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.PTPRD demethylation regulates the proliferation, migration, and chemoresistance of gastric cancer cells through the PI3K/Akt/mTOR pathway
LIU Yanhuia,b ; GAO Ziyua ; REN Pengb ; DU Yuxinb ; LIU Caixiaa ; XING Zhiweia
Chinese Journal of Cancer Biotherapy 2025;32(1):48-55
[摘 要] 目的:探究蛋白酪氨酸磷酸酶D(PTPRD)去甲基化通过PI3K/Akt/mTOR通路对胃癌细胞增殖、迁移及化疗耐药性的影响。方法:体外培养胃癌细胞MKN-74、MKN-45和人胃黏膜上皮细胞GES-1并检测PTPRD表达。常规培养MKN-45细胞及耐药MKN-45/5-FU细胞,分别转染PTPRD空载体(NC组、NC/5-FU组)、PTPRD过表达腺病毒(PTPRD组、PTPRD/5-FU组)、shRNA空载体(sh-NC组、sh-NC/5-FU组)、shRNA-PTPRD慢病毒(sh-PTPRD组、sh-PTPRD/5-FU组)和PTPRD过表达腺病毒 + 10 μmol/L 740Y-P处理(PTPRD + 740Y-P组、PTPRD + 740Y-P/5-FU组)。MTT法、划痕愈合实验检测各组细胞的增殖活力和迁移能力,细胞自噬实验检测细胞的自噬水平,WB法检测细胞中EMT和PI3K/Akt/mTOR通路相关蛋白的表达。采用0、2.5、5、10、20、40 μmol/L的5-aza处理MKN-45细胞,qPCR法、MTT法检测细胞中PTPRD mRNA表达和细胞增殖活力。结果:PTPRD mRNA和蛋白在胃癌细胞中均呈低表达(P < 0.05)。与MKN-45组相比,PTPRD组自噬体与自噬溶酶体数量、PTPRD、上皮钙黏素(E-cadherin)、BAX蛋白表达均增加(均P < 0.05),细胞增殖活力、细胞迁移率、p-PI3K、波形蛋白(vimentin)、p-Akt、p-mTOR蛋白表达均降低(均P < 0.05),sh-PTPRD组细胞增殖活力、细胞迁移率、p-PI3K、vimentin、p-Akt、p-mTOR蛋白表达均增加(均P < 0.05),自噬体与自噬溶酶体数量、PTPRD、E-cadherin、BAX蛋白表达均减少(均P < 0.05);与PTPRD组相比,PTPRD + 740Y-P组细胞增殖活力、细胞迁移率、p-PI3K、vimentin、p-Akt、p-mTOR蛋白表达均增加(均P < 0.05),自噬体与自噬溶酶体数量、PTPRD、E-cadherin、BAX蛋白表达减少(均P < 0.05)。随着5-aza浓度的增加,MKN-45细胞中PTPRD mRNA表达增加、细胞增殖活力均降低(均P < 0.05)。与MKN-45/5-FU组相比,PTPRD/5-FU组细胞迁移率、细胞增殖活力均降低(均P < 0.05),sh-PTPRD/5-FU组细胞迁移率、细胞增殖活力均增加(均P < 0.05);与PTPRD/5-FU组相比,PTPRD + 740Y-P/5-FU组细胞迁移率、细胞增殖活力均增加(均P < 0.05)。结论:PTPRD在胃癌细胞中呈低表达状态,PTPRD去甲基化可能通过抑制PI3K/Akt/mTOR信号通路抑制胃癌细胞增殖、迁移并增强其对化疗的敏感性。
3.Role of autophagy in treatment of paracetamol-induced liver injury
Guojing XING ; Lifei WANG ; Longlong LUO ; Xiaofeng ZHENG ; Chun GAO ; Xiaohui YU ; Jiucong ZHANG
Journal of Clinical Hepatology 2025;41(2):389-394
N-acetyl-p-aminophenol (APAP) is an antipyretic analgesic commonly used in clinical practice, and APAP overdose can cause severe liver injury and even death. In recent years, the incidence rate of APAP-induced liver injury (AILI) tends to increase, and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI, involving the mechanisms such as APAP protein conjugates, oxidative stress, JNK activation, mitochondrial dysfunction, inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI, in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.
