengzhou, Chongqing, and Kunming cities, China, using a combination of purposive sampling and stratified cluster random sampling. A self administered questionnaire was used to assess adolescents dietary rhythm, and the Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms. Binary Logistic regression model was employed to analyze the associations between adolescent dietary rhythm and depressive symptoms, while the associations between adolescent dietary rhythm and depressive symptoms across gender and physical activity levels were stratified by gender and physical activity levels.
Results:
The detection rate of depressive symptoms in adolescents was 44.4%. The respective differences in the detection rates of depressive symptoms among adolescents of different genders, physical activity levels, and dietary rhythm disorders were statistically significant ( χ 2=157.51, 105.02, 3 282.50, P <0.01). Taking the low disordered dietary rhythm group as the reference, binary Logistic regression analyses showed that after adjusting for confounding factors such as age, gender,family location, family economic situation, whether only child, parental education level, and learning burden, physical activity levels, depressive symptoms were positively correlated with adolescents in the moderate disordered dietary rhythm group ( OR=2.63, 95%CI =2.45-2.83) and the high disordered dietary rhythm group ( OR=6.38, 95%CI = 5.93- 6.86). In addition, after stratifying by gender, dietary rhythm were positively correlated with depressive symptoms. The moderate disordered group (male: OR=2.62, 95%CI =2.37-2.89, female: OR=2.67, 95%CI =2.40-2.97) and the highly disordered group (male: OR=5.74, 95%CI =5.19-6.35, female: OR=7.11, 95%CI =6.40-7.89) were positively correlated with depressive symptoms. After stratification by physical activity levels, low, moderate and above physical activity levels among adolescents in the disordered dietary rhythm group (low physical activity: OR=2.91, 95%CI =2.58-3.29, moderate and above physical activity: OR= 2.50, 95%CI =2.28-2.74), high disordered group (low physical activity: OR=6.51, 95%CI =5.94- 7.13 , moderate and higher physical activity: OR=6.18, 95%CI =5.47-6.97) were positively associated with depressive symptoms ( P <0.01). There was an interaction between dietary rhythm and physical activity levels in regard to the development of depressive symptoms in adolescents, taking the group with moderate and above physical activity levels and low disordered dietary rhythm as the reference,the detection rate of which was higher in adolescents with low levels of physical activity and those in the moderate or high disordered dietary rhythm group ( OR=1.50, 3.90, 95%CI=1.39-1.61, 3.63-4.19, P <0.01).
Conclusions
Dietary rhythm disorders were found to be positively associated with depressive symptoms in adolescents. Regular dietary behaviors and increased physical activity play an important positive role in promoting adolescent mental health.
8.Buyang Huanwu decoction promotes angiogenesis and improves hemorheological parameters after cervical spinal cord injury
Luchun Xu ; Yongdong Yang ; Guozheng Jiang ; Yushan Gao ; Jiawei Song ; Yukun Ma ; Jiaojiao Fan ; Guanlong Wang ; Xing Yu ; Xiangsheng Tang
Journal of Traditional Chinese Medical Sciences 2024;11(4):456-465
Objective:
To explore the effects of Buyang Huanwu decoction (BYHWD) on vascular neogenesis and hemorheological parameters following cervical spinal cord injury (SCI).
Methods:
An acute cervical SCI model was established using 84 female Sprague–Dawley rats. Functional recovery of the rats was evaluated using the forelimb locomotor scale score, forelimb grip strength test, and Basso-Beattie-Bresnahan score. The animals were subsequently euthanized at days 7 and 28 postoperatively. The gross morphology, neuronal survival, and myelin sheath in the injured area were evaluated using hematoxylin and eosin (HE), Nissl, and luxol fast blue (LFB) staining, respectively. Immunofluorescence staining was used to observe CD31 expression 7 days post-injury. Furthermore, the expression of CD31, neuronal nuclear protein (NeuN), and myelin basic protein (MBP) were evaluated 28 days post-injury. Additionally, vascular endothelial growth factor A (VEGFA) and VEGF receptor-2 (VEGFR-2) expression was evaluated using western blotting. Whole-blood viscosity, plasma viscosity, and red blood cell aggregation were measured using a hemorheometer.
Results:
From postoperative days 3–28, motor function in the BYHWD group began to recover considerably compared to the SCI group. BYHWD effectively restored spinal cord histopathology. In addition, the number of NeuN-positive cells, and fluorescence intensity of CD31at 7 and 28 days and MBP significantly increased in the BYHWD group compared with the SCI group (all P < .05). Moreover, this decoction significantly upregulated the expression of VEGFA and VEGFR-2 (all P < .05). BYHWD improved the hemorheology results (i.e., except erythrocyte aggregation index in the low-dose group), revealing statistically significant differences compared with the SCI group (all P < .05).
