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.Discovery and proof-of-concept study of a novel highly selective sigma-1 receptor agonist for antipsychotic drug development.
Wanyu TANG ; Zhixue MA ; Bang LI ; Zhexiang YU ; Xiaobao ZHAO ; Huicui YANG ; Jian HU ; Sheng TIAN ; Linghan GU ; Jiaojiao CHEN ; Xing ZOU ; Qi WANG ; Fan CHEN ; Guangying LI ; Chaonan ZHENG ; Shuliu GAO ; Wenjing LIU ; Yue LI ; Wenhua ZHENG ; Mingmei WANG ; Na YE ; Xuechu ZHEN
Acta Pharmaceutica Sinica B 2025;15(10):5346-5365
Sigma-1 receptor (σ 1R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K i < 4 nmol/L) and selective σ 1R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ 1R in relation to σ 2R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ 1R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.
3.Correlation between the expression of serum miR-1298-5p,miR-625-5p and miR-155 and the degree of Helicobacter pylori infection in elderly gastric cancer patients
Chunli TANG ; Shujuan FAN ; Sheng TAO ; Jianning LIU ; Feng SU ; Caiyun YUAN ; Meiling ZHU ; Ruimei ZHONG ; JiaoJiao CAO ; Yun WANG
International Journal of Laboratory Medicine 2025;46(2):151-156
Objective To explore the correlation between the expression of serum microRNA(miR)-1298-5p,miR-625-5p,and miR-155 with the degree of Helicobacter pylori(Hp)infection in elderly gastric cancer patients.Methods From January 2021 to November 2023,120 elderly patients with gastric cancer admitted to the hospital from January 2021 to November 2023 were selected as the gastric cancer group,and 130 non-gas-tric cancer patients who underwent gastroscopy were selected as the control group.The expression levels of miR-1298-5p,miR-625-5p and miR-155 in serum were detected by fluorescence quantitative PCR(qPCR).Car-bon 13 urea breath test was used to detect the positive rate of Hp infection in two groups,and the degree of Hp infection in elderly patients with gastric cancer were evaluated.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum miR-1298-5p,miR-625-5p,and miR-155 expression levels for Hp infection in elderly gastric cancer patients.Pearson method was applied to analyze the correlation between serum miR-1298-5p,miR-625-5p,miR-155 expression and positive rate of Hp infection in elderly gas-tric cancer patients.Results Compared with the control group,the expression levels of miR-1298-5p and miR-625-5p in serum of gastric cancer group decreased(P<0.05),while the positive rate of Hp infection and the expression level of serum miR-155 increased(P<0.05).The expression levels of serum miR-1298-5p and miR-625-5p in elderly gastric cancer patients with Hp grade Ⅰ,Ⅱ,and Ⅲ infection were lower than those without Hp infection,while the expression level of miR-155 was higher(P<0.05).Patients with poor differ-entiation,lymph node metastasis,and TNM stage Ⅲ-Ⅳ had lower expressions of serum miR-1298-5p and miR-625-5p(P<0.05),and higher expression of miR-155(P<0.05)than those with moderate-high differen-tiation,no lymph node metastasis,and TNM stage Ⅰ-Ⅱ.The expression levels of serum miR-1298-5p and miR-625-5p were negatively correlated with the positive rate of Hp infection in elderly patients with gastric cancer(r=-0.443,-0.386,both P<0.001),and the expression levels of serum miR-155 were positively correlated with the positive rate of Hp infection(r=0.525,P<0.001).The area under the curve(AUC)of serum miR-1298-5p,miR-625-5p and miR-155 combined diagnosis of Hp infection in elderly gastric cancer pa-tients was higher than that of single diagnosis(P<0.05).Conclusion The expression levels of miR-1298-5p and miR-625-5p in serum of elderly gastric cancer patients with Hp infection decrease,while the expression level of miR-155 increases.These three factors are related to the degree of Hp infection and have good diag-nostic value for the occurrence of Hp infection.