4.Constructing a model of degenerative scoliosis using finite element method:biomechanical analysis in etiology and treatment
Kai HE ; Wenhua XING ; Shengxiang LIU ; Xianming BAI ; Chen ZHOU ; Xu GAO ; Yu QIAO ; Qiang HE ; Zhiyu GAO ; Zhen GUO ; Aruhan BAO ; Chade LI
Chinese Journal of Tissue Engineering Research 2025;29(3):572-578
BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.
5.A Meta-Analysis on the Efficacy and Safety of Xihuang Pill/Capsule( 西黄丸/胶囊) as an Adjuvant to Radio⁃therapy and Chemotherapy in the Treatment of Malignant Digestive Tract Tumors
Mengyi LI ; Lei ZHANG ; Lijun WANG ; Xing GAO
Journal of Traditional Chinese Medicine 2025;66(9):912-919
ObjectiveTo evaluate the efficacy and safety of Xihuang Pill/Capsule (西黄丸/胶囊, XP/XC) as an adjuvant to radiotherapy and/or chemotherapy in the treatment of malignant digestive tract tumors. MethodsA systematic search was conducted in the China Biomedical Literature Database, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, VIP Database, PubMed, Web of Science, Embase, and Cochrane Library for randomized controlled trials (RCTs) published before March 6, 2024, regarding the use of XP/XC in clinical adjuvant treatment of malignant digestive tract tumors. The methodological quality of the included studies was assessed using the risk of bias assessment tool. RevMan 5.4 was used to perform a Meta-analysis on 1-year survival rate, 2-year survival rate, clinical efficacy, including objective response rate and disease control rate, Karnofsky Performance Status (KPS) score, immune markers (CD3+, CD4+, CD8+, and CD4+/CD8+ ratio), and adverse event rates (incidence of gastrointestinal reactions and bone marrow suppression). ResultsThirteen RCTs involving 962 patients were included, with 527 patients in the experimental group and 435 patients in the control group. Meta-analysis results showed that the experimental group had better outcomes than the control group in terms of 2-year survival rate [RR = 0.49, 95% CI (0.31, 0.78)], objective response rate [RR = 0.68, 95% CI (0.60, 0.77)], disease control rate [RR = 0.85, 95% CI (0.80, 0.91)], and immune markers CD3+ [MD = -7.99, 95% CI (-9.12, -6.86)], CD4+ [MD = -5.42, 95% CI (-7.11, -3.74)], and CD4+/CD8+ ratio [MD = -0.26, 95% CI (-0.32, -0.20)] (P<0.05). However, no statistically significant differences were found between the experimental and control groups in terms of 1-year survival rate [RR = 0.91, 95% CI (0.73, 1.14)], KPS [MD = -3.73, 95% CI (-8.67, 1.21)], CD8+ [MD = -0.53, 95% CI (-1.45, 0.39)], incidence of gastrointestinal reactions [RR = 0.82, 95% CI (0.46, 1.46)], and incidence of bone marrow suppression [RR = 0.93, 95% CI (0.72, 1.20)] (P>0.05). ConclusionCompared with radiotherapy/chemotherapy alone, the combination of XP/XC with radiotherapy/chemotherapy can effectively improve clinical efficacy and 2-year survival rate, enhance immune function, and achieve similar adverse event rates as radiotherapy/chemotherapy alone in patients with malignant digestive tract tumors.
6.Research on the chemical compositions and their biological activities of Piper nigrum L.
Xing GAO ; Fengping ZHAO ; Wentao WANG ; Wei TIAN ; Canhui ZHENG ; Xin CHEN
Journal of Pharmaceutical Practice and Service 2025;43(7):313-319
Piper nigrum L. is an evergreen climbing vine, which belongs to the genus Piperia in the Piperaceae family. Piper nigrum L., which known as the “king of spices”, is used as both food and medicine. The main active substances in Piper nigrum L. are alkaloids mainly composed of amides, and essential oil, as well as phenolic compounds. In this paper, the chemical compositions, especially amide alkaloids, and their biological activities of Piper nigrum L. were summarized. These studies showed that Piper nigrum L., as a medicinal and food plant, had a wide range of biological activities and was deserved further research and in-depth utilization.