Conclusion
BYHWD effectively promoted angiogenesis, improved hemorheological parameters, and protected neurons and myelin sheaths, ultimately promoting the recovery of neurological function after cervical SCI in rats. These findings suggest that BYHWD promotes vascular neogenesis through the VEGFA/VEGFR-2 pathway.
9.Multi-omics Approach Reveals Influenza-A Virus Target Genes Associated Genomic,Clinical and Immunological Characteristics in Cancers
Wang JIAOJIAO ; Liao YONG ; Yang PINGLIAN ; Ye WEILE ; Liu YONG ; Xiao CHUNXIA ; Liao WEIXIONG ; Chen CHUNBO ; Liu ZHIPING ; Huang ZUNNAN
Biomedical and Environmental Sciences 2024;37(7):698-715
Objective To examine the precise function of influenza A virus target genes(IATGs)in malignancy. Methods Using multi-omics data from the TCGA and TCPA datasets,33 tumor types were evaluated for IATGs.IATG expression in cancer cells was analyzed using transcriptome analysis.Copy number variation(CNV)was assessed using GISTICS 2.0.Spearman's analysis was used to correlate mRNA expression with methylation levels.GSEA was used for the enrichment analysis.Pearson's correlation analysis was used to examine the association between IATG mRNA expression and IC50.The ImmuCellAI algorithm was used to calculate the infiltration scores of 24 immune cell types. Results In 13 solid tumors,IATG mRNA levels were atypically expressed.Except for UCS,UVM,KICH,PCPG,THCA,CHOL,LAMI,and MESO,most cancers contained somatic IATG mutations.The main types of CNVs in IATGs are heterozygous amplifications and deletions.In most tumors,IATG mRNA expression is adversely associated with methylation.RT-PCR demonstrated that EGFR,ANXA5,CACNA1C,CD209,UVRAG were upregulated and CLEC4M was downregulated in KIRC cell lines,consistent with the TCGA and GTEx data. Conclusion Genomic changes and clinical characteristics of IATGs were identified,which may offer fresh perspectives linking the influenza A virus to cancer.
10.Network pharmacology analysis on Panacis Quinquefolii Radix- Acori Tatarinowii Rhizoma for diabetes encephalopathy and experimental verification of its anti-inflammatory mechanism
Lin LIU ; Jiaojiao ZHANG ; Dongxue WANG ; Jingfei KANG ; Kai WANG ; Yang YANG
International Journal of Traditional Chinese Medicine 2024;46(1):56-62
Objective:To predict the mechanism of Panacis Quinquefolii Radix- Acori Tatarinowii Rhizoma (PQ-AT) in the treatment of diabetes encephalopathy (DE) using network pharmacology combined with molecular docking; To conduct experimental verification.Methods:The active components and targets of PQ and AT were screened by TCMSP database. The GeneCards and Disgenet were used to collect DE related target genes. String database and Cytoscape software were used to structure PPI network and perform visualization analysis. The common targets were imported into Metascape platform for GO annotation and KEGG enrichment analysis. Molecular docking was used to verify the binding ability of active components to core targets. Rats were randomly divided into a blank group, a model group, and a low-dose group of PQ-AT (1.08 g/kg), a high-dose group of PQ-AT (2.16 g/kg), and a metformin group (0.18 g/kg) using a random number table. To establish the rat model of diabetes encephalopathy, intraperitoneal injection of streptozotocin was used in addition to the blank group. After a 12-week drug intervention, TNF-α and Cyclooxygenase-2 (PTGS2) protein expression in the cerebral cortex of rats was detected using Western blot.Results:A total of 26 active components in PQ-AT and 107 related targets of DE were obtained, mainly including TNF, JUN, and PTSG2, which were mainly concentrated in TNF signaling pathway, cancer and other signal pathways. Molecular docking showed that the main active components of PQ-AT had relatively stable binding activity with TNF-α and PTGS2. Western blot results shows that compared with the model group, the expressions of PTGS2 and TNF-α significantly decreased in each administration group ( P<0.05 or P<0.01). Conclusion:PQ-AT can act on TNF, CASP3, JUN, STAT3, PTGS2 and other core targets to regulate signal pathways such as TNF, and inhibit inflammatory reaction to achieve the effect of treating DE.


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