4.Comparison of the efficacy of acupuncture-related therapies in treating postoperative pain in patients with osteoporotic vertebral compression fractures after percutaneous kyphoplasty or percutaneous vertebroplasty: A network meta-analysis
Jiaojiao Fan ; Yushan Gao ; Yang Xiong ; Duoduo Li ; Luchun Xu ; Guozheng Jiang ; Guanlong Wang ; Xing Yu ; Yongdong Yang
Journal of Traditional Chinese Medical Sciences 2025;2025(4):470-482
ObjectiveTo evaluate the clinical efficacy of different acupuncture-related therapies in treating postoperative pain in patients with osteoporotic vertebral compression fractures (OVCFs) after percutaneous kyphoplasty (PKP) or percutaneous vertebroplasty (PVP) using a network meta-analysis.MethodsA systematic search was conducted in PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database (SinoMed) from their inception to January 15, 2025. Outcome measures included the Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI) score, and overall efficacy rate. Literature screening, data extraction, and risk-of-bias assessment were independently performed by two researchers. Data analysis was conducted using Stata 17.0 software.ResultsA total of 35 randomized controlled trials involving 2860 patients were included. The data analysis revealed that, in terms of improving VAS and ODI scores, the top three effective therapies were Fu's subcutaneous needling, wrist-ankle acupuncture, and acupotomy. For the overall efficacy rates in pain treatment, the top three therapies were wrist-ankle acupuncture, warm acupuncture and moxibustion, and Fu's subcutaneous needling. Based on the combined results across the three outcome measures, Fu's subcutaneous needling was found to be the most effective in relieving pain and improving lumbar function.ConclusionFu's subcutaneous needling, wrist-ankle acupuncture, warm acupuncture and moxibustion, and acupotomy were all effective in treating postoperative pain post-PKP/PVP and improving lumbar function. However, further high-quality, large-sample studies are required to confirm these findings.
5.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.
6.The value of quantitative parameters of diffusion weighted imaging in differentiating the nature of ovarian epithelial tumors
Jiaojiao FAN ; Yang LIU ; Ruichao LIU ; Guanxiong LI ; Ziteng XIE ; Wei XIA
Journal of Practical Radiology 2024;40(9):1468-1471,1498
Objective To investigate the value of minimum apparent diffusion coefficient(ADCmin)and delta apparent diffusion coefficient(dADC)of quantitative parameters of MR diffusion weighted imaging(DWI)in differentiating benign from stage Ⅰ malignant ovarian epithelial tumors.Methods A total of 112 patients with primary ovarian epithelial tumors confirmed by operation and pathology(43 benign tumors and 69 stage Ⅰ malignant tumors)were retrospectively selected.All patients underwent routine MRI and DWI before operation.The ADCmin and dADC of solid portion were measured and compared between the two groups.Logistic regression anal-ysis and receiver operating characteristic(ROC)curve were used to evaluate diagnostic performance of each parameter alone and in combination in differentiating ovarian epithelial benign and stage Ⅰ malignant tumors.Results The ADCmin was greater in benign tumors than that in stage Ⅰ malignant tumors,while dADC was smaller in benign tumors than that in stage Ⅰ malignant tumors(P<0.05).Logis-tic regression analysis showed that ADCmin and dADC were independent risk factors for stage Ⅰ malignant tumors.With threshold of 1.183 × 10-3 mm2/s for ADCmin and 0.579 × 10-3 mm2/s for dADC,the area under the curve(AUC)was 0.802 and 0.857,sensitivity and specificity of 0.885,0.808,0.714,0.857,respectively.According to regression equation logit(P)=7.154+0.267 × dADC-1.016 X ADCmin,the AUC(0.951)was greater than that of single parameter,the sensitivity was 0.890,the specificity was 0.995.Conclusion ADCmin and dADC are useful for differentiating ovarian epithelial benign from stage Ⅰ malignant tumors,and ADCmin combined with dADC can improve the diagnose accuracy before operation.