7.Research progress on the treatment role and chemical synthesis methods of isoselenoazolones
Wentao WANG ; Xing GAO ; Fengping ZHAO ; Canhui ZHENG ; Xin CHEN
Journal of Pharmaceutical Practice and Service 2025;43(8):367-372
Glutathione peroxidase (GSH-Px) is a key selenoenzyme that protects the body from oxidative damage. A series of small molecular organic selenium compounds have been designed and synthesized as functional mimics of GPx, among which isoselenazolones are the most widely studied. Taking ebselen as a representative, the catalytic mechanism of isoselenazolones in mimicing GSH-Px activity in vivo, the therapeutic effects of isoselenazolones in stroke, sensorineurium deafness and tinnitus, treatmentresistant depression (TRD) and coronavirus disease 2019 (COVID-19), and research on their chemical synthesis methods were summarized and discussed in this paper.
8.Rapid health technology assessment of inclisiran in the treatment of atherosclerotic cardiovascular disease with hypercholesterolemia
Xing GAO ; Tianya LIU ; Qian ZHANG ; Bo ZHANG ; Wei LI ; Ling LIU
China Pharmacy 2025;36(19):2460-2465
OBJECTIVE To evaluate the efficacy, safety and economy of inclisiran in the treatment of atherosclerotic cardiovascular disease with hypercholesterolemia. METHODS A rapid health technology assessment (HTA) approach was employed. HTA reports, systematic reviews(SR)/meta-analyses, and pharmacoeconomic studies related to inclisiran were systematically identified through comprehensive searches of Chinese and English databases, including PubMed, Embase, the Cochrane Library, CNKI and Wanfang database, supplemented by HTA institutional repositories. The search timeframe spanned from database inception to April 2025. The results of the studies were descriptively analysed and summarized through literature screening, data extraction and literature quality assessment. RESULTS The final analysis included 22 studies, comprising one HTA report, 15 SR/meta-analyses, and 6 pharmacoeconomic evaluations. Regarding therapeutic efficacy, compared with control group, inclisiran could significantly reduce the levels of low-density lipoprotein cholesterol, proprotein convertase subtilisin/kexin type 9, total cholesterol, triacylglycerol, apolipoprotein B, and lipoprotein(a), increase the level of high-density lipoprotein cholesterol, and reduce the risk of adverse cardiovascular events. In terms of safety, the inclisiran group showed no significant difference compared with the control group in the risk of total adverse events, serious adverse events, or non-serious adverse events; however, an increased incidence of injection site reactions was observed, most of which were mild. In terms of cost-effectiveness, there were discrepancies in research conclusions both domestically and internationally. More studies indicated that inclisiran did not demonstrate cost-effectiveness advantage and would require an appropriate price reduction to meet cost-effectiveness criteria. CONCLUSIONS Inclisiran demonstrates favorable efficacy and acceptable safety in treating atherosclerotic cardiovascular disease with hypercholesterolemia, though its economic profile requires improvement.
9.Unregistered treatment situation among pulmonary tuberculosis patients in Quzhou City from 2017 to 2023
YAN Qingxiu ; WANG Wei ; HAO Xiaogang ; GAO Yu ; FANG Chunfu ; ZHANG Xing ; LIU Wenfeng
Journal of Preventive Medicine 2025;37(8):799-803
Objective:
To analyze the unregistered treatment situation and its influencing factors among pulmonary tuberculosis patients in Quzhou City, Zhejiang Province from 2017 to 2023, so as to provide a basis for promoting the management of tuberculosis patients and optimizing disease prevention and control strategies.
