1.Creation and Exploration of the"Organized Fill-in-the-Blank Format"Disci-pline Construction Model for Forensic Medicine in the New Era
Zhi-Wen WEI ; Hong-Xing WANG ; Jun-Hong SUN ; Hao-Liang FAN ; Hong-Liang SU ; Le-Le WANG ; Wen-Ting HE ; Zhe CHEN ; Jie ZHANG ; Xiang-Jie GUO ; Ji LI ; Geng-Qian ZHANG ; Xin-Hua LIANG ; Jiang-Wei YAN ; Qiang-Qiang ZHANG ; Cai-Rong GAO ; Ying-Yuan WANG ; Hong-Wei WANG ; Jun XIE ; Bo-Feng ZHU ; Ke-Ming YUN
Journal of Forensic Medicine 2025;41(1):25-29
Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.
2.Construction of core outcome set for clinical research on traditional Chinese medicine treatment of simple obesity.
Tong-Tong WU ; Yan YU ; Qian HUANG ; Xue-Yin CHEN ; Fu-Ming-Xiang LIU ; Li-Hong YANG ; Chang-Cai XIE ; Shao-Nan LIU ; Yu CHEN ; Xin-Feng GUO
China Journal of Chinese Materia Medica 2025;50(12):3423-3430
Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans
;
Obesity/therapy*
;
Medicine, Chinese Traditional
;
Randomized Controlled Trials as Topic
;
Treatment Outcome
;
Drugs, Chinese Herbal/therapeutic use*
3.Safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2 in patients with advanced integrin α v β 3-positive tumors: A first-in-human study.
Huimin SUI ; Feng GUO ; Hongfei LIU ; Rongxi WANG ; Linlin LI ; Jiarou WANG ; Chenhao JIA ; Jialin XIANG ; Yingkui LIANG ; Xiaohong CHEN ; Zhaohui ZHU ; Fan WANG
Acta Pharmaceutica Sinica B 2025;15(2):669-680
Integrin α v β 3 is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2, a novel integrin α v β 3-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α v β 3-avid tumors were recruited to accept 177Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. 177Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of 177Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α v β 3-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.
4.mRNA display-enabled discovery of proximity-triggered covalent peptide-drug conjugates.
Ruixuan WANG ; Siqi RAN ; Jiabei GUO ; Da HU ; Xiang FENG ; Jixia ZHOU ; Zhanzhi ZHANG ; Futian LIANG ; Jiamin SHANG ; Lingxin BU ; Kaiyi WANG ; Junyi MAO ; Huixin LUO ; Rui WANG
Acta Pharmaceutica Sinica B 2025;15(10):5474-5485
Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>1013 variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N3 via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC50 ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.
5.Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway.
Mao-Feng ZHONG ; Yu-Jun LUO ; Yu-Yu GUO ; Shuang XIANG ; Wan-Fu LIN
Journal of Integrative Medicine 2025;23(6):683-693
OBJECTIVE:
Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis.
METHODS:
Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels.
RESULTS:
In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A.
CONCLUSION
JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683-693.
Carcinoma, Hepatocellular/blood supply*
;
Humans
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STAT3 Transcription Factor/metabolism*
;
Interleukin-8/metabolism*
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Liver Neoplasms/blood supply*
;
Aurora Kinase A/metabolism*
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Neovascularization, Pathologic/drug therapy*
;
Animals
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Signal Transduction/drug effects*
;
Mice
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Drugs, Chinese Herbal/therapeutic use*
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Cell Line, Tumor
;
Mice, Inbred BALB C
;
Mice, Nude
;
Angiogenesis
6.Associations of Exposure to Typical Environmental Organic Pollutants with Cardiopulmonary Health and the Mediating Role of Oxidative Stress: A Randomized Crossover Study.
Ning GAO ; Bin WANG ; Ran ZHAO ; Han ZHANG ; Xiao Qian JIA ; Tian Xiang WU ; Meng Yuan REN ; Lu ZHAO ; Jia Zhang SHI ; Jing HUANG ; Shao Wei WU ; Guo Feng SHEN ; Bo PAN ; Ming Liang FANG
Biomedical and Environmental Sciences 2025;38(11):1388-1403
OBJECTIVE:
The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress.
METHODS:
A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators.
RESULTS:
Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function.