7.Research progress on neurological mechanisms of language development in preterm infants
Jiaojiao FAN ; Tian HONG ; Jiali BAN ; Qinfen ZHANG
Chinese Journal of Perinatal Medicine 2024;27(11):959-964
Preterm infants significantly lag behind full-term infants in various behavioral and cognitive aspects of language development. The maturity of the nervous system in preterm infants may be a key factor limiting their language development. In terms of brain structure, preterm infants typically have smaller brain volumes, slower developmental speeds, and are more susceptible to injury, which may hinder the development of information processing and language abilities. Functionally, the brain activity patterns of preterm infants differ from those of full-term infants, involving different brain activation regions and network connectivity when processing language-related tasks. This suggests that preterm infants may require more effort or adopt different neural pathways for language comprehension and output. This article reviews the research progress on the neural mechanisms of language development in preterm infants to provide insights for further research in this area.
8.Role of checklist-based management in the weekly work point mechanism of a multi-campus hospital in Ningxia
Xiangnan WANG ; Wei LIU ; Fan DING ; Kai DING ; Jiaojiao LI ; Mincui XI ; Xuanhuo WANG ; Yanjie ZHANG
Modern Hospital 2024;24(5):737-739
The integrated management of multi-campus public hospitals is a mandate for national assessment and compul-sory requirement for high-quality advancement of public hospitals.A challenge in multi-campus hospital management is to accel-erate the standardization of various hospital campuses and facilitate the information sharing among them.Based on the manage-ment practices of multi-campus hospitals in Ningxia,this paper discussed the challenges encountered in the integrated manage-ment of multi-campus hospitals.It proposed strategies to enhance homogeneous management and inter-hospital coordination in multi-hospital and multi-campus hospital to provide valuable references.
9.The efficacy and safety of recombinant human thrombopoietin in the treatment of thrombocytopenia caused by tumor radiotherapy
Bing WANG ; Aifu WANG ; Wenshu LIU ; Jiaojiao FAN ; Weicheng TIAN ; Weili WANG ; Boyu LIU
Journal of International Oncology 2023;50(11):661-667
Objective:To observe the efficacy and safety of recombinant human thrombopoietin (rhTPO) in the treatment of radiation induced thrombocytopenia (RIT) .Methods:From January 2019 to March 2021, 204 cases (including 101 cases of radiotherapy alone and 103 cases of concurrent chemoradiotherapy) were collected retrospectively after radiotherapy and with decreased in blood platelet count <75×10 9/L in Jilin Cancer Hospital. These patients received rhTPO 15 000 U, once a day, subcutaneous, for at least 4 consecutive days, or met the withdrawal criteria blood platelet count ≥100×10 9/L, or the absolute value of blood platelet increase ≥50×10 9/L. The characteristics of blood platelet decline, treatment efficacy, and safety were analyzed. Results:The numbers of radiotherapy treatments with platelets lower than 75×10 9/L in the radiotherapy alone group and the concurrent chemoradiotherapy group were 19 (13, 22) and 13 (10, 17) times, respectively, indicating that patients in the concurrent chemoradiotherapy group experienced platelet decline earlier ( Z=-5.27, P<0.001), the lowest values of platelet decline in the two groups were 68 (45, 74) ×10 9/L and 62 (44, 74) ×10 9/L, respectively, with no statistically significant difference ( Z=-1.15, P=0.252). After received rhTPO treatment, the numbers of days that the two groups of patients had platelets <50×10 9/L were 7 (3, 13) d and 7 (5, 11) d, respectively, with no statistically significant difference ( Z=-1.13, P=0.281). After the patients received radiotherapy, rhTPO was started when the platelet count dropped to <75×10 9/L. The number of days required to recover to 75×10 9/L was 4 (2, 10) d in the radiotherapy alone group and 4 (2, 8) d in the concurrent chemoradiotherapy group, with no statistically significant difference ( Z=-1.07, P=0.285) ; the number of days required for platelets to recover