Methods:
Data of pulmonary tuberculosis patients including demographic information, etiological results, and mortality status were collected through the China Disease Prevention and Control Information System Infectious Disease Reporting and Surveillance System and the Tuberculosis Management Information System. Pulmonary tuberculosis patients not matched in the Tuberculosis Management Information System were defined as unregistered treatment patients, and the unregistered treatment rate was analyzed. Factors affecting unregistered treatment among pulmonary tuberculosis patients were analyzed using a multivariable logistic regression model.
Results:
A total of 10 779 pulmonary tuberculosis patients were reported in Quzhou City from 2017 to 2023, including 7 700 males (71.44%) and 3 079 females (28.56%). There were 5 484 cases aged <65 years, accounting for 50.88%. Among them, 630 cases were unregistered treatment, with an unregistered treatment rate of 5.84% (95%CI: 5.42%-6.38%). Multivariable logistic regression analysis showed pulmonary tuberculosis patients aged ≥65 years (OR=1.829, 95%CI: 1.512-2.212) had a higher risk of being unregistered treatment than those aged <65 years; patients with non-local household registration (OR=5.710, 95%CI: 4.724-6.901) had a higher risk than local patients; and patients engaged in housework/unemployed (OR=2.001, 95%CI: 1.421-2.818) or other occupations (OR=2.396, 95%CI: 1.789-3.137) had a higher risk than farmers. The mortality of unregistered treatment pulmonary tuberculosis patients was higher than the registered treatment patients (26.67% vs. 5.02%),with a significantly elevated mortality risk (OR=7.147, 95%CI: 5.738-8.902).
Conclusions
The unregistered treatment rate among pulmonary tuberculosis patients was well controlled in Quzhou City from 2017 to 2023, but the elderly, patients with non-local household registration, and those engaged in housework/unemployed had a higher risk of unregistered treatment. It is recommended to improve medical and social security policies, strengthen health education on tuberculosis prevention, enhance treatment adherence, and reduce mortality risk.
10.Mediating effect of activities of daily living among patients with chronic obstructive pulmonary disease on caregiver ability and caregiver burden
LIU Wei ; GAO Xing ; WANG Danxin ; ZHANG Ling ; WANG Shiyuan ; LI Huiyan
Journal of Preventive Medicine 2025;37(11):1151-1154,1159
Objective:
To analyze the mediating effect of activities of daily living (ADL) among patients with chronic obstructive pulmonary disease (COPD) on caregiver ability and caregiver burden, so as to provide a basis for improving the quality of care.
Methods:
From February 2024 to March 2025, COPD patients and their caregivers from the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in Haikou were selected using convenience sampling method. Data on the basic characteristics of both caregivers and patients were collected through questionnaire surveys. The Chinese version of the Family Caregiver Capacity Scale, the Chinese version of the Caregiver Burden Inventory, and the Barthel Index were used to assess caregiver ability, caregiver burden, and patients' ADL, respectively. The mediating effect of ADL among COPD patients on caregiver ability and caregiver burden was analyzed using the Process macro 4.0, with the significance tested via the Bootstrap method.
Results:
A total of 348 caregivers were surveyed, among whom 274 (78.74%) were females and 74 (21.26%) were males. The majority of caregivers were aged 40 years and above, with 291 individuals (83.62%). The relationship between caregivers and patients was primarily that of being their children, with 185 individuals (53.16%). Correspondingly, 348 COPD patients were surveyed, and the predominant type of medical insurance was the New Rural Cooperative Medical Scheme, with 172 cases (49.43%). The median scores of caregiver ability, caregiver burden, and patients' ADL were 19.00 (interquartile range, 5.00), 47.00 (interquartile range, 8.00) and 45.00 (interquartile range, 15.00) points, respectively. Mediating analysis showed that caregiver ability directly affected caregiver burden, with an effect value of 0.693 (95%CI: 0.553-0.832). It also indirectly affected caregiver burden through the patients' ADL, with an effect value of 0.104 (95%CI: 0.029-0.179). This mediating effect accounted for 13.05% of the total effect.
Conclusion
The ADL of COPD patients played a mediating role between caregiver ability and caregiver burden, with caregiver ability exerting a significant positive indirect effect on caregiver burden through patients' ADL.


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