CONCLUSION
Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans
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Oxidative Stress/drug effects*
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Male
;
Cross-Over Studies
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Female
;
Young Adult
;
Environmental Pollutants/toxicity*
;
Environmental Exposure/adverse effects*
;
Biomarkers/blood*
;
Adult
;
Blood Pressure/drug effects*
;
Polycyclic Aromatic Hydrocarbons/urine*
;
Beijing
7.Identify the metabolites of total saponins of Platycodonis Radix in blood based on intestinal bacteria-mediated method
Xi-wa WU ; Xin-yu ZHANG ; Yuan-han ZHONG ; Xue-mei ZHANG ; Yu ZHOU ; Yan FENG ; Qian QIN ; Shou-wen ZHANG ; Guo-yue ZHONG ; Jin-xiang ZENG
Acta Pharmaceutica Sinica 2024;59(11):3141-3152
The identification of the components absorbed in serum of platycosides in total saponins fraction of Platycodonis Radix
8.The role and mechanism of miR-34a/SIRT1 in intensive care unit acquired weakness
Zheng-Xiao LIN ; Zhao-Xia XU ; Juan CHEN ; Jian HU ; Guo-Yun ZHU ; Zhong-Li ZHU ; Jian FENG ; Fu-Xiang LI
Medical Journal of Chinese People's Liberation Army 2024;49(7):796-803
Objective To investigate the role and underlying mechanisms of miR-34a/SIRT1 in intensive care unit acquired weakness(ICU-AW).Methods(1)C2C12 mouse skeletal muscle cells were induced to differentiate into myotubes,and were divided into two groups:model group[ICU-AW group,treated with lipopolysaccharides(LPS)for 12 hours]and normal control group(treated with the same amount of sterile water for 12 hours).Western blotting was used to detect the protein expression level of Muscle ring finger 1(MuRF-1),atrophy gene 1(Atrogin-1)and Sirtuin-1(SIRT1).RT-qPCR was used to assess the mRNA expression level of microRNA-34a(miR-34a),MuRF-1,Atrogin-1 and SIRT1,and light microscope was used to observe the growth and differentiation of C2C12 skeletal muscle cells in each group.(2)ICU-AW cells were further subdivided into control group(treated with siRNA transfection agent intervention),Scra siRNA group(treated with transfection agent and non-specific siRNA),miR-34a siRNA group(treated with transfection agent and specific siRNA intervention),vehicle group(treated with agonist solvent dimethyl sulfoxide)and SRT1720 group(treated with SIRT1 agonist SRT1720).Western blotting was used to detect the protein expression level of SIRT1,Atrogin-1 and MuRF-1 in each group.RT-qPCR was used to detect the miR-34a and the mRNA expression level of SIRT1,Atrogin-1 and MuRF-1 in each group.(3)In addition,another group of ICU-AW cells were divided into control group(treated with siRNA transfection),miR-34a siRNA group(treated with transfection agent and specific siRNA intervention),miR-34a siRNA+vehicle group(treated with transfection agent,specific siRNA and Dimethyl sulfoxide intervention)and miR-34a siRNA+EX-527 group(treated with transfection agent,specific siRNA and SIRT1 inhibitor EX-527).Western blotting was used to detect the protein expression level of Atrogin-1 and MuRF-1.RT-qPCR was used to assess the mRNA expression level of Atrogin-1 and MuRF-1.Results Myotube differentiation was observed on the 4th day.Compared with control group,myotube atrophy was obvious in ICU-AW group.RT-qPCR and Western blotting results revealed that,compared with normal control group,in ICU-AW group,the mRNA and protein expression levels of Atrogin-1 and MuRF-1 significantly increased(P<0.05),and the expression level of miR-34a significantly increased(P<0.05),while the mRNA and protein expression levels of SIRT1 significantly decreased(P<0.05).RT-qPCR results showed that,compared with control group(treated with siRNA transfection agent intervention)and Scra siRNA group,the expression of miR-34a and mRNA expression of Atrogin-1 and MuRF-1 in miR-34a siRNA group significantly decreased(P<0.05),while the mRNA expression of SIRT1 significantly increased(P<0.05),meanwhile the protein expression of Atrogin-1 and MuRF-1 decreased significantly(P<0.01),and the protein expression of SIRT1 significantly increased(P<0.05).RT-qPCR results also showed that,compared with vehicle group,the mRNA expression of Atrogin-1 and MuRF-1 in SRT1720 group decreased significantly(P<0.05),while SIRT1 increased significantly(P<0.05).Western blotting results demonstrated that,compared with control group and Scra siRNA group,the protein expression of Atrogin-1 and MuRF-1 in miR-34a siRNA group decreased significantly(P<0.05),while SIRT1 increased significantly(P<0.05).RT-qPCR and Western blotting results indicated that,compared with miR-34a siRNA+vehicle group,the mRNA and protein expression of Atrogin-1 and MuRF-1 in miR-34a siRNA+EX-527 group increased significantly(P<0.05).Conclusion Overactivation of miR-34a in ICU-AW contributes to skeletal muscle atrophy by inhibiting the expression of SIRT1,which may play an important role in the pathogenesis of ICU-AW.
9.Effect of minocycline on polarization of types M1/M2 microglia in spinal cord in rats after spinal nerve ligation
Zhihong CHENG ; Song FENG ; Xia WANG ; Ruinan NI ; Yang GUO ; Yu XIANG ; Zhengwei YANG ; Bin PENG
Journal of Army Medical University 2024;46(15):1740-1750
Objective To investigate the effect of minocycline(Mino)on the polarization of types M1/M2 microglia(pro-and anti-inflammatory type)in the spinal dorsal horn of rats with neuropathic pain(NP)induced by spinal nerve ligation(SNL)and its underlying mechanism.Methods A total of 36 adult male SD rats were randomly stratified into Sham-operation(Sham)group,SNL group and Mino+SNL group by stratified random sampling based on body weight.Mechanical pain threshold and cold nociceptive thresholds of rat hind paw were measured in 1 d before and 14 d after modelling.Spinal cord tissue at the lumbar 5(L5)segment was taken at 14 d after modelling,and the total number of microglia as well as the numbers of M1 and M2 microglia in the spinal dorsal horn were measured with immunohistochemistry and stereology.With aid of bioinformatics techniques,the core target in the spinal cord,Cst7,was selected.Then,the protein levels of microglia marker Iba-1,M1 microglia marker iNOS,M2 microglia marker CD206,Cst7 encoded protein cystatin F(CF)and pathway CatS/CX3CL1/CX3CR1 were detected with Western blotting.The expression levels of TNF-α,IL-6 and IL-10 in the spinal cord tissues were measured with ELISA.Results The mechanical pain and cold nociceptive thresholds were both significantly higher in the M+SNL group than the SNL group at 7~14 d after modelling(P<0.01).The total number of microglia and the numbers of M1/M2 microglia in the spinal dorsal horn as well as the expression levels of CatS,CX3CL1,CX3CR1,TNF-α,IL-6,and IL-10 in the spinal cord tissues were obviously increased,and the expression level of CF was notably decreased in the SNL model group than the Sham group(P<0.01).While,Mino treatment remarkably reversed above phenomena,with decreased total number of microglia and number of M1 microglia as well as expression levels of CatS,CX3CL1,CX3CR1,TNF-α and IL-6,and increased number of M2 microglia as well as CF and IL-10 levels when compared with the SNL group(P<0.05).Conclusion Mino alleviates SNL induced neuropathic pain,probably through up-regulating CF in the microglia,and thus inhibiting the CatS/CX3CL1/CX3CR1 signaling pathway,promoting the conversion of microglia from type M1 to M2 to balance the imbalance in the M1/M2 polarization,and thus reducing neuroinflammation.
10.Research progress of NLRP3 inflammasome inhibitors
Chen-Guang LI ; Feng-Yi MAI ; Jing-Rong LIANG ; Wen-Tao YANG ; Jie GUO ; Jun-Xiang SHU ; Li-Zu XIAO
Chinese Pharmacological Bulletin 2024;40(10):1801-1808
NLRP3 can recruit proteins such as ASC and pro-caspase1 to form NLRP3 inflammasomes after being stimulated by pathogen and danger signals in vivo,and then induce pyropto-sis and promote the inflammatory reactions to maintain the home-ostasis.However,the overactivation of NLRP3 inflammasomes is closely related to many inflammatory and autoimmune diseases in humans.Targeted inhibition of NLRP3 inflammasomes can sig-nificantly inhibit inflammation and alleviate the relative symp-toms.Therefore,it is an important research direction for treating diseases of NLRP3 inflammasome that searching for effective in-hibitors targeting NLRP3 inflammasome activation and achieving clinical transformation.This review summarizes the latest re-search progress based on the sources of NLRP3 inflammasome inhibitors.

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