to 100×10 9/L or for the absolute value to increase by 50×10 9/L was 8 (6, 14) d in the radiotherapy alone group and 11 (8, 16) d in the concurrent chemoradiotherapy group. The recovery time of the concurrent chemoradiotherapy group was longer than that of the radiotherapy alone group ( Z=-3.64, P<0.001). Regardless of the baseline level, there was no statistically significant difference in the number of days for platelets to recover to 75×10 9/L after rhTPO treatment between the radiotherapy alone group and the concurrent chemoradiotherapy group ( Z=-1.42, P=0.155; Z=-0.97, P=0.332). The number of days required for the two groups of patients to recover to 100×10 9/L or for the absolute value to increase by 50×10 9/L were 8 (6, 14) d and 11 (8, 16) d, respectively, with a statistically significant difference ( Z=-3.64, P<0.001). The numbers of days required for the two groups of patients with baseline platelets ≥50×10 9/L to recover to 100×10 9/L or for the absolute value to increase by 50×10 9/L were 8 (4, 12) d and 10 (8, 16) d, respectively, with a statistically significant difference ( Z=-3.12, P=0.002). However, there was no statistically significant difference in the number of days required for the two groups of patients with baseline platelets <50×10 9/L to recover to 100×10 9/L or for the absolute value to increase by 50×10 9/L ( Z=-1.88, P=0.061). The total platelet elevation rate of rhTPO within 20 days of radiotherapy treatment for both groups of patients was 93.63% (191/204), of which 95.05% (96/101) was for radiotherapy alone and 92.23% (95/103) for concurrent chemoradiotherapy, with no statistically significant difference ( χ2=0.68, P=0.410). In addition, there was no statistically significant difference in gender ( χ2=3.47, P=0.063), age ( χ2=2.79, P=0.095), TNM staging ( χ2=5.07, P=0.167), and baseline platelet count ( χ2=0.62, P=0.822) between the two groups.During the radiotherapy cycle, 27 patients (13.23%) received blood platelet infusion, and 158 patients (77.45%) completed the radiotherapy plan without interruption. No rhTPO-related adverse reactions were found. Conclusion:rhTPO in the treatment for RIT can effectively promote the recovery of blood platelet without any adverse reactions, and has good safety.
10.CircR2Disease v2.0:An Updated Web Server for Experimentally Validated circRNA-disease Associations and Its Application
Fan CHUNYAN ; Lei XIUJUAN ; Tie JIAOJIAO ; Zhang YUCHEN ; Wu FANG-XIANG ; Pan YI
Genomics, Proteomics & Bioinformatics 2022;20(3):435-445
With accumulating dysregulated circular RNAs(circRNAs)in pathological processes,the regulatory functions of circRNAs,especially circRNAs as microRNA(miRNA)sponges and their interactions with RNA-binding proteins(RBPs),have been widely validated.However,the collected information on experimentally validated circRNA-disease associations is only preliminary.Therefore,an updated CircR2Disease database providing a comprehensive resource and web tool to clarify the relationships between circRNAs and diseases in diverse species is necessary.Here,we present an updated CircR2Disease v2.0 with the increased number of circRNA-disease associations and novel characteristics.CircR2Disease v2.0 provides more than 5-fold experimentally validated circRNA-disease associations compared to its previous version.This version includes 4201 entries between 3077 circRNAs and 312 disease subtypes.Secondly,the information of circRNA-miRNA,circRNA-miRNA-target,and circRNA-RBP interactions has been manually collected for various diseases.Thirdly,the gene symbols of circRNAs and disease name IDs can be linked with various nomenclature databases.Detailed descriptions such as samples and journals have also been integrated into the updated version.Thus,CircR2Disease v2.0 can serve as a platform for users to systematically investigate the roles of dysregulated circRNAs in various diseases and further explore the posttranscriptional regulatory function in diseases.Finally,we propose a computational method named circDis based on the graph convolutional network(GCN)and gradient boosting decision tree(GBDT)to illustrate the applications of the CircR2Disease v2.0 